bluuebunny/crossref_metadata_2025 huggingface dataset:
Anava Upaya in the Saivagama Nusantara Text
Authors: Suwantana I Gede , Nerawati Ni Gusti Ayu Agung , Bintang Ida Ayu Putu , Wariati Ni Luh Gede
Published: February 2025

Anava upaya is one of the four teachings of Yoga in Saivagama. This teaching emphasizes the use of body parts as objects of meditation. There are five types of this anava upaya, namely dhyana, ucchara, varna, karana, and sthana kalpana. Dhyana is meditation on the dissolution of the physical elements from the grossest to the subtlest and ends with Siva. Ucchara is a meditation technique using prana as an object. Varna is a meditation technique using the sounds that come out of the in-breath and out-breath. Karana is a technique of using both the gross and the subtle bodies of the cause. Finally, sthana kalpana is a technique with the use of in and out breaths, as well as various objects outside the body as media for meditation such as rituals, pictures and the like. This work descriptively describes the five types of yoga in the Saivagama Nusantara text. All these techniques are used in order to re-realize the True Self that has been hidden by avidya. Through these five types of effort or yoga, sadhakas are expected to be able to achieve moksha, namely the liberation of the atma from the bondage of samsara.
Empowering the University Students: Career Development Centers as Catalysts for Motivation and Self-Actualization
Authors: Dr. Manzoor Raza   , Abida Raza  , Mubeen Butt
Published: February 2025

The current study examined career development centers as catalysts for  motivation and self-actualization among university students in district Sargodha. Quantitative research approach with survey technique methods were used for data collection in the study. The main objective of the study was to examine the impact of career development center in motivation of university students on career planning and to explore the factors that influence the motivation and self-actualization of university students. The hypothesis of the study was that  there is no relationship between Career development centres and motivation and self-actualization. Populations in the study were all current BS and M.Phil students of university of Lahore, Sargodha Campus and University of Sargodha, Main Campus. Multistage sampling technique was used to select the research participants from both universities. By using multistage sampling, 300 male and female students at graduate level were selected. Descriptive statistics, frequency, percentage, mean and standard deviation were used in analyzing data and reporting the study findings, chi square test of association was used to find association of career development center vs motivation and self-actualization. The main conclusion of the study was that there was clear and significant relationship between career development center , motivation and self-actualization. On the basis of conclusions it was recommended that career development centers should develop and apply strategies for engaging and supporting students at university level.
Key words: Career development centers, Motivation, self actualization, Multistage sampling, relationship, basis, relationship, conclusion, recommended, strategies
A Review of Urdu Children's Literature in Khyber Pakhtunkhwa (In the Context of Contemporary Requirements)
Authors: Nisar Ali  , Dr. Mian Humayun  , Dr. Ghuncha Begum
Published: February 2025

The importance of children's literature in Urdu literature is Muslim. Since the beginning of writing Urdu literature, children's literature has also started, which consists of not hundreds but thousands of pages. Children's literature has some important features that distinguish it from other literature. Curiosity, wonder and responsiveness are basic characteristics that are naturally present in every child. It is essential for children's literature that children's literature should be based on knowledge and morals and its objectives should include the best education and training so that natural abilities can be developed in the new generation. Thus, children's literature is a boon because the most important task and gift of parents to their children is their best education. Although Urdu children's literature in Khyber Pakhtunkhwa was started at the beginning of the 20th century, but due to some inevitable reasons, it could not progress rapidly. Yes, in Khyber Pakhtunkhwa, most of the books written for children have been created in the context of child psychology and education, and hundreds of writers have written books for children's mental training and emotional well-being on numerous topics. In this article, various aspects of children's literature have been reviewed.
Key words: Urdu children's literature, poets, Nisar, tradition of children's literature, Ghalib, Mir, symptoms, curiosity, Khyber Pakhtunkhwa, fiction, novels, stories.
Prix de thèse de la division Catalyse : Ultradispersed sulfide catalysts: how many atoms for an active site?
Authors: Ryaboshapka Daria , Afanasiev Pavel
Published: February 2025

While sulfide nanoparticles have been extensively studied for hydrotreatment catalysis, the role of few-atom sulfide clusters or single atoms in catalysts has received far less attention. Although these small entities are often present in conventional catalysts, their contribution has largely been overlooked. To date, their structure remains unclear, and it is unknown whether they can compete with sulfide nanoparticles in terms of catalytic performance. In this work, we aim to shed light onto these questions and determine the minimum number of atoms required to define the active site for three industrially relevant catalytic reactions
IMPACT OF ELECTRONIC WORD-OF-MOUTH AS ONE OF THE MOST INFLUENTIAL DIGITAL MARKETING STRATEGIES ON PURCHASE INTENTION, WITH THE MODERATING ROLE OF BRAND EQUITY
Authors: Taalohi Elahe
Published: February 2025

