bluuebunny/crossref_metadata_2025 huggingface dataset:
Linear Parameter Varying and Reinforcement Learning Approaches for Trajectory Tracking Controller of Autonomous Vehicles
Authors: Mihály András , Vu Van Tan , Do Trong Tu , Thinh Kieu Duc , Vinh Nguyen Van , Gáspár Péter
Published: September 2024

This research focuses on controlling the motion trajectory of autonomous vehicles by using a combination of two high-performance control methods: Linear Parameter Varying (LPV) and Reinforcement Learning (RL). First, a single-track motion model is researched and developed with coordinate systems to determine the car's motion trajectory through signals from GPS. Then, the LPV control method is used to design a controller to control the car's motion trajectory. Reinforcement learning method with detailed training procedures is used to combine with the advantages of LPV controller. Finally, the simulation results are evaluated in the time domain through the use of specialized CarSim software, which clearly demonstrates the superiority of the research method.
EVALUASI PENERAPAN ISAK NO 35 TERHADAP PENYUSUNAN LAPORAN KEUANGAN PUSAT PENGEMBANGAN ANAK HERMON TOLOMBUKAN
Authors: Owu Ribka Yuliana Syaloom
Published: September 2024

Penelitian ini bertujuan untuk mengevaluasi bagaimana Interpretasi Standar Akuntansi Keuangan (ISAK) Nomor 35 diterapkan dalam penyusunan laporan keuangan Pusat Pengembangan Anak Hermon Tolombukan. Tujuan dari interpretasi ini adalah untuk meningkatkan transparansi dan akuntabilitas laporan keuangan entitas yang tidak berorientasi pada laba. ISAK No. 35 merupakan pedoman akuntansi bagi entitas nirlaba, yang meliputi pelaporan aktivitas, neraca, arus kas, dan perubahan aset bersih. Pusat Pengembangan Anak sebagai lembaga nirlaba harus mematuhi standar ini untuk memastikan transparansi, akuntabilitas,  serta kelayakan penyajian laporan keuangan kepada pemangku kepentingan Penelitian ini menggunakan metode deskriptif kualitatif dengan pendekatan studi kasus untuk mengidentifikasi sejauh mana Pusat Pengembangan Anak Hermon Tolombukan telah menerapkan ISAK No. 35 dalam penyusunan laporan keuangannya. Data diperoleh melalui wawancara, dokumentasi, dan observasi langsung terhadap proses penyusunan laporan keuangan. Hasil penelitian menunjukkan bahwa penerapan ISAK Nomor 35 pada PPA yang ada belum sesuai dengan standar akuntansi yang ada. Dengan pelaporan yang sesuai akan memberikan dampak positif terhadap peningkatan akurasi dan transparansi laporan keuangan. Penelitian ini merekomendasikan perlunya pelatihan lebih lanjut bagi pengelola keuangan dan evaluasi berkala untuk memastikan standar akuntansi diterapkan secara konsisten dan efektif. Dengan evaluasi ini, diharapkan dapat meningkatan pembaruan sistem pencatatan keuangan, dan teknis lebih lanjut evaluasi ini diharapkan dapat membantu memastikan penerapan ISAK No. 35 dapat dilaksanakan secara menyeluruh. Serta  kualitas dan akuntabilitas laporan keuangan Pusat Pengembangan Anak Hermon Tolombukan di masa mendatang.
Протизапальна активність ліпосомальної форми кверцетину
Authors: Суворова З. С.
Published: September 2024

Останнім часом у плані пошуку нових протизапальних засобів значний інтерес викликає ліпосомальний препарат Ліпофлавон, що містить природний флавоноїд – 3,3’,4’,5,7-пентаоксифлавон (кверцетин).
Мета дослідження – вивчити протизапальну активність ліпосомальної форми кверцетину (Ліпофлавону) на різних моделях ексудативного запалення.
Протизапальну активність ліпосомальної форми кверцетину – Ліпофлавону вивчали на моделях ексудативного запалення в мишей, викликаного субплантарним уведенням різних флогогенних агентів.
Отримані результати показали, що ліпосомальна форма кверцетину – Ліпофлавон у діапазоні доз 3,8–15,2 мг/кг (за кверцетином) статистично достовірно інгібує набряк, який викликаний карагеніном з (-37,09) % до (-63,43) %. Експериментальне запалення, що викликане іншим флогогенним агентом – гістаміном, також демонструє антиексудативний ефект Ліпофлавону в межах від (-27,61) % до (-32,73) %. На моделі серотонінового набряку позитивна динаміка протизапальної дії ліпосо- мальної форми кверцетину знаходиться в діапазоні від (-17,95) % до (-32,00) %. Антиексудативна активність Ліпофлавону перевищує таку диклофенаку натрію на моделі ексудативного карагенінового набряку та знаходиться на одному рівні з дією референтного препарату за впливу інших флогогенних агентів.
Literatura científica sobre sistemas de innovación regionales: Un estudio bibliométrico de la evolución y las tendencias actuales
Authors: López Zurita Santiago , Garcés Toro Diana , Camacho Estrada Sara
Published: September 2024

