bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal shift and accuracy of machine learning in heart transplant outcomes
Authors: Sabovcik F , Miller R , Cauwenberghs N , Hoffmann R , Haddad F , Kuznetsova T 
Published: October 2021

Abstract

Background
Accurate prediction of outcomes following a heart transplant is critical to explaining risks and benefits to patients and decision-making when considering potential organ offers. Given the large number of potential variables to be considered, this task may be most efficiently performed using machine learning (ML).

Purpose
We trained and tested different ML algorithms to accurately predict outcomes following a cardiac transplant using the United Network of Organ Sharing (UNOS) database.

Methods
We included 67 939 adult and pediatric patients enrolled in the UNOS database between January 1994 and December 2016 who underwent cardiac transplantation (median age 53 [IQR 38 – 60], 72.7% males). In our models, as an input, we included 114 features that have been collected from recipients and donors prior to transplant. The primary outcome was all-cause mortality at one-year post-transplant. We evaluated three different ML methods: XGBoost, Random Forest (RF) and L2 regularized logistic regression. Algorithms were trained and tested using shuffled 10-fold cross-validation (CV) as well as rolling CV. In the rolling CV, to mimic prospective procedure, ML models were trained by incrementally adding patients according to transplant year and testing models on the data in the following year. The hyperparameters, controlling the learning process, were tuned using Bayesian optimization. Prognostic accuracy for one-year all-cause mortality was characterized using the area under the receiver-operating characteristic curve (AUC).

Results
In total, 8,394 patients died within 1 year of transplant. We observed a substantial difference in prognostic accuracy between the shuffled 10-fold CV and the rolling CV. In the 10-fold CV, XGBoost and RF achieved high predictive performance with AUC of 0.848 (95% CI: 0.842–0.854) and 0.891 (95% CI: 0.886–0.896), respectively. In the rolling CV, which is a more realistic setting, AUC dropped to 0.673 (95% CI: 0.661–0.684) for XGBoost and 0.670 (0.657–0.683) for RF. Predictive performance of L2 regularized logistic regression remained stable across the two CV procedures, achieving AUC 0.669 (95% CI: 0.662–0.676) in the 10-fold shuffled CV and 0.665 (95% CI: 0.649–0.680) in the rolling CV procedure (Figure).

Conclusions
Our study suggests that ML models could be used to predict mortality in the first year post-transplant. We also show that the choice of CV procedure is crucial for evaluating ML models, particularly in data collected over a long period of time. The difference between the shuffled and rolling CV in the predictive performance of the tree-based ML models might indicate temporal dataset shift. In the rolling CV, all three methods achieved similar predictive performance.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders (FWO)
Structural and molecular markers of aging heart: Sechenov University classification
Authors: Kogan E A , Syrkin A L , Blagova O V 
Published: October 2021

Abstract

Background
The process of aging at the level of the cells is connecting with arising of senescence cell, that are characterized by several possible signs, including damage to the mitochondria and contraction of telomeres, epigenetic changes, impaired regulation of protein metabolism, sensitivity to nutrients, mitochondrial dysfunction, stem cell collapse, impaired intercellular communication. Postmitotic cells may also develop senescence and are called amitosenescence cells (AMCs).

Goal
To investigate structural and molecular characteristic of aging heart with special identification of AMCs and creating classification of aging heart status.

Methods
Study was performed on 52 biopsies (endomyocardial and operative) of the heart and 48 autopsy cases (38 women and 62 men) with diagnosis of dilated cardiomyopathies, chronic ischemic heart disease, hypertensive cardiomyopathies, rheumatic heart disease and their combination. All patients were divided in two groups according to the age of patients: 1 group included 80 patients (average age 72.9±13.3 years) and 2 control group - 20 patients (average age 42.9±13.3 years). Serial paraffin sections were stained with hematoxylin and eosin, picrofuchsin; p16ink, Apocas, CD68 and CD 45 were detected by immunohistochemistry (DakoCytomation). We have calculated percent of AMC, Apo and RCB in 30 fields of vision on X400 magnification.

