bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving 10-year cardiovascular risk prediction in apparently healthy people: flexible addition of risk modifiers on top of SCORE2
Authors: Hageman Steven H J , Petitjean Carmen , Pennells Lisa , Kaptoge Stephen , Pajouheshnia Romin , Tillmann Taavi , Blaha Michael J , McClelland Robyn L , Matsushita Kunihiro , Nambi Vijay , Klungel Olaf H , Souverein Patrick C , van der Schouw Yvonne T , Verschuren W M Monique , Lehmann Nils , Erbel Raimund , Jöckel Karl-Heinz , Di Angelantonio Emanuele , Visseren Frank L J , Dorresteijn Jannick A N 
Published: June 2023

Abstract

Aims
In clinical practice, factors associated with cardiovascular disease (CVD) like albuminuria, education level, or coronary artery calcium (CAC) are often known, but not incorporated in cardiovascular risk prediction models. The aims of the current study were to evaluate a methodology for the flexible addition of risk modifying characteristics on top of SCORE2 and to quantify the added value of several clinically relevant risk modifying characteristics.

Methods and results
Individuals without previous CVD or DM were included from the UK Biobank; Atherosclerosis Risk in Communities (ARIC); Multi-Ethnic Study of Atherosclerosis (MESA); European Prospective Investigation into Cancer, The Netherlands (EPIC-NL); and Heinz Nixdorf Recall (HNR) studies (n = 409 757) in whom 16 166 CVD events and 19 149 non-cardiovascular deaths were observed over exactly 10.0 years of follow-up. The effect of each possible risk modifying characteristic was derived using competing risk-adjusted Fine and Gray models. The risk modifying characteristics were applied to individual predictions with a flexible method using the population prevalence and the subdistribution hazard ratio (SHR) of the relevant predictor. Risk modifying characteristics that increased discrimination most were CAC percentile with 0.0198 [95% confidence interval (CI) 0.0115; 0.0281] and hs-Troponin-T with 0.0100 (95% CI 0.0063; 0.0137). External validation was performed in the Clinical Practice Research Datalink (CPRD) cohort (UK, n = 518 015, 12 675 CVD events). Adjustment of SCORE2-predicted risks with both single and multiple risk modifiers did not negatively affect calibration and led to a modest increase in discrimination [0.740 (95% CI 0.736–0.745) vs. unimproved SCORE2 risk C-index 0.737 (95% CI 0.732–0.741)].

Conclusion
The current paper presents a method on how to integrate possible risk modifying characteristics that are not included in existing CVD risk models for the prediction of CVD event risk in apparently healthy people. This flexible methodology improves the accuracy of predicted risks and increases applicability of prediction models for individuals with additional risk known modifiers.
Community factors and excess mortality in the COVID-19 pandemic in England, Italy and Sweden
Authors: Parkes Brandon , Stafoggia Massimo , Fecht Daniela , Davies Bethan , Bonander Carl , de’ Donato Francesca , Michelozzi Paola , Piel Frédéric B , Strömberg Ulf , Blangiardo Marta 
Published: June 2023

Abstract

Background
Analyses of coronavirus disease 19 suggest specific risk factors make communities more or less vulnerable to pandemic-related deaths within countries. What is unclear is whether the characteristics affecting vulnerability of small communities within countries produce similar patterns of excess mortality across countries with different demographics and public health responses to the pandemic. Our aim is to quantify community-level variations in excess mortality within England, Italy and Sweden and identify how such spatial variability was driven by community-level characteristics.

Methods
We applied a two-stage Bayesian model to quantify inequalities in excess mortality in people aged 40 years and older at the community level in England, Italy and Sweden during the first year of the pandemic (March 2020–February 2021). We used community characteristics measuring deprivation, air pollution, living conditions, population density and movement of people as covariates to quantify their associations with excess mortality.

Results
We found just under half of communities in England (48.1%) and Italy (45.8%) had an excess mortality of over 300 per 100 000 males over the age of 40, while for Sweden that covered 23.1% of communities. We showed that deprivation is a strong predictor of excess mortality across the three countries, and communities with high levels of overcrowding were associated with higher excess mortality in England and Sweden.