Introducción: Los Sistemas de Innovación Regionales (RIS, por sus siglas en inglés) tienen relevancia como mecanismo para aumentar la competitividad de los territorios. Objetivo: El presente estudio tiene como objetivo sistematizar la producción científica sobre RIS a través de la base de datos Scopus. Metodología: Se realizó un análisis bibliométrico de 1555 documentos sobre RIS publicados entre 2000 y 2022. Se utilizaron herramientas como bibliometrix R-package y VOSviewer, para identificar tendencias y patrones. Resultados: De esta forma se encontró que la investigación sobre RIS la lidera en número de publicaciones China, Reino Unido y España, y en citas Suecia. Trippl, Cooke e Isaksen son los autores más influyentes, y las investigaciones colaborativas predominan, con instituciones europeas a la cabeza. Conclusión: Los RIS son un campo de creciente interés académico; sin embargo, la actividad científica está concentrada en países desarrollados, lo que sugiere la necesidad de una mayor inclusión de regiones menos estudiadas para aprovechar el potencial de estos sistemas. Área de estudio general: Ciencias sociales. Área de estudio específica: Sistemas de Innovación. Tipo de estudio: Artículo original
The Influence of The Phrase 'Online' on the Fulfillment of Public Participation in the Formation of Laws Through the DPR Legislative Information System
Authors: Pujianti Yuwinda Sari , Perwira Indra , Junaenah Inna
Published: September 2024

This research aims to analyze the influence of the phrase 'Online' on the fulfillment of Public Participation in Law Formation through the DPR's legislative information system. This research uses a normative legal research approach which includes legislative, conceptual and historical approaches. Method: The data collection approach in this research is library research. The data obtained is then processed through three stages, namely data reduction, data presentation, and drawing conclusions. Results: Research findings show that the term 'online' in article 96 of Law Number 13 of 2022 requires the DPR to be able to assist in implementing community involvement, one of which is through sileg. Apart from that, based on the provisions of Secretary General Number 13 of 2020 and the parliamentary website guidelines that have been prepared by the IPU, improvements and developments need to be made in the implementation of Sileg. Novelty: The novelty of this research comes from the research object, namely the formation of laws through the DPR Legislative Information System in the context of the influence of the phrase 'Online' on the fulfillment of community participation. Conclusion: Adequate information in Sileg at all stages of law formation can facilitate and encourage public participation in providing input on each bill that is being discussed and/or will be discussed in the DPR. The ideal implementation of sileg is as an online medium for people to carry out more meaningful community activities.
The Influence of Profitability, Leverage, Liquidity and Company Size on Dividend Policy
Authors: Wiasih Dina Retno , Tubastuvi Naelati , Purwidianti Wida , Bagis Fatmah
Published: September 2024

This research aims to determine the influence of profitability, leverage, liquidity and company size on dividend policy. This research uses quantitative methods, purposive sampling techniques, and multiple regression analysis with SPSS 26. 27 primary consumer goods sector companies listed on the Indonesia Stock Exchange (BEI) for the 2019-2022 period constitute the population in this study and the number of observation samples is 108. The methodological approach uses purposive sampling, namely a non-probability sampling technique, to ensure the intended sample size, namely with the criteria of companies that distribute their financial reports in rupiah, companies that earn profits every year, and companies that distribute dividends. This research shows the results that liquidity has a positive and significant effect on dividend policy, leverage has no significant effect on dividend policy, profitability and company size have no effect on dividend policy.
Ethical Leadership and Counterproductive Work Behavior: The Mediating Role of Job Satisfaction
Authors: Dewanata Muhammad Faaiz Pandu
Published: September 2024

Intense competition among public institutions underscores the need for effective human resource management. This study investigates Counterproductive Work Behavior (CWB), a concern for academics, professionals, and policymakers. CWB, a response to workplace dissatisfaction, is examined among 121 permanent nurses at Pandan Arang Hospital. Findings show that ethical leadership is negatively associated with CWB and positively linked to job satisfaction, which fully mediates the relationship between ethical leadership and CWB. The study contributes theoretically by advancing understanding of how ethical leadership influences CWB via job satisfaction, offering practical implications for organizations aiming to reduce CWB and promote ethical leadership practices.
Ecological niche segregation between sympatrically breeding blue petrels and thin-billed prions
Authors: Delord K , Cherel Y , Kato A , Bustamante P , Barbraud C
Published: September 2024

Ecological niche theory predicts coexisting species will segregate spatially, temporally or trophically to limit competition. Few studies have investigated niche segregation in multiple dimensions during the breeding season in sympatric, morphologically similar seabird species. Moreover, these studies showed discrepancies between theoretical predictions and observations. We tested the hypothesis of niche segregation during breeding between 2 sympatric small-sized seabirds, the blue petrel Halobaena caerulea and the thin-billed prion Pachyptila belcheri, by quantifying foraging niche and trophic differences. Combining at-sea GPS and isotopic (stable carbon and nitrogen) data, we assessed spatial, foraging habitat and trophic segregation. We found strong latitudinal and longitudinal segregation between species during incubation. Mean maximum distance from the colony during foraging trips was ~2330 and ~1300 km for blue petrels and thin-billed prions, respectively. Foraging habitat segregation varied during incubation, with blue petrels foraging close to the ice edge and prions foraging in oceanic areas far from ice. Although sample size was low, there was also some evidence for spatial and habitat segregation during chick-rearing, with prions foraging in areas with negative sea surface height anomalies. Trophic segregation was revealed by differences in stable isotopes, with blue petrels feeding on higher trophic level prey than prions (mean plasma δ15N : 9.6 ± 0.4 and 9.0 ± 0.3‰, respectively). Spatial distribution and diet are the primary segregation mechanisms, and patterns of segregation may result from competitive exclusion rather than niche specialization. Spatial and trophic segregation may have evolved to minimize competition, allowing co-existence of these 2 abundant sympatric breeding species.
Nothing Reigns but Confusion and Anarchy: Disease and Military Discipline in the Late-Eighteenth-Century Caribbean
Authors: Bienko Joseph
Published: September 2024

