bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure 4 from Co-occurring EGFR p.E709X Mutation Mediates Primary Resistance to the Third-Generation EGFR-TKIs in EGFR p.G719X-Mutant Patients with Advanced NSCLC
Authors: Pang Lanlan , Huang Yihua , Zhuang Weitao , Zhang Yaxiong , Liao Jun , Hao Yue , Hao Feng , Wang Guoqian , Chen Ze-xin Chase , Zhu Yu , Li Mengzhen , Song Zhengbo , Deng Bo Peng , Li Jing , Zhang Li , Fang Wenfeng
Published: June 2024

Supplementary Figure 4. Drug sensitivity of different EGFR-TKIs in Ba/F3 cells expressing indicated EGFR p.G719S or EGFR p.E709K/G719S. (Data obtained from a public dataset of one published article, Reference: Nature. 2021 Sep; 597(7878):732-737.)
Supplementary Figure 3 from Co-occurring EGFR p.E709X Mutation Mediates Primary Resistance to the Third-Generation EGFR-TKIs in EGFR p.G719X-Mutant Patients with Advanced NSCLC
Authors: Pang Lanlan , Huang Yihua , Zhuang Weitao , Zhang Yaxiong , Liao Jun , Hao Yue , Hao Feng , Wang Guoqian , Chen Ze-xin Chase , Zhu Yu , Li Mengzhen , Song Zhengbo , Deng Bo Peng , Li Jing , Zhang Li , Fang Wenfeng
Published: June 2024

Supplementary Figure 3. Genomic characteristics was found between patients receiving afatinib or the third-generation EGFR-TKIs.
Supplementary Figure 2 from Co-occurring EGFR p.E709X Mutation Mediates Primary Resistance to the Third-Generation EGFR-TKIs in EGFR p.G719X-Mutant Patients with Advanced NSCLC
Authors: Pang Lanlan , Huang Yihua , Zhuang Weitao , Zhang Yaxiong , Liao Jun , Hao Yue , Hao Feng , Wang Guoqian , Chen Ze-xin Chase , Zhu Yu , Li Mengzhen , Song Zhengbo , Deng Bo Peng , Li Jing , Zhang Li , Fang Wenfeng
Published: June 2024

Supplementary Figure 2. Impact of EGFR p.E709X mutation in patients harboring EGFR p.G719X mutant patients and genomic features of EGFR p.G719X mutant patients with NSCLC in the validation cohort.
Data from A Phase I Trial of Nab-Paclitaxel/Bevacizumab (AB160) Nano-Immunoconjugate Therapy for Gynecologic Malignancies
Authors: Kalogera Eleftheria , Nevala Wendy K. , Finnes Heidi D. , Suman Vera J. , Schimke Jill M. , Strand Carrie A. , Kottschade Lisa A. , Kudgus Rachel A. , Buhrow Sarah A. , Becher Laura R. , Geng Liyi , Glaser Gretchen E. , Grudem Megan E. , Jatoi Aminah , Klampe Carolyn M. , Kumar Amanika , Langstraat Carrie L. , McWilliams Robert R. , Wahner Hendrickson Andrea E. , Weroha S. John , Yan Yiyi , Reid Joel M. , Markovic Svetomir N. , Block Matthew S.
Published: June 2024

AbstractPurpose:
AB160 is a 160-nm nano-immunoconjugate consisting of nab-paclitaxel (ABX) nanoparticles noncovalently coated with bevacizumab (BEV) for targeted delivery into tissues expressing high levels of VEGF. Preclinical data showed that AB160 resulted in greater tumor targeting and tumor inhibition compared with sequential treatment with ABX then BEV. Given individual drug activity, we investigated the safety and toxicity of AB160 in patients with gynecologic cancers.
Patients and Methods:
A 3+3 phase I trial was conducted with three potential dose levels in patients with previously treated endometrial, cervical, and platinum-resistant ovarian cancer to ascertain the recommended phase II dose (RP2D). AB160 was administered intravenously on days 1, 8, and 15 of a 28-day cycle (ABX 75–175 mg/m2, BEV 30–70 mg/m2). Pharmacokinetic analyses were performed.
Results:
No dose-limiting toxicities (DLT) were seen among the three dose levels tested. Grade 3/4 toxicities included neutropenia, thromboembolic events, and leukopenia. DL2 (ABX 150 mg/m2, BEV 60 mg/m2) was chosen as the RP2D. Seven of the 19 patients with measurable disease (36.8%) had confirmed partial responses (95% confidence interval, 16.3%–61.6%). Pharmacokinetic analyses demonstrated that AB160 allowed 50% higher paclitaxel dosing and that paclitaxel clearance mirrored that of therapeutic antibodies.
Conclusions:
The safety profile and clinical activity of AB160 supports further clinical testing in patients with gynecologic cancers; the RP2D is DL2 (ABX 150 mg/m2, BEV 60 mg/m2).
Data from Co-occurring EGFR p.E709X Mutation Mediates Primary Resistance to the Third-Generation EGFR-TKIs in EGFR p.G719X-Mutant Patients with Advanced NSCLC
Authors: Pang Lanlan , Huang Yihua , Zhuang Weitao , Zhang Yaxiong , Liao Jun , Hao Yue , Hao Feng , Wang Guoqian , Chen Ze-xin Chase , Zhu Yu , Li Mengzhen , Song Zhengbo , Deng Bo Peng , Li Jing , Zhang Li , Fang Wenfeng
Published: June 2024

