bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic inactivation of β-catenin is salubrious, whereas its activation is deleterious in desmoplakin cardiomyopathy
Authors: Olcum Melis , Fan Siyang , Rouhi Leila , Cheedipudi Sirisha , Cathcart Benjamin , Jeong Hyun-Hwan , Zhao Zhongming , Gurha Priyatansh , Marian Ali J 
Published: August 2023

Abstract

Aims
Mutations in the DSP gene encoding desmoplakin, a constituent of the desmosomes at the intercalated discs (IDs), cause a phenotype that spans arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy. It is typically characterized by biventricular enlargement and dysfunction, myocardial fibrosis, cell death, and arrhythmias. The canonical wingless-related integration (cWNT)/β-catenin pathway is implicated in the pathogenesis of ACM. The β-catenin is an indispensable co-transcriptional regulator of the cWNT pathway and a member of the IDs. We genetically inactivated or activated β-catenin to determine its role in the pathogenesis of desmoplakin cardiomyopathy.

Methods and results
The Dsp gene was conditionally deleted in the 2-week-old post-natal cardiac myocytes using tamoxifen-inducible MerCreMer mice (Myh6-McmTam:DspF/F). The cWNT/β-catenin pathway was markedly dysregulated in the Myh6-McmTam:DspF/F cardiac myocytes, as indicated by a concomitant increase in the expression of cWNT/β-catenin target genes, isoforms of its key co-effectors, and the inhibitors of the pathway. The β-catenin was inactivated or activated upon inducible deletion of its transcriptional or degron domain, respectively, in the Myh6-McmTam:DspF/F cardiac myocytes. Genetic inactivation of β-catenin in the Myh6-McmTam:DspF/F mice prolonged survival, improved cardiac function, reduced cardiac arrhythmias, and attenuated myocardial fibrosis, and cell death caused by apoptosis, necroptosis, and pyroptosis, i.e. PANoptosis. In contrast, activation of β-catenin had the opposite effects. The deleterious and the salubrious effects were independent of changes in the expression levels of the cWNT target genes and were associated with changes in several molecular and biological pathways, including cell death programmes.

Conclusion
The cWNT/β-catenin was markedly dysregulated in the cardiac myocytes in a mouse model of desmoplakin cardiomyopathy. Inactivation of β-catenin attenuated, whereas its activation aggravated the phenotype, through multiple molecular pathways, independent of the cWNT transcriptional activity. Thus, suppression but not activation of β-catenin might be beneficial in desmoplakin cardiomyopathy.
Building a large gene expression-cancer knowledge base with limited human annotations
Authors: Marchesin Stefano , Menotti Laura , Giachelle Fabio , Silvello Gianmaria , Alonso Omar 
Published: August 2023

Abstract
Cancer prevention is one of the most pressing challenges that public health needs to face. In this regard, data-driven research is central to assist medical solutions targeting cancer. To fully harness the power of data-driven research, it is imperative to have well-organized machine-readable facts into a knowledge base (KB). Motivated by this urgent need, we introduce the Collaborative Oriented Relation Extraction (CORE) system for building KBs with limited manual annotations. CORE is based on the combination of distant supervision and active learning paradigms and offers a seamless, transparent, modular architecture equipped for large-scale processing. We focus on precision medicine and build the largest KB on ‘fine-grained’ gene expression–cancer associations—a key to complement and validate experimental data for cancer research. We show the robustness of CORE and discuss the usefulness of the provided KB.
Database URL https://zenodo.org/record/7577127
Competency-based cardiac imaging for patient-centred care. A statement of the European Society of Cardiology (ESC). With the contribution of the European Association of Cardiovascular Imaging (EACVI), and the support of the Association of Cardiovascular Nursing & Allied Professions (ACNAP), the Association for Acute CardioVascular Care (ACVC), the European Association of Preventive Cardiology (EAPC), the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Heart Rhythm Association (EHRA), and the Heart Failure Association (HFA) of the ESC
Authors: Westwood Mark , Almeida Ana G , Barbato Emanuele , Delgado Victoria , Dellegrottaglie Santo , Fox Kevin F , Gargani Luna , Huber Kurt , Maurovich-Horvat Pál , Merino Jose L , Mindham Richard , Muraru Denisa , Neubeck Lis , Nijveldt Robin , Papadakis Michael , Pontone Gianluca , Price Susanna , Rosano Giuseppe M C , Rossi Alexia , Sade Leyla Elif , Schulz-Menger Jeanette , Weidinger Franz , Achenbach Stephan , Petersen Steffen E 
Published: August 2023