Results
AMCs were found in the myocardium of 77 aging patients and only in 2 young patients (premature aging?). AMCs were characterized by prominent degenerative changes, p16ink expression and accumulation of lipofuscin. Reduction of capillary bad (RCB), increased number of apoptotic bodies and presence of CD68+ macrophages and CD45+ lymphocytes were found in stroma. There were three aging heart status degree: 1 – presence less than 15% of AMCs, 0,1% of Apo and RCB –less than 15% (20 patients); 2 – presence 16–30% of AMCs, 0,2- 1% of Apo and RCB – 16–30% (35); 3 – presence more than 31% of AMCs, 1–2% of Apo and RCB – more than 31% (27).

Conclusion
Aging heart has increased number of amitosenecence cells that results severity and chronicity of heart diseases in aging patients.

Funding Acknowledgement
Type of funding sources: None.
Reduced RNA editing in the failing human heart mediates alternative circular RNA splicing
Authors: Kokot K , Kneuer J , John D , Moebius-Winkler M , Mueller M , Andritschke M , Gaul S , Sheikh B , Haas J , Thiele H , Leuschner F , Dimmeler S , Meder B , Laufs U , Boeckel J N 
Published: October 2021

Abstract

Background and purpose
Post-transcriptional RNA editing is an important mechanism in the development of human diseases. RNA editing can affect RNA stability and alternative splicing. The aim of our study was to characterize RNA editing and its impact on alternative RNA splicing in the healthy and failing human heart.

Methods and results
Human heart samples of heart failure (HF) patients (n=20) and controls (n=10) were analyzed using RNA sequencing with subsequent analysis of RNA editing. We identified adenosine-to-inosine (A-to-I) editing as the major form of RNA editing in human hearts, being reduced in HF patients. Consistently, we found the editing enzyme ADAR2 reduced in HF patients. A-to-I RNA editing predominantly occurred in intronic regions of protein-coding genes, specifically in repetitive, primate-specific Alu elements which can affect RNA splicing. Indeed, we found 173 circular RNAs (circRNAs) regulated by alternative mRNA splicing in the failing heart.
Loss of ADAR2 led to reduced RNA editing concomitant with an increase of circRNA, while overexpression reduced circRNA expression and enhanced RNA editing.

Conclusion
A-to-I editing is the major type of RNA editing in the human heart, being reduced in HF. We demonstrate a primate-specific alternative RNA splicing mechanism mediated by RNA editing in human hearts. The findings may be relevant to diseases with reduced RNA editing such as cancer, neurological and cardiac diseases.

Funding Acknowledgement
Type of funding sources: None.
Improvement in mitochondrial oxidative phosphorylation of cardiomyocytes derived from human-induced pluripotent stem cells using micropatterned anisotropic substrates
Authors: Jouve C , Donnarumma E , Seguret M , Pereira C , Vermersch E , Al-Sayed Z , Wai T , Hulot J S 
Published: October 2021

Abstract

Background/Introduction
Alterations in cellular bioenergetic events owing to metabolic dysfunctions are well demonstrated in heart failure (HF). Cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) have the potential to model metabolic alterations as observed in the human failing hearts, which however requires precise arrangements of the respiratory chain complexes.

Purpose
Develop a method to improve the hiPSC-CMs architecture by using a micropatterned substrate (repeated lines of 30 μm-width separated with a cell repellant) that promotes elongation and anisotropy.

Methods
Cardiomyocyte differentiation was performed using a chemically defined method and 35 days later the generated hiPSC-CMs were cultured on unpatterned vs. micropatterned substrates for 7 additional days. Energy metabolic profiles were then measured using the Seahorse analyzer and mitochondrial components were analyzed by fluorescence microscopy and western blot.

Results
Cultures on micropatterned anisotropic substrates resulted in the generation of elongated cell morphology, rod-shaped hiPSC-CMs with improved sarcomere organization scores, and more aligned Z-lines. We first found a specific increase in oxidation phosphorylation (OXPHOS) activity in micropatterned CMs with a significant increase in the oxygen consumption rate (OCR) linked to basal respiration (58.4±24.0 vs 40.6±21.0 pmol/min, p&lt;0.01), ATP production (49.6±19.1 vs 33.2±18.8 pmol/min, p&lt;0.001) and maximal respiration (239.1±119.0 vs 123.0±68.5 pmol/min, p&lt;0.001). Micropatterned CMs showed a better electron transport chain activity that explains the significantly decreased glycolytic function observed by Seahorse (17.2±9.9 vs 23.9±7.2 mpH/min, p&lt;0.001). Micropatterned CMs displayed a more organized mitochondrial network, without evident change in mitochondrial mass. Transcriptomic profiling of micropatterned vs. unpatterned CMs revealed no significant differences. We next evaluated the proteomic profiling and found no significant change in the micropatterned CMs OXPHOS proteins expression.

