bluuebunny/crossref_metadata_2025 huggingface dataset:
Reflections on the Special Issue: Burning of the Qur’an
Authors: Meyer Verena , Skovgaard-Petersen Jakob , Frydenlund Iselin , Larsson Göran
Published: December 2024

The following three short texts are the outcome of a roundtable discussion at the European Association for the Study of Religion (EASR) conference held on 19 August 2024 in Gothenburg. The focus of the roundtable was the special issue, Burning of the Qur’an, which was edited by Göran Larsson, Iselin Frydenlund, and Torkel Brekke and published in Temenos, Vol. 60, No. 1 (2024). The special issue contained articles on the development in Sweden, Norway, Denmark, and Finland and a meta reflection on the burning of the Qur’an from a British and South Asian perspective. At the EASR conference the editors invited Assistant Professor Verena Meyer from Leiden University and Professor Jakob Skovgaard-Petersen from the University of Copenhagen to comment on and discuss the special issue. This section of Temenos publishes Meyer’s and Skovgaard-Petersen’s responses, with a short reply from Iselin Frydenlund and Göran Larsson. The discussion focuses on research ethics (‘why study a controversial topic’), legal frameworks, and the lack of ‘Muslim voices’ in the study of controversial topics.
3-year Outcomes of Rotating Suture with Root Z-epicanthoplasty for Lower Lid Epiblepharon
Authors: Kim Daeseon , Kim Ju Mi , Cho Won-Kyung
Published: December 2024

Purpose: To report the clinical outcomes of Root Z-epicanthoplasty combined with lower eyelid rotation suturing in patients with lower eyelid epiblepharon, focusing on a 3-year follow-up.Methods: Patients who underwent Root Z-epicanthoplasty combined with lower eyelid rotation suturing from March 2012 to February 2020 were included. Patients aged < 15 years, and who had a minimum 3-year follow-up, were included. We assessed changes in best corrected visual acuity (BCVA), cycloplegic refraction, astigmatism, and surgical outcomes. To evaluate the influence of preoperative amblyopia, patients were divided into subgroups based on amblyopic status; surgical outcomes were compared between these groups. In addition, subgroups were divided based on age at operation and astigmatism were compared between subgroups.Results: A total of 55 patients (109 eyes) exhibited successful correction of lower eyelid epiblepharon without recurrence; one case experienced a delayed episode of lower palpebral conjunctival hemorrhage. Significant changes were observed of BCVA improvement, myopic shift of cycloplegic refraction, and astigmatism reduction three years post-surgery (p < 0.001, p < 0.001, p = 0.024). In the group without preoperative amblyopia (86 eyes), significant changes were noted in BCVA, cycloplegic refraction, and astigmatism (p < 0.001, p < 0.001, p = 0.025). In patients with preoperative amblyopia (23 eyes), significant improvements were observed in BCVA and myopic shift in cycloplegic refraction (p < 0.001, p = 0.003), whereas astigmatism showed no significant change (p = 0.431). There is significant reduction of astigmatism in under 6-year-old group (p = 0.011) and no significant reduction of astigmatism in over 6-year-old group (p = 0.589).Conclusions: Root Z-epicanthoplasty with lower eyelid rotation suturing demonstrated a low complication rate and no recurrence over 3-year follow-up, confirming its effectiveness in correcting lower eyelid epiblepharon. The procedure also positively influenced visual development and reduction of astigmatism in pediatric patients.
Apocrine Hidrocystoma of Bulbar Conjunctiva
Authors: Lee Chae Yoon , Kim Sang Soo
Published: December 2024

Purpose: To present a case of apocrine hidrocystoma occurring that occurred in the bulbar conjunctiva.Case summary: A 36-year-old male patient presented with a mass in the left conjunctiva noted a week prior to his visit. During the initial physical examination, slit-lamp examination revealed a relatively well-demarcated pink mass in the lateral part of the left bulbar conjunctiva. Orbital computed tomography showed a well-defined, contrast-enhancing mass measuring 4 × 10 × 21 mm in the left lateral conjunctival area, suggestive of a conjunctival epidermoid cyst. An excisional biopsy of the cystic mass was performed. Histopathological examination confirmed that the lesion was an apocrine hidrocystoma.Conclusions: Apocrine hidrocystoma occurring in the bulbar conjunctiva is extremely rare but should be considered in the differential diagnosis of a conjunctival cyst or mass.
Análise do perfil epidemiológico e internações de pacientes com tuberculose no município de Pinheiro-Maranhão entre 2019-2024
Authors: Pereira Gabriel Henrique , Sarges Adriana Figueredo , Garcia Cleydiane Sousa , Ribeiro Larissa Adriana Lobato , Ribeiro Ana Kerly , Machado Lana Costa , Ribeiro Raquel Iris Madeira , Amorim Marcos Antônio Azevedo
Published: December 2024