AbstractPurpose:
The current National Comprehensive Cancer Network (NCCN) guidelines recommend afatinib or osimertinib as the preferred first-line treatment strategy for patients with advanced NSCLC harboring EGFR p.G719X mutation. However, in the absence of head-to-head trials comparing afatinib with osimertinib in EGFR p.G719X-mutant patients, it is unclear which regimen is the preferred treatment option.
Experimental Design:
A large cohort of 4,228 treatment-naïve patients with lung cancer who underwent targeted next-generation sequencing (NGS) testing was screened for EGFR p.G719X mutation. A multicenter cohort involving 68 EGFR p.G719X-mutant patients with advanced NSCLC and NGS profiling was retrospectively enrolled to evaluate clinical responses to afatinib (n = 37) and the third-generation EGFR-TKIs (n = 31). Ba/F3 cells stably expressing the EGFR p.G719A mutation were created to investigate the response to EGFR-TKIs in vitro.
Results:
Concurrent EGFR p.E709X mutations, being the most frequent co-occurring EGFR mutation in EGFR p.G719X-mutant NSCLC (∼30%), exerted a detrimental effect on outcomes in patients treated with third-generation EGFR-TKI [G719X/E709X vs. G719X; objective response rate (ORR): 0.00% vs. 47.62%, P < 0.001; mPFS: 7.18 vs. 14.2 months, P = 0.04, respectively]. Conversely, no significant difference was found in the treatment efficacy of afatinib between EGFR p.G719X/E709X and EGFR p.G719X patients (G719X/E709X vs. G719X; ORR: 71.43% vs. 56.67%, P = 0.99; mPFS: 14.7 vs. 15.8 months, P = 0.69, respectively). In vitro experiments elucidated a resistant drug sensitivity and poor inhibition of EGFR phosphorylation in Ba/F3 cells expressing EGFR p.G719A/E709K mutation upon the third-generation EGFR-TKI treatment.
Conclusions:
Co-occurring EGFR p.E709X mutation mediated primary resistance to the third-generation EGFR-TKIs in EGFR p.G719X-mutant patients but remained sensitive to afatinib. A personalized treatment strategy should be undertaken based on the coexisting EGFR p.E709X mutation status.
RNA Sequencing Screens the Key Genes and Pathways in a Mouse Model of HFpEF
Authors: Sun Yuxi , Li Jiaxin , Zhang Xinxin , Wang Ning , Liu Ying
Published: June 2024

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a common syndrome with high morbidity and mortality but without available evidence-based therapies. It is essential to investigate changes in gene expression profiles in preclinical HFpEF animal models, with the aim of searching for novel therapeutic targets. Methods: Wild-type male C57BL/6J mice were administrated with a combination of high-fat diet (HFD) and inhibition of constitutive nitric oxide synthase using N-nitro-l-arginine methyl ester (l-NAME) for 5 and 7 weeks. RNA sequencing was conducted to detect gene expression profiles, and bioinformatic analysis was performed to identify the core genes, pathways, and biological processes involved. Results: A total of 1,347 genes were differentially expressed in the heart at week 5 and 7 post-intervention. Gene Ontology enrichment analysis indicated that these greatly changed genes were involved mainly in cell adhesion, neutrophil chemotaxis, cell communication, and other functions. Using hierarchical cluster analysis, these differentially expressed genes were classified into 16 profiles. Of these, three significant profiles were ultimately identified. Gene co-expression network analysis suggested troponin T type 1 (Tnnt1) directly regulated 31 neighboring genes and was considered to be at the core of the associated gene network. Conclusion: The combined application of RNA sequencing, hierarchical cluster analysis, and gene network analysis identified Tnnt1 as the most important gene in the development of HFpEF.
Exploring Terebinth Cross-Sensitivity in Individuals with Pistachio Sensitivity
Authors: Çelik Velat , Kılıc Fedli Emre , Tanrıverdi Hüseyin
Published: June 2024

Introduction: Terebinth (Pistacia terebinthus) belongs to the same botanical family as pistachio (Pistacia vera) and cashew (Anacardium occidentale). Although it is known that there is cross-sensitivity between pistachio and cashew, the cross-sensitivity of terebinth with pistachio or cashew has not been investigated. The objective of our study was to evaluate the sensitivity to terebinth in children with pistachio sensitivity. Methods: This study was conducted between September 2021 and June 2022 at Adıyaman University Faculty of Medicine Hospital. It analyzed the results of children who underwent skin prick testing (SPT) for food allergy. Of the 712 food skin prick tests reviewed, 27 children were identified with pistachio sensitivity. Prick tests with commercial extract for cashew and prick-to-prick tests for terebinth were applied to these children. Results: The median age was two, and 78% were male. Of the children with pistachio sensitivity, 96% demonstrated cross-sensitivity to terebinth and 100% to cashew. There was a strong correlation between the size of SPT responses in pistachio, cashew, and terebinth. Only four children had previously consumed terebinth, and two of these children had allergic reactions. Conclusion: Our study demonstrates a high cross-sensitivity between terebinth, pistachio, and cashew. We recommend that individuals with pistachio or cashew allergy/sensitivity avoid terebinth until tests confirm it is safe to consume. Further studies are needed to demonstrate the clinical significance of this cross-sensitivity and identify the major allergen involved.
Nurturing Excellence: Exploring the Level of Professional Development Strategies for Quality Assurance in a Multi-Campus Higher Education Institution
Authors: De Ramos Lovella C. , Codilla Jr. Leo L.
Published: June 2024