Abstract
Imaging plays an integral role in all aspects of managing heart disease and cardiac imaging is a core competency of cardiologists. The adequate delivery of cardiac imaging services requires expertise in both imaging methodology—with specific adaptations to imaging of the heart—as well as intricate knowledge of heart disease. The European Society of Cardiology (ESC) and the European Association of Cardiovascular Imaging have developed and implemented a successful education and certification programme for all cardiac imaging modalities. This programme equips cardiologists to provide high quality competency-based cardiac imaging services ensuring they are adequately trained and competent in the entire process of cardiac imaging, from the clinical indication via selecting the best imaging test to answer the clinical question, to image acquisition, analysis, interpretation, storage, repository, and results dissemination. This statement emphasizes the need for competency-based cardiac imaging delivery which is key to optimal, effective and efficient, patient care.
Thyroglobulin and thyroglobulin antibody: an updated clinical and laboratory expert consensus
Authors: Giovanella Luca , D’Aurizio Federica , Algeciras-Schimnich Alicia , Görges Rainer , Petranovic Ovcaricek Petra , Tuttle R Michael , Visser W Edward , Verburg Frederik A ,   hsTg&TgAb Consensus Working Group, Borowczyk Martyna , Chiovato Luca , Duntas Leonidas , Section Thyroid , Feldt-Rasmussen Ulla , Knappe Luisa , Leenhardt Laurence , Magri Flavia , Rimmele Harald , Seregni Ettore 
Published: August 2023

AbstractObjectiveThyroglobulin measurement is the cornerstone of modern management of differentiated thyroid cancer, with clinical decisions on treatment and follow-up based on the results of such measurements. However, numerous factors need to be considered regarding measurement with and interpretation of thyroglobulin assay results.DesignThe present document provides an integrated update to the 2013 and 2014 separate clinical position papers of our group on these issues.MethodsIssues concerning analytical and clinical aspects of highly-sensitive thyroglobulin measurement will be reviewed and discussed based on an extensive analysis of the available literature.ResultsThyroglobulin measurement remains a highly complex process with many pitfalls and major sources of interference, especially anti-thyroglobulin antibodies, need to be assessed, considered and, when necessary, dealt with appropriately.ConclusionsOur expert consensus group formulated 53 practical, graded recommendations for guidance on highly-sensitive thyroglobulin and TgAb in laboratory and clinical practice, especially valuable where current guidelines do not offer sufficient guidance.
Development and validation of osteoporosis risk assessment score in patients with heart failure: comparison with the osteoporosis self-assessment tool for Asians
Authors: Numazawa Ryo , Katano Satoshi , Yano Toshiyuki , Koyama Masayuki , Nagaoka Ryohei , Fujisawa Yusuke , Yamano Kotaro , Honma Suguru , Ohori Katsuhiko , Kouzu Hidemichi , Katayose Masaki , Furuhashi Masato , Tsuchihashi Kazufumi , Hashimoto Akiyoshi 
Published: August 2023

Abstract

Aims
Osteoporosis is prevalent and is associated with poor prognosis in patients with heart failure (HF). However, bone mineral density measurement by a dual-energy X-ray absorptiometry (DEXA) scan is not always available in a daily clinical setting or large-scale population-based studies.

Methods and results
A single-centre, cross-sectional observational study was conducted with 387 patients [median age: 77 years (interquartile range: 68–83 years); 37% women]. Bone mineral densities were measured by DEXA scans, and osteoporosis was diagnosed as ≤−2.5 standard deviation of the bone mineral densities in healthy young adults. Osteoporosis risk assessment score (ORAS) was developed using significant predictors from a logistic regression model for osteoporosis and was subsequently validated. Osteoporosis was found in 103 (27%) of the 387 HF patients. Multivariate logistic regression analyses yielded the ORAS based on sex, body mass index, handgrip strength, and anti-coagulant therapy utilization. The C-index of ORAS in the developmental set (0.796, 95% confidence interval: 0.747–0.845) was similar to the bootstrap validation of the prediction model (0.784) and tended to be higher than that of the osteoporosis self-assessment tool for Asians (OSTA). A nomogram of ORAS, established on the basis of the final logistic regression model, demonstrated 100% sensitivity at the lowest score (35 points), with an optimal cut-off point of 127 points, yielding 85% sensitivity and 62% specificity.