Objetivo: Analisar o perfil epidemiológico de pacientes com tuberculose, seja eles internados pela doença ou que foram diagnosticados pela mesma no município de Pinheiro-Maranhão. Metodologia: Trata-se de uma pesquisa documental de fonte direta utilizando o sistema Departamento de Informática do Sistema Único de Saúde do Brasil (DATASUS) em um estudo transversal epidemiológico e de natureza quantitativa. Resultados: Foram coletados 127 casos confirmados e 55.942 internações por Tuberculose (TB) durante o período de 2019 a 2024 no Município de Pinheiro – MA. Divididos em tópicos de internações e casos por sexo, sendo o sexo masculino com maior incidência de casos confirmados com 63,78% e com sexo feminino liderando os casos de internações com 57,55%. Além disso os casos e internações por raça possuem a cor parda com maior incidência representando 82% e 58% de ambas as variáveis. Os casos confirmados por escolaridade tiveram maior incidência da 1ª e 8ª serie, com 25,20% da amostra. Enquanto as hospitalizações e diagnósticos por idade teve maior representatividade na faixa etária de 20 a 49 anos. Por população vulnerável a ter a doença os infectados com AIDS foram os mais atingidos. Aos gastos hospitalares observou-se que em 6 anos o total ficou entre 49.122.122,17, enquanto aos óbitos avaliou-se um menor número entre 2023 e 2024. Considerações Finais: Percebe-se que a vasta informações da literatura acerca a TB. Todavia, o desafio maior está associado ao sistema de saúde que possa alcançar e notificar e tratar a TB.
Annacardium occidentale linn no tratamento de lesões cutâneas inflamatórias e o processo cicatricial
Authors: Santos Joana Ferreira dos , Medeiros Beatriz de Freitas , Gomes Viviany Azevedo , Angelino Êmilly Mendes , Silva Yasmin Vitória Jó da , Araújo Cristina Ruan Ferreira de , Mariz Saulo Rios , Lemos Jordão Ana Janaína Jeanine Martins de Lemos
Published: December 2024

A pele é o maior órgão humano, lesões nesta estrutura podem resultar em limitações funcionais, envolvendo um processo de reparo tecidual complexo. Feridas crônicas representam um grande problema de saúde pública no Brasil, com impacto nos custos e na qualidade de vida dos pacientes. A Fitoterapia, especialmente com o uso do Anacardium occidentale, conhecido como cajueiro, tem sido apontada como uma terapia eficiente para promover a cicatrização de feridas, embora haja controvérsias sobre sua eficácia. Este trabalho visa realizar uma revisão narrativa sobre os potenciais terapêuticos, eficácia e segurança do Anacardium occidentale Linn no tratamento de lesões cutâneas, a partir da literatura disponível nas principais bases de dados. Dentre os artigos analisados, 8 foram selecionados e organizados em uma tabela em ordem cronológica pelo ano de publicação, bem como objetivos, metodologias do artigo avaliado, resultados e conclusões de cada estudo eleito para elaboração dos resultados e discussões. O uso do A. occidentale mostrou benefícios no tratamento de diversas enfermidades, como lesões cutâneas, inflamações, doenças bucais e processos gastrointestinais. Efeitos terapêuticos incluem ação anti-inflamatória, cicatrizante, além de estimular a reparação tecidual, com diferentes partes da planta sendo utilizadas. O estudo destacou que o cajueiro possui propriedades terapêuticas, principalmente no tratamento de lesões inflamatórias na pele devido aos seus metabólitos ativos. Apesar de ser uma planta medicinal acessível e de baixo custo, é necessário mais pesquisas toxicológicas para confirmar a segurança do seu uso. O A. occidentale mostra-se promissor para uso terapêutico, mas mais estudos são necessários para definir eficácia e segurança.
Movimentos sociais e a mídia étnica: Entre diálogos críticos e decoloniais nas redes digitais
Authors: Costa Bruna Pollyana Almeida da
Published: December 2024

A comunicação e o fazer comunicacional, na contemporaneidade utilizam a linguagem como instrumento de poder e dominação social. Nesse sentido, o objetivo geral deste estudo é analisar os movimentos sociais e a mídia étnica, entre diálogos críticos e decoloniais nas redes digitais. Metodologia, trata-se de uma pesquisa bibliográfica narrativa de cunho qualitativa. Concluiu-se que ao longo do estudo, as análises, as problematizações e as representações realizadas pelos movimentos sociais étnicos não se esgota aqui, tampouco as perspectivas de estudos críticos, decoloniais e assumidas nessa pesquisa como um traço distintivo entre os movimentos. A mídia é um trabalho que, de modo aproximativo e reflexivo, busca problematizar as construções (re)afirmativas a respeito do processo de identificação do ser indígena nesta sociedade envolvente. Assim, o que vem sendo exposto em rede social é uma parte da sua significação. O que se veicula/publiciza são parte das lutas por direitos e das ‘redes de mobilização’.
Cuidados paliativos e Medicina de Família e Comunidade: Perspectivas da abordagem familiar em desafios da finitude de vida
Authors: Morcerf Cely Carolyne Pontes , Lima Gabriel Barbosa de , Martins Vitor Agostinho , Marques João Mazzoncini de Azevedo
Published: December 2024

Tendo como centro de valores de formação a visão humanística, o cuidado centrado na pessoa, habilidades de gerenciamento populacionais e o acompanhamento longitudinal em trabalho com diferentes ciclos vitais, a medicina de família e comunidade é uma especialidade médica responsável pela abordagem do sofrimento e do entendimento do impacto de determinantes sociais no comportamento de relações interpessoais e familiares, associada a manifestações e agravamentos de patologias, nas diferentes fases de transição da vida. Dentro dessa abordagem, a especialidade possui em sua formação o desenvolvimento de habilidades de comunicação que fortalecem questões como empatia e compaixão na essência da prática diária da medicina, utilizando instrumentos familiares de forma a aproximar famílias do processo decisório e de cuidados com o paciente em um forma horizontal e participativa. Assim, a medicina de família e comunidade se desenvolve como uma especialidade estratégica para o trabalho inserido no alívio da dor, cuidado integral individual e familiar, assim como no acompanhamento longitudinal de doenças ameaçadoras à vida e de pessoas em fase de finitude da vida, inseridos no contexto dos cuidados paliativos, desde a atenção primária até a assistência em ambiente hospitalar. O presente artigo objetiva discutir com base na literatura, sobre oportunidades da visão biopsicossocial da medicina de família em uma perspectiva de necessidades e potencialidades de ampliação dos cuidados paliativos.
Acesso e longitudinalidade do cuidado em saúde prisional: Perspectivas da medicina de família na abordagem de populações e doenças negligenciadas
Authors: Morcerf Cely Carolyne Pontes , Coutinho Guilherme Moreira de Queiroz , Rasmussen Emilly Barboza , Marques João Mazzoncini de Azevedo
Published: December 2024