Electronic word-of-mouth (eWOM) is considered one of the most powerful sources for sharing customer information, opinions, experiences, and evaluations after purchasing products or receiving services from various brands via social network communication channels. Hence, this research aims to explore the impact of eWOM, a leading digital marketing strategy, on purchase intention, with brand equity serving as a moderating variable. A quantitative approach was adopted to fulfill the research objectives. The study is applied in terms of purpose and descriptive survey in nature. Data were gathered from a sample of 170 online customers of the Ofogh Kourosh chain stores in District 22 of Tehran Province using convenience sampling and an online questionnaire. Statistical analyses, such as data normality and scale reliability, were performed using SPSS 24, while the measurement model and hypothesis testing were carried out using SmartPLS 3. The structural model assessment results and analyses conducted based on the research objectives supported the hypotheses. The findings showed that eWOM, with brand equity’s moderating role, significantly and positively impacts purchase intention. Lastly, the study offers recommendations and strategies for leveraging eWOM in social media marketing to boost its effectiveness on purchase intention in chain stores.
THE EFFECTIVENESS OF ACCEPTANCE AND COMMITMENT GROUP THERAPY ON MINDFULNESS AND HEALTH-ORIENTED LIFESTYLE OF DIABETIC PATIENTS
Authors: Bakhtiari Bahareh
Published: February 2025

The aim of this study was to evaluate the effectiveness of Acceptance and Commitment Therapy (ACT) group therapy on mindfulness and health-oriented lifestyle in diabetic patients. The research employed a quasi-experimental design, with both a control group and an experimental group. The study population consisted of all type 1 diabetic patients who visited hospitals in Borujerd city in 1401. A total of 40 participants were selected using random sampling, with 20 individuals assigned to the experimental group and 20 to the control group. The research utilized Brown and Ryan’s (2003) mindfulness questionnaire and Laali et al.’s (2013) health-oriented lifestyle questionnaire. Data were analyzed using multivariate analysis of covariance (MANCOVA). The results revealed that ACT group therapy significantly improved both mindfulness and health-oriented lifestyle in the experimental group compared to the control group. Therefore, it can be concluded that ACT group therapy has a positive effect on the mindfulness and health-oriented lifestyle of diabetic patients.
Pengaruh Kualitas Kehidupan Kerja, Komunikasi Organisasi, Dan Kepuasan Kerja Terhadap Kinerja Karyawan
Authors: Hidayat Nasrul Nur
Published: February 2025

This study aims to investigate the impact of quality of work life, organizational communication, and job satisfaction on employee performance at Preksu Ayam Geprek Susu. With a population of 40 employees, the study used a nonprobability sampling method with a purpose sampling technique (saturated sampling), which selects the entire population as a sample. The data obtained was analyzed using multiple linear regression tests. The results showed that the quality of work life, organizational communication, and job satisfaction together have a significant influence on employee performance. This shows that these elements influence each other in creating optimal performance in the workplace. This study makes an important contribution to the understanding of the factors that affect employee performance, especially in business environments such as Preksu Ayam Geprek Susu. Thus, management can pay attention and improve these aspects to improve overall organizational performance. The result of this reseach highlights the importance of paying attention to nonfinancial factors such as job satisfaction and organizational communication in improving employee productivity and wellbeing.
Peran Kompensasi, Lingkungan Kerja, dan Kepemimpinan Transformasional Terhadap Loyalitas Pegawai
Authors: Riyadi Muhammad Fuad
Published: February 2025

This research aims to determine the role of compensation on employee loyalty, the role of the work environment on employee loyalty, the role of transformational leadership on employee loyalty, and the role of compensation, work environment and transformational leadership together. the same for Employee Loyalty. The research used is quantitative research. This research was conducted at the Yogyakarta City Road Traffic and Transportation Department Office. The number of employees in the office is 107 employees, in calculating the number of respondents in this study using the Slovin Formula which produces 66 respondents. The data collection method uses a questionnaire and is homogeneous or independent. This research uses Data Quality Test, Classic Assumption Test (Normality Test, Heteroscedasticity Test, and Multicollinearity Test), Multiple Linear Regression Analysis and Hypothesis Testing. The results of this research show that the Compensation Variable plays a positive and significant role in Employee Loyalty. Work Environment variables play a positive but not significant role in Employee Loyalty. The Transformational Leadership variable plays a positive and significant role in Employee Loyalty. Compensation variables, work environment and transformational leadership simultaneously (together) play a role in employee loyalty.
Analisis Tantangan Pengembangan Bahan Ajar Buku PAI Kurikulum Merdeka pada Kelas 5 SD
Authors: Murdani A M. Febri , Alvionita Intan , Sari HS Devi Purnama , Rahmawati Ella Sari , Setywati Berti Endah , Kurniawan Kurniawan , Indrawari Karliana
Published: February 2025