Conclusion
These results highlight some international similarities in factors affecting mortality that will help policy makers target public health measures to increase resilience to the mortality impacts of this and future pandemics.
Age and sex differences in cause-specific excess mortality and years of life lost associated with COVID-19 infection in the Swedish population
Authors: Lundberg Christina E , Santosa Ailiana , Björk Jonas , Brandén Maria , Cronie Ottmar , Lindgren Martin , Edqvist Jon , Åberg Maria , Adiels Martin , Rosengren Annika 
Published: June 2023

AbstractBackgroundEstimating excess mortality and years of life lost (YLL) attributed to coronavirus disease 19 (COVID-19) infection provides a comprehensive picture of the mortality burden on society. We aimed to estimate the impact of the COVID-19 pandemic on age- and sex-specific excess mortality and YLL in Sweden during the first 17 months of the pandemic.MethodsIn this population-based observational study, we calculated age- and sex-specific excess all-cause mortality and excess YLL during 2020 and the first 5 months of 2021 and cause-specific death [deaths from cardiovascular disease (CVD), cancer, other causes and deaths excluding COVID-19] in 2020 compared with an average baseline for 2017–19 in the whole Swedish population.ResultsCOVID-19 deaths contributed 9.9% of total deaths (98 441 deaths, 960 305 YLL) in 2020, accounting for 75 151 YLL (7.7 YLL/death). There were 2672 (5.7%) and 1408 (3.0%) excess deaths, and 19 141 (3.8%) and 3596 (0.8%) excess YLL in men and women, respectively. Men aged 65–110 years and women aged 75–110 years were the greatest contributors. Fewer deaths and YLL from CVD, cancer and other causes were observed in 2020 compared with the baseline adjusted to the population size in 2020.ConclusionsCompared with the baseline, excess mortality and YLL from all causes were experienced in Sweden during 2020, with a higher excess observed in men than in women, indicating that more men died at a younger age while more women died at older ages than expected. A notable reduction in deaths and YLL due to CVD suggests a displacement effect from CVD to COVID-19.
Automatic Differentiation is no Panacea for Phylogenetic Gradient Computation
Authors: Fourment Mathieu , Swanepoel Christiaan J , Galloway Jared G , Ji Xiang , Gangavarapu Karthik , Suchard Marc A , Matsen IV Frederick A 
Published: June 2023

Abstract
Gradients of probabilistic model likelihoods with respect to their parameters are essential for modern computational statistics and machine learning. These calculations are readily available for arbitrary models via “automatic differentiation” implemented in general-purpose machine-learning libraries such as TensorFlow and PyTorch. Although these libraries are highly optimized, it is not clear if their general-purpose nature will limit their algorithmic complexity or implementation speed for the phylogenetic case compared to phylogenetics-specific code. In this paper, we compare six gradient implementations of the phylogenetic likelihood functions, in isolation and also as part of a variational inference procedure. We find that although automatic differentiation can scale approximately linearly in tree size, it is much slower than the carefully implemented gradient calculation for tree likelihood and ratio transformation operations. We conclude that a mixed approach combining phylogenetic libraries with machine learning libraries will provide the optimal combination of speed and model flexibility moving forward.
Trans reproduction: Continuity, cis-normativity, and trans inequality in law
Authors: Sørlie Anniken 
Published: June 2023

