bluuebunny/crossref_metadata_2025_split huggingface dataset:
COSGAP: COntainerized Statistical Genetics Analysis Pipelines
Authors: Akdeniz Bayram Cevdet , Frei Oleksandr , Hagen Espen , Filiz Tahir Tekin , Karthikeyan Sandeep , Pasman Joëlle , Jangmo Andreas , Bergstedt Jacob , Shorter John R , Zetterberg Richard , Meijsen Joeri , Sønderby Ida Elken , Buil Alfonso , Tesli Martin , Lu Yi , Sullivan Patrick , Andreassen Ole A , Hovig Eivind 
Published: May 2024

Abstract

Summary
The collection and analysis of sensitive data in large-scale consortia for statistical genetics is hampered by multiple challenges, due to their non-shareable nature. Time-consuming issues in installing software frequently arise due to different operating systems, software dependencies, and limited internet access. For federated analysis across sites, it can be challenging to resolve different problems, including format requirements, data wrangling, setting up analysis on high-performance computing (HPC) facilities, etc. Easier, more standardized, automated protocols and pipelines can be solutions to overcome these issues. We have developed one such solution for statistical genetic data analysis using software container technologies. This solution, named COSGAP: “COntainerized Statistical Genetics Analysis Pipelines,” consists of already established software tools placed into Singularity containers, alongside corresponding code and instructions on how to perform statistical genetic analyses, such as genome-wide association studies, polygenic scoring, LD score regression, Gaussian Mixture Models, and gene-set analysis. Using provided helper scripts written in Python, users can obtain auto-generated scripts to conduct the desired analysis either on HPC facilities or on a personal computer. COSGAP is actively being applied by users from different countries and projects to conduct genetic data analyses without spending much effort on software installation, converting data formats, and other technical requirements.

Availability and implementation
COSGAP is freely available on GitHub (https://github.com/comorment/containers) under the GPLv3 license.
PathwayNexus: a tool for interactive metabolic data analysis
Authors: Eberhard Philipp , Kern Martin , Aichem Michael , Borlinghaus Hanna , Klein Karsten , Delp Johannes , Suciu Ilinca , Moser Benjamin , Dietrich Daniel , Leist Marcel , Schreiber Falk 
Published: May 2024

Abstract

Motivation
High-throughput omics methods increasingly result in large datasets including metabolomics data, which are often difficult to analyse.

Results
To help researchers to handle and analyse those datasets by mapping and investigating metabolomics data of multiple sampling conditions (e.g. different time points or treatments) in the context of pathways, PathwayNexus has been developed, which presents the mapping results in a matrix format, allowing users to easily observe the relations between the compounds and the pathways. It also offers functionalities like ranking, sorting, clustering, pathway views, and further analytical tools. Its primary objective is to condense large sets of pathways into smaller, more relevant subsets that align with the specific interests of the user.

Availability and implementation
The methodology presented here is implemented in PathwayNexus, an open-source add-on for Vanted available at www.cls.uni-konstanz.de/software/pathway-nexus.

Contact
falk.schreiber@unikonstanz.de

Supplementary information
Website: www.cls.uni-konstanz.de/software/pathway-nexus
Intraperitoneal chemotherapy for peritoneal metastases of gastric origin: a systematic review and meta-analysis
Authors: Guchelaar Niels A D , Nasserinejad Kazem , Mostert Bianca , Koolen Stijn L W , van der Sluis Pieter C , Lagarde Sjoerd M , Wijnhoven Bas P L , Mathijssen Ron H J , Noordman Bo J 
Published: May 2024

Abstract

Background
Gastric cancer with peritoneal metastases is associated with a dismal prognosis. Normothermic catheter-based intraperitoneal chemotherapy and normothermic pressurized intraperitoneal aerosol chemotherapy (PIPAC) are methods to deliver chemotherapy intraperitoneally leading to higher intraperitoneal concentrations of cytotoxic drugs compared to intravenous administration. We reviewed the effectiveness and safety of different methods of palliative intraperitoneal chemotherapy.

Methods
Embase, MEDLINE, Web of Science and Cochrane were searched for articles studying the use of repeated administration of palliative intraperitoneal chemotherapy in patients with gastric cancer and peritoneal metastases, published up to January 2024. The primary outcome was overall survival.