Penelitian ini bertujuan untuk mengidentifikasi tantangan yang dihadapi dalam pengembangan bahan ajar Pendidikan Agama Islam (PAI) pada tingkat sekolah dasar, khususnya di daerah yang menerapkan Kurikulum Merdeka. Penelitian ini menggunakan pendekatan kualitatif dengan metode studi kasus untuk menggali secara mendalam faktor-faktor teknis, pedagogis, dan sosial-budaya yang memengaruhi proses pengembangan bahan ajar. Subjek penelitian melibatkan guru PAI kelas 5 di SD N 60 Rejang Lebong sebagai representasi daerah dengan keterbatasan akses dan sumber daya. Teknik pengumpulan data meliputi wawancara semi-terstruktur, observasi kelas, dan studi dokumentasi bahan ajar. Hasil penelitian menunjukkan bahwa tantangan teknis yang dihadapi mencakup keterbatasan infrastruktur teknologi, minimnya anggaran, dan kurangnya pelatihan teknis untuk guru. Tantangan pedagogis melibatkan keterbatasan guru dalam menerapkan metode pembelajaran inovatif dan variatif, yang masih didominasi oleh pendekatan ceramah. Sementara itu, tantangan sosial-budaya meliputi kurangnya relevansi bahan ajar dengan nilai-nilai lokal dan minimnya partisipasi masyarakat dalam proses pengembangan bahan ajar. Tantangan-tantangan ini berdampak langsung pada kualitas pembelajaran, motivasi siswa, dan keterlibatan orang tua serta masyarakat. Bahan ajar yang kurang relevan dan menarik menyebabkan rendahnya partisipasi siswa dan minimnya dukungan orang tua. Penelitian ini menekankan pentingnya kolaborasi antara guru, pemerintah, dan masyarakat dalam mengembangkan bahan ajar yang kontekstual, inovatif, dan sesuai dengan kebutuhan lokal. Implikasi penelitian ini diharapkan dapat menjadi landasan untuk perbaikan kualitas bahan ajar PAI dalam mendukung implementasi Kurikulum Merdeka.
Una aproximación al mercado de trabajo de la CAPV a través de distintas fuentes estadísticas
Authors:   Gobierno Vasco, Izagirre Aintzane , Pascual Xabier ,   Gobierno Vasco
Published: February 2025

En este trabajo se hace una descripción del mercado de trabajo de la CAPV abarcando un periodo de diez años, a fin de aproximar al lector a la estructura del empleo de dicho territorio. Se inicia el artículo con una comparación entre los datos de los registros administrativos de afiliados a la Seguridad Social y de parados con los derivados de la encuesta de empleo del Instituto Vasco de Estadística-Eustat, poniendo de manifiesto los diferentes colectivos que incluye cada uno, para continuar con un análisis más en profundidad de esta última, dado su carácter de instrumento destinado a la descripción del mercado laboral. Posteriormente, se expone una aproximación a la evolución del empleo y del paro por comarcas, para terminar con una omparación de nuestras tasas con las de los principales países europeos.
Escenarios de empleo en el medio y largo plazo: retos y alternativas
Authors:   IKERTALDE, de Andrés Juan José , Arteche Iñigo ,   IKERTALDE
Published: February 2025

El artículo desarrolla un ejercicio de simulación de Escenarios de empleo de la CAPV a medio y largo plazo (años 1996, 2001 y 2006) para, partiendo de ese soporte cuantitativo, ofrecer distintas consideraciones en relación a las incógnitas que suponen los retos planteados. Así, introduce el debate sobre la potencial distribución sectorial del empleo a generar—el previsible proceso de terciarización—; su repercusión en términos de tamaño y cultura empresarial —la importancia de las PYMES—; el papel del cambio del nivel formativo de la población activa en ese proceso; y la evolución del marco de relaciones laborales.
'El contrato de trabajo a largo plazo como obligación legal. Los efectos de la flexibilización de los contratos laborales
Authors:   Universidad de Valladolid, de Santiago Hernando Rafael
Published: February 2025

En este trabajo se construye un modelo para estudiar dos cuestiones. En primer lugar, se analizan los efectos de una medida que hiciera obligatorios los contratos a largo plazo. En segundo lugar, se estudia qué pasaría si ahora se permitieran, por ejemplo, lo que la legislación española denomina «contratos de duración determinada». Las conclusiones indican que si esa medida flexibilizadora se introduce en la fase expansiva del ciclo, los efectos serán positivos en términos de desempleo; si se introduce en época de recesión, y no se permite que vaya acompañada de reducciones salariales, traerá consigo un aumento del paro.
'Las instituciones y los resultados macroeconómicos (a corto plazo)
Authors:   Universidad de East Anglia, Hargreaves Heap Shaun P.
Published: February 2025

Este artículo revisa el porqué del creciente interés por las instituciones. El autor mantiene que la explicación de este interés es el reconocimiento de cómo las instituciones afectan a los resultados económicos. Esta idea se basa en que muchas interrelaciones económicas toman la forma de uno u otro de los tres juegos «clásicos» (el dilema del prisionero, el juego de coordinación y el chicken) y el resultado de estosjuegos (y, de aquí, los resultados económicos) está influido por el marco ínstitucíonal de estas interrelacíones. El artículo proporciona un ejemplo detallado de este argumento a través de una revisión de la literatura que relaciona los resultados en el desempleo con las instituciones que determinan los salarios en los países de la OCDE.
AVALIAÇÃO FÍSICO-QUÍMICA DE POLPAS INDUSTRIALIZADAS DE MURUCI (BYRSONIMA CRASSIFÓLIA)
Authors: Camarão Matheus Ramon Blanco , Amaro Marcos Vinicios Pompeu , Vale Gilberto Nascimento do , Guajajara Suyane de Sousa Ribeiro , Carvalho Rosely Ramos de , Lobato Junior Ernani de Sousa , Bezerra Filho Ricardo Barbosa , Coutinho Jesus de Nazaré Melo , Souza Ewerton Carvalho de , Silva Antonio dos Santos
Published: February 2025