Construído em um processo histórico de necessidade da exclusão e enclausuramento do socialmente e legalmente determinando como conduta criminosa, o caráter biopsicossocial da criminalidade continua potencializando o número de populações que superlotam o sistema prisional, porém em uma proporção que diverge das reais necessidades em investimento na reeducação, nas possibilidades de reinserção psicossocial e da garantia de direitos humanos dentro do regime de privação de liberdade, principalmente do acesso à saúde. Dentro das lacunas e fragilidades existentes para a plena garantia da saúde em toda a visão de bem estar físico e mental, é uma problemática crescente a existência de doenças negligenciadas que mesmo estando em processo de redução na população geral, ainda são uma realidade presente e de difícil manejo no seguimento das populações negligenciadas, necessitando de uma organização em saúde que possibilite o direcionamento de estudos e abordagens que empoderem e auxiliem na educação, prevenção e promoção dessas populações marginalizadas. A partir desse cenário, a medicina de família e comunidade se apresenta como formação médica estratégica para o trabalho em áreas e zonas negligenciadas. O presente trabalho tem como objetivo realizar uma revisão narrativa de literatura sobre a questão do acesso e do cuidado integral necessários no âmbito da saúde prisional, tendo a medicina de família e comunidade como responsável pela coordenação do cuidado e o entendimento geral de crescimento e identificação de doenças negligenciadas nesses seguimentos invisibilizados da sociedade.
A Odontologia digital como coadjuvante no planejamento do sorriso em pacientes com problemas ortodônticos
Authors: Araújo Janiocastro Mendonça de , Santos Marcos Severino dos , Guillou Joyce Quintela Carvalho
Published: December 2024

A Odontologia digital tem promovido avanços significativos no planejamento estético e ortodôntico, proporcionando maior precisão e eficiência nos tratamentos. Este estudo teve como objetivo revisar a literatura científica publicada entre 2010 e 2024, e outras pontuais, analisando o impacto das tecnologias digitais no diagnóstico e tratamento ortodôntico. Foram selecionados artigos das bases PubMed, SciELO e Google Acadêmico, com foco em tecnologias como scanners intraorais, setup digital, tomografia computadorizada de feixe cônico (CBCT), impressão 3D, softwares de planejamento digital e outros. A análise incluiu apenas estudos que discutissem a aplicação prática dessas ferramentas no contexto ortodôntico. Os resultados destacam que a Odontologia digital tem transformado o planejamento ortodôntico, tornando os tratamentos mais eficientes, previsíveis e personalizados, evidenciando o impacto positivo dessas inovações na eficiência clínica e no conforto do paciente. Tecnologias como o setup digital, scanners intraorais, sistemas CAD/CAM e impressão 3D têm melhorado a visualização do diagnóstico e a comunicação com os pacientes, além de otimizar a produção de dispositivos ortodônticos personalizados. O uso dessas ferramentas, embora eficaz, apresenta desafios como o alto custo de implementação e a necessidade de capacitação técnica avançada. No entanto, a integração dessas tecnologias promete um futuro promissor para a Ortodontia, com potencial para transformar ainda mais a área, sendo um pilar fundamental na criação de sorrisos harmoniosos e personalizados.
A nagygépes vasúti alépítményjavítási technológia bevezetése a magyar vasútépítésben
Authors: Horváth Róbert , Szigeti Cecília , Major Zoltán
Published: December 2024

A magyar vasúti hálózat európai törzshálózatba (TEN-T) tartozó elemeinek teljes körű felújítása, modernizációja fokozott ütemben kezdődött meg a 2009-2016 közötti KÖZOP finanszírozási program keretében. A korszerű technológiák bevezetése kézenfekvő megoldás volt a vasúti alépítmény rehabilitációjának elvégzéséhez is tekintve a program során munkáltatás alá vett jelentős vágányhosszakat. A Magyarországon új technológia honosításához azonban a tervezési, műszaki ellenőrzési és kivitelezési folyamatokat szabályozó előírásrendszereket is meg kellett újítani. A kivitelezési munkák megkezdése előtt a vasúti nagygépes alépítményjavítási technológiához nélkülözhetetlen törtszemcsés kiegészítő réteg anyagának hazai körülmények között elérhető kőbányákból származó keverékét is ki kellett kísérletezni. A honosítási folyamat során a tervezési és műszaki ellenőrzési metódusok eleinte párhuzamosan folytak a korábban alkalmazott eljárásokkal míg az egyenértékűség igazolásra került. Laboratóriumi tesztek és próbaszakaszok építésével történt a kőanyag keverékterv és a technológia véglegesítése. Az alkalmazott új építési módszer a magas műszaki színvonal és a konvencionális technológiához képest igen gyors kivitelezési idő miatt jelentős vágányzári idő csökkenést eredményezett és több fontos környezetvédelmi szempontból is előnyös folyamat alkalmazását is lehetővé tette. A gépláncok a teljes zúzottkő recycling technológiával a be és kiszállítandó kőanyagok mennyiségét csökkentették, mint az alépítményi kiegészítőréteg, mint az ágyazati kőanyag tekintetében. A korszerű vasúti nagygépes alépítményjavítási technológia alkalmazásának köszönhetően az elért magas műszaki színvonal mellett az átépítési munkák CO2 kibocsátása és ezzel párhuzamosan a vasútvonalak ökológiai lábnyoma is csökkent.
Boldogabb családok, hatékonyabb munka: A CRM ereje
Authors: Tick Andrea , Szabó Gyöngyi , Reicher Regina Zsuzsánna
Published: December 2024