Conclusion
Osteoporosis risk assessment score exhibits superior predictive performance to OSTA in predicting osteoporosis in HF patients, establishing itself as a valuable tool for early detection in both daily clinical practice and large-scale population-based studies.
Twenty-five years of catheter ablation of ventricular tachycardia: a look back and a look forward
Authors: Natale Andrea , Zeppenfeld Katja , Della Bella Paolo , Liu Xu , Sabbag Avi , Santangeli Pasquale , Sommer Philipp , Sticherling Christian , Zhang Xiaodong , Di Biase Luigi 
Published: August 2023

Abstract
This article will discuss the past, present, and future of ventricular tachycardia ablation and the continuing contribution of the Europace journal as the platform for publication of milestone research papers in this field of ventricular tachycardia ablation.
Trends in United States Family Forest Owners’ Attitudes, Behaviors, and General Characteristics from 2006 to 2018
Authors: Sass Emma M , Butler Brett J , Caputo Jesse , Huff Emily S 
Published: August 2023

AbstractFamily forest owners (FFOs) control a plurality of forestland in the United States, and the decisions these landowners make have a profound impact on the landscape. Most research on FFOs consists of cross-sectional studies, although many of these recognize the importance of capturing long-term trends to understand whether and how FFO attitudes, behaviors, and general characteristics are changing. We use data from the 2006, 2013, and 2018 iterations of the USDA Forest Service, National Woodland Owner Survey (NWOS), with a bootstrapping approach to identify significant changes across these time periods among FFOs with 4+ hectares of forestland. Total FFO hectares decreased and FFO ownerships trended downward over the study period. A decreasing proportion of FFOs owned farms or homes near their forestland, harvested timber, or received advice. Demographic shifts include an increase in age and education level from 2006 to 2018, and an increase in FFOs of color from 2006 to 2013. Overall, we find a trend towards decreased traditional engagement and management and a slight increase in owning land for its amenity values. Understanding temporal trends in FFO characteristics, attitudes, and behaviors will help policymakers and forestry professionals inform and update their outreach, technical support, and financial assistance programs.Study Implications: Families and individuals hold more forestland than any other ownership group in the United States. We use nationwide survey data from 2006, 2013, and 2018 to determine whether and how these landowners are changing over time. The total forestland held by FFOs decreased between 2006 and 2018, and there has been a decrease in traditional forest management and engagement, such as through timber harvesting and nearby farm ownership. This study provides insights for policies, programs, and outreach and a foundation for future long-term comparisons of this group.
Genome assembly of the foot-flagging frog, Staurois parvus: a resource for understanding mechanisms of behavior
Authors: Holtz Mika A , Racicot Riccardo , Preininger Doris , Stuckert Adam M M , Mangiamele Lisa A 
Published: August 2023

Abstract
Elaborate and skilled movements of the body have been selected in a variety of species as courtship and rivalry signals. One roadblock in studying these behaviors has been a lack of resources for understanding how they evolved at the genetic level. The Bornean rock frog (Staurois parvus) is an ideal species in which to address this issue. Males wave their hindlimbs in a “foot-flagging” display when competing for mates. The evolution of foot flagging in S. parvus and other species is accompanied by increases in the expression of the androgen receptor gene within its neuromuscular system, but it remains unclear what genetic or transcriptional changes are associated with this behavioral phenotype. We have now assembled the genome of S. parvus, resulting in 3.98 Gbp of 22,402 contigs with an N50 of 611,229 bp. The genome will be a resource for finding genes related to the physiology underlying foot flagging and to adaptations of the neuromuscular system. As a first application of the genome, we also began work in comparative genomics and differential gene expression analysis. We show that the androgen receptor is diverged from other anuran species, and we identify unique expression patterns of genes in the spinal cord and leg muscle that are important for axial patterning, cell specification and morphology, or muscle contraction. This genome will continue to be an important tool for future -omics studies to understand the evolution of elaborate signaling behaviors in this and potentially related species.
The Genomic Basis of Adaptation to High Elevations in Africanized Honey Bees
Authors: Everitt Turid , Wallberg Andreas , Christmas Matthew J , Olsson Anna , Hoffmann Wolfgang , Neumann Peter , Webster Matthew T 
Published: August 2023

