bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hereditary Hemochromatosis Variant Associations with Incident Nonliver Malignancies: 11-Year Follow-up in UK Biobank
Authors: Atkins Janice L. , Pilling Luke C. , Torti Suzy V. , Torti Frank M. , Kuchel George A. , Melzer David 
Published: June 2022

Abstract

Background:
In European ancestry populations, iron overload disorder hereditary hemochromatosis is predominantly caused by HFE p.C282Y and p.H63D mutations. Male p.C282Y homozygotes have markedly increased hepatic malignancy incidence, but risks for other cancers in male and female homozygotes are unclear.

Methods:
451,143 UK Biobank European ancestry participants (aged 40–70 years; 54.3% female) were followed (mean 11.6 years) via hospital admissions and national cancer registries. We estimated risks of any incident cancer (other than nonmelanoma and liver cancer) and common incident cancers [bladder, blood (with subanalyses of leukemia and lymphoma), bone, brain, breast, colorectal, kidney, lung, melanoma, esophageal, ovarian, pancreatic, prostate and stomach] in those with p.C282Y and p.H63D genotypes, compared with participants without HFE mutations.

Results:
Male p.C282Y homozygotes (n = 2,890, 12.1% with baseline diagnosed hereditary hemochromatosis) had increased incidence of prostate cancer [6.8% vs. 5.4% without mutations; HR = 1.32; 95% confidence interval (CI), 1.07–1.63; P = 0.01; Bonferroni adjusted P = 0.17] during follow-up. In life table estimates from ages 40 to 75 years, 14.4% of male p.C282Y homozygotes are projected to develop prostate cancer (versus 10.7% without mutations, excess 3.8%; 95% CI, 1.3–6.8). No increases in risks were found for other studied cancers in male or female p.C282Y homozygotes, or in any other p.C282Y/p.H63D genotype groups of either sex.

Conclusions:
In a large community sample of male p.C282Y homozygotes, there is suggestive evidence of increased prostate cancer incidence, with no evidence of excess of other studied (nonliver) cancers.

Impact:
Replication of results in other large community genotyped cohorts are needed to confirm if clinical monitoring for prostate cancer is necessary in p.C282Y homozygous males.
Abstract 6295: Grape seed procyanidins inhibit cell proliferation & induce apoptosis in both human breast & liver cancer cell lines
Authors: Alneanaey Rana Hamed , Taha Nabil , Lebda Mohammed , Hashem Aml , Sultan Ahmed 
Published: June 2022

Abstract
As a potential anticancer agent, grape seed procyanidins (GSPs) have been shown to be effective in treating and preventing various cancer types, but the mechanistic inhibitory effect at cellular and molecular levels in most of the cancer types remains unclear. The objective of the present study was to investigate the potential influence of GSPs on both liver and breast cancers. The anticancer efficacy of GSPs was investigated in vitro, using two human cancer cell lines; human hepatocellular carcinoma (HepG2) and human breast carcinoma, Zr-75-1.The potential influence of extracted GSPs was examined on cell proliferation, clonogenic assays, morphological alteration, and western blot was used to analyze the expression of oncogenic signaling pathways of STAT3, β-catenin, T-ERK, and pERK, Bax, Bcl-2, mutant-p53, and caspase enzyme activity assay was measured by caspase colorimetric assay.Our data showed that GSPs treatment inhibits both cellular viability and proliferation in a concentration-and time-dependent fashion in both breast and liver cancer cell lines after 48h. Furthermore, mechanistic studies showed that GSPs induced late apoptosis by 72% that was associated with cell morphological changes, histone release from fragmented DNA, caspase-3 activation in a dose-dependent manner after 48h. Furthermore, GSPs down-regulated pERK, STAT3, β-catenin, and mutant p53 levels as well as increased p21and Bax, pro-apoptotic signal, in both breast and liver cancer cells as determined by western blot analysis. All in all, our findings suggest that GSPs inhibit breast and liver cancer cells proliferation and induce cell apoptosis by suppressing the oncogenic signaling pathways that play a role in cancer progression which in turn introduce GSPs as a promising phytochemical for cancer treatment.
Citation Format: Rana Hamed Alneanaey, Nabil Taha, Mohammed Lebda, Aml Hashem, Ahmed Sultan. Grape seed procyanidins inhibit cell proliferation & induce apoptosis in both human breast & liver cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6295.
Abstract SY11-02: Long-read sequencing reveals complex patterns of wraparound transcription in polyomaviruses
Authors: DeCaprio James A. , Nomburg Jason , Meyerson Matthew 
Published: June 2022