Napjaink pandémiás helyzete, valamint az erősödő gazdasági és energetikai válság egyre inkább felerősíti a versengést a vállalatok ügyfélekért folytatott harcában éppúgy, mint a munkavállalókért folytatott küzdelemben. A széles piaci kínálattal és az ebből eredő árverseny növekedésének köszönhetően a vevők gyakrabban váltanak márkát vagy szolgáltatót. Az új típusú munkavállaló kevésbé elkötelezett és ennek következtében gyakrabban vált munkahelyet. A vállalatok versenyképességének megőrzésére, javítására fókuszáló vezetők egyre nagyobb figyelmet fordítanak nem csak a vevői elégedettségre, de a munkavállalói elégedettségre is. Minden gazdasági szervezet ilyen irányú törekvéseit is támogathatja a CRM rendszer, mely tartós, nehezen utánozható versenyelőnyt eredményezhet a már egyébként is meglevő vállalaton belüli családbarát politika mellett. Kutatásunk kvalitatív és kvantitatív módszertanra épül és célja, a munkavállalói igények feltárása a családbarát munkahelyen, a vállalati szolgáltatások, elvárások és ezek elfogadásának és értékelésének vizsgálata. Eredményeink azt mutatják, hogy a munkavállalói elégedettséget és elköteleződést nagymértékben befolyásolja a családbarát munkahely kialakítása és a munkavállalói igények folyamatos nyomonkövetése.
Current and controversial issues in the neuroendocrine neoplasms treatment tactics
Authors: Gorbunova V. A. , Evdokimova E. V. , Artamonova E. V.
Published: December 2024

Neuroendocrine neoplasms (NENs) are a heterogeneous group of diseases that include well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The increase in the incidence of NETs in recent decades, especially in Russia – from 0.05 to 5.19% per 100 thousand population from 2001 to 2019, determines a significant increase in interest among doctors and scientists in this problem. Existing domestic and foreign recommendations raise a number of controversial issues that require informed decisions in the course of new clinical trials.
Choice of therapy for HER2-positive metastatic breast cancer in real clinical practice: analysis of physician preferences in Russian Federation
Authors: Artamonova E. V. , Lubennikova E. V.
Published: December 2024

Metastatic breast cancer still remains an incurable disease, requiring lifelong treatment. Introduction of targeted therapy into clinical practice has radically changed treatment approaches of HER2-positive breast cancer, making it possible to significantly increase the life expectancy. The treatment algorithm for HER2-positive metastatic breast cancer appears to be quite clear and is reflected in both international and Russian recommendations. To assess actual clinical practice in the Russian Federation, a survey study “Therapy of Her2-positive breast cancer” was conducted. This publication presents results dedicated to the treatment of metastatic HER2-positive breast cancer. 50 specialists from 43 cities took part in the survey. Only heads of departments or their deputies who were personally involved in determining the treatment for patients were allowed to participate. Expertise of this level allows us to reliably assess the actual clinical practice that has developed in the Russian Federation and determine directions for optimizing therapeutic approaches. Despite ongoing questions about the availability of drugs, doctors primarily focus on the effectiveness of treatment. The main first-line therapy in the Russian Federation is the combination of trastuzumab with pertuzumab. However, experts noted that in conditions of unlimited access to drugs, the number of prescriptions for this regimen in the first line would increase by 13%. Doctors also agree that the use of a subcutaneous form of this combination of drugs would optimize the treatment process. Trastuzumab emtansine remains the standard of second-line therapy and, according to the survey results, almost all patients for whom it is indicated receive this type of therapy. Experts predict more frequent use of trastuzumab emtansine in first-line therapy, given the widespread use of neoadjuvant regimens with pertuzumab. The most significant changes are expected in the third line of therapy with the introduction of the new conjugate – trastuzumab deruxtecan. The survey results demonstrate high awareness and commitment of physicians to modern principles of treatment of HER2-positive mBC.
Responses of Banana Cigar End Rot Pathogen to Chemical Fungicides
Authors: Gul Nasreen , Khanzada Anam Mehwish , Khanzada Muhammad Ali , Rajput Abdul Qayoom , Shah Gulam Serwer , Sahito Oan Muhammad
Published: December 2024