AbstractA range of different genetic architectures underpin local adaptation in nature. Honey bees (Apis mellifera) in the Eastern African Mountains harbor high frequencies of two chromosomal inversions that likely govern adaptation to this high-elevation habitat. In the Americas, honey bees are hybrids of European and African ancestries and adaptation to latitudinal variation in climate correlates with the proportion of these ancestries across the genome. It is unknown which, if either, of these forms of genetic variation governs adaptation in honey bees living at high elevations in the Americas. Here, we performed whole-genome sequencing of 29 honey bees from both high- and low-elevation populations in Colombia. Analysis of genetic ancestry indicated that both populations were predominantly of African ancestry, but the East African inversions were not detected. However, individuals in the higher elevation population had significantly higher proportions of European ancestry, likely reflecting local adaptation. Several genomic regions exhibited particularly high differentiation between highland and lowland bees, containing candidate loci for local adaptation. Genes that were highly differentiated between highland and lowland populations were enriched for functions related to reproduction and sperm competition. Furthermore, variation in levels of European ancestry across the genome was correlated between populations of honey bees in the highland population and populations at higher latitudes in South America. The results are consistent with the hypothesis that adaptation to both latitude and elevation in these hybrid honey bees are mediated by variation in ancestry at many loci across the genome.
Circulating Growth Differentiation Factors 11 and 8, Their Antagonists Follistatin and Follistatin-Like-3, and Risk of Heart Failure in Elders
Authors: Kizer Jorge R , Patel Sheena , Ganz Peter , Newman Anne B , Bhasin Shalender , Lee Se-Jin , Cawthon Peggy M , LeBrasseur Nathan K , Shah Sanjiv J , Psaty Bruce M , Tracy Russell P , Cummings Steven R 
Published: August 2023

Abstract

Background
Heterochronic parabiosis has identified growth differentiation factor (GDF)-11 as a potential means of cardiac rejuvenation, but findings have been inconsistent. A major barrier has been lack of assay specificity for GDF-11 and its homolog GDF-8.

Methods
We tested the hypothesis that GDF-11 and GDF-8, and their major antagonists follistatin and follistatin-like (FSTL)-3, are associated with incident heart failure (HF) and its subtypes in elders. Based on validation experiments, we used liquid chromatography–tandem mass spectrometry to measure total serum GDF-11 and GDF-8, along with follistatin and FSTL-3 by immunoassay, in 2 longitudinal cohorts of older adults.

Results
In 2 599 participants (age 75.2 ± 4.3) followed for 10.8 ± 5.6 years, 721 HF events occurred. After adjustment, neither GDF-11 (HR per doubling: 0.93 [0.67, 1.30]) nor GDF-8 (HR: 1.02 per doubling [0.83, 1.27]) was associated with incident HF or its subtypes. Positive associations with HF were detected for follistatin (HR: 1.15 [1.00, 1.32]) and FLST-3 (HR: 1.38 [1.03, 1.85]), and with HF with preserved ejection fraction for FSTL-3 (HR: 1.77 [1.03, 3.02]). (All HRs per doubling of biomarker.) FSTL-3 associations with HF appeared stronger at higher follistatin levels and vice versa, and also for men, Blacks, and lower kidney function.

Conclusions
Among older adults, serum follistatin and FSTL-3, but not GDF-11 or GDF-8, were associated with incident HF. These findings do not support the concept that low serum levels of total GDF-11 or GDF-8 contribute to HF late in life, but do implicate transforming growth factor-β superfamily pathways as potential therapeutic targets.
CircASPH Enhances Exosomal STING to Facilitate M2 Macrophage Polarization in Colorectal Cancer
Authors: Zhang Yuting , Guo Jiakun , Zhang Liyin , Li Ying , Sheng Kangliang , Zhang Yawei , Liu Liu , Gong Wenbin , Guo Kun 
Published: August 2023