The fruit industry has grown significantly, driven mainly by the production of frozen fruit pulps, an affordable alternative that allows the availability of fruits both in season and off-season. To meet consumer demands and Brazilian legislation, commercialized fruit pulps must present physical, chemical and sensory characteristics similar to those of fresh fruit, in addition to ensuring microbiological safety. In this context, the present study aimed to evaluate the physicochemical quality of frozen muruci pulps commercialized in Pará, in addition to applying statistical techniques to discriminate the pulps. The results obtained in this research demonstrated that the muruci pulps commercialized by the three factories in Pará have good physicochemical quality, standing out for their acidic pH, which hinders microbial proliferation and contributes to greater product stability. The multivariate techniques applied to the physicochemical variables showed high efficiency in discriminating the samples according to the producing factory, reaching 100% accuracy with PCA and 93.33% with AHA. Thus, these techniques, especially PCA, can be used to predict the origin of the pulps analyzed.
HIGIENIZAÇÃO DAS MÃOS NO CONTEXTO DA ASSISTÊNCIA À SAÚDE
Authors: Goldoni Elicleia Morais , Ramos Sirlei
Published: February 2025

According to the World Health Organization (WHO), infections are responsible for 25% of deaths worldwide. Among these infections, those that occur in the hospital environment constitute a serious public health problem. It is known that the hands of health professionals are considered one of the main mechanisms of transmission of pathogens that cause these infections, thus demonstrating the importance of cleaning them in order to reduce the incidence of infections. In this scenario, the nursing team of the Hospital Infection Control Commission is fundamental because it brings care for the prevention and control of infection both for other professionals and for patients through training and awareness actions on the subject. In this sense, this project aims to identify, through a literature review, the challenges encountered by the Hospital Infection Control Commission for the implementation of measures for adequate hand hygiene in the context of health care. For this, a descriptive, qualitative and exploratory study will be carried out, which will use a systematic review of the literature in order to analyze and synthesize the scientific knowledge obtained through the results of research already carried out. Articles from three electronic databases will be considered, the National Library of Medicine, Latin American and Caribbean Literature in Health Sciences and the Ministry of Health’s Virtual Library. The research period will be between October 2022 and November 2022 and retrospective articles covering 10 years, between 2012 and 2022 will be included. Finally, it is expected, through this study, to identify the challenges of nursing in the Infection Control Commission Hospital to design and implement measures for proper hand hygiene by health professionals.
PRINCIPAIS ASPECTOS DO PERCURSO DA EDUCAÇÃO EM ANGOLA: DA ERA COLONIAL ÀS ELEIÇÕES GERAIS DE 2017
Authors: Francisco Ilda da Costa
Published: February 2025

This study is an excerpt from a master’s dissertation which aims to describe the main aspects of education in Angola based on the historical process. It is a bibliographical study, presented chronologically in four stages: The colonial era, the arrival of the Portuguese in Angola in 1482. The post-colonial era, the proclamation of independence in 1975. The era of the peace agreement in 2002 and the general elections in 2017. Based on this journey, we understand that the aspects linked to the struggle for political and social rights, the reorganization of the education system, democratization and the reform of the state mark out the meaning of education for Angolan citizens.
Publicidade e gênero: a discriminação nociva de gênero como publicidade abusiva
Authors: Xavier José Tadeu Neves , Milhoranza Mariângela Guerreiro
Published: February 2025

A publicidade brasileira tem sido historicamente marcada pela utilização de estereótipos que reforçam a cultura da discriminação nociva de gênero. Considerando os parâmetros regulatórios da publicidade previstos no Código de Defesa do Consumidor, o anúncio publicitário que retrata estereótipos negativos de gênero deve ser reconhecido como publicidade abusiva, sujeita, portanto, às sanções que lhe são próprias. Seguindo a tendência mundial, tramitam no Congresso Nacional projetos de lei que visam tipificar a vedação de publicidade que estabeleça discriminação de gênero
Teoria constitucional do Direito do Trabalho brasileiro na perspectiva de Oliveira Vianna
Authors: Eça Vitor Salino de Moura , Fonseca Bruno Gomes Borges da
Published: February 2025

Com base no método dialético e na técnica de pesquisa documental indireta, este artigo analisa as principais ideias defendidas por Oliveira Vianna e, com base nelas, uma teoria constitucional supostamente adaptada à realidade brasileira, sem prejuízo da ausência de originalidade e da presença de oscilações e fragilidades. O Estado teorizado por Oliveira Vianna era unitário, centralizador, interventor, autoritário e corporativista; rechaçava a federação, a maior autonomia dos estados federados, a democracia pautada em partidos políticos e os movimentos comunistas e socialistas; tal Estado seria sustentado por um pretenso regime democrático corporativo (ou de classes) e cristão. Posteriormente, com base nessa teoria constitucional defendida por Oliveira Vianna, compuseram-se aqui categorias analíticas com o objetivo de manejá-las na condição de alicerces constitutivos do Direito do Trabalho brasileiro, o que permitiu uma resposta ao problema impulsionador desta pesquisa
Fake news: regulação ou metarregulação?
Authors: Amato Lucas Fucci
Published: February 2025