In vitro study was carried out to investigate the responses of cigar end rot pathogen Musicillium theobromae (Turconi) Zare & W. Gams (syn. Verticillium theo­bromae E.W. Mason & S. Hughes) to chemical fungicides viz., Gemstar, Score, Tilt, Nativo, Tecto, Scholar and Aerosal. The efficacy of fungicides against cigar end rot was determined by measuring the colony growth, fresh weight of biomass and dry weight of biomass. Among seven fungicides evaluated against colony growth of M. theobromae, Tecto was highly effective followed by Aerosal and Score. Gemstar and Scholar appeared less effective than other fungicides. Although, all fungicidal treatments significantly reduced the fungus growth as compared to the control. The test pathogen M. theobromae failed to grow at all concentrations of Tecto; able to produce less growth at 0.1 ppm of Aerosal;  0.1 and 1 ppm of Score. Similarly, 100 and 1000 ppm of Tilt and Nativo appeared highly effective, as no growth of test pathogen was observed in these treatments. In regards of fresh biomass weight, all fungicidal treatments were effective in reducing the growth of M. theobromae in liquid culture. However, some were more effective than others. Fungicides like Score, Tilt, Nativo, Tecto and Aerosal were highly effective, their all concentrations produced no or negligible amount of fresh biomass of M. theobromae. Among different fungicides, Gemstar appeared significantly less effective than other fungicides; it’s all concentrations produced more or less fresh biomass of test pathogen. The test fungus was only able to grew at lower concentration (0.1 ppm) of Scholar, but produced negligible growth at 1 to 1000 ppm. In term of dry biomass production, most of the fungicides were highly effective against M. theobromae, produced either no or negligible dry biomass weight. However, few fungicides such as Scholar and Gemstar produced comparatively more dried biomass weight as compared to the control. Although, both of these fungicides produced significantly less dried biomass as compared to the control. The other fungicides like Aerosal, Nativo, Tecto, Score and Tilt were highly effective in reducing the dry biomass weight of M. theobromae. Further studies should be conducted to evaluate the effective fungicides like fungicides like Tecto, Score. Tilt, Nativo and Aerosal under field and storage conditions against cigar end rot of banana.
Disc degeneration influences the strain magnitude and stress distribution within the adjacent trabecular bone
Authors: Raftery Kay A. , Kargarzadeh Alireza , Tavana Saman , Newell Nicolas
Published: December 2024

Introduction

Up to one in five will suffer from osteoporotic vertebral fracture within their lifetime. Accurate fracture prediction poses challenges using bone mineral density (BMD) measures. Trabecular bone strains may be influenced by the underlying intervertebral disc (IVD). Understanding how disc degeneration alters load distribution to the vertebra may demonstrate that supplementing fracture risk tools with IVD metrics could improve predictions. The aim of this study was to assess the influence of IVD degeneration on the stress and strain magnitude and distribution in the trabecular bone of adjacent vertebrae.

Methods

Ten human cadaveric lumbar bi-segment specimens (20 IVDs, 9 degenerated, 11 non-degenerated) were µCT-imaged under 1000N. Digital volume correlation was used to quantify axial, principal, maximum shear, and von Mises strain in the superior and inferior regions of the vertebra. Volumetric BMD from quantitative-CT was used to calculate Young’s modulus, which was then registered with the von Mises strain field to calculate internal von Mises stress.

Results

Two bi-segments fractured during mechanical testing, resulting in N = 8 endplate regions per group. Trabecular bone adjacent to degenerated IVDs presented higher maximum principal and shear strains in the anterior region, relative to non-degenerated (peak ε1: 6,020 ± 1,633 µε versus 3,737 ± 1,548 µε, p < 0.01; peak γmax: 6,202 ± 1948 µε versus 3,938 ± 2086 µε, p < 0.01). Von Mises stress distribution was significantly skewed towards the anterior region in the degenerated group only (28.3% ± 10.4%, p < 0.05). Reduced disc height correlated with increased central-region axial compressive strain, decreased central-region BMD, and increased anterior region von Mises stress (all p < 0.05).

Discussion

Disc degeneration may encourage high strains to be experienced within the anterior region of the adjacent bone, owing to changes in load distribution. This study demonstrates the potential of utilising IVD metrics in fracture risk assessment, to inform clinical decision making and preventative treatment.
Congenital hyperinsulinism in the Ukraine: a 10-year national study
Authors: Globa Evgenia , Christesen Henrik Thybo , Mortensen Michael Bau , Houghton Jayne A. L. , Nielsen Anne Lerberg , Detlefsen Sönke , Flanagan Sarah E.
Published: December 2024

Introduction

Congenital Hyperinsulinism (CHI) has not been previously studied in Ukraine. We therefore aimed to elucidate the genetics, clinical phenotype, histological subtype, treatment and long-term outcomes of Ukrainian patients with CHI.

Methods

Forty-one patients with CHI were recruited to the Ukrainian national registry between the years 2014-2023. Genetic testing (n=40), 18F-fluorodihydroxyphenylalanin and 68Ga-DOTANOC PET/CT imaging followed by surgical treatment and subsequent histological analysis (n=19) was performed through international collaboration.

Results

Pathogenic variants were identified in 19/22 (86.3%) individuals with persistent CHI (p-CHI) and 8/18 (44.4%) with early remission CHI (er-CHI). Pathogenic variants in the K-ATP channel genes were the only identified genetic cause of p-CHI (ABCC8 (n=17) and KCNJ11 (n=2)) with greater genetic heterogeneity observed in those with er-CHI (ABCC8 (n=3), KMT2D (Kabuki Syndrome, n=1), Beckwith-Wiedemann syndrome (n=2) and INSR (Donohue syndrome (n=2)). Histological analysis performed on 19 children with persistent CHI confirmed focal disease in 14 (73.7%), diffuse disease in two (10.5%) and atypical histology in three (15.8%). After surgery, complete recovery was observed in all 14 with focal disease, while relapse occurred in three patients with diffuse or atypical histology.