Abstract
Polyomaviruses (PyV) are ubiquitous pathogens that can cause devastating human diseases. Due to the small size of their genomes, PyV utilize complex patterns of RNA splicing to maximize their coding capacity. Despite the importance of PyV to human disease, their transcriptome architecture is poorly characterized. Here, we compare short- and long-read RNA sequencing data from eight human and non-human PyV. We provide a detailed transcriptome atlas for BK polyomavirus (BKPyV), an important human pathogen, and the prototype PyV, simian virus 40 (SV40). We identify pervasive wraparound transcription in PyV, wherein transcription runs through the polyA site and circles the genome multiple times. Comparative analyses identify novel, conserved transcripts that increase PyV coding capacity. One of these conserved transcripts encodes superT, a T antigen containing two RB-binding LxCxE motifs. We find that superT-encoding transcripts are abundant in PyV-associated human cancers. Together, we show that comparative transcriptomic approaches can greatly expand known transcript and coding capacity in one of the simplest and most well-studied viral families.
Citation Format: James A. DeCaprio, Jason Nomburg, Matthew Meyerson. Long-read sequencing reveals complex patterns of wraparound transcription in polyomaviruses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY11-02.
Abstract SY27-03: Using the cancer dependency map
Authors: Hahn William C. 
Published: June 2022

Abstract
Although molecular profiling of human tumors is now routine, the use of this data to guide therapy remains limited to a subset of patients. In particular, pediatric cancers often harbor a signature molecular alteration but few other mutations. To complement genome characterization studies, we have used genome scale gain and loss of function approaches to identify genes required for cell survival and transformation. Specifically, we have performed both genome scale RNAi and CRISRP-Cas9 screens in hundreds of cancer cell lines to identify differentially essential genes and the context that specifies gene dependency. These studies now allow us to define a Cancer Dependency Map. Using these datasets and approaches, we have defined new categories of potential cancer targets, identify synthetic lethal candidates in pediatric and adult cancers and have developed a method to systematically identify molecular pleiotropy. These approaches promise to further operationalize precision cancer medicine.
Citation Format: William C. Hahn. Using the cancer dependency map [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY27-03.
Abstract SY41-03: Cancer specific amino acid metabolism
Authors: Maddocks Oliver 
Published: June 2022

Abstract
The growth & proliferation of cancer cells is fundamentally dependent on metabolic processes, and tumours frequently display altered metabolism compared with healthy tissues. To sustain enhanced growth, and to resist stresses associated with cancer treatments, cancer cells become highly dependent on the uptake of exogenous nutrients, particularly amino acids. Amino acid metabolism supports tumour growth and survival in numerous ways, particularly in the provision of anabolic precursors for macromolecule (e.g. protein and DNA) synthesis, as well as stress responsive antioxidant pathways (e.g. glutathione/GSH synthesis). We have shown that uptake of exogenous serine and glycine is key nutrient dependency for many cancer cells, simultaneously supporting THF-dependent one carbon metabolism and GSH synthesis. More recently we have defined a role for immune-regulated IDO1 dependent tryptophan metabolism as an alternative one-carbon source for nucleotide synthesis, underlining the potential flexibility of tumour metabolism. The sensitivity of certain cancer cells to cysteine starvation is well established, and multiple mechanisms contribute to cysteine withdrawal sensitivity, including transsulfuration activity and methylation reactions. We have recently defined a role for methionine driven polyamine metabolism in sensitising cells to cysteine starvation, particularly in the context of MTAP gene deletion. Improved understanding of cancer specific amino acid metabolism is defining genetically driven metabolic vulnerabilities that can be therapeutically exploited by a combination of diet and small molecules.
Citation Format: Oliver Maddocks. Cancer specific amino acid metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY41-03.
Privações da Vida Cotidiana do Autismo na Cidade: desafios às políticas públicas
Authors: Machado Márcia Francisca Lombo , Ansara Soraia 
Published: June 2022