Abstract
Exosomes are considered a mediator of communication within the tumor microenvironment (TME), which modulates cancer progression through transmitting cargos between cancer cells and other cancer-related cells in TME. Circular RNAs (circRNAs) have emerged to be regulators in colorectal cancer (CRC) progression, but most of them have not been discussed in CRC. This study aims to investigate the role of circRNA aspartate beta-hydroxylase (circASPH) in CRC progression and its correlation with exosome-mediated TME. At first, we determined that circASPH was upregulated in CRC samples and cell lines. Functionally, the circASPH deficiency suppressed the malignant processes of CRC cells and also inhibited in vivo tumor growth via enhancing antitumor immunity. Mechanically, circASPH facilitated macrophage M2 polarization by upregulating exosomal stimulator of interferon genes (STING). CircASPH interacted with insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) to stabilize IGF2BP2 protein, therefore enhancing the stability of m6A-modified STING mRNA. In turn, coculture of STING-overexpressed macrophages recovered the suppression of silenced circASPH on the malignancy of CRC cells both in vitro and in vivo. Our study demonstrated that circASPH enhances exosomal STING to facilitate M2 macrophage polarization, which further accelerates CRC progression. The findings support circASPH as a promising therapeutic target for CRC treatment.
Monovalent SARS-CoV-2 mRNA Vaccine Does not Boost Omicron-Specific Immune Response in Diabetic and Control Pediatric Patients
Authors: Sariol Alan , Vickers Molly A , Christensen Shannon M , Weiskopf Daniela , Sette Alessandro , Norris Andrew W , Tansey Michael J , Pinnaro Catherina T , Perlman Stanley 
Published: August 2023

Abstract
While the immunogenicity of SARS-CoV-2 vaccines has been well described in adults, pediatric populations have been less studied. In particular, children with type 1 diabetes are generally at elevated risk for more severe disease after infections, but are understudied in terms of COVID-19 and SARS-CoV-2 vaccine responses. We investigated the immunogenicity of COVID-19 mRNA vaccinations in 35 children with type 1 diabetes (T1D) and 23 controls and found that these children develop levels of SARS-CoV-2 neutralizing antibody titers and spike protein-specific T cells comparable to nondiabetic children. However, in comparing the neutralizing antibody responses in children who received 2 doses of mRNA vaccines (24 T1D; 14 controls) with those who received a third, booster dose (11 T1D; 9 controls), we found that the booster dose increased neutralizing antibody titers against ancestral SARS-CoV-2 strains but, unexpectedly, not Omicron lineage variants. In contrast, boosting enhanced Omicron variant neutralizing antibody titers in adults.
Novel insights into genetic susceptibility for colorectal cancer from transcriptome-wide association and functional investigation
Authors: Chen Zhishan , Song Wenqiang , Shu Xiao-Ou , Wen Wanqing , Devall Matthew , Dampier Christopher , Moratalla-Navarro Ferran , Cai Qiuyin , Long Jirong , Van Kaer Luc , Wu Lan , Huyghe Jeroen R , Thomas Minta , Hsu Li , Woods Michael O , Albanes Demetrius , Buchanan Daniel D , Gsur Andrea , Hoffmeister Michael , Vodicka Pavel , Wolk Alicja , Marchand Loic Le , Wu Anna H , Phipps Amanda I , Moreno Victor , Ulrike Peters , Zheng Wei , Casey Graham , Guo Xingyi 
Published: August 2023

Abstract

Background
Transcriptome-wide association studies have been successful in identifying candidate susceptibility genes for colorectal cancer (CRC). To strengthen susceptibility gene discovery, we conducted a large transcriptome-wide association study and an alternative splicing transcriptome-wide association study in CRC using improved genetic prediction models and performed in-depth functional investigations.

Methods
We analyzed RNA-sequencing data from normal colon tissues and genotype data from 423 European descendants to build genetic prediction models of gene expression and alternative splicing and evaluated model performance using independent RNA-sequencing data from normal colon tissues of the Genotype-Tissue Expression Project. We applied the verified models to genome-wide association studies (GWAS) summary statistics among 58 131 CRC cases and 67 347 controls of European ancestry to evaluate associations of genetically predicted gene expression and alternative splicing with CRC risk. We performed in vitro functional assays for 3 selected genes in multiple CRC cell lines.

Results
We identified 57 putative CRC susceptibility genes, which included the 48 genes from transcriptome-wide association studies and 15 genes from splicing transcriptome-wide association studies, at a Bonferroni-corrected P value less than .05. Of these, 16 genes were not previously implicated in CRC susceptibility, including a gene PDE7B (6q23.3) at locus previously not reported by CRC GWAS. Gene knockdown experiments confirmed the oncogenic roles for 2 unreported genes, TRPS1 and METRNL, and a recently reported gene, C14orf166.

Conclusion
This study discovered new putative susceptibility genes of CRC and provided novel insights into the biological mechanisms underlying CRC development.