n higher education, professional development plays a crucial role in ensuring the quality of teaching and learning. This study examines the level of professional development in quality assurance among faculty members of a multi-campus higher education institution. The study's objective was to assess the level of quality assurance professional development strategies. Quantitative data were collected using a survey questionnaire. Weighted mean was employed for data analysis. The study contributes to knowledge by revealing varying effectiveness across professional development strategies. The participants' level of agreement on the key components of professional development initiatives, the faculty members generally agree on the effectiveness and importance of needs assessment, relevance and customization, pedagogical training, and evaluation and feedback. Based on the findings, the study recommends reinforcing faculty engagement strategies, tailoring professional development programs, addressing workload challenges, and leveraging existing opportunities. The findings of this study enrich the understanding of the interplay between professional development and quality assurance in higher education, providing valuable insights for educational institutions to enhance the quality of teaching and learning.
Application of a Learning Model Based on Scientific Literacy to Improve Reasoning Ability Students' Critical Thinking
Authors: Siagian Gunaria , Gunawan Revi Gina , Festiyed  , Asrizal  , Skunda  , Desnita
Published: June 2024

The purpose of this study was to apply a scientific literacy-based learning model to improve students' critical thinking reasoning abilities in class X SMA Negeri 3 Pematangsiantar. The method used in this study is a Quasi Experimental Design quantitative research method. The results of the study show that the application of scientific literacy-based learning models can improve students' critical thinking reasoning abilities. The hypothesis in this study is that there is an increase in students' critical thinking reasoning abilities in class X SMA Negeri 3 Pematangsiantar. Based on the results of calculations using the t test, it can be concluded that the hypothesis is accepted, namely t_count of 6.217 greater than ttable of 2.002. The results of this study are expected to be useful for related parties such as teachers and further researchers.
Level and Extent of Financial Literacy of Personnel in the Department of Education, District of Subic, Zambales
Authors: Amante Josua J.
Published: June 2024

This study aimed to determine the level and extent of financial literacy of personnel in the Department of Education, District of Subic, Zambales.  This study is limited to one hundred fifty-eight (158) personnel in the selected schools in the district of Subic.  In this study, descriptive research design was adopted. The researcher utilized a self-made survey questionnaire in gathering the data vital to this study. The data gathered from the self-made survey questionnaire were tallied, tabulated, and interpreted accordingly to the following statistical tools: Frequency and Percentage Count, Weighted Mean, Likert Scale and Analysis of Variance.
From the given findings, the following conclusions were drawn: First, majority of the respondents were female, age 30-39 years old, bachelor’s degree holder, 0-5 years in service, currently in the teaching position and have no training on financial literacy. Second, the respondents were found to have an awareness of their personal financial literacy in terms of financial management, budgeting, investing and savings. Third, it is also found out that the respondents were aware of their personal extend of the financial literacy skills in terms of trainings and seminars, adherence to policy and their behavior towards financial literacy. Fourth, it was also found out that there was a significant difference in the level of financial literacy of the respondents when grouped according to profile variables highest educational attainment and position. Fifth, there is a significant difference on the extent of financial literacy when grouped according to profile variable sex and highest educational attainment. The length of service has a significant difference only on the adherence to policy.
Lastly, based on the results of the study, the researcher may recommend a training program to enhance the financial literacy of the respondents.
In the light of the findings of the study, the following recommendations were made: 1.) The DepEd Subic District may implement awareness on what is important in financial literacy to their personnel; 2.) the respondents may strengthen their budgeting and investing skills through attending related training offered by the division of Zambales; 3.) the respondents may improve their financial literacy extent through attending trainings and seminars and develop their financial literacy behavior; 4.) DepEd Division of Zambales administrators may ensure the inclusions of financial management, budgeting, investing and savings on the training to improve the level of financial literacy of personnel; 5.) the teaching and non-teaching personnel financial literacy and financial behavior may be improved through attending various trainings and seminars; 6.) the researcher may recommend or propose a training program to enhance the financial literacy of the DepEd personnel; 7.) a replication of this study in other districts within the division of Zambales is suggested for further research.
The Effect of Internal Control System Towards Sustainable Quality Governance in A State University: Basis for Establishing a Sustainable Quality Governance in State University
Authors: Borbe Candy Angelica B.
Published: June 2024