ResumoEste artigo apresenta dados que evidenciam as questões da cidade na correlação de forças para obtenção de políticas públicas para pessoas com autismo. Trazendo parte de uma pesquisa que investigou a relação da vida cotidiana com a participação das famílias dos autistas na tomada de decisões para a democratização dos espaços e serviços, o estudo articula a discussão sobre saúde e intersetorialidade à cidade e à constituição da cidadania. A investigação revelou que a urgência em prover os itens fundamentais ao desenvolvimento dos filhos com autismo se confronta com as discrepâncias do espaço urbano provocando rupturas na vida cotidiana e concorrendo contra a organização coletiva e o engajamento das famílias na gestão de políticas públicas da cidade, limitando a participação política em soluções efetivas às suas demandas. Palavras-chave: participação; políticas públicas; direito à cidade; famílias de autistas; cidadania. AbstractThis paper presents data that highlight the city's issues in the correlation of forces to obtain public policies for people with autism. Bringing part of a research that investigated the relationship of daily life with the participation of autistic families in decision making for the democratization of spaces and services, the study articulates the discussion on health care and “intersectoriality” (in the sense of global vision and cooperation among sectors).to the city and to the constitution of citizenship. The investigation revealed that the urgency to provide the essential items for the development of children with autism is confronted with the discrepancies of the urban space causing ruptures in daily life and competing against the collective organization and the engagement of the families in the management of public policies of the city, restricting the political participation for effective solutions to their demands. Keywords: participation; public policy; right to the city; autistic families; citizenship. Resumen Este artículo presenta datos de un estudio que investigó la relación de la vida cotidiana con la participación de familias autistas en la toma de decisiones para la democratización de espacios y servicios destacando los problemas de la ciudad en la correlación de fuerzas para obtener políticas públicas para personas con autismo. De esta manera, el estudio articula la discusión sobre salud e "intersectorialidad" a la gestión de la ciudad y a la constitución de la ciudadanía. La investigación reveló que la urgencia de proporcionar los elementos esenciales para el desarrollo de niños con autismo se contrapone a las discrepancias del espacio urbano causando rupturas en la vida cotidiana de las familias, creando dificultades para su organización colectiva e intervención en la gestión de las políticas públicas de la ciudad, restringiendo la participación política a soluciones efectivas a sus demandas. Palabras-chave: participación; políticas públicas; derecho a la ciudad; familias de autistas; ciudadanía
Educação preventiva e promoção da saúde na escola: desafios para orientação sexual em São Paulo
Authors: Barboza Renato , Machado Pirotta Kátia Cibelle , Pupo Ligia Rivero 
Published: June 2022

Considerando-se a escassa produção científica sobre orientação sexual em redes de ensino, investigou-se os programas implementados pela Secretaria Municipal de Educação de São Paulo, nos anos de 2001 a 2006. O artigo objetiva identificar as concepções e dificuldades dos diretores e coordenadores pedagógicos no desenvolvimento das ações de orientação sexual na rede pública de ensino. No período investigado, três projetos destacaram-se pela duração e forte presença na rede escolar, constituindo um cenário privilegiado para o estudo da educação preventiva e da promoção da saúde entre adolescentes. Realizou-se um estudo descritivo-retrospectivo, de abordagem qualitativa, com oito informantes-chave que foram entrevistados em profundidade. As principais categorias de análise foram: ações pontuais na disciplina de Ciências; pouco poder, baixa legitimidade e resistência dos professores; avanços percebidos; fragilidades na avaliação; alta rotatividade dos educadores; e, descontinuidade dos projetos. A análise evidenciou dificuldades estruturais e pedagógicas. As ações frequentemente dependeram do interesse pessoal dos profissionais em detrimento de um projeto coletivo. Com a mudança da gestão, houve descontinuidade dos projetos nas escolas. O estudo subsidia o campo da educação preventiva e da promoção da saúde, respaldando o saber-fazer dos educadores e indica caminhos para a superação das lacunas na instituição escolar.
Palavras chave: Políticas públicas; Educação em saúde; Educação sexual; Desenvolvimento de programas; Promoção da saúde.
A Luta pela Visibilidade na Campanha 'Ficha Limpa': mídia, movimentos sociais e combate à corrupção política
Authors: Guimarães Thiago 
Published: June 2022