Conclusion

A genetic diagnosis was achieved for 67.5% (27/40) of the cohort with a higher pick-up rate observed in those with p-CHI. The genetics and imaging studies enabled subtype-targeted treatment with surgical cure achieved in all individuals with focal disease.
Hepatocyte nuclear factor 4-α is necessary for high fat diet-induced pancreatic β-cell mass expansion and metabolic compensations
Authors: de Ramos Francieli Caroline , Barth Robson , Santos Marcos Rizzon , Almeida Milena dos Santos , Ferreira Sandra Mara , Rafacho Alex , Boschero Antônio Carlos , Santos Gustavo Jorge dos
Published: December 2024

Aims

This study investigates the role of Hepatocyte Nuclear Factor 4α (HNF4α) in the adaptation of pancreatic β-cells to an HFD-induced obesogenic environment, focusing on β cell mass expansion and metabolic adaptations.

Main methods

We utilized an HNF4α knockout (KO) mouse model, with CRE-recombinase enzyme activation confirmed through tamoxifen administration. KO and Control (CTL) mice were fed an HFD for 20 weeks. We monitored body weight, food intake, glucose tolerance, insulin sensitivity, and insulinemia. Also, to assess structural and metabolic changes, histological analyses of pancreatic islets and liver tissue were conducted.

Key findings

KO mice displayed lower fasting blood glucose levels compared to CTL mice after tamoxifen administration, indicating impaired glucose-regulated insulin secretion. HFD-fed KO mice consumed less food but exhibited greater weight gain and perigonadal fat accumulation, reflecting higher energy efficiency. Histological analysis revealed more pronounced liver steatosis and fibrosis in KO mice on HFD. Glucose intolerance and insulin resistance were exacerbated in KO mice, highlighting their inability to adapt to increased metabolic demand. Structural analysis showed that KO mice failed to exhibit HFD-induced β cell mass expansion, resulting in reduced islet diameter and number, confirming the critical role of HNF4α in β cell adaptation.

Significance

This study demonstrates that HNF4α is essential for the proper metabolic and structural adaptation of pancreatic β-cells in response to an obesogenic environment. The lack of HNF4α impairs β cell functionality, leading to increased susceptibility to glucose intolerance and insulin resistance. These findings underscore the importance of HNF4α in maintaining glucose homeostasis and highlight its potential as a therapeutic target for diabetes management in obesity.
Activated hepatic stellate cell-derived small extracellular vesicles facilitate M2 macrophage polarization and hepatoma progression via miR-27a-3p
Authors: Sun Yufeng , He Xiaoqian , Han Jiayi , Yin Wenxuan , Wang Haichen , Li Jing , Liu Weiqi , Kuai Xingwang , Lv Jiaying , Ji Juling
Published: December 2024

The progression of hepatoma is heavily influenced by the microenvironment. Tumor-associated macrophages (TAMs) are considered to play a critical role in the tumor microenvironment (TME) and increase the aggressiveness of hepatoma. The activation of hepatic stellate cells (HSCs) is involved in hepatoma progression, and accumulating evidence demonstrates a change in microRNA (miRNA) expression during HSC activation. Therefore, the potential roles of HSCs-related miRNAs in macrophage differentiation and hepatoma progression deserve to be explored. The present study aimed to investigate the effects of miRNAs carried by small extracellular vesicles (sEVs) released by activated HSCs on hepatoma progression. The results indicated that miR-27a-3p was significantly upregulated in cells and corresponding sEVs during the activation of primary rat HSCs and human HSC line-LX2 cells. Furthermore, miR-27a-3p contributed to the proliferation and migration of hepatoma cells and promoted M2 polarization of macrophage. HSC-sEVs overexpressing miR-27a-3p can directly facilitate tumor progression and modulate macrophage polarization, indirectly contributing to hepatoma progression. Finally, Sprouty2 (SPRY2) was verified to be the target gene of miR-27a-3p. In conclusion, activated HSC-derived sEVs with high levels of miR-27a-3p might induce M2 macrophage polarization and promote hepatoma progression, providing new insights into the mechanism of hepatoma progression.
NRF-1 transcription factor regulates expression of an innate immunity checkpoint, CD47, during melanomagenesis
Authors: Makwana Kuldeep , Velazquez Edwin J. , Marzese Diego M. , Smith Bethany , Bhowmick Neil A. , Faries Mark B. , Hamid Omid , Boiko Alexander D.
Published: December 2024

Transmembrane integrin-associated protein CD47 functions as a potent innate immunity checkpoint and is upregulated by many types of malignant cells, including melanoma during tumor progression. Binding of CD47 to its target receptor, SIRPα, on myeloid cell lineages leads to the initiation of the downstream signaling cascades that inhibit innate immunity anti-tumor responses. Molecular mechanisms underlying upregulation of CD47 during melanoma progression remain largely unknown. In this report, we performed ATAC-Sequencing on patient-derived melanoma cells, as well as, the analysis of ATAC-Seq datasets covering clinical melanoma samples to demonstrate a significant increase in chromatin accessibility for the CD47 promoter region in comparison to normal cells and tissues. Additionally, profiling of multiple CD47 transcript isoforms established that upregulation of CD47 in malignant cells occurs at the mRNA level. Using chromatin immunoprecipitation (ChIP) approaches along with the analysis of ChIP-Seq cancer datasets, we identified the transcription factor NRF-1 which binds at multiple sites within the proximal CD47 promoter region. In combination with serial deletions of CD47 promoter, we defined the minimal DNA region required for its activation, as well as, specific DNA locations within that region, which are preferentially occupied by NRF-1 in tumor cells.
Development of a recombinant human IgG1 monoclonal antibody against the TRBV5-1 segment of the T cell receptor for the treatment of mature T cell neoplasms
Authors: Pitaro Michele , Antonini Giovanni , Arcovito Alessandro , Buccisano Francesco , De Lauro Alfredo , Irno Consalvo Maria , Gallo Valentina , Giacon Noah , Mangiatordi Giuseppe Felice , Pacelli Maddalena , Pitaro Maria Teresa , Polticelli Fabio , Sorrenti Matteo , Venditti Adriano
Published: December 2024

Background

Mature T-cell neoplasms arise from the neoplastic transformation of a single T lymphocyte, and all cells in a neoplastic clone share the same V segment in the beta chain of the T-cell receptor (TCR). These segments may represent an innovative target for the development of targeted therapies.