This study aimed to determine the relationship between the internal control system and quality governance in a State University, Laguna State Polytechnic University (LSPU). The 110 Administrative Council of LSPU were the respondents, and the survey questionnaire was used to measure the level of implementation of Internal Control System components such as Control environment, Risk Assessment, Control Activities, Information and Communication and Monitoring and the observance of elements of governance such as Transparency, Accountability, Participation and Predictability in LSPU. The findings showed a significant relationship between Internal Control System and quality Governance. Monitoring, Information and Communication components significantly impacted the sustainability of quality governance. The researcher recommended a more comprehensive assessment of the internal control system, with a focus on monitoring and information and communication, which negatively affect governance quality. The study also suggested using interviews or direct observation for data collection.
Risk Management among Department of Tourism-Accredited Hotels in Region VIII
Authors: Dadulla Daffodel M. , Cabatingan Albim Y. , Delantar Alexander Franco A.
Published: June 2024

he study assessed the risk management implementation and the degree of likelihood and severity of risks affecting the Department of Tourism-Accredited hotels in Region VIII.  In addition, it took into account if there is a significant difference between the perspectives of middle management and rank-and-file employees and the significant relationship of risk management implementation and likelihood and severity of risks and its facilitating and impeding factors.  To attain these, the study utilized both quantitative framework through survey and a qualitative method through interview.  Sixteen hotels participated the study.  Overall, establishments demonstrated an implemented category yet presence of variability suggests the need for continuous improvement in implementation.  As to likelihood and severity of risks it is perceived as “unlikely to happen” yet “very severe” suggesting to roll-out proactive measures.  It showed significant difference in viewpoints where the middle management have a better grasps of risk management than the rank-and-file employees.  While for the test of significant relationship it has a clear negative correlation while no significant correlation was found between risk management and severity of risks.  It revealed themes reactive approach rather than proactive risk management where these hotels need to embody a culture of proactive culture, employee education and training, budget allocation and get rid of being resistance to change and lack of cooperation to enhanced strategies to risk management. Based on the findings, a comprehensive risk management plan anchored to ISO 31000-2018 will be helpful to lessen the vulnerability to various risks to safeguard its stakeholders especially it guests.
Response of Sugarcane Setts to Bio-Stimulant Solutions at Tillering Stage
Authors: Oñal, Jr. Paulino A , Andrade Francis E. , Jayme Glen R. , Montorio John Edcelest O.
Published: June 2024

The study aims to determine the response of sugarcane setts to the different level of concentrations bio-stimulant solutions (BSS) that can accelerate the rooting and tillering.  The study was conducted at UNO-R School of Agriculture, Philippines from October 15, 2023 -January 15, 2024. Phil 99-1793 variety is used. It was laid out in Completely Randomized Design with 4 treatments, replicated 4 times. The treatments were; no BSS (control), 200ml, 300ml, and 400ml BSS. Cane setts were prepared a day before planting. Leaf sheaths were remove and viable eye buds was selected. Setts were soaked in water for 24 hours and air-dried for 30 minutes before planting. The BSS were diluted in water before application. It was applied at plant base 15, 45, and 75 days after planting (DAP). Statistical analysis revealed highly significant on root weight and length with 110grams and 100.33cm for 400ml BSS, respectively. Great significant result also was observe for the tiller height at 30DAP and 60DAP with 26.10cm and 43.08cm respectively for 400ml BSS treatment. On tiller weight at 90DAP, number of tillers at 30DAP and number nodes at 90DAP statistics indicates a significant result with 752grams, 1.75tillers and 8.10nodes for 400ml BSS treatment. Application of 400ml BSS shorten the germination to only 5.30days while control treatment germinated at 8.03days. Application of 400ml BSS also increases the biomass with 4,310,00kg/hectare higher than the control with 2,242.50 kg/hectare. The study recommends the application of 400ml of BSS to accelerate the rooting and tillering of sugarcane setts up to 90DAP.
Arquitetura e humanização em saúde: aproximando saberes e perspectivas
Authors: Medeiros Luciana de
Published: June 2024

El tema de la humanización en salud y el papel del ambiente físico hospitalario en el proceso de recuperación de los pacientes ha asumido un papel importante en las reflexiones de diferentes campos del saber. En Brasil, el uso del término humanización se consolidó a través de la implementación de una política dentro del Sistema Único de Salud que promovió una serie de cambios en el escenario de gestión de servicios, diseño y construcción de establecimientos con diferentes niveles de complejidad. Así, el artículo presenta una discusión sobre este movimiento y su relación con la arquitectura, enfatizando teorías y conceptos relevantes para su estudio, posibilidades de aplicación en el diseño arquitectónico y desarrollo de investigaciones en el área. A partir de una revisión narrativa de la literatura interdisciplinaria, nacional e internacional sobre el tema, fue posible verificar la influencia directa de los estudios persona-ambiente y el uso de enfoques cualitativos, basados en multimétodos, en el conjunto de aspectos recurrentes en los trabajos producidos en años recientes
Brinquedos TDAH e TEA: um estudo de caso utilizando design thinking e gerenciamento de projetos em seus desenvolvimentos
Authors: Canfield Daniel de Salles , Bernardes Maurício Moreira e Silva , Barbosa Luiza Justiniano Tolentino , Aseka Sofia Satie Basso
Published: June 2024

El objetivo de esta investigación es desarrollar juguetes dirigidos a niños con TDAH y TEA utilizando DTPMf, un framework que combina Design Thinking con Gestión de Proyectos. Se llevó a cabo un estudio de caso único de nueve meses en una empresa brasileña de juguetes, con recolección de datos utilizando DTPMf (15 herramientas, 15 miembros del equipo de proyecto y ocho entrevistados) y análisis de datos basado en análisis de contenido, con soporte de software NVivo. Como resultado, se desarrollaron seis nuevos juguetes de madera para satisfacer las necesidades específicas de los niños con TDAH y TEA. La originalidad de esta investigación está relacionada con el uso de DTPMf en un estudio de caso y en el desarrollo de una línea de productos dirigida a un público poco explorado en Brasil. Aunque DTPMf había demostrado previamente su eficiente ejecución en línea, solo se realizó una reunión presencial debido a COVID-19, lo que es una limitación del estudio. Como implicación práctica, a través de una rutina de desarrollo de nuevos productos, la empresa introdujo diferentes principios, roles, etapas, eventos y herramientas, generando juguetes únicos e innovadores. Además, los diseñadores de juguetes pueden utilizar este estudio como base para futuros proyectos inclusivos.
Arquitetura de interiores inclusiva: ambientes residenciais sensíveis a crianças com transtorno do espectro autista (TEA)
Authors: Ramos Larissa Leticia Andara , Lopes Yasmin Franco
Published: June 2024