This article relates how tropical disease ravaged the British army in the late-eighteenth-century Caribbean, using the San Juan expedition of 1780 as a case study. Based on eighteenth-century European understandings of epidemiology, martial and medicinal officials of the San Juan expedition believed that the outbreak of pestilence within the British army reflected a failure in discipline, properly provisioning troops, as well as overall leadership and planning. Thus, despite natural agents playing a significant role in stalling Britain's advance in Nicaragua, eighteenth-century military and medical authorities dictated that difficulties caused by disease and the environment could be overcome by human might. While the British ultimately could not overcome the devastating effects that tropical diseases had on the army, human agency also led to the expedition's failure. The British did not maintain good relations with their Indigenous allies, the Miskito, which resulted in their abandonment of the campaign. Consequently, they were left without crucial soldiers, guides, and labourers who were necessary to continue the invasion of Central America. Moreover, the Spaniards’ stout defence of their territory also hindered the British expeditionary force, stalling their advance at the Castillo de la Inmaculada Concepción. As a result, both natural and human agency dictated the outcome of the San Juan expedition.
Flagellating Females: Insense and Insensibility in Plantation Jamaica
Authors: Northrop Chloe
Published: September 2024

This article examines the participation of white women in whipping enslaved individuals in the West Indies throughout the eighteenth century in both fiction and historical examples. While sensibility and sentimentality were growing in popularity in metropolitan England, white women in the West Indies encountered and participated in scenes of violence that shocked many metropolitan viewers. During the last decade of the eighteenth century, images appeared that seem to condemn the African Slave Trade and promote abolitionist rhetoric. While these scenes of suffering do portray the brutal reality of whipping in the West Indies, these depictions also emerge at a period in which flogging became more overtly sexualized. Examining the 1792 print ‘A Forcible Appeal for the Abolition of the Slave Trade’ by Richard Newton, this article contextualizes the flagellation and sexual undertones of the white woman in the print. Comparing this print to the flagellation erotica, often sold in the same establishments as prints like Newton's, the sexual undertones in the print are complicated. Through the fetishization of the pain of enslaved women, metropolitan inhabitants of England could voyeuristically indulge in these scenes of misery without explicitly seeking out flagellation or pornographical works.
Identidade Profissional em um Mestrado Profissional: trajetórias em busca de Parker Pyne
Authors: Paula Enio Freire de , Gonzaga Bruno César Cardoso
Published: September 2024

Neste artigo, em uma perspectiva insubordinada de escrita a quatro mãos, socializamos as nossas experiências – baseados na compre-ensão de Jorge Larrosa (2002) – enquanto orientador e orientando – vivenciadas no decorrer dos processos de construção de uma pesquisa vinculada a um programa de Mestrado Profissional, centrada em discutir a Identidade Profissional de Professores de Matemática. Ao iniciarmos a pesquisa, nossas emoções estavam inseridas no contexto da pandemia de Covid-19, no Brasil. O objetivo é expor, intencionalmente, as nossas vulnerabilidades nos processos e as ações de agência profissional articuladas em conjunto para as decisões acordadas. Para tanto, construímos questões fomentadoras de discussão que subsidiaram a construção de memoriais de formação, nos quais registramos nossas experiências no processo. Entre os resultados da análise conjunta de um desses memoriais, cabe destacarmos que vivenciar o mestrado é uma experiência conjunta, sendo o mestrado profissional mais um lócus representativo do movimento de constituição da IP.
Vulnerabilidade, agência profissional e colaboração: estudo de caso entre professoras de Matemática
Authors: Grando Regina Célia , Jacomelli-Alves Karina Zolia
Published: September 2024

Neste artigo, discutimos um caso que envolve duas professoras de Matemática que trabalham juntas na mesma rede municipal de ensino, há mais de duas décadas, e que colaboram em diversas atividades, há, aproximadamente, 15 anos. Através do relato de uma delas, referente à sua perspectiva sobre a experiência com sua colega de profissão, buscamos refletir acerca das dimensões de vulnerabilidade e de agência profissional. Estes aspectos são essenciais para o desenvolvimento da identidade profissional docente, conforme analisado por Cyrino (2017). Além disso, a narrativa em questão também nos conduziu a ponderar sobre a relevância da colaboração entre professores de Matemática e seu impacto significativo em suas identidades profissionais.
O processo de constituição da identidade de professoras que ensinam Matemática
Authors: Oliveira Natália Raquel Brisolla , Nacarato Adair Mendes
Published: September 2024

Este trabalho visa compreender, a partir da narrativa de duas professoras que ensinam Matemática, a constituição de suas identidades. Apoia-se no método (auto)biográfico e teve os dados produzidos por meio de entrevistas narrativas com as duas professoras. Posteriormente, as entrevistas foram transcritas e os dados, organizados em biogramas de modo a identificar, mediante incidentes críticos, as experiências de vulnerabilidade vivenciadas pelas professoras e se essas experiências contribuíram para o desenvolvimento de agência mediada. Os incidentes críticos marcam momentos de ruptura nos quais as professoras vão atribuindo sentidos às concepções sobre si mesmas e aos conhecimentos e valores sobre o ensino da matemática. Nesse movimento, acontece o processo de constituição identitária.
Percepções de professores de Matemática experientes sobre sua trajetória profissional e o movimento de constituição de sua identidade
Authors: Oliveira Julio Cezar Rodrigues de , Cyrino Márcia Cristina de Costa Trindade
Published: September 2024