Results
Twenty-three studies were included, representing a total of 999 patients. The pooled median overall survival was 14.5 months. The pooled hazard ratio of the two RCTs using intraperitoneal paclitaxel and docetaxel favoured the intraperitoneal chemotherapy arm. The median overall survival of intraperitoneal paclitaxel, intraperitoneal docetaxel and PIPAC with cisplatin and doxorubicin were respectively 18.4 months, 13.2 months and 9.0 months. All treatment methods had a relatively safe toxicity profile. Conversion surgery after completion of intraperitoneal therapy was performed in 16% of the patients.

Conclusions
Repeated intraperitoneal chemotherapy, regardless of method of administration, is safe for patients with gastric cancer and peritoneal metastases. Conversion surgery after completion of the intraperitoneal chemotherapy is possible in a subset of patients.
The limits of waste as a resource: a critique and a proposition towards a new scalar imagination for the circular economy model
Authors: Zavos Stylianos , Pyyhtinen Olli 
Published: May 2024

Abstract
In the article, we critically confront the idea of waste-to-resource at the heart of the circular economy. We discuss some of the blind spots and shortcomings of three circular economy principles: designing out waste, emulating natural systems and decoupling economic growth from resource use. We suggest that their limitations are intimately connected to a scalar reasoning ruled by strict, disjunctive categories. Instead, we advance a flat, relational, trans-scalar approach and propose that the potential of a sustained circular economy promise requires a novel scalar imagination attentive to its multiple co-constituted spatialities, social relations and fluid materials.
SGLT2 inhibition to target kidney aging
Authors: Russo Elisa , Zanetti Valentina , Macciò Lucia , Benizzelli Giulia , Carbone Federico , La Porta Edoardo , Esposito Pasquale , Verzola Daniela , Garibotto Giacomo , Viazzi Francesca 
Published: May 2024

ABSTRACT
Anti-aging therapy is the latest frontier in the world of medical science, especially for widespread diseases such as chronic kidney disease (CKD). Both renal aging and CKD are characterized by increased cellular senescence, inflammation and oxidative stress. A variety of cellular signalling mechanisms are involved in these processes, which provide new potential targets for therapeutic strategies aimed at counteracting the onset and progression of CKD. At the same time, sodium–glucose co-transporter 2 inhibitors (SGLT2is) continuously demonstrate large beneficial effects at all stages of the cardiorenal metabolic continuum. The broad-spectrum benefits of SGLT2is have led to changes in several treatment guidelines and to growing scientific interest in the underlying working principles. Multiple mechanisms have been studied to explain these great renal benefits, but many things remain to be solved. With this in mind, we provide an overview of the experimental evidence for the effects of SGLT2is on the molecular pathway’s ability to modulate senescence, aging and parenchymal damage, especially at the kidney level. We propose to shed some light on the role of SGLT2is in kidney care by focusing on their potential to reduce the progression of kidney disease across the spectrum of aging and dysregulation of senescence.
Tubular biomarkers in proteinuric kidney disease: histology correlation and kidney prognosis of tubular biomarkers
Authors: Carbayo Javier , Verdalles Úrsula , Díaz-Crespo Francisco , Lázaro Alberto , González-Nicolás Marian , Arroyo David , Blanco David , García-Gámiz Mercedes , Goicoechea Marian 
Published: May 2024

ABSTRACT

Background
Proteinuria is not only a biomarker of chronic kidney disease (CKD) but also a driver of CKD progression. The aim of this study was to evaluate serum and urinary tubular biomarkers in patients with biopsied proteinuric kidney disease and to correlate them with histology and kidney outcomes.

Methods
A single-center retrospective study was conducted on a cohort of 156 patients from January 2016 to December 2021. The following urinary and serum biomarkers were analyzed on the day of kidney biopsy: beta 2 microglobulin (β2-mcg), alpha 1 microglobulin (α1-mcg), neutrophil gelatinase-associated lipocalin (NGAL), urinary kidney injury molecule-1 (uKIM-1), monocyte chemoattractant protein-1 (MCP-1), urinary Dickkopf-3 (uDKK3), uromodulin (urinary uUMOD), serum kidney injury molecule-1 (sKIM-1) and serum uromodulin (sUMOD). A composite outcome of kidney progression or death was recorded during a median follow-up period of 26 months.

Results
Multivariate regression analysis identified sUMOD (β–0.357, P &lt; .001) and uDKK3 (β 0.483, P &lt; .001) as independent predictors of interstitial fibrosis, adjusted for age, estimated glomerular filtration rate (eGFR) and log proteinuria. Elevated levels of MCP-1 [odds ratio 15.61, 95% confidence interval (CI) 3.52–69.20] were associated with a higher risk of cortical interstitial inflammation &gt;10% adjusted for eGFR, log proteinuria and microhematuria. Upper tertiles of uDKK3 were associated with greater eGFR decline during follow-up. Although not a predictor of the composite outcome, doubling of uDKK3 was a predictor of kidney events (hazard ratio 2.26, 95% CI 1.04–4.94) after adjustment for interstitial fibrosis, eGFR and proteinuria.