La arquitectura interfiere con la forma de vivir y sentir el entorno construido. Es capaz de influir en las interrelaciones del individuo con el espacio, incluido su comportamiento y emociones. Identificar las particularidades y necesidades de los niños con Trastorno del Espectro Autista (TEA) y su funcionamiento sensorial es importante para comprender la influencia que el entorno, especialmente el doméstico, puede tener sobre ellos y cómo esta relación puede ser positiva, haciendo la arquitectura de vida más amigable. Este artículo, resultado de un Trabajo de Conclusión de Curso en Arquitectura e Urbanismo, además de reflexionar sobre el tema, destaca recomendaciones de diseño para ambientes residenciales sensibles a niños autistas. Para ello, se consideró una fase de fundamentación teórica y una fase experimental, en las que los conceptos explorados se ilustraron en un ensayo de diseño de arquitectura interior para adecuar una unidad habitacional tipo departamento. Los resultados resaltan la necesidad de que el ambiente del hogar promueva el confort, la seguridad y la autonomía; respetar características únicas, así como coadyuvar en el desarrollo social y mental, a través de estrategias de estimulación sensorial, integración ambiental, legibilidad espacial y mitigación de riesgos. El ensayo de diseño presentado no pretende universalizar pautas ni ser un ejemplo general sino sacar a la luz recomendaciones que puedan guiar a arquitectos y diseñadores.
Descrição e análise de um projeto interdisciplinar sobre a Covid-19: uma proposta de divulgação científica a partir do gênero 3MT
Authors: Abreu-Tardelli Lilia Santos , Oliveira Gabriela Aguiar de
Published: June 2024

The aim of this article is to describe a project for the scientific dissemination of videos about Covid-19 focusing on primary school students (6 to 11 years old) in a school in the northwest of São Paulo state. It also aims to present the results of the analysis of two of the scripts and videos, highlighting linguistic and multimodal aspects based on the theoretical-methodological framework of Sociodiscursive Interactionism (ISD) and the didactic genre model (3MT), in order to verify similarities and differences with the genre model of the 3MT proposed by Abreu-Tardelli (2020; 2021). The criteria for the videos’ selection was the ones that had the highest number of views on YouTube. The analysis highlights the presence of explicative sequences, voices in direct speech to present the problematization and resolution phase, and the use of comparisons of the theme with familar locations and comparisons of scientific terms with everyday actions, showing a close approximation with the proposal of 3MT. It also contributes to health literacy, as they highlight the importance of considering language usage strategies to be understood by the target audience, as proposed by the 3MT.
Letramento em saúde em documentos do século XVIII: contribuições da Filologia
Authors: Módolo Marcelo , Madeira Maria de Fátima Nunes
Published: June 2024

The text of the first document presented in this article to illustrate the issue of health literacy, a publication from 1768, stands out for resorting to different forms of knowledge organization to convince the authorities of the need for mass use of the inoculation process against smallpox, a disease that affected Europe and Brazil. It is a letter from the English doctor, dr. Gualter Wade, who, living in Portugal, was responding to a query about what would be new and worthy of imitation in the fight against smallpox. In addition to the representativeness of the language used in the document, a sample of the doctor's effort to prove the safety of inoculation for the elimination of bladders, the topic comes in handy with the current debates, in which the efficacy of vaccines against infectious diseases is still being discussed. The second document, from 1775, handwritten by the captain-general of the captaincy of São Paulo, Martim Lopes Lobo de Saldanha, and addressed to the then secretary of State for the Navy and Overseas, Martinho de Melo e Castro, is a counterpoint to the approach to the sanitary issue, in relation to the 1768 document, since homemade and ineffective measures continued to be used in the colony.
Representações discursivas e relações de poder de profissionais de saúde na prática de cuidado paliativo neonatal
Authors: Pereira Luciara de Oliveira , Vieira Viviane Cristina
Published: June 2024

This work aims to investigate how healthcare workers discursively represent the practices involved in neonatal palliative care, in a Neonatal Intensive Care Unit of a public hospital in the Federal District, Brazil. This study is theoretically and methodologically based in Critical Discourse Analysis, using the discursive-ethnography approach, which allowed us to reflect on the interactions and representations of 14 interviews with healthcare workers, from different professions, considering the ideologies involved in the context of their relationships. The results reveal a dependence on high technology to maintain life, leading to reflections on the limits of postponing neonatal death, considering the child's dignity and quality of life. Representations related to problems such as social inequality suggest that professionals need knowledge and understanding about how to relate to these families and how to deal with the issue of palliative care.
Broadening the scope: Multiple functional connectivity networks underlying threat conditioning and extinction
Authors: Cushing Cody A. , Peng Yujia , Anderson Zachary , Young Katherine S. , Bookheimer Susan Y. , Zinbarg Richard E. , Nusslock Robin , Craske Michelle G.
Published: June 2024