Tomando como referência teórica principal a sociologia sistêmica desenvolvida por Niklas Luhmann e suas aplicações no Direito, este artigo reflete sobre os desafios para o tratamento jurídico da disseminação de notícias falsas. Aborda primeiramente a coevolução entre formas de sociedade e meios de disseminação da comunicação, delimitando as fake news como fenômeno típico de uma sociedade digital. A seguir, define a emergência da autorregulação privada como uma expressão do Direito contemporâneo e nota a necessidade da metarregulação: de regular (pelo Direito estatal) a autorregulação (privada). Finalmente, analisa o art. 31 do Projeto de Lei das fake news (ou Lei Brasileira de Liberdade, Responsabilidade e Transparência na Internet). Assim, o texto destaca as potencialidades do instituto da “autorregulação regulada” previsto nessa legislação para que sejam construídas experimentalmente normas capazes de disciplinar os comportamentos e as responsabilidades emergentes com o desenvolvimento das novas tecnologias e plataformas digitais
A produção normativa das agências reguladoras: limites para eventual controle da atuação regulatória da Anvisa em resposta à Covid-19
Authors: Salinas Natasha Schmitt Caccia , Sampaio Patrícia Regina Pinheiro , Parente Ana Tereza Marques
Published: February 2025

Este artigo tem por objetivo analisar a produção normativa da Anvisa em resposta à crise de saúde pública gerada pelo novo coronavírus. Com base em levantamento das medidas regulatórias adotadas pela Agência entre os meses de janeiro a junho de 2020, constatou-se que a Anvisa produziu um elevado número de normas que: (i) não seguiram ritos ordinários do processo administrativo normativo; e (ii) flexibilizaram exigências e obrigações do setor regulado na outorga de atos de liberação econômica. O artigo busca analisar se (e sob que condições) os Poderes Judiciário e Legislativo deverão adotar uma postura de deferência em relação a eventuais questionamentos dessas normas. Conclui-se que, em regra, os atos normativos produzidos pela Anvisa durante a pandemia merecem deferência. No entanto, a necessidade de que seja demonstrado embasamento técnico persiste, mesmo que este se apoie em normas provenientes de órgãos internacionalmente reconhecidos
Composição do Conselho de Administração de organizações sociais quanto aos membros natos representantes do Poder Público
Authors: Saddy André
Published: February 2025

O presente artigo tem como objeto a análise da composição do Conselho de Administração por pessoas jurídicas de direito privado que ostentam a qualificação de organizações sociais quanto aos representantes das entidades e dos órgãos públicos. Para isso, focou-se inicialmente no conceito de organizações sociais para então entrar na questão da (in)constitucionalidade ou (i)legalidade do Conselho de Administração das organizações sociais conforme disciplinam os arts. 5º, III, e 15, § 2º, do Decreto nº 9.190/2017. Considerando esse diploma constitucional/legal, passou-se a identificar que os diretamente responsáveis pela supervisão, financiamento e controle da atividade são, na verdade, apenas o órgão supervisor e, se houver, o(s) intervencionista(s). No entanto, apesar de pouco factível e esdrúxula, não sendo ela a interpretação aqui defendida, poder-se-iam interpretar os enunciados no sentido disjuntivo e, por conseguinte, supervisor, financiador e controlador seriam órgãos distintos
Direito financeiro da crise: a modulação da legislação orçamentário-financeira para o combate aos efeitos da Covid-19
Authors: Amaral Júnior José Levi Mello do , Araujo Fabiano de Figueirêdo
Published: February 2025

Este artigo objetiva investigar a modelagem da normatização financeira e orçamentária para o enfrentamento dos efeitos da Covid-19, configurada como um efetivo Direito Financeiro da Crise. Essa modelagem acarretou a suspensão do paradigma normativo ordinário de controle fiscal em favor de uma normatização extraordinária, evidenciada por três fatos: o reconhecimento da calamidade fiscal da União, a concessão de medida liminar na Ação Direta de Inconstitucionalidade nº 6.357 e a Emenda Constitucional nº 106/2020. A construção de um Direito Financeiro da Crise é um mecanismo adequado para o enfrentamento da Covid-19, mas acaba demonstrando a tendência de preocupação mais conjuntural que estrutural da legislação orçamentária brasileira
Mobilizando a agenda dos direitos coletivos, assegurando espaço institucional: Ministério Público e Defensoria Pública na transição democrática
Authors: Lima Flávia Danielle Santiago , Lamenha Bruno
Published: February 2025

Como a tutela coletiva se converteu numa plataforma para o fortalecimento institucional na transição institucional à democracia no Brasil? O presente artigo aborda a reformatação do Ministério Público e a criação da Defensoria Pública como frutos da mobilização na Assembleia Nacional Constituinte entre 1987 e 1988, considerada a proteção dos direitos transindividuais, com repercussões na ordem jurídica subsequente. Para tal fim, a pesquisa adota o método dedutivo: com base na teoria neoinstitucional, elege o institucionalismo histórico como marco teórico para a abordagem proposta. Como resultado, verificou-se uma trajetória comum partilhada entre as instituições a partir do longo processo de liberalização do regime civil-militar (1964-1985) e consolidação constitucional, em que a Constituição da República Federativa do Brasil de 1988 se tornou ponto de chegada para o Ministério Público e de partida para as pretensões da Defensoria Pública, com o estabelecimento de competições em relação à titularidade da tutela coletiva
A justiça restaurativa como estratégia contemporânea de controle social penal
Authors: Oliveira Cristina Rego de
Published: February 2025