Methods

A specific V segment of the TCR beta chain (TRBV5-1) was analyzed using bioinformatic tools, identifying three potential antigenic peptides. One of these peptides, selected for synthesis, was used to screen a library of human single-chain variable fragments (scFv) through phage display. One fragment demonstrated high affinity and specificity for the antigen and was used to produce a human monoclonal antibody of the IgG1 class.

Results

Surface plasmon resonance (SPR) studies confirmed the high affinity of the monoclonal antibody for the antigen in the nanomolar range. Flow cytometry analysis on patients’ samples demonstrated that the antibody, conjugated with a fluorochrome, selectively binds to tumor T lymphocytes expressing TRBV5-1, without binding to other lymphocytes or blood cell components.

Conclusions

The development of fully human IgG1 monoclonal antibodies targeting specific V segments of the TCR beta chain represents a potential therapeutic option for patients with mature T-cell neoplasms.
Association between diabetes mellitus and trochanteric bone mineral density in individuals with osteoporotic fractures: a retrospective study
Authors: Guo Shao-han , Xu Jian , Xu Min-zhe , Li Chong , Gong Ya-qin , Lu Ke
Published: December 2024

Background

The relationship between diabetes mellitus (DM) and bone mineral density (BMD) in patients with osteoporotic fractures (OPFs) remains complex and heterogeneous, specifically between the genders. This study aimed to explore the association between diabetes status and trochanteric BMD in a cohort of patients with OPFs and elucidate the differences between male and female patients.

Methods

This retrospective analysis was performed on 710 admitted patients aged 50 years or older with OPFs. In this study, the exposure variable was diabetes status. Trochanteric BMD comprised the dependent variable. While controlling for covariance influences, generalized estimating equations (GEE) were applied to examine the independent link between diabetes status and trochanteric BMD in OPFs patients. Moreover, a subgroup analysis was also conducted to validate the result’s stability.

Results

A substantial positive association was noted between diabetes status and trochanteric BMD in diabetic patients, as determined by the fully adjusted model (β = 0.017, 95% CI 0.001 to 0.033, p = 0.035). Furthermore, the sex-specific analysis showed a significant positive relationship between diabetes status and trochanteric BMD in male patients (β = 0.040, 95% CI 0.006 to 0.075, p = 0.022), whereas no significant relationship was observed in female patients (β = 0.010, 95% CI −0.008 to 0.028, p = 0.256).

Conclusion

This study highlighted the significant sex differences in the impact of diabetes on trochanteric BMD among patients with OPFs. The male diabetic patients had higher trochanteric BMD than their non-diabetic counterparts; however, this association was not evident in female patients. Further research is necessary to understand the underlying mechanisms that contribute to these sex-specific differences and to evaluate the clinical implications of managing fracture risk in diabetic patients.
Breast pericytes: a newly identified driver of tumor cell proliferation
Authors: Del Toro Katelyn , Licon-Munoz Yamhilette , Crabtree William , Oper Tristan , Robbins Christine , Hines William C.
Published: December 2024

Introduction

Effective treatment of breast cancer remains a formidable challenge, partly due to our limited understanding of the complex microenvironmental factors that contribute to disease pathology. Among these factors are tissue-resident perivascular cells, which play crucial roles in shaping vascular basement membranes, maintaining vessel integrity, and communicating with adjacent endothelial cells. Despite their essential functions, perivascular cells have been relatively overlooked. Identifying them by immunostaining has been challenging due to their low abundance, inherent heterogeneity, and shared marker expression with other cell types. These challenges have hindered efforts to purify pericytes and generate primary cell models for studying their biology.

Methods

Using a recently developed FACS method, we successfully identified and purified each cell type from breast tissues, allowing us to deep-sequence their transcriptomes and generate primary cell models of each cell type—including pericytes. Here, we used these data to analyze cell-type-specific gene expression in tumors, which revealed a strong association between pericyte-specific genes and breast cancer patient mortality. To explore this association, we defined the heterogeneity of breast pericytes using single-cell RNA sequencing and identified a broad marker for visualizing perivascular cells in breast tumors.

Results

Remarkably, we discovered perivascular cells dissociated from vessels and emerged as a dominant mesenchymal cell type in a subset of breast tumors that contrasted with their normal perivascular location. Moreover, when we purified pericytes from the breast and cultured them alongside breast tumor cells, we discovered that they induced rapid tumor cell growth significantly greater than isogenic fibroblast controls.