Conclusions
Tubular markers may have prognostic value in proteinuric kidney disease, correlating with specific histologic parameters and identifying cases at higher risk of CKD progression.
Inhibition of TBL1 cleavage alleviates doxorubicin-induced cardiomyocytes death by regulating the Wnt/β-catenin signal pathway
Authors: Lee Sun-Ho , Lee Jangho , Oh Jaewon , Hwang Jin-Taek , Lee Hae-Jeung , Byun Hwa Kyung , Kim Hyeong-Jin , Suh David , Yoon Ho-Geun , Park Sahng Wook , Kang Seok-Min , Kwon Chulan , Lee Seung-Hyun , Choi Hyo-Kyoung 
Published: May 2024

Abstract

Aims
Doxorubicin (DOX) is a widely used anthracycline anticancer agent; however, its irreversible effects on the heart can result in DOX-induced cardiotoxicity (DICT) after cancer treatment. Unfortunately, the pathophysiology of DICT has not yet been fully elucidated, and there are no effective strategies for its prevention or treatment. In this investigation, the novel role of transducin beta-like protein 1 (TBL1) in developing and regulating DICT was explored.

Methods and results
We observed a reduction in TBL1 protein expression levels as well as cleavage events in the transplanted cardiac tissues of patients diagnosed with Dilated Cardiomyopathy and DICT. It was revealed that DOX selectively induces TBL1 cleavage at caspase-3 preferred sites—D125, D136, and D215. Interestingly, overexpression of the uncleaved TBL1 mutant (TBL1uclv) variant reduced apoptosis, effectively preventing DOX-induced cell death. We confirmed that cleaved TBL1 cannot form a complex with β-catenin. As a result, Wnt reporter activity and Wnt target gene expression collectively indicate a decrease in Wnt/β-catenin signalling, leading to DICT progression. Furthermore, the cleaved TBL1 triggered DOX-induced abnormal electrophysiological features and disrupted calcium homeostasis. However, these effects were improved in TBL1uclv-overexpressing human-induced pluripotent stem cell-derived cardiomyocytes. Finally, in a DICT mouse model, TBL1uclv overexpression inhibited the DICT-induced reduction of cardiac contractility and collagen accumulation, ultimately protecting cardiomyocytes from cell death.

Conclusion
Our findings reveal that the inhibition of TBL1 cleavage not only mitigates apoptosis but also enhances cardiomyocyte function, even in the context of DOX administration. Consequently, this study's results suggest that inhibiting TBL1 cleavage may be a novel strategy to ameliorate DICT.
Pan-Enteric Crohn’s Capsule [Eliakim] Score Reliability and Responsiveness to Change in Active Crohn’s Disease
Authors: Ukashi Offir , Lahat Adi , Ungar Bella , Levy Hadar , Finkel Orel , Eidler Pinhas , Ben-Horin Shomron , Eliakim Rami , Kopylov Uri 
Published: May 2024

Abstract

Background and Aims
Pan-enteric capsule endoscopy (PillCam Crohn’s capsule [PCC]) is a useful tool in diagnosing and monitoring Crohn’s disease [CD]. Eliakim score [ES] reliability and its strong correlation to Lewis score [LS] and to inflammatory biomarkers have been previously demonstrated using PCC in quiescent CD. We aimed to examine ES performance in active CD and its responsiveness to clinical/biochemical change over time.

Methods
Patients with CD who have started biologics were included, and were prospectively followed based on clinical visits, biomarkers, and PCC at baseline, after 14 and 52 weeks. Crohn’s disease activity index [CDAI], C-reactive protein [CRP], and faecal calprotectin [FC] levels were determined, and LS and ES were calculated [independently reviewed by two experienced readers]. Inter-class classification [ICC], Spearman’s baseline correlation, and repeated-measures correlation [RMC] analyses were performed.