Threat learning processes are thought to be foundational to anxiety and fear-related disorders. However, the study of these processes in the human brain has largely focused on specific brain regions, owing partly to the ease of translating between these regions in human and nonhuman animals. Moving beyond analyzing focal regions of interest to whole-brain dynamics and connectivity during threat learning is essential for understanding the neuropathology of fear-related disorders in humans. In this study, 223 participants completed a 2-day Pavlovian threat conditioning paradigm while undergoing fMRI. Participants completed threat acquisition and extinction. Extinction recall was assessed 48 hours later. Using a data-driven group independent component analysis (ICA), we examined large-scale functional connectivity networks during each phase of threat learning. Connectivity networks were tested to see how they responded to conditioned stimuli during early and late phases of threat acquisition and extinction as well as during early trials of extinction recall. A network overlapping with the default mode network involving hippocampus, ventromedial prefrontal cortex (vmPFC), and posterior cingulate was implicated in threat acquisition and extinction. Another network overlapping with the salience network involving dorsal anterior cingulate cortex (dACC), mPFC, and inferior frontal gyrus was implicated both in threat acquisition and in extinction recall. Other networks overlapping with parts of the salience, somatomotor, visual, and frontoparietal networks were involved in the acquisition or in the extinction of learned threat responses. These findings help support the functional cooperation of specific brain regions during threat learning in a model-free fashion while introducing new findings of spatially independent functional connectivity networks during threat and safety learning. Rather than being a single process in a core network of regions, threat learning involves multiple brain networks operating in parallel performing different functions at different timescales. Understanding the nature and interplay of these dynamics will be critical for comprehensive understanding of the multiple processes that may be at play in the neuropathology of anxiety and fear-related disorders.
The Paradox of Abolition: Sugar Production and Slave Demography in Danish St. Croix, 1792–1804
Authors: Roberts Justin , Morgan Philip D. , Christensen Rasmus
Published: June 2024

In 1792, the Danish government announced the abolition of the transatlantic slave trade and granted St. Croix planters a grace period to import slaves before the cessation. Despite hopes for improved conditions for the enslaved after the abolition, surging sugar prices prompted planters to increase imports of enslaved Africans. Census data, slave trade records, and land tax registers illustrate how St. Croix planters, in the face of impending abolition, exacerbated mortality rates among the enslaved and hindered efforts to create a naturally reproducing enslaved population. The short-term acceleration of slave importation after the Danish decision to end the slave trade increased the total mortality rates of Africans throughout the Atlantic region.
Money for Everyone
Authors: McCants Anne E. C.
Published: June 2024

Money, a ubiquitous yet enigmatic concept, defies clear definition despite its long historical use. Naismith’s Making Money in the Early Middle Ages reveals the complexity of early medieval monetary systems, identifying three important developments in their history (the decline of Roman imperial money, the shift from gold currency in favor of silver, and the gradual rise in coin usage over the long Middle Ages). In exploring money’s symbolic and practical characteristics, the book illustrates money’s impact on social relations and hierarchies, opening the door for the human questions that carry implications for justice. By integrating distinct methodologies, the author presents a nuanced understanding of money’s significance in shaping medieval societies, offering an exemplary model for interdisciplinary scholarship.
Fusion Philosophy and Epistemic Injustice
Authors: Butnor Ashby
Published: June 2024

I use the concept of epistemic injustice to think through the practice and methodology of comparative, or “fusion,” philosophy. I make two related claims: 1) the philosophical ethnocentrism displayed by academic departments in the U.S. is a case of epistemic injustice, primarily willful ignorance, that ought to be rectified; 2) the corrective to this problem, namely, fusion philosophy, is itself epistemically problematic in its tendency toward ontological expansiveness, that is, an unjustified claim to all traditions as one’s own. In the end, I hope to show how a robust practice of self-reflexivity can counter this potentially colonizing tendency of fusion philosophizing.
A Clarification and Defense of Quine’s Naturalism
Authors: Chen Bo
Published: June 2024

Naturalism is the dominant characteristic of W. V. Quine’s philosophy. The current study presents a more comprehensive and sympathetic clarification of Quine’s naturalized epistemology (NE hereafter), and vindicates its main positions by critically responding to the three objections to Quine’s NE: it is the replacement of traditional epistemology (TE hereafter), it is viciously circular, and it is devoid of normative dimension, and to Williamson’s three charges to naturalism (mainly Quine’s brand), finally concludes that the three objections and Williamson’s three charges to Quine’s NE are mainly perhaps caused by misreading or misinterpretation, so all of them failed, and that there are still illuminating, reasonable, and valuable insights in Quine’s NE, which are worthy of further development.
“Perpetuum studium et exercitationem mortificandae carnis”
Authors: Ha Sam Neulsaem
Published: June 2024

Many scholars have argued and assumed that Protestantism broke away from virtue ethics. However, recent scholarship has revealed that it is not necessarily the case. This article’s aim is to go a step further than that. It will explore the subject even more fully by digging deeper into a specific element of virtue ethics in Calvin, namely, his thought on habit formation. I argue that Calvin’s distinctive habit formation plays a significant role in his ethics. In my analysis, although Calvin appreciates the limit of habit’s power, he emphasizes the significance of divinely initiated and guided habit formation.
On Hosting, Pilgrimage and “Indirect Mission”
Authors: Coleman Simon
Published: June 2024