Conclusion(s)
We developed a novel method for modeling metabolic activity in hiPSC-CMs based on micropatterned cultures. Our data show that the linear architectural pattern drives the formation and efficiency of OXPHOS function in cardiomyocytes with a mitochondrial structural reorganization.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Agence Nationale de la Recherche
The state of health in the European Union in 2019
Authors: Vasco Santos J , Padron Monedero A , Bikbov B , Grad DA , Plass D , Mechili E-A , Gazzelloni F , Fischer F , Sulo G , Ngwa CH , Noguer-Zambrano I , Peñalvo J , Haagsma JA , Kissimova-Skarbek K , Monasta L , Ghith N , Sarmiento-Suarez R , Hrzic R , Haneef R , O'Caoimh R , Cuschieri S , Mondello S , Kabir Z , Devleesschauwer B 
Published: October 2021

Abstract

Background
The European Union (EU) faces many health-related challenges. Accurate and timely data on mortality and morbidity from diseases and injuries and their trends over time are essential for health planning and priority setting.

Methods
We use the GBD 2019 study estimates and 95% uncertainty intervals for the whole EU and each country to evaluate age-standardized death, YLL, YLD and DALY rates for Level 2 causes. We evaluate trends by comparing estimates for the year 2019 with those for the year 2010.

Results
In 2019, the age-standardized death and DALY rates in the EU were 465.8 and 20 251.0 per 100 000 inhabitants, respectively. Between 2010 and 2019, there were significant decreases for age-standardized, death and YLL rates across EU countries. However, YLD rates remained mainly unchanged, with increases in the Netherlands and the ‘. The largest decreases in age-standardized DALY rates were observed for HIV/AIDS and sexually transmitted diseases and transport injuries (both -19%). On the other hand, only diabetes and kidney diseases showed a significant increase for age-standardized DALY rates in the EU (3.5%). Mental disorders showed an increasing age-standardized YLD rate, as well.

Conclusions
Overall, there was a visible trend of improvement in the health status in the EU with substantial differences between countries. EU health policy makers need to tackle incidence of diseases and injuries, with specific attention to causes such as mental disorders. There are many opportunities for mutual learning among otherwise similar countries with different patterns of disease.
Burden of diseases and injuries attributable to risk factors in the European Union in 2019
Authors: Vasco Santos J , Padron Monedero A , Kocbach Bolling A , Bikbov B , Unim B , Grad DA , Plass D , Fischer F , Violante FS , Sulo G , Ngwa CH , Noguer-Zambrano I , Peñalvo J , Haagsma JA , Kissimova-Skarbek K , Monasta L , Ghith N , Sigurvinsdóttir R , Sarmiento-Suarez R , Haneef R , Mondello S , Breitner S , Kabir Z , Devleesschauwer B 
Published: October 2021

Abstract

Background
In addition to information on mortality and morbidity from diseases and injuries, it is important to identify the attributable burden of risk factors to allow for health planning and prioritization.

Methods
For the whole EU and each country, using estimates and 95% uncertainty intervals from the GBD 2019 study, we report attributable (all-cause and by level 2 risk factors) age-standardized death and DALY rates, as well as summary exposure values (SEV). We evaluate trends by comparing estimates for the year 2019 with those for the year 2010.

Results
Age-standardized death and DALY rates attributable to risk factors declined by 10.7% (95%UI 13.8%-7.6%) and 9.1% (95%UI 12.0%-6.3%), between 2010 and 2019 in the EU. While there was a decreasing trend for both age-standardized death and DALY rates for almost all risk factors, some showed an increasing trend on SEV, including low physical activity and intimate partner violence.