Results
Seventy-four patients were included (age: 30.5 [range 23.3–45.0] years old, male 50%). In total, 142 PCCs were read [baseline, 62; week 14, 58; week 52, 22]. Inter-rater agreement was high for both LS and ES (ICC: 0.872 [p &lt; 0.001] and 0.925 [&lt;0.001], respectively). Baseline correlations between FC&ES [r = 0.509 [p &lt; 0.001]) and FC&LS (r = 0.467 [p &lt; 0.001]) were comparable [p = 0.56]. RMCs between the inflammatory biomarkers and ES were higher than between the former and LS (Reader 1: CRP r = 0.306 vs r = 0.138 [p = 0.057], FC r = 0.479 vs r = 0.297 [p = 0.034]; Reader 2 CRP r = 0.376 vs r = 0.204 [p = 0.035], FC r = 0.549 vs r = 0.412 [p = 0.075]). Moreover, ES was better correlated to CDAI than LS [p = 0.036].

Conclusions
ES is a reliable scoring system in assessing pan-enteric mucosal inflammation in active CD, and might have a better responsiveness to clinical/biochemical change over time compared to LS.
Mitral annular disjunction and its progression during childhood in Marfan syndrome
Authors: Doan Tam T , Iturralde Chavez Alejandra , Valdes Santiago O , Weigand Justin D , Wilkinson James C , Parthiban Anitha , Stephens Sara B , Pignatelli Ricardo H , Morris Shaine A 
Published: May 2024

Abstract

Aims
Data on mitral annular disjunction (MAD) in children with Marfan syndrome (MFS) are sparse. To investigate the diagnostic yield of MAD by echocardiography and cardiac magnetic resonance imaging (CMR), its prevalence and progression during childhood.

Methods and results
We included patients &lt;21 years old with MFS, defined by 2010 Ghent criteria and a pathogenic FBN1 variant or ectopia lentis. Two readers measured systolic separation between the mitral valve (MV) posterior hinge point and left ventricular (LV) myocardium on initial and subsequent imaging. MAD was defined as MV-LV separation ≥2 mm, MV prolapse (MVP) as atrial displacement ≥2 mm. Kappa coefficients evaluated echocardiogram–CMR agreement. Bland–Altman and intraclass correlation coefficients (ICCs) assessed inter-rater and inter-modality reliability. Univariable mixed-effects linear regression was used to evaluate longitudinal changes of MAD. MAD was detected in 60% (110/185) eligible patients. MVP was present in 48% (53/110) of MAD and MAD in 90% (53/59) of MVP. MAD detection by CMR and echocardiography had 96% overall agreement (Kappa = 0.89, P &lt; 0.001) and a 0.32 mm estimate bias (95% CI 0.00, 0.65). ICC by echocardiography, CMR, and between modalities were 0.97 (95% CI 0.93, 0.98), 0.92 (95% CI 0.79, 0.97), and 0.91 (95% CI 0.85, 0.94), respectively. MAD was associated with aortic root dilation (P &lt; 0.001). MAD was found in children of all ages, increased +0.18 mm/year (95% CI +0.14, +0.22) during a median duration of 5.5 years (IQR 3.1, 7.5 years). MAD indexed by height yielded a constant value +0.0002 mm/m/year (95% CI −0.0002, +0.0005 mm/m/year).

Conclusion
MAD was common in pediatric MFS and was associated with aortic root dilation. MAD detection by echocardiography and CMR was highly reliable, suggesting that routine assessment in MFS is feasible. MAD was present in neonates and progressed over time but remained constant when indexing by height. Further studies are needed to evaluate MAD as a biomarker for clinical outcomes in pediatric MFS.
Psychometric validation of the short version of the Information Needs in Cardiac Rehabilitation scale through a first global assessment
Authors: Ghisi Gabriela Lima de Melo , da Cruz Mayara Moura Alves , Vanderlei Luiz Carlos Marques , Liu Xia , Xu Zhimin , Jiandani Mariya Prakash , Cuenza Lucky , Kouidi Evangelia , Giallauria Francesco , Mohammed Jibril , Maskhulia Lela , Trevizan Patricia Fernandes , Batalik Ladislav , Pereira Danielle Gomes , Tourkmani Nidal , Burazor Ivana , Venturini Elio , Lira Gerlene Grudka , Rehfeld Manuella Bennaton Cardoso Vieira , Neves Victor Ribeiro , Borges Geovana de Jesus , Kim Won-Seok , Cha Seungwoo , Zhang Ling , Grace Sherry L 
Published: May 2024

Abstract

Aims
Tailored education is recommended for cardiac patients, yet little is known about information needs in areas of the world where it is most needed. This study aims to assess (i) the measurement properties of the Information Needs in Cardiac Rehabilitation short version (INCR-S) scale and (ii) patient’s information needs globally.