O objetivo deste artigo é identificar e discutir percepções de professores de Matemática experientes a respeito de elementos de sua trajetória profissional que explicitam o movimento de constituição de sua identidade profissional. Nesta pesquisa, foram realizadas entrevistas semiestruturadas com quatro professores de Matemática experientes, que atuaram como protagonistas na construção de casos multimídia para a formação de professores que ensinam Matemática. Os elementos da trajetória profissional que denotam o movimento de constituição da IP de professores de Matemática experientes são: a reflexão sobre si, as ações na busca pelo sentido de agência e o compromisso com a formação dos alunos, com a profissionalização e com a educação. Nesse sentido, conhecer e investigar esses elementos torna possível repensar a organização e a gestão dos programas de formação de professores (tanto inicial quanto continuada) com o objetivo de promover o movimento de constituição da IP de (futuros) PEM.
Carboxymethyl chitosan nanoparticle-modulated cationic hydrogels doped with copper ions for combating bacteria and facilitating wound healing
Authors: Li Yaqin , Lu Jianping , Shi Jingru , Zhang Lingjiao , Mu Haibo , Cui Tong
Published: September 2024

The simultaneous administration of antibacterial treatment and acceleration of tissue regeneration are crucial for the effective healing of infected wounds. In this work, we developed a facile hydrogel (PCC hydrogel) through coordination and hydrogen interactions by polymerizing acrylamide monomers in the presence of carboxymethyl chitosan nanoparticles and copper ions. The prepared PCC hydrogel demonstrated effective bacterial capture from wound exudation and exhibited a potent bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Furthermore, slow release of copper ions from the hydrogel facilitated wound healing by promoting cell migration, collagen deposition and angiogenesis. Additionally, the PCC hydrogel possessed excellent biocompatibility and hemostatic properties. The practical effectiveness of PCC hydrogel in addressing bacterial infections and facilitating wound healing was verified using a mouse model of MRSA-induced wound infections. Overall, this work presents a simple yet efficient multifunctional hydrogel platform that integrates antibacterial activity, promotion of wound healing, and hemostasis for managing bacteria-associated wounds.
Quantitative assessment of the oral microvasculature using optical coherence tomography angiography
Authors: Zhang Tianyu , Zhang Yilong , Liao Jinpeng , Shepherd Simon , Huang Zhihong , Macluskey Michaelina , Li Chunhui
Published: September 2024

Introduction

Early diagnosis of oral squamous cell carcinoma can greatly improve treatment success rate and patient survival. Although Optical Coherence Tomography (OCT) based Angiography (OCTA) is a promising in vivo technique in oral imaging, there is a need for objective assessment of oral microvasculature.

Methods

This study aimed to demonstrate a comprehensive methodology of quantitative assessing OCTA intraoral scanning results to provide measurable, reproducible data and to avoid subjective visual interpretations. Data were collected from 37 healthy subjects in total across four intraoral sites—buccal mucosa (n = 32), labial mucosa (n = 24), floor of the mouth (n = 13), and hard palate (n = 8)—using a non-invasive swept-source OCT system. Four quantitative metrics—vessel area density, vessel skeleton density, vessel diameter index, and a newly proposed weighted Tortuosity Index—were used to assess OCTA images in oral applications.

Results

The quadruple quantitative assessment’s repeatability was evaluated to be reliable. Analysis of a benign ulcer case revealed differences in these metrics compared to healthy cases.

Discussion/Conclusion

In conclusion, we demonstrated a comprehensive method to quantify microvasculature in the oral cavity, showing considerable promise for early diagnosis and clinical management of oral diseases.
Decreased ATF5 level contributes to improved mitochondrial function in oocytes exposed to vitrification stress
Authors: Zhou Guizhen , Liu Aiju , Bai Jiachen , Liu Hongyu , Zhu Yixiao , Luo Yuwen , Zheng Lv , Hou Yunpeng , Li Jun , Fu Xiangwei
Published: September 2024

Background

Mitochondrial unfolded protein response (mtUPR) plays an essential role in the response of mitochondria to stress-induced damage. Activating of transcription factor 5 (ATF5) can help to sustain mitochondrial function and regulate organelle recovery under mitochondrial stress. Vitrification is a stressor that disrupts mitochondrial activity and cell homeostasis. However, little is known about the function of ATF5 in response to the extreme biophysical and chemical stresses during oocyte vitrification.

Methods

The expression of ATF5 and mtUPR biomarkers were measured in fresh and vitrified oocytes. Subsequently, oocytes with ATF5 deficiency were constructed by siRNA microinjection, and the function of ATF5 in mitochondrial function and oocyte development were analyzed in vitrified oocytes. Furthermore, transcriptome analysis was performed to uncover the molecular network regulated by ATF5 in response to oocyte vitrification.