Conclusions
Despite the improvement of health metrics attributable to risk factors, several modifiable behavioral and metabolic risk factors remain unchanged over the years. It is crucial to ensure a swift implementation of evidence-based policies and interventions in EU member states to achieve the targets of the Sustainable Development Goals.
The resetting of a local health system: an opportunity for health promotion
Authors: Bou Monclús MA , Casamitjà Sot MT , Mantas Jiménez S , Mallolas Jiménez J , Ventura Taberner N , Sunyer Serrat J , Parreño Ariza RM , González Cateura A , Rodríguez Arjona MD ,   HP Group of Professionals for Health Promotion of Girona
Published: October 2021

Abstract

Background
The COVID-19 pandemics brings a window of opportunity for the 2021-2025 Health Plan of Catalonia to better address the social determinants of health. Different public organisms are leading the Health Promotion (HP) agenda without a real integration of the approach. An interdisciplinary group of health professionals working on HP carried out a qualitative study to assess barriers, facilitators and recommendations of health professionals and public policy managers for applying HP.

Methods
Six focus groups with 52 purposively selected professionals of different health disciplines and three in-depth interviews with public policy managers were conducted between March 2017-February 2020 until saturation was reached. An external expert on Sociology conducted all interviews and codification was done by three researchers from the group. Literature review helped to complete triangulation.

Results
The salutogenic approach was mostly unknown. The health system was not set with a people-centred perspective and HP not integrated within health services. Different public organisms competed for leadership and resources in HP. There was limited expenditure for the primary health care services working on HP. Coordination across healthcare services levels and sectors was scarce. Roles and responsibilities related to HP were not defined. Health professionals were not aware of evidence-based approaches. Some interdepartmental public health plans were already designed but not fully deployed, mainly due to lack of funding and disaggregated mechanisms of governance and financing. Initiatives such as the Municipal Health Committees or social prescription were positively perceived.

Conclusions
The Catalan Public Health Agency and health providers should work aligned. Financing and reallocation of resources for Public Health and HP should be enhanced. Health should be a core value in educational plans. Local and regional stakeholders should have a higher role in resetting health services.

Key messages
Governance for Health in All Policies needs intersectoral partnerships. The health system should be rebuilt to properly address the social determinants of health in the post-COVID era.
Cross-sectional associations between number and ages of children and maternal physical activity
Authors: Simpson RF , Hesketh KR , Crozier SR , Baird J , Cooper C , Godfrey KM , Harvey NC , Westgate K , Inskip HM , van Sluijs EMF 
Published: October 2021

Abstract

Background
Physical activity (PA) has many health benefits, but parenthood is often associated with reduced PA in mothers. Determinants of adult PA are diverse, but ages and number of children may be key factors linked to maternal PA. Few studies have compared PA levels of mothers of school-aged children with those who have younger children, which is vital considering that maternal PA patterns may change at transition to formal schooling. Studies using device-assessment to investigate this association are also sparse. We aimed to investigate the association between number and ages of children and maternal device-measured moderate-to-vigorous PA (MVPA).

Methods
Cross-sectional analyses were conducted using data from 848 mothers from the Southampton Women's Survey when the index child was 4 or 6-7 years old. Two-level random intercept linear models were run to investigate associations between self-reported number (1, 2, 3+) and ages (4y and under, 5y and over, both age groups) of children, and their potential interaction, and accelerometer-assessed log-transformed minutes of maternal MVPA. Results are presented as % difference in minutes of MVPA.

Results
41% of mothers met PA guidelines (150 minutes of MVPA/week). Women who had any children 5y and over engaged in more MVPA than those with only children 4y and under (e.g. % difference in minutes of MVPA: 42.2, 95% CI 18.7 to 70.4 for mothers with only children 5y and over vs those with only children 4y and under). Mothers with 2 or 3+ children did less MVPA than those with 1 child (e.g. 13.9, 1.0 to 25.2 less MVPA for women with 2 children vs those with 1 child).

Conclusions
Mothers with multiple children or any children 4y and under do less MVPA than those with 1 child or only school-aged children. Interventions and policies are needed to support these mothers to increase their time spent doing MVPA, especially considering the additional health benefits associated with this level of intensity of PA.