A justiça restaurativa surge como um modelo diferenciado de resolução do conflito penal que se propõe recompor os danos decorrentes da ofensa, por meio de um processo participativo e dialogado entre os sujeitos envolvidos no problema – vítima, autor e comunidade –, razão pela qual suas ferramentas são consideradas mecanismos informais de controle. Com base em revisão bibliográfica crítica, o artigo levantará a hipótese de que no Brasil a cooptação da justiça restaurativa pela racionalidade estruturante do sistema de justiça penal faz com que esses modelos sejam nada mais que a sua extensão, do que resulta a reconfiguração do controle formal sobre a população mediante estratégias renovadas e invisíveis
A incidência da supressio na obrigação alimentar entre ex-cônjuges
Authors: Rosa Luiz Carlos Goiabeira
Published: February 2025

Atualmente tem-se constatado o entendimento de que princípios antes afetos ao Direito dos Contratos podem ser aplicados ao Direito de Família. Nesse sentido, o presente trabalho tem por objetivo demonstrar que o princípio da supressio é aplicável à obrigação alimentícia entre ex-cônjuges, e assim deve ser para que se efetive a boa-fé e até mesmo o princípio da solidariedade. Adotou-se o método dedutivo, tendo por premissa geral a boa-fé objetiva como decorrência dos princípios da solidariedade e da eticidade para se chegar à premissa específica de que a supressio pode e deve ser aplicada aos alimentos devidos entre ex-cônjuges
O dever de fundamentação das decisões judiciais: a relativização dos limites entre common law e civil law no CPC
Authors: Bomfim Rainer , Bahia Alexandre Gustavo Melo Franco de Moraes
Published: February 2025

A presente pesquisa, sob a vertente jurídico-sociológica, objetiva investigar a relativização dos limites entre common law e civil law no domínio processual civil com o advento do Código de Processo Civil de 2015 – especificamente quanto ao dever de fundamentação das decisões judiciais –, bem como verificar se o diálogo entre common law e civil law suscitado pelo novo Código é um mecanismo jurídico que promove o dever de fundamentação e coíbe decisões judiciais nulas, de modo a garantir o contraditório e a segurança jurídica processual. Para isso, sustenta-se este trabalho em três eixos de investigação: a análise conceitual do dever de fundamentar, a comparação entre os sistemas common law e civil law e o estudo dos aportes teóricos sobre o risco do julgamento em tese nas decisões dos juízes
Crítica e reformulação da teoria do bem jurídico: proposta de um referente circunstancial
Authors: Devos Bryan Alves , Khaled Junior Salah Hassan , Divan Gabriel Antinolfi
Published: February 2025

O texto objetiva delinear e criticar a noção de bem jurídico no paradigma garantista, visando superar algumas de suas insuficiências. Como problema, questiona a necessidade e viabilidade de se preservar a busca por um referente material que dê conta de guiar a criminalização. A hipótese é de que tal busca não consegue superar suas aporias, por não escapar de sua própria circularidade e adotar o critério idealista de justificação do poder punitivo. Quanto ao referencial teórico, o artigo propõe a abordagem realista marginal e um olhar agnóstico para a questão da pena, acompanhados da proposta de um referente circunstancial para que sejam identificados os bens jurídicos factualmente passíveis de proteção por meio do Direito Penal: os direitos fundamentais do criminalizado. A investigação faz uso do método dedutivo e adota como procedimento a revisão bibliográfica pertinente
Simulate modified Nonmem models using NMsim
Authors: Rashid Jahidur , Cassani Simone , Banker Christopher , Delff Philip
Published: February 2025

Objectives: Many questions throughout the drug development stages can be answered using simulations of a modified pharmacometric model. NMsim automates the simulation of Nonmem models and provides a concise interface for modifying the control stream integrated into the simulation command. We aim to showcase these features through some examples that are highly relevant in pharmacometrics.Methods: A standard popPK model estimated on a publicly available data set was used. The NMsim R package was shown to address questions like the following with simple R code: • How will the concentration-time profile be affected if switching formulation and reducing absorption rate by a range of fold-values?• How will a dose delay of different amounts of time affect the predicted concentration-time profile?• What is the expected concentration-time profile in patients with a certain DDI effect on clearance and bioavailability?• How does log-likelihood depend on different assumed values of absorption rate?The seamless workflow of NMsim allows the codes to be readily applicable to most Nonmem popPK models.Results: NMsim provides a flexible and concise interface for modifying control streams prior to simulation or estimation. Model-agnostic code examples were provided and results shown illustrated how simply a model-based approach to some questions common to drug development can be performed.Conclusions: Although the examples provided in this work address selected questions related to certain parameters of a popPK model, we hope to inspire the audience to see that these features provide a powerful tool to easily explore the implications of various properties of a pharmacometric model. All software, code, and data used are freely available for the audience to modify to their own needs.Citations: [1] 2024. NMsim: An R package that can simulate Nonmem models. https://philipdelff.github.io/NMsim[2] 2024. NMsim: Seamless ‘Nonmem’ Simulation Platform. https://cran.r-project.org/web/packages/NMsim
Population pharmacokinetics and exposure-safety of DS-6157a in patients with advanced gastrointestinal stromal tumor (GIST)
Authors: Tran Brittany , Fallon Maura , Follman Kristin , Iadevaia Sergio , Kundu Madan , Laadem Abderrahmane , Lau Yvonne , Nishioka Satoshi , Shi Julia , Zhang Xinyuan
Published: February 2025