Discussion

These findings identify perivascular cells as a key microenvironmental factor in breast cancer, highlighting the critical need for further research to explore their biology and identify specific stimulatory mechanisms that could be targeted therapeutically.
Cost-effectiveness analysis of anlotinib plus chemotherapy with or without benmelstobart versus chemotherapy alone for extensive-stage small-cell lung cancer in China
Authors: You Caicong , Zhang Jiahao , Lei Jianying , Fu Wu , Zheng Bin , Liu Maobai , Li Na
Published: December 2024

Objectives

The ETER701 trial demonstrated that benmelstobart combined with anlotinib and etoposide-carboplatin (EC) significantly extends survival in patients with extensive-stage small cell lung cancer (ES-SCLC), setting a new record for median overall survival. In contrast, anlotinib plus EC only significantly prolongs progression-free survival. However, there is currently no evidence evaluating the cost-effectiveness of these regimens as first-line treatments. Therefore, this study assesses the cost-effectiveness of these three first-line treatment options from the perspective of the Chinese healthcare system.

Methods

A time-varying Markov model was constructed to simulate the disease progression of a 62-year-old patient with ES-SCLC, assessing direct medical costs, health benefits, and incremental cost-effectiveness ratios (ICER). Both flexible and standard parametric models were included to fit and extrapolate survival data. The probabilities, costs, and health utilities required for the model were sourced from literature, databases, and expert consultations. Additionally, sensitivity and scenario analyses were conducted to explore the impact of various parameters on model uncertainty.

Results

Compared to EC alone, the combination of benmelstobart, anlotinib, and EC added $80,879.12 in cost for 0.7288 quality-adjusted life years (QALYs), an ICER of $110,970.19/QALY. Anlotinib plus EC added $4,107.86for 0.1951 QALYs, an ICER of $21,056.19/QALY. At a $37,598/QALY threshold, the cost-effectiveness probability for benmelstobart combination is 0%, and for anlotinib combination is 80.42%. A 73.79% price cut for benmelstobart is needed for cost-effectiveness.

Conclusions

In China, benmelstobart combined with anlotinib and EC is not a cost-effective first-line treatment for ES-SCLC; however, reducing the price of benmelstobart by 73.79% could make this regimen cost-effective. In contrast, anlotinib combined with EC may represent a more cost-effective first-line treatment option.
Disentangling genotype and environment specific latent features for improved trait prediction using a compositional autoencoder
Authors: Powadi Anirudha , Jubery Talukder Zaki , Tross Michael C. , Schnable James C. , Ganapathysubramanian Baskar
Published: December 2024

In plant breeding and genetics, predictive models traditionally rely on compact representations of high-dimensional data, often using methods like Principal Component Analysis (PCA) and, more recently, Autoencoders (AE). However, these methods do not separate genotype-specific and environment-specific features, limiting their ability to accurately predict traits influenced by both genetic and environmental factors. We hypothesize that disentangling these representations into genotype-specific and environment-specific components can enhance predictive models. To test this, we developed a compositional autoencoder (CAE) that decomposes high-dimensional data into distinct genotype-specific and environment-specific latent features. Our CAE framework employed a hierarchical architecture within an autoencoder to effectively separate these entangled latent features. Applied to a maize diversity panel dataset, the CAE demonstrated superior modeling of environmental influences and out-performs PCA (principal component analysis), PLSR (Partial Least square regression) and vanilla autoencoders by 7 times for ‘Days to Pollen’ trait and 10 times improved predictive performance for ‘Yield’. By disentangling latent features, the CAE provided a powerful tool for precision breeding and genetic research. This work has significantly enhanced trait prediction models, advancing agricultural and biological sciences.
Rosa rugosa R2R3-MYB transcription factors RrMYB12 and RrMYB111 regulate the accumulation of flavonols and anthocyanins
Authors: Shi Yufeng , Lu Taoran , Lai Sanyan , Li Song , Zhang Ling , Liu Rong , Ouyang Lin , Zhao Xinxin , Jiang Yuqin , Yan Zhen , Zhang Ju , Miao Baohe
Published: December 2024

Roses (Rosa rugosa) are a famous flower with high ornamental and economic value. But the petals of roses are usually pink and purple, which restricted its application in garden settings. Flavonols and anthocyanins are crucial secondary metabolites related to flower pigmentation in plants. While MYB transcription factors involved in the biosynthesis pathway of anthocyanins have been identified in roses, the functional characterization of the MYB transcription factor regulating flavonol synthesis in R. rugosa remains unexplored. In this study, we isolated and characterized the R2R3-MYB transcription factors RrMYB12 and RrMYB111 involved in regulation of the flavonol biosynthetic pathway from R. rugosa. The bioinformatics analysis indicated that both the RrMYB12 and RrMYB111 belong to the R2R3-MYB subgroup 7 family. qRT-PCR analysis showed that RrMYB12 and RrMYB111 were expressed at low levels in roots and flowers. And transactivation activity assay indicated that RrMYB12 and RrMYB111 were transcriptional activators. The overexpression of RrMYB12 and RrMYB111 in tobacco resulted in an elevation of flavonol levels and a reduction in anthocyanin levels in flowers due to the upregulation of structural genes involved in flavonol synthesis, while the biosynthesis genes for the anthocyanin pathway were significantly downregulated. The transient reporter assay demonstrated that RrMYB12 exhibited strong activation of the promoters of RrCHS and RrFLS in Nicotiana benthamiana leaves following transient transformation. Furthermore, it was observed that RrMYBs displayed binding specificity to the promoter region of CsFLS.The functional characterization of the flavonol synthesis regulatory factors RrMYB12 and RrMYB111 offers a deeper understanding of the regulatory mechanism governing flavonol biosynthesis in roses, while also presenting an effective tool for genetic manipulation aimed at creating new varieties.