Results

In the present study, the mitochondrial membrane potential and ATP levels were decreased in ATF5 knockdown oocytes, in line with the phenotypes observed in vitrified oocytes. In addition, ATF5 knockdown resulted in decreased mitochondrial temperature, reduced unfolded protein levels, abnormal mitochondrial dynamics (fusion and fission), and increased autophagy. Subsequent experiments indicated that mtUPR was suppressed in oocytes with ATF5 knockdown. Interestingly, ATF5 was aberrantly upregulated in oocytes exposed to vitrification stress. Reduced ATF5 expression to a homeostatic level in vitrified oocytes led to accumulated unfolded protein levels and increased mitochondrial membrane potential. Moreover, increased mitochondrial dynamics and an increased germinal vesicle breakdown (GVBD) rate were detected after in vitro maturation. Transcriptome analysis revealed that ATF5 is involved in the vitrification stress response, and ATF5 regulated the in vitro maturation potential in vitrified oocytes through the cAMP-PKA and PI3K/AKT pathways.

Discussion

Our findings indicate that mtUPR was initiated in response to vitrification stimuli, and downregulated ATF5 level to a homeostatic state contributes to improved mitochondrial function in oocytes exposed to vitrification stress. Our results highlight the crucial role of ATF5 in the regulation of mitochondrial function in vitrified oocytes through mediating mtUPR.
Artificial intelligence based real-time prediction of imminent heart failure hospitalisation in patients undergoing non-invasive telemedicine
Authors: Hinrichs Nils , Meyer Alexander , Koehler Kerstin , Kaas Thomas , Hiddemann Meike , Spethmann Sebastian , Balzer Felix , Eickhoff Carsten , Falk Volkmar , Hindricks Gerhard , Dagres Nikolaos , Koehler Friedrich
Published: September 2024

Background

Remote patient management may improve prognosis in heart failure. Daily review of transmitted data for early recognition of patients at risk requires substantial resources that represent a major barrier to wide implementation. An automated analysis of incoming data for detection of risk for imminent events would allow focusing on patients requiring prompt medical intervention.

Methods

We analysed data of the Telemedical Interventional Management in Heart Failure II (TIM-HF2) randomized trial that were collected during quarterly in-patient visits and daily transmissions from non-invasive monitoring devices. By application of machine learning, we developed and internally validated a risk score for heart failure hospitalisation within seven days following data transmission as estimate of short-term patient risk for adverse heart failure events. Score performance was assessed by the area under the receiver-operating characteristic (ROCAUC) and compared with a conventional algorithm, a heuristic rule set originally applied in the randomized trial.

Results

The machine learning model significantly outperformed the conventional algorithm (ROCAUC 0.855 vs. 0.727, p < 0.001). On average, the machine learning risk score increased continuously in the three weeks preceding heart failure hospitalisations, indicating potential for early detection of risk. In a simulated one-year scenario, daily review of only the one third of patients with the highest machine learning risk score would have led to detection of 95% of HF hospitalisations occurring within the following seven days.

Conclusions

A machine learning model allowed automated analysis of incoming remote monitoring data and reliable identification of patients at risk of heart failure hospitalisation requiring immediate medical intervention. This approach may significantly reduce the need for manual data review.
Generating normative data from web-based administration of the Cambridge Neuropsychological Test Automated Battery using a Bayesian framework
Authors: Wragg Elizabeth , Skirrow Caroline , Dente Pasquale , Cotter Jack , Annas Peter , Lowther Milly , Backx Rosa , Barnett Jenny , Cree Fiona , Kroll Jasmin , Cormack Francesca
Published: September 2024

Introduction

Normative cognitive data can distinguish impairment from healthy cognitive function and pathological decline from normal ageing. Traditional methods for deriving normative data typically require extremely large samples of healthy participants, stratifying test variation by pre-specified age groups and key demographic features (age, sex, education). Linear regression approaches can provide normative data from more sparsely sampled datasets, but non-normal distributions of many cognitive test results may lead to violation of model assumptions, limiting generalisability.

Method

The current study proposes a novel Bayesian framework for normative data generation. Participants (n = 728; 368 male and 360 female, age 18–75 years), completed the Cambridge Neuropsychological Test Automated Battery via the research crowdsourcing website Prolific.ac. Participants completed tests of visuospatial recognition memory (Spatial Working Memory test), visual episodic memory (Paired Associate Learning test) and sustained attention (Rapid Visual Information Processing test). Test outcomes were modelled as a function of age using Bayesian Generalised Linear Models, which were able to derive posterior distributions of the authentic data, drawing from a wide family of distributions. Markov Chain Monte Carlo algorithms generated a large synthetic dataset from posterior distributions for each outcome measure, capturing normative distributions of cognition as a function of age, sex and education.

Results

Comparison with stratified and linear regression methods showed converging results, with the Bayesian approach producing similar age, sex and education trends in the data, and similar categorisation of individual performance levels.

Conclusion

This study documents a novel, reproducible and robust method for describing normative cognitive performance with ageing using a large dataset.
Association between serum estradiol levels and abdominal aortic calcification in postmenopausal woman: a cross-sectional study
Authors: He Lan , Li Xu , Shen E , He Yong-Ming
Published: September 2024

Background

The association between Estradiol (E2) levels and abdominal aortic calcification (AAC) in postmenopausal women remains unclear.