Objectives: DS-6157a is a first-in-class antibody–drug conjugate (ADC) that targets G protein-coupled receptor 20 (GPR20) and comprises a humanized anti-GPR20 monoclonal antibody that is covalently conjugated to an enzyme-cleavable linker, and a topoisomerase I inhibitor payload (DXd, also known as MAAA-1181a) at a drug-to-antibody ratio of ~8. We aimed to characterize the pharmacokinetics (PK) of DS-6157a (intact ADC) and DXd (released payload) through the development of a population PK (PopPK) model and to evaluate exposure–response (ER) relationships for select safety endpoints.Methods: PopPK and ER models were developed using data from a first-in-human dose escalation study of DS-6157a (n=34) in patients with GIST, with DS-6157a dosages ranging from 1.6–12.8 mg/kg Q3W (once every three weeks) intravenous (IV) administration.[1] Nonlinear mixed effects modeling was used to develop the PopPK model. First, a sequential DS-6157a – payload model was developed. A final simultaneous DS-6157a and payload model was then developed. Exposure-safety analyses for select safety endpoints were conducted using multivariate logistic regression. Exposure metrices of DS-6157a and DXd as predicted by the PopPK model were evaluated in the exposure-safety analyses.Results: DS-6157a PK was well described with a 2-compartment PK model with linear elimination, and baseline body weight on the volume of the central compartment was identified as a significant covariate. DXd PK was well described with a 1-compartment PK model with time-dependent payload release rate and parallel linear and nonlinear elimination. Baseline albumin on DXd clearance was found to be a significant covariate in PopPK. A univariate logistic regression model comprised of an intercept term and a slope coefficient for DXd steady-state minimum concentration best predicted the occurrence of any CTCAE Grade and Grade ≥3 neutropenia and thrombocytopenia events. No covariates were found to be significant in the exposure-safety analysis.Conclusions: PK of DS-6157a and DXd were well characterized by the PopPK model. Although there were limited efficacy signals,[1] positive ER relationships for safety endpoints (neutropenia and thrombocytopenia) were observed.Citations: [1] George S, et al. Clin Cancer Res. 2023;29(18):3659–3667.
A Longitudinal Model-based Meta-Analysis (MBMA) of Body Weight in Obesity Trials
Authors: Ahadieh Sima , Ahn Jae Eun , Ravva Patanjali
Published: February 2025

Objective: This MBMA aimed to evaluate weight loss efficacy of glucagon-like peptide-1 (GLP1) agonists including liraglutide, semaglutide (SC and oral), orforglipron, GLP-1/glucose-dependent insulinotropic peptide (GIP) receptor agonist tirzepatide, and GLP-1/glucagon receptor agonist efinopegdutide in obesity trials. Methods: A comprehensive literature search of electronic databases (Medline, Embase, Biosis, and clinicaltrials.gov) was conducted for relevant randomized controlled trials (RCTs) published up until January 2024 for the drugs of interest listed above and the primary endpoint of body weight percent change from baseline in obesity patients. Each publication returned from the literature search was reviewed for relevancy and digitized into a MBMA data file. NONMEM 7.5.0 (ICON plc) was used for analyses and R 4.2.1 was used for data cleaning, modification, and plotting. The total effect consisted of drug effect and placebo effect. Emax models, differentiated by class and formulation, were used to characterize dose response relationships, and an exponential model plateaued with respect to time was used to assess placebo responses as well as reaching the maximum drug effect. The covariates of interest included existence of diabetes type 2 (T2DM) comorbidity, average baseline body weight, and intensive behavioral therapies added to pharmacological interventions. A loss of response over time was also evaluated via a durability function. The final model was used to predict percent changes from baseline in body weight, and the mean and confidence intervals (CI) for each treatment. A shiny app was developed for interactive assessments of analysis results. Results: The final MBMA dataset included 70 citations out of which 33 studies with 89 study arms were included in the quantitative analysis compromising 18023 subjects. The MBMA demonstrated significant body weight reductions across GLP1, GLP1/GIP, GLP1/Glucagon receptor compared to placebo. The effects of diabetes comorbidity and intensive behavioral therapy were significant on the drug effect. Durability function in placebo effect improved the model. The predicted percent changes in body weight [95% CI] for liraglutide 3 mg, semaglutide SC 2.4 mg, semaglutide oral 50 mg, orforglipron 45 mg, efinopegdutide 10 mg, and tirzepatide 10 and 15 mg, and placebo after 72 weeks for non-diabetic obese patients were -8.08 [-7.39, -8.77], -14.3 [-13.1, -15.4], -16.4 [-13.6, -18.7], -17.8 [-16.0, -19.6], -12.0 [-9.14, -14.5], -20.0 [-17.9, -22.2], -21.9 [-19.7, -24.4], and -1.79 [-1.35 , -2.26] respectively. Conclusion: Longitudinal changes in body weight by GLP1 classes were characterized via MBMA. This analysis provided a benchmark and information about the dose-response relationship as well as temporal dynamics in body weight changes for future trial designs.Citations: no citations
Disease progression modeling of myositis from real-world data
Authors: Zhao Yuan , Mould Diane , Denis Deborah , Oddis Chester , Venkatakrishnan Karthik , Gao Wei , Goteti Kosalaram
Published: February 2025