Key messages
Most mothers are insufficiently physically active to gain the associated health benefits. Interventions to increase MVPA particularly need to target mothers of younger children and those with multiple children.
Managing the pandemic in the reception system for migrants: the Italian experience
Authors: Sisti LG , Cammilli M , Diodati A , Menghini M , Fazioli C , Petrelli A , Di Napoli A , Cavani A , Mirisola C , Costanzo G 
Published: October 2021

Abstract

Issue
Italy represents a well-known European transit and destination country for Migrants and Refugees (M&Rs) with more than 77.000 migrants currently hosted in the reception system. Pandemic did not impact the M&Rs' influx with more than 30.000 disembarked in 2020. In line with the WHO and international organizations alerts to protect the health of M&Rs, Italy included M&Rs in its pandemic response.

Description of the practice
With the mandate of the Ministry of Health and thanks to the collaboration with the Ministry of the Interior and other institutional and governmental bodies, the Italian National Institute for Health, Migration and Poverty developed a comprehensive strategy to protect M&Rs' health in Italy during the COVID-19 pandemic, either into the reception system and outside.

Results
Interim evidence - based operating procedures including instructions regarding the early detection and the management of potential suspected and confirmed COVID-19 cases, from the first arrival throughout the entire reception system path, have been published. A national survey on the incidence of COVID-19 cases in the reception system has been performed in 2020. Dedicated information flows on the incidence of COVID-19 cases at the arrival in Italy and in the reception system and a periodic monitoring of the implementation of the afore-mentioned operating procedures have been established in 2021. Data collected have shown a daily mean incidence ratio lower for migrants hosted in the reception system than for the general population, as well as the same regarding the new COVID-19 cases among newly arrived migrants.

Lessons
The strategy adopted was found to be effective in protecting M&Rs' health during the pandemic. In particular, the Italian reception system has globally shown a good performance in limiting the COVID-19 spread. Moreover, the influx of newly arrived migrants did not represent an additional epidemiological risk in terms of burden of infection.

Key messages
The production of evidence-based procedures and the establishment of effective information flows have proved to be effective in managing and monitoring the pandemic in regards to M&Rs. The Italian reception system has turned to play as a protective factor in limiting the COVID-19 spread and the systematic screening of newly arrived M&Rs did not shown an additional COVID-19 burden.
Impact of COVID-19 on economic and working conditions in Italy. Data from PASSI and PASSI d’Argento
Authors: Possenti V , Minardi V , Contoli B , Lana S , Scardetta P , Masocco M 
Published: October 2021

Abstract

Background
Having affected multiple life aspects globally, the COVID-19 pandemic will generate long-term consequences on productive sector and economy. The two Italian population-based surveillance systems PASSI (18-69yy) and PASSI d'Argento (65+) have annexed a COVID-module to the standard questionnaires' sections to investigate also changes of economic and working conditions related to the COVID-19 crisis.

Methods
We analysed data on a sample of 2,613 PASSI and 2,288 PASSI d'Argento interviews, collected between August and December 2020.

Results
Among adults, 34% refers a worsening of their financial resources because of the COVID-19 crisis: above all if socially deprived people, with many difficulties (52%) or with a low educational level (41%). Despite keeping up working, 31% of employed people worked less due to the COVID crisis, with a lower wage; 5.5% lost the job and a certain number had to give it up. The worsening of economic resources correlates to changes in working conditions due to the pandemic crisis, but the latter did not fully determine the former. Economic losses are more frequent among people in search of employment (52% vs 35% of occupied or 28% of inactive), those who lost their job (76%) or, despite keeping up working, earn less (66%), but interest also individuals who have not undergone changes per the working condition and volume (19%). The association between worsened economic resources and social disadvantage (low education and economic difficulties) is significant, even adjusting for job or wage loss. Even among older persons, a lower but non-negligible quota (16%) declares economic worsening due to the pandemic-related crisis. The percentage triples (29%) on difficulty making ends meet.

Conclusions
Since the analysis of preliminary findings, it emerges how the impact of this crisis is and will not be the same to all, but will emphasize inequalities, at the expense of the most vulnerable individuals, at any age.

Key messages
In Italy, the COVID-19 pandemic has affected the main social determinants of people health because it has worsened economic and working conditions. This crisis is emphasizing health inequalities, at the expense of the most vulnerable individuals, at any age.