Abstract
In recent years, increasing numbers of jurisdictions are abolishing sterilization requirements for legal gender recognition and are introducing self-declared change of legal gender. The abolition of this requirement leads to a change in the reproductive capacities of legal men and legal women, enabling legal men to become pregnant and to give birth, and legal women to beget children. The change in the reproductive capacities of the legal genders leads to biopolitical questions about how states do and should govern trans reproduction after decades of state-regulated sterilization. This article uses the situation in Norway to explore the regulation of trans reproduction and aims to explain why trans people’s reproductive rights are lesser than those of cis people. It first investigates the Norwegian regulation of medically assisted reproduction and how it applies to people who have changed their legal gender. It shows that trans people are excluded from accessing medically assisted reproduction because their legal gender does not fit the conceptions of reproduction and gender under the Norwegian Biotechnology Act. Second, the article explores why trans people’s reproductive rights are limited, and argues that the law is based on cis-normative assumptions about reproduction, pregnancy, and the desire to become pregnant. Such assumptions, it is argued, permeate the law and lead to discrimination against trans people. The Norwegian legislature has not given any reasons as to why trans people’s reproductive rights are limited. The article demonstrates that although the sterilization requirement for legal gender recognition is abolished, the law continues to concentrate on cis realities and to restrict trans people’s ability to form a family with children.
Grounded in reality: artificial intelligence in medical education
Authors: Krive Jacob , Isola Miriam , Chang Linda , Patel Tushar , Anderson Max , Sreedhar Radhika 
Published: June 2023

Abstract

Background
In a recent survey, medical students expressed eagerness to acquire competencies in the use of artificial intelligence (AI) in medicine. It is time that undergraduate medical education takes the lead in helping students develop these competencies. We propose a solution that integrates competency-driven AI instruction in medical school curriculum.

Methods
We applied constructivist and backwards design principles to design online learning assignments simulating the real-world work done in the healthcare industry. Our innovative approach assumed no technical background for students, yet addressed the need for training clinicians to be ready to practice in the new digital patient care environment. This modular 4-week AI course was implemented in 2019, integrating AI with evidence-based medicine, pathology, pharmacology, tele-monitoring, quality improvement, value-based care, and patient safety.

Results
This educational innovation was tested in 2 cohorts of fourth year medical students who demonstrated an improvement in knowledge with an average quiz score of 97% and in skills with an average application assignment score of 89%. Weekly reflections revealed how students learned to transition from theory to practice of AI and how these concepts might apply to their upcoming residency training programs and future medical practice.

Conclusions
We present an innovative product that achieves the objective of competency-based education of students regarding the role of AI in medicine. This course can be integrated in the preclinical years with a focus on foundational knowledge, vocabulary, and concepts, and in clinical years with a focus on application of core knowledge to real-world scenarios.
Biological traits of the zoophytophagous predatory mirid Nesidiocoris poppiusi (Heteroptera: Miridae), a candidate biocontrol agent in China
Authors: Wang Lili , Zhang Yibo , Huang Ningxing , Di Ning , Tian Lixia , Zhu Zhengyang , Liu Junxiu , Wang Su 
Published: June 2023

Abstract
Mirid predators are increasingly used in biological control of multiple greenhouse crops pests. However, due to great morphological similarity and tiny body size, some mirid predators have been largely confused with their allied species. Nesidiocoris tenuis Reuter as a commercial mirid predator was confused largely with Nesidiocoris poppiusi Carvalho in China. To evaluate the biocontrol potential of N. poppiusi, its biological traits and the functional response to Bemisia tabaci Gennadius were studied compared with N. tenuis under laboratory conditions. The results showed that no significant differences of the developmental times from the first instar to adult stages between the 2 mirids fed on Corcyra cephalonica Stainton eggs were observed, while N. poppiusi had better population growth parameters than N. tenuis. Under the condition with prey, both female and male of N. poppiusi lived significantly longer than those of N. tenuis. It could lay 74.0 eggs, which was significantly higher than that of N. tenuis (30.2 eggs). Under the condition without prey, both N. poppiusi and N. tenuis couldn't complete development to adulthood on tomato, tobacco, muskmelon, and cabbage leaves, however, tobacco and tomato were more suitable than the other 2 plants. A type II functional response was observed for both males and females of the 2 predators. Nesidiocoris poppiusi females consumed significantly more B. tabaci pupae than N. tenuis when prey densities were large than 30. Our results indicated that N. poppiusi could be a promising candidate for biological control of B. tabaci.
Lazarus stars: numerical investigations of stellar evolution with star-lifting as a life extension strategy
Authors: Scoggins Matthew T , Kipping David 
Published: June 2023