Objectives: The idiopathic inflammatory myopathies are a heterogenous group of rare connective tissue diseases with the hallmark clinical manifestation of progressive muscle weakness with subgroups including polymyositis (PM), dermatomyositis (DM) or immune mediated necrotizing myopathy (IMNM). The objectives of this analysis were to develop models describing the disease progression or trajectory reflected by clinical endpoints and to identify predictors of a change in disease activity.Methods: The data source of the Myositis Registry from the University of Pittsburgh was used to develop the model. After data exploration, two clinical endpoints, physician global activity (PGA) and cutaneous disease activity (CUTNA) visual analog scales were chosen for modeling based on the availability of the longitudinal data and the data trajectories. Different approaches were tested using the original scale values, transformation of integer values for bounded integer model (BIM) and Markov model. Various model functions have been evaluated including linear progression, exponential progression, an inverse Bateman function and a remission/progression model. Covariates of demographics and clinical characteristics were evaluated based on the likelihood ratio test, general linear model and covariate plots. Statistically significant covariates were included in a full model and retained in the final model in a stepwise regression during the back elimination. Visual predictive checks to assess frequency of scores and proportion of data at each score over time and multiple diagnostic approaches including agreement plots were performed to evaluate the model performance. Results: The PGA model was developed using pooled dataset from PM, DM and IMNM (Nf50, 122 and 13, respectively) after determining the trajectories were similar while the CUTNA model was based on DM population only (Nf120). The time course of PGA and CUTNA scores over time were best described using a BIM approach, and a function describing remission and progression was best for both endpoints. For the PGA endpoint, positive AJo1 antibody status, higher baseline PGA score, and the presence of heliotrope rash were identified as covariates which were predictive of poorer outcomes than the reference patients. For patients with muscle weakness in the neck there was a greater likelihood of a better outcome than for the reference patient. For the CUTNA endpoint, only covariates on Baseline could be estimated. Heliotrope rash, symmetrical proximal weakness of upper extremities and other dermatomyositis rash were predictive of higher CUTNA score.Conclusions: Disease progression models have been successfully developed for PGA and CUTNA using the real-world data. Covariates have been identified for each model which could provide valuable information to inform future clinical trial design in myositis patients.Citations: NA
SAS Macro for Validation of NONMEM Data Items Pertaining to Implicit Expansion of Dose Records in Oral Dose Population Pharmacokinetic Datasets
Authors: Sukumar Prema , Maloney Matt , Chen Weidong
Published: February 2025

Objectives: Oral dose drugs are often not exclusively administered in clinic, leaving patients to take at home doses and report their dosing history. As a result, complete dosing information is not always available for oral dose studies. In analysis of Population Pharmacokinetic (popPK) datasets, two methods can account for the unrecorded doses. The first is to insert a record for each unrecorded dose event into the dataset. The second is an implicit expansion of dose records with NONMEM standard data items ADDL (additional identical doses given) and II (interdose interval). Oral dose studies have also been shown to contain multiple dose interruptions or reductions due to adverse events, unrecorded dose times, as well as dose titrations or other protocol specified dose regimen complexities that can at times deviate from the actual administered dose frequency. Given these complexities, a validation tool for the data integrity of PopPK dose records was targeted for development to identify anomalies resulting from ADDL/II expansion.Methods: A SAS macro was created to accompany PopPK dataset generation for validation of oral dose records. The macro is called using the following syntax: “%check_addl(dsin, )” where “dsin” is the dosing records of a PopPK dataset to use as the input, and “obs” optionally specifies how many records to print in the output with default as "max". By utilizing NONMEM, CDISC ADaM PopPK and SDTM rules and guidance, the macro first ensures that certain data variables are present and structured as expected to mitigate user error. The macro works by performing a series of queries on the data where the expected return from the macro is no results. Any return from the macro indicates possible areas of exploration including fixing errors in PopPK data preparation, consultations with data management teams if applicable, or left to the discretion of the pharmacometrician.Results: The following queries are returned by the macro: • Check that ADDL=0 when II=0• Check if records with dose time >=24:00hr (next day) are created• Check for different dosing schedules on the same day• Check if doses with EXDOSFRQ > 24hrs overlap with other dose records• Check for periods of unrecorded dosing• Check if the actual doses on a specific day does not match EXDOSFRQ• Check if BID doses have both doses in AM or both doses in PMConclusions: Given potential for data abnormalities and the need for imputation of missing dose times, a macro that can be run on a completed dosing dataset provides useful validations on data integrity prior to PopPK analysis steps. The macro efficiently runs queries that check on standard items that can be seen for all PopPK datasets that use ADDL/II dose expansion. The macro has the potential to save both time and needless exclusions that could be avoided if issues are found and dealt with at the time of PopPK dose dataset generation.Citations: NA