Methods and results
In this cross-sectional study, English, simplified Chinese, Portuguese, or Korean versions of the INCR-S were administered to in- or out-patients via Qualtrics (January 2022–November 2023). Members of the International Council of Cardiovascular Prevention and Rehabilitation community facilitated recruitment. Importance and knowledge sufficiency of 36 items were rated. Links to evidence-based lay education were provided where warranted. A total of 1601 patients from 19 middle- and high-income countries across the world participated. Structural validity was supported upon factor analysis, with five subscales extracted: symptom response/medication, heart diseases/diagnostic tests/treatments, exercise and return-to-life roles/programmes to support, risk factors, and healthy eating/psychosocial management. Cronbach’s alpha was 0.97. Construct validity was supported through significantly higher knowledge sufficiency ratings for all items and information importance ratings for all subscales in cardiac rehabilitation (CR) enrolees vs. non-enrolees (all P &lt; 0.001). All items were rated as very important—particularly regarding cardiac events, nutrition, exercise benefits, medications, symptom response, risk factor control, and CR—but more so in high-income countries in the Americas and Western Pacific. Knowledge sufficiency ranged from 30.0 to 67.4%, varying by region and income class. Ratings were highest for medications and lowest for support groups, resistance training, and alternative medicine.

Conclusion
Identification of information needs using the valid and reliable INCR-S can inform educational approaches to optimize patients’ health outcomes across the globe.
Modifiable risk factors and risk of myocardial infarction in offspring with parental disease
Authors: Møller Amalie Lykkemark , Larson Martin G , Xanthakis Vanessa , Vasan Ramachandran S , Andersson Charlotte 
Published: May 2024

Abstract

Aims
Children of patients with early-onset myocardial infarction (MI) are at increased risk, but the importance of concordant vs. discordant parent–offspring risk factor profiles on MI risk is largely unknown. We quantified the long-term absolute risk of MI according to shared risk factors in adulthood.

Methods and results
We sampled data on familial predisposed offspring and their parents from the Framingham Heart Study. Early MI was defined as a history of parental MI onset before age 55 in men or 65 in women. Individuals were matched 3:1 with non-predisposed offspring. Cardiovascular risk factors included obesity, smoking, hypertension, high cholesterol, and diabetes. We estimated the absolute 20-year incidence of MI using the Aalen–Johansen estimator. At age 40, the 20-year risk of MI varied by cholesterol level [high cholesterol 25.7% (95% confidence interval 11.2–40.2%) vs. non-high cholesterol 3.4% (0.5–6.4)] among predisposed individuals, and this difference was greater than in controls [high cholesterol 9.3% (1.5–17.0) vs. non-high cholesterol 2.5% (1.1–3.8)]. Similar results were observed for prevalent hypertension [26.7% (10.8–42.5) vs. 4.0% (0.9–7.1) in predisposed vs. 10.8% (3.2–18.3) and 2.1% (0.8–3.4) in controls]. Among offspring without risk factors, parental risk factors carried a residual impact on 20-year MI risk in offspring [0% (0–11.6) for 0–1 parental risk factors vs. 3.3% (0–9.8) for ≥2 parent risk factors at age 40, vs. 2.9% (0–8.4) and 8.5% (0–19.8) at age 50 years].

Conclusion
Children of patients with early-onset MI have low absolute risks of MI in the absence of midlife cardiovascular risk factors, especially if the parent also had a low risk factor burden prior to MI.
Sexually discordant selection is associated with trait-specific morphological changes and a complex genomic response
Authors: Audet Tyler , Krol Joelle , Pelletier Katie , Stewart Andrew D , Dworkin Ian 
Published: May 2024

Abstract
Sexes often have differing fitness optima, potentially generating intra-locus sexual conflict, as each sex bears a genetic “load” of alleles beneficial to the other sex. One strategy to evaluate conflict in the genome is to artificially select populations discordantly against established sexual dimorphism (SD), reintroducing attenuated conflict. We investigate a long-term artificial selection experiment reversing sexual size dimorphism in Drosophila melanogaster during ~350 generations of sexually discordant selection. We explore morphological and genomic changes to identify loci under selection between the sexes in discordantly and concordantly size-selected treatments. Despite substantial changes to overall size, concordant selection maintained ancestral SD. However, discordant selection altered size dimorphism in a trait-specific manner. We observe multiple possible soft selective sweeps in the genome, with size-related genes showing signs of selection. Patterns of genomic differentiation between the sexes within lineages identified potential sites maintained by sexual conflict. One discordant selected lineage shows a pattern of elevated genomic differentiation between males and females on chromosome 3L, consistent with the maintenance of sexual conflict. Our results suggest visible signs of conflict and differentially segregating alleles between the sexes due to discordant selection.