ABSTRACT
The aging and gradual brightening of the Sun will challenge Earth’s habitability in the next few billion years. If life exists elsewhere in the Universe, the aging of its host star similarly poses an existential threat. One solution, which we dub a Lazarus star, is for an advanced civilization to remove (or star-lift) mass from their host star at a rate that offsets the increase in luminosity, keeping the flux on the habitable planet(s) constant and extending the lifetime of their star. While this idea has existed since 1985 when it was first proposed by Criswell, numerical investigations of star-lifting have been lacking. Here, we use the stellar evolution code mesa to find mass versus age and $\dot{M}$ versus age relations that would hold the flux on surrounding planets constant. We explore initial mass ranging from $0.2$ to $1.2\, {\rm M}_{\odot }$. For most stars with a mass initially below about 0.4 M⊙, we find that star-lifting increases their main-sequence lifetimes up to 500 Gyr until they approach the hydrogen burning limit and star-lifting is no longer possible. For more massive stars, star-lifting increases main-sequence lifetimes by 1–100 Gyr, though they still enter the red-giant phase. For example, a Sun-like star has a main-sequence lifetime that can be increased by up to 3 Gyr. This requires a mass-loss rate of about $0.05\, {\rm \mathit{ M}}_{\mathrm{Ceres}}$ per year. We compare star-lifting to other survival strategies and briefly discuss methods for detecting these engineered stars.
A different view of wind in X-ray binaries: the accretion disc corona source 2S 0921-630
Authors: Tomaru Ryota , Done Chris , Odaka Hirokazu , Tanimoto Atsushi 
Published: June 2023

ABSTRACT
Accretion disc coronae (ADC) sources are very high inclination neutron star or black hole binaries, where the outer accretion flow blocks a direct view of the central source. The weak observed X-ray emission is instead produced mainly by scattering of the intrinsic radiation from highly ionized gas surrounding the source, the ADC. However, the origin of this scattering material is still under debate. We use the ADC source 2S 0921-630 (V395 Car) to test whether it is consistent with a thermal-radiative wind produced by the central X-ray source illuminating and puffing up the outer disc. This wind is clearly visible in blueshifted absorption lines in less highly inclined systems, where the source is seen directly through this material. Using the phenomenological photoionized plasma model, we first characterize the parameter that drives emission lines observed in 2S0921 in XMM–Newton and Chandra data. Following this, we run the Monte Carlo radiation transfer simulation to get scattered/reprocessed emissions in the wind, with the density and velocity structure obtained from the previous work. Our model agrees with all the wind emission lines in the Chandra high and medium energy grating spectra for an intrinsic source luminosity of L &gt; 0.2 LEdd. This result strongly favours thermal-radiative winds as the origin of the ADC. We also show how high-resolution spectra via microcalorimeters can provide a definitive test by detecting blueshifted absorption lines.
Multiomic analysis of cohesin reveals that ZBTB transcription factors contribute to chromatin interactions
Authors: Wang Rui , Xu Qiqin , Wang Chenlu , Tian Kai , Wang Hui , Ji Xiong 
Published: June 2023

Abstract
One bottleneck in understanding the principles of 3D chromatin structures is caused by the paucity of known regulators. Cohesin is essential for 3D chromatin organization, and its interacting partners are candidate regulators. Here, we performed proteomic profiling of the cohesin in chromatin and identified transcription factors, RNA-binding proteins and chromatin regulators associated with cohesin. Acute protein degradation followed by time-series genomic binding quantitation and BAT Hi-C analysis were conducted, and the results showed that the transcription factor ZBTB21 contributes to cohesin chromatin binding, 3D chromatin interactions and transcriptional repression. Strikingly, multiomic analyses revealed that the other four ZBTB factors interacted with cohesin, and double degradation of ZBTB21 and ZBTB7B led to a further decrease in cohesin chromatin occupancy. We propose that multiple ZBTB transcription factors orchestrate the chromatin binding of cohesin to regulate chromatin interactions, and we provide a catalog of many additional proteins associated with cohesin that warrant further investigation.
Mechanistic insight into AP-endonuclease 1 cleavage of abasic sites at stalled replication fork mimics
Authors: Hoitsma Nicole M , Norris Jessica , Khoang Thu H , Kaushik Vikas , Chadda