Este trabalho investiga a relação entre mídia e movimentos sociais a partir da trajetória da campanha Ficha Limpa (2008-2010), que resultou na coleta de 1,3 milhão de assinaturas e aprovação de projeto de lei de iniciativa popular que tornou mais rígidos os critérios para postulação de candidatos em eleições no Brasil. Inicialmente apresenta-se uma proposta de abordagem comunicacional dos fenômenos sociais, a captá-los em processos de interação entre sujeitos em produção e interpretação de sentidos. Discute-se aspectos da relação entre mídia e democracia. Argumenta-se, a despeito do reconhecimento do cenário de crise na comunicação pública contemporânea, pela manutenção do potencial da mídia de revigoramento do debate em esferas públicas diversas. Nesse sentido, considera-se o papel da internet e de novas mediações tecnológicas na reconfiguração das ações estratégicas de atores coletivos cívicos. À luz desse referencial, examina-se o papel da mídia na promoção de debates públicos ampliados, bem como características das relações entre meios de comunicação e movimentos sociais, analisados integralmente em suas dimensões de oportunidade política, mobilização de recursos e processos simbólicos. Recorre-se a uma visão integrada do conceito de enquadramento, em sua tradição na literatura da comunicação e dos movimentos sociais, para o estudo de discursos mobilizados durante a campanha. Descrito o panorama histórico da iniciativa, com ênfase nas estruturas de oportunidade política que envolveram seu surgimento e desenvolvimento, passa-se à análise empírica de como os temas da campanha Ficha Limpa

Este artigo analisa a relação entre mídia e movimentos sociais a partir da trajetória da campanha Ficha Limpa (2008-2010), que resultou na coleta de 1,3 milhão de assinaturas e aprovação de projeto de lei de iniciativa popular que tornou mais rígidos os critérios para postulação de candidatos em eleições no Brasil. Inicialmente apresenta-se uma proposta de abordagem comunicacional dos fenômenos sociais, a captá-los em processos de interação entre sujeitos em produção e interpretação de sentidos. Discute-se aspectos da relação entre mídia e democracia. Argumenta-se, a despeito do reconhecimento do cenário de crise na comunicação pública contemporânea, pela manutenção do potencial da mídia de revigoramento do debate em esferas públicas diversas. Nesse sentido, considera-se o papel da internet e de novas mediações tecnológicas na reconfiguração das ações estratégicas de atores coletivos cívicos. À luz desse referencial, examina-se o papel da mídia na promoção de debates públicos ampliados, bem como características das relações entre meios de comunicação e movimentos sociais, analisados integralmente em suas dimensões de oportunidade política, mobilização de recursos e processos simbólicos.

na reconfiguração da ação coletiva e na promoção de práticas de participação social.
Microarchitectural Changes of Cardiovascular Calcification in Response to In Vivo Interventions Using Deep-Learning Segmentation and Computed Tomography Radiomics
Authors: Patel Nikhil Rajesh , Setya Kulveer , Pradhan Stuti , Lu Mimi , Demer Linda L. , Tintut Yin 
Published: June 2022

Background:
Coronary calcification associates closely with cardiovascular risk, but its progress is accelerated in response to some interventions widely used to reduce risk. This paradox suggests that qualitative, not just quantitative, changes in calcification may affect plaque stability. To determine if the microarchitecture of calcification varies with aging, Western diet, statin therapy, and high intensity, progressive exercise, we assessed changes in a priori selected computed tomography radiomic features (intensity, size, shape, and texture).