Methods

614 postmenopausal women from the 2013-2014 NHANES survey cycle were included in this study. The study population was divided into 3 groups according to E2 tertiles: Tertile1 (2.12-3.57pg/mL), Tertile2 (3.60-7.04pg/mL), and Tertile3 (7.06-38.4pg/mL). Estrogen concentration data were natural logarithmically transformed. A Kauppila score > 5 was regarded as prominent arterial calcification and was used to define (EAAC). Logistic regression models were used to assess the association between E2 levels and EAAC prevalence. Subgroup analyses were performed to test whether the association between E2 levels and EAAC prevalence was consistent in different groups. Sensitivity analyses tested the stability of the model in women older than 45 years.

Results

EAAC prevalence was significantly higher in Tertile1 (16.6%) than in Tertile2 (9.8%) and Tertile3 (8.3%). On a continuous scale, the adjusted model showed a 58% [OR (95%CI), 1.58 (1.02, 2.54)] increase in the risk of EAAC prevalence for per unit decrease in ln(E2). On a categorical scale, the adjusted model showed that Tertile1 and Tertile2 were 2.55 [OR (95%CI), 2.55 (1.10, 5.92)] and 1.31[OR (95%CI), 1.31(1.03, 2.57)] times higher risk of suffering from EAAC than Tertile3, respectively.

Conclusion

This study found that a higher prevalence of AAC in postmenopausal women is closely associated with lower serum E2 levels. Our research further underscores the importance of E2 in maintaining cardiovascular health in postmenopausal women and suggests that monitoring E2 levels may aid in the early prevention and management of AAC and related cardiovascular diseases.
Intestinal flora and bile acid interactions impact the progression of diabetic kidney disease
Authors: Xu Jia , Wang Nan , Yang Li , Zhong Jing , Chen Ming
Published: September 2024

In recent years, with the rapid development of omics technologies, researchers have shown that interactions between the intestinal flora and bile acids are closely related to the progression of diabetic kidney disease (DKD). By regulating bile acid metabolism and receptor expression, the intestinal flora affects host metabolism, impacts the immune system, and exacerbates kidney injury in DKD patients. To explore interactions among the gut flora, bile acids and DKD, as well as the related mechanisms, in depth, in this paper, we review the existing literature on correlations among the gut flora, bile acids and DKD. This review also summarizes the efficacy of bile acids and their receptors as well as traditional Chinese medicines in the treatment of DKD and highlights the unique advantages of bile acid receptors in DKD treatment. This paper is expected to reveal a new and important potential strategy for the clinical treatment of DKD.
Associations between metabolic overweight/obesity phenotypes and mortality risk among patients with chronic heart failure
Authors: Zhou You , Xie Yingli , Dong Jingjing , He Kunlun
Published: September 2024

Background

Metabolic disorders and overweight or obesity are highly prevalent and intricately linked in patients with chronic heart failure (CHF). However, it remains unclear whether there is an interactive effect between these conditions and the prognosis of heart failure, and whether such an interaction is influenced by stratification based on age and sex.

Methods

A total of 4,955 patients with CHF were enrolled in this study. Metabolic status was assessed according to the presence or absence of metabolic syndrome (MetS). BMI categories included normal weight and overweight or obesity (BMI < 24, ≥ 24 kg/m2). Patients were divided into four phenotypes according to their metabolic status and BMI: metabolically healthy with normal weight (MHNW), metabolically unhealthy with normal weight (MUNW), metabolically healthy with overweight or obesity (MHO), and metabolically unhealthy with overweight or obesity (MUO). The incidence of primary outcomes, including all-cause and cardiovascular (CV) death, was recorded.

Results

During a mean follow-up of 3.14 years, a total of 1,388 (28.0%) all-cause deaths and 815 (16.4%) CV deaths were documented. Compared to patients with the MHNW phenotype, those with the MUNW (adjusted hazard ratio [aHR], 1.66; 95% confidence interval [CI], 1.38–2.00) or MUO (aHR, 1.42 [95% CI, 1.24–1.63]) phenotypes had a greater risk of all-cause death, and those with the MHO phenotype (aHR, 0.61 [95% CI, 0.51–0.72]) had a lower risk of all-cause death. Moreover, the above phenomenon existed mainly among males and elderly females (aged ≥ 60 years). In nonelderly females (aged < 60 years), the detrimental effects of MetS were lower (aHR, 1.05 [95% CI, 0.63–1.75] among MUNW group and aHR, 0.52 [95% CI, 0.34–0.80] among MUO group), whereas the protective effects of having overweight or obesity persisted irrespective of metabolic status (aHR, 0.43 [95% CI, 0.26–0.69] among MHO group and aHR, 0.52 [95% CI, 0.34–0.80] among MUO group). Similar results were obtained in the Cox proportional risk analysis of the metabolic overweight/obesity phenotypes and CV death.

Conclusions

In male and elderly female patients with CHF, the detrimental effects of MetS outweighed the protective benefits of having overweight or obesity. Conversely, in nonelderly females, the protective effects of having overweight or obesity were significantly greater than the adverse impacts of MetS.
Improving availability and utilization of forest inventory and land use map data using Linked Open Data
Authors: Giménez-García José M. , Vega-Gorgojo Guillermo , Ordóñez Cristóbal , Crespo-Lera Natalia , Bravo Felipe
Published: September 2024

Introduction

Modern forestry increasingly relies on the management of large datasets, such as forest inventories and land cover maps. Governments are typically in charge of publishing these datasets, but they typically employ disparate data formats (sometimes proprietary ones) and published datasets are commonly disconnected from other sources, including previous versions of such datasets. As a result, the usage of forestry data is very challenging, especially if we need to combine multiple datasets.

Methods and results

Semantic Web technologies, standardized by the World Wide Web Consortium (W3C), have emerged in the last decades as a solution to publish heterogeneous data in an interoperable way. They enable the publication of self-describing data that can easily interlink with other sources. The concepts and relationships between them are described using ontologies, and the data can be published as Linked Data on the Web, which can be downloaded or queried online. National and international agencies promote the publication of governmental data as Linked Open Data, and research fields such as biosciences or cultural heritage make an extensive use of Semantic Web technologies. In this study, we present the result of the European Cross-Forest project, addressing the integration and publication of national forest inventories and land cover maps from Spain and Portugal using Semantic Web technologies. We used a bottom-up methodology to design the ontologies, with the goal of being generalizable to other countries and forestry datasets. First, we created an ontology for each dataset to describe the concepts (plots, trees, positions, measures, and so on) and relationships between the data in detail. We converted the source data into Linked Open Data by using the ontology to annotate the data such as species taxonomies. As a result, all the datasets are integrated into one place this is the Cross-Forest dataset and are available for querying and analysis through a SPARQL endpoint. These data have been used in real-world use cases such as (1) providing a graphical representation of all the data, (2) combining it with spatial planning data to reveal the forestry resources under the management of Spanish municipalities, and (3) facilitating data selection and ingestion to predict the evolution of forest inventories and simulate how different actions and conditions impact this evolution.

Discussion

The work started in the Cross-Forest project continues in current lines of research, including the addition of the temporal dimension to the data, aligning the ontologies and data with additional well-known vocabularies and datasets, and incorporating additional forestry resources.
The multifaceted roles of B lymphocytes in metabolic dysfunction–associated steatotic liver disease
Authors: Li Huige , Xia Ning
Published: September 2024

Recent evidence suggests that adaptive immune cells are important contributors to metabolic dysfunction–associated steatotic liver disease (MASLD, formerly non-alcoholic fatty liver disease, NAFLD). In liver biopsies from MASLD patients, the accumulation of intrahepatic B cells is positively correlated with the MASLD activity score. Hepatic B-cell infiltration is observed in experimental models of metabolic dysfunction-associated steatohepatitis (MASH, formerly non-alcoholic steatohepatitis, NASH). Intrahepatic B2 cells have been shown to contribute to MASLD/MASH by activating T cells, macrophages and hepatic stellate cells, and by producing pathogenic IgG antibodies. In mice fed a MASH diet, selective depletion of B2 cells reduces steatohepatitis and fibrosis. Intestinal B cells are metabolically activated in MASH and promote T-cell activation independently of TCR signaling. In addition, B cells have been shown to contribute to liver fibrosis by activating monocyte-derived macrophages through the secretion of IgA immunoglobulins. Furthermore, our recent study indicates that certain B cell subsets, very likely regulatory B cells, may play a protective role in MASLD. This review summarizes the molecular mechanisms of B cell functions and discusses future research directions on the different roles of B cells in MASLD and MASH.
1,25-dihydroxyvitamin-D3 distinctly impacts the paracrine and cell-to-cell contact interactions between hPDL-MSCs and CD4+ T lymphocytes
Authors: Behm Christian , Miłek Oliwia , Schwarz Katharina , Rausch-Fan Xiaohui , Moritz Andreas , Andrukhov Oleh
Published: September 2024

Introduction

Human periodontal ligament-derived mesenchymal stromal cells (hPDL-MSCs) possess a strong ability to modulate the immune response, executed via cytokine-boosted paracrine and direct cell-to-cell contact mechanisms. This reciprocal interaction between immune cells and hPDL-MSCs is influenced by 1,25-dihydroxyvitamin-D3 (1,25(OH)2D3). In this study, the participation of different immunomodulatory mechanisms on the hPDL-MSCs-based effects of 1,25(OH)2D3 on CD4+ T lymphocytes will be elucidated using different co-culture models with various cytokine milieus.

Material and methods

hPDL-MSCs and CD4+ T lymphocytes were co-cultured indirectly and directly with inserts (paracrine interaction only) or directly without inserts (paracrine and direct cell-to-cell contact interaction). They were stimulated with TNF-α or IL-1β in the absence/presence of 1,25(OH)2D3. After five days of co-cultivation, the CD4+ T lymphocyte proliferation, viability, and cytokine secretion were analyzed. Additionally, the gene expression of soluble and membrane-bound immunomediators was determined in hPDL-MSCs.

Results

In the indirect and direct co-culture model with inserts, 1,25(OH)2D3 decreased CD4+ T lymphocyte proliferation and viability. The direct co-culture model without inserts caused the opposite effect. 1,25(OH)2D3 mainly decreased the CD4+ T lymphocyte-associated secretion of cytokines via hPDL-MSCs. The degree of these inhibitions varied between the different co-culture setups. 1,25(OH)2D3 predominantly decreased the expression of the soluble and membrane-bound immunomediators in hPDL-MSCs to a different extent, depending on the co-culture models. The degree of all these effects depended on the absence and presence of exogenous TNF-α and IL-1β.

Conclusion

These data assume that 1,25(OH)2D3 differently affects CD4+ T lymphocytes via the paracrine and direct cell-to-cell contact mechanisms of hPDL-MSCs, showing anti- or pro-inflammatory effects depending on the co-culture model type. The local cytokine microenvironment seems to be involved in fine-tuning these effects. Future studies should consider this double-edged observation by executing different co-culture models in parallel.
Whole slide image-based weakly supervised deep learning for predicting major pathological response in non-small cell lung cancer following neoadjuvant chemoimmunotherapy: a multicenter, retrospective, cohort study
Authors: Han Dan , Li Hao , Zheng Xin , Fu Shenbo , Wei Ran , Zhao Qian , Liu Chengxin , Wang Zhongtang , Huang Wei , Hao Shaoyu
Published: September 2024

Objective

Develop a predictive model utilizing weakly supervised deep learning techniques to accurately forecast major pathological response (MPR) in patients with resectable non-small cell lung cancer (NSCLC) undergoing neoadjuvant chemoimmunotherapy (NICT), by leveraging whole slide images (WSIs).

Methods

This retrospective study examined pre-treatment WSIs from 186 patients with non-small cell lung cancer (NSCLC), using a weakly supervised learning framework. We employed advanced deep learning architectures, including DenseNet121, ResNet50, and Inception V3, to analyze WSIs on both micro (patch) and macro (slide) levels. The training process incorporated innovative data augmentation and normalization techniques to bolster the robustness of the models. We evaluated the performance of these models against traditional clinical predictors and integrated them with a novel pathomics signature, which was developed using multi-instance learning algorithms that facilitate feature aggregation from patch-level probability distributions.

Results

Univariate and multivariable analyses confirmed histology as a statistically significant prognostic factor for MPR (P-value< 0.05). In patch model evaluations, DenseNet121 led in the validation set with an area under the curve (AUC) of 0.656, surpassing ResNet50 (AUC = 0.626) and Inception V3 (AUC = 0.654), and showed strong generalization in external testing (AUC = 0.611). Further evaluation through visual inspection of patch-level data integration into WSIs revealed XGBoost’s superior class differentiation and generalization, achieving the highest AUCs of 0.998 in training and robust scores of 0.818 in validation and 0.805 in testing. Integrating pathomics features with clinical data into a nomogram yielded AUC of 0.819 in validation and 0.820 in testing, enhancing discriminative accuracy. Gradient-weighted Class Activation Mapping (Grad-CAM) and feature aggregation methods notably boosted the model’s interpretability and feature modeling.

Conclusion

The application of weakly supervised deep learning to WSIs offers a powerful tool for predicting MPR in NSCLC patients treated with NICT.
RNA modifications in cancer immune therapy: regulators of immune cells and immune checkpoints
Authors: Qin Xiangyu , Liu Huali , Zhang Qixuan , Che Yuhang , Lei Tianyu , Tang Fang , Hu Qinyong
Published: September 2024

RNA modifications are epigenetic changes that alter the structure and function of RNA molecules, playing a crucial role in the onset, progression, and treatment of cancer. Immune checkpoint inhibitor (ICI) therapies, particularly PD-1 blockade and anti-CTLA-4 treatments, have changed the treatment landscape of virous cancers, showing great potential in the treatment of different cancer patients, but sensitivity to these therapies is limited to certain individuals. This review offers a comprehensive survey of the functions and therapeutic implications of the four principal RNA modifications, particularly highlighting the significance of m6A in the realms of immune cells in tumor and immunotherapy. This review starts by providing a foundational summary of the roles RNA modifications assume within the immune cell community, focusing on T cells, NK cells, macrophages, and dendritic cells. We then discuss how RNA modifications influence the intricate regulatory mechanisms governing immune checkpoint expression, modulation of ICI efficacy, and prediction of ICI treatment outcomes, and review drug therapies targeting genes regulated by RNA modifications. Finally, we explore the role of RNA modifications in gene editing, cancer vaccines, and adoptive T cell therapies, offering valuable insights into the use of RNA modifications in cancer immunotherapy.
Prognostic implications of tumor-infiltrating lymphocytes in non-small cell lung cancer: a systematic review and meta-analysis
Authors: Yan Qin , Li Shuai , He Lang , Chen Nianyong
Published: September 2024

Background

Tumor-infiltrating lymphocytes (TILs) have demonstrated potential as prognostic biomarkers across various cancer types. However, their prognostic implications in non-small cell lung cancer (NSCLC) remain ambiguous.

Methods

An exhaustive electronic search was executed across the Pubmed, EMBASE, Web of Science, and Cochrane Library databases to locate relevant studies published up until December 19, 2023. Studies were eligible if they assessed the association between TILs and overall survival (OS) and disease-free survival (DFS) in NSCLC patients. The OS and DFS were subsequently extracted for analysis. The prognostic significance of TILs was evaluated by calculating the Pooled Hazard Ratios (HRs) and their corresponding 95% Confidence Intervals (CIs).

Results

The meta-analysis incorporated 60 studies, which collectively included 15829 NSCLC patients. The collective analysis indicated that NSCLC patients exhibiting TILs infiltration demonstrated a significantly improved OS(HR: 0.67; 95%CI: 0.55-0.81). Subgroup analyses, based on TIL subtypes (CD8+, CD3+ and CD4+), consistently revealed a favorable prognostic impact on OS. However, it was observed that FOXP3+ was correlated with a poor OS (HR: 1.35; 95% CI: 0.87-2.11).

Conclusion

This comprehensive systematic review and meta-analysis substantiate the prognostic significance of TILs in patients diagnosed with NSCLC. Notably, elevated TILs infiltration correlates with a favorable prognosis, particularly among CD8+, CD3+ and CD4+ subtypes.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023468089 PROSPERO, identifier CRD42023468089.