This paper brings together perspectives on hosting and pilgrimage to show how both can contribute to forms of “indirect mission”: a type of social action where overt intervention for missionary purposes is kept to a minimum, but where an implicit missionary intent is retained. While bringing in comparative material on cathedrals, my ethnographic focus is on the English pilgrimage site of Walsingham, a location of both Anglican and Roman Catholic shrines. I show how shrines work to become sites of reception for publics ranging from pious pilgrims to members of the general population as they seek recognition within both Catholic and secular liberal contexts.
Diuqin lechiguanae gen. et sp. nov., a new unenlagiine (Theropoda: Paraves) from the Bajo de la Carpa Formation (Neuquén Group, Upper Cretaceous) of Neuquén Province, Patagonia, Argentina
Authors: Porfiri Juan D. , Baiano Mattia A. , dos Santos Domenica D. , Gianechini Federico A. , Pittman Michael , Lamanna Matthew C.
Published: June 2024

Background

Unenlagiine paravians are among the most relevant Gondwanan theropod dinosaur clades for understanding the origin of birds, yet their fossil record remains incomplete, with most taxa being represented by fragmentary material and/or separated by lengthy temporal gaps, frustrating attempts to characterize unenlagiine evolution.

Results and conclusions

Here we describe Diuqin lechiguanae gen. et sp. nov., a new unenlagiine taxon from the Upper Cretaceous (Santonian) Bajo de la Carpa Formation of the Neuquén Basin of Neuquén Province in northern Patagonia, Argentina that fills a substantial stratigraphic gap in the fossil record of these theropods. Although known only from a very incomplete postcranial skeleton, the preserved bones of Diuqin differ from corresponding elements in other unenlagiines, justifying the erection of the new taxon. Moreover, in several morphological aspects, the humerus of Diuqin appears intermediate between those of geologically older unenlagiines from the Neuquén Basin (e.g., Unenlagia spp. from the Turonian–Coniacian Portezuelo Formation) and that of the stratigraphically younger, larger-bodied Austroraptor cabazai from the Campanian–Maastrichtian Allen Formation. Consequently, the morphology of the new taxon appears to indicate a transitional stage in unenlagiine evolution. Phylogenetic analysis recovers Diuqin as a paravian with multiple plausible systematic positions, but the strongest affinity is with Unenlagiinae. The humerus of the new form exhibits subcircular punctures near its distal end that are interpreted as feeding traces most likely left by a conical-toothed crocodyliform, mammal, or theropod, the latter potentially corresponding to a megaraptorid or another unenlagiine individual. Thus, in addition to filling important morphological and temporal gaps in unenlagiine evolutionary history, the new taxon also offers information relating to the paleoecology of these theropods.
A systematic review and bioinformatic study on clinical, paraclinical, and genetic factors predisposing to stent restenosis following percutaneous coronary intervention
Authors: Shahsanaei Farzad , Gharibzadeh Abdullah , Behrooj Soudabeh , Abbaszadeh Shahin , Nourmohammadi Mahboobeh
Published: June 2024

Background

Stent restenosis is a relatively common phenomenon among patients with coronary heart disease undergoing percutaneous coronary intervention (PCI). It seems that a set of clinical, laboratory, and even genetic factors make people susceptible to such a phenomenon and in fact, this is multi-factorial. We aimed to first determine the underlying clinical and laboratory risk factors for the occurrence of stent re-stenosis after PCI based on a systematic review study, and after that, through a bioinformatics study, to evaluate the related genes and microRNAs with the occurrence of stent re-stenosis.

Main text

In the first step, the manuscript databases including Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane were deeply searched by the two blinded investigators for all eligible studies based on the considered keywords to introduce clinical and laboratory determinants of stent re-stenosis. In the bioinformatic phase, and following a review of the literature to identify genes and microRNAs involved in restenosis, the interaction of each gene with other genes associated with stent re-stenosis was determined by GeneMANIA network analysis and Cytoscape software. Overall, 67 articles (including 40,789 patients) on clinical and biochemical predictors for stent restenosis and 25 articles on genetic determinants of this event were eligible for the final analysis. The predictors for this event were categorized into four subgroups patient-based parameters including traditional cardiovascular risk profiles, stent-based parameters including type and diametric characteristics of the stents used, coronary lesion-based parameters including several two target lesions and coronary involvement severity and laboratory-based parameters particularly related to activation of inflammatory processes. In the bioinformatic phase, we uncovered 42 genes that have been described to be involved in such a phenomenon considering a special position for genes encoding inflammatory cytokines. Also, 12 microRNAs have been pointed to be involved in targeting genes involved in stent re-stenosis.

Conclusions

The incidence of stent re-stenosis will be the result of a complex interaction of clinical risk factors, laboratory factors mostly related to the activation of inflammatory processes, and a complex network of gene-to-gene interactions.
Prognosis of remaining fetus in twin pregnancy after demise of one fetus according to its location
Authors: Jung Young Mi , Park Sun Min , Kim Hyun Ji , Choi Bo Young , Won Seunghyun , Park Jee Yoon , Oh Kyung Joon
Published: June 2024

Background

To investigate the prognosis of the remaining fetus in twin pregnancy after experiencing one fetal demise in the first trimester according to the location of the demised fetus.