Methods:

Longitudinal computed tomography scans of mice (

Apoe
−/−

) exposed to each of these conditions were autosegmented by deep learning segmentation, and radiomic features of the largest deposits were analyzed.

Results:
Over 20 weeks of aging, intensity and most size parameters increased, but surface-area-to-volume ratio (a measure of porosity) decreased, suggesting stabilization. However, texture features (coarseness, cluster tendency, and nonuniformity) increased, suggesting heterogeneity and likely destabilization. Shape parameters showed no significant changes, except sphericity, which showed a decrease. The Western diet had significant effects on radiomic features related to size and texture, but not intensity or shape. In mice undergoing either pravastatin treatment or exercise, the selected radiomic features of their computed tomography scans were not significantly different from those of their respective controls. Interestingly, the total number of calcific deposits increased significantly less in the 2 intervention groups compared with the respective controls, suggesting more coalescence and/or fewer de novo deposits.

Conclusions:
Thus, aging and standard interventions alter the microarchitectural features of vascular calcium deposits in ways that may alter plaque biomechanical stability.
Understanding cannabis use in Singapore: profile of users and drug progression
Authors: Chia Doris Xin Yi , Ng Charis Wei Ling , Asharani Pezhummoottil Vasudevan Nair , Au Yong Sabina , Tan Jun Wen , Zainuldin Noor Azizah Bte , Chua Samuel Kee Guan , Low Lambert Tchern Kuang , Cheok Christopher Cheng Soon , Kandasami Gomathinayagam 
Published: June 2022

Introduction:
Cannabis has consistently been the third most commonly abused drug among drug arrestees in Singapore over the past few years. Accordingly, this study aimed to understand the profile of cannabis users in Singapore and explore the effects of cannabis use on drug progression.

Methods:
A total of 450 participants who had used cannabis at least once in their lifetime were recruited from the National Addictions Management Service, prisons, the Community Rehabilitation Centre and halfway houses from August 2017 to May 2018. A face-to-face questionnaire was administered and descriptive analyses were conducted.

Results:
The mean participant age was 40.9 ± 14.51 years, and 93.1% of them were male. The participants generally initiated cannabis use during adolescence, at a mean onset age of 16.5 ± 4.46 years. Most (89.6%) were introduced to cannabis by peers. Approximately half of them (46.9%) had used cannabis before other illicit drugs and 42.1% of them had used heroin as the succeeding drug.

Conclusion:
In Singapore, cannabis use is often initiated during adolescence, largely under peer influence. Cannabis users may progress to other illicit drugs, particularly heroin, later in life.
Profiles of women presenting for abortions in Singapore at the National University Hospital: focus on married women
Authors: Pek Xiang Wen Gregory , Teoh Wei Shan , Wu Duoduo , Singh Kuldip 
Published: June 2022

Introduction:
In this study, we aimed to identify the differences in sociodemographic variables and reasons for termination of pregnancy (TOP) between married women and single/divorced women. We hope that this study can guide future policies and interventions to reduce the incidence of unsupported pregnancies in this profile group of women.

Methods:
We retrospectively evaluated the sociodemographic data of 802 women who underwent an abortion for social reasons at our institution in Singapore from January 2016 to September 2018. We compared the sociodemographic variables, reasons for and methods of TOP between married and single/divorced women.

Results:
We analysed data from 524 married women (65.3%) and 278 single/divorced women (34.7%). Married women were more likely to be of older age (29.5 years vs. 24.5 years, P < 0.001), had more living children and higher educational qualifications. The top two cited reason for abortions among married women were having enough children (42.0%) and the inability to afford another child (18.7%). Multivariate analysis showed that women aged >19 years and having more living children were independently associated with recurrent TOPs. Having a tertiary education was noted to be associated with less recurrent TOPs.

Conclusion:
The most common reasons married women cited for having TOP include having enough children and the lack of financial capacity to afford another child. Recommendations to support women ought to be personalised and comprehensive in addressing their needs rather than offering a standardised support method. Greater emphasis should be placed on post-TOP family planning counselling to reduce repeated TOP.