Methods

This was a retrospective study of twin pregnancies with one fetal demise after the first trimester (14 weeks of gestation) delivered between September 2004 and September 2022. The study population was divided into two groups based on the location of the demised fetus as determined by the last recorded ultrasonography results: Group 1 included twin pregnancies where the presenting fetus was demised (n = 36) and Group 2 included twin pregnancies where the non-presenting fetus was demised (n = 44). The obstetric and neonatal outcomes were also reviewed.

Results

A total of 80 pregnant women were included. The median gestational age for the diagnosis of fetal demise was 24.1 weeks. The gestational age of the demised fetus was not different between Groups 1 and 2; however, the gestational age of the remaining fetus at delivery was significantly earlier in Group 1 than it was in Group 2 (33.8 vs. 37.3 weeks, P = .004). The rate of preterm birth before 28 weeks was almost five times higher in Group 1 than in Group 2 (22.2% vs. 4.5%, P = .037). Regression analysis demonstrated significant differences between Groups 1 and 2. Respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, retinopathy of prematurity, and jaundice were more common in Group 1 than in Group 2; however, the association was not significant after adjusting for gestational age at delivery.

Conclusions

When the presenting fetus is demised in a twin pregnancy, the remaining fetus tends to be delivered earlier than when the non-presenting fetus is demised.
Novel prognostic nomograms for postoperative patients with oral cavity squamous cell carcinoma in the central region of China
Authors: Xu Xue-Lian , Xu Jin-Hong , He Jia-Qi , Li Yi-Hao , Cheng Hao
Published: June 2024

Background

Oral cavity squamous cell carcinoma (OCSCC) is the most common pathological type in oral tumors. This study intends to construct a novel prognostic nomogram model based on China populations for these resectable OCSCC patients, and then validate these nomograms.

Methods

A total of 607 postoperative patients with OCSCC diagnosed between June 2012 and June 2018 were obtained from two tertiary medical institutions in Xinxiang and Zhengzhou. Then, 70% of all the cases were randomly assigned to the training group and the rest to the validation group. The endpoint time was defined as overall survival (OS) and disease-free survival (DFS). The nomograms for predicting the 3-, and 5-year OS and DFS in postoperative OCSCC patients were established based on the independent prognostic factors, which were identified by the univariate analysis and multivariate analysis. A series of indexes were utilized to assess the performance and net benefit of these two newly constructed nomograms. Finally, the discrimination capability of OS and DFS was compared between the new risk stratification and the American Joint Committee on Cancer (AJCC) stage by Kaplan-Meier curves.

Results

607 postoperative patients with OCSCC were selected and randomly assigned to the training cohort (n = 425) and validation cohort (n = 182). The nomograms for predicting OS and DFS in postoperative OCSCC patients had been established based on the independent prognostic factors. Moreover, dynamic nomograms were also established for more convenient clinical application. The C-index for predicting OS and DFS were 0.691, 0.674 in the training group, and 0.722, 0.680 in the validation group, respectively. Besides, the calibration curve displayed good consistency between the predicted survival probability and actual observations. Finally, the excellent performance of these two nomograms was verified by the NRI, IDI, and DCA curves in comparison to the AJCC stage system.

Conclusion

The newly established and validated nomograms for predicting OS and DFS in postoperative patients with OCSCC perform well, which can be helpful for clinicians and contribute to clinical decision-making.
Identification of the cytoplasmic DNA-Sensing cGAS-STING pathway-mediated gene signatures and molecular subtypes in prostate cancer
Authors: Yang Jie , Xu Zihan , Zheng Weitao , Li Yifan , Wei Qiang , Yang Lu
Published: June 2024

Background

Considering the age relevance of prostate cancer (PCa) and the involvement of the cGAS-STING pathway in aging and cancer, we aim to classify PCa into distinct molecular subtypes and identify key genes from the novel perspective of the cGAS-STING pathway. It is of significance to guide personalized intervention of cancer-targeting therapy based on genetic evidence.

Methods

The 430 patients with PCa from the TCGA database were included. We integrated 29 key genes involved in cGAS-STING pathway and analyzed differentially expressed genes and biochemical recurrence (BCR)-free survival-related genes. The assessments of tumor stemness and heterogeneity and tumor microenvironment (TME) were conducted to reveal potential mechanisms.

Results

PCa patients were classified into two distinct subtypes using AURKB, TREX1, and STAT6, and subtype 1 had a worse prognosis than subtype 2 (HR: 21.19, p < 0.001). The findings were validated in the MSKCC2010 cohort. Among subtype 1 and subtype 2, the top ten mutation genes were MUC5B, DNAH9, SLC5A10, ZNF462, USP31, SIPA1L3, PLEC, HRAS, MYOM1, and ITGB6. Gene set variation analysis revealed a high enrichment of the E2F target in subtype 1, and gene set enrichment analysis showed significant enrichment of base excision repair, cell cycle, and DNA replication in subtype 1. TME evaluation indicated that subtype 1 had a significantly higher level of T cells follicular helper and a lower level of plasma cells than subtype 2.

Conclusions

The molecular subtypes mediated by the cGAS-STING pathway and the genetic risk score may aid in identifying potentially high-risk PCa patients who may benefit from pharmacologic therapies targeting the cGAS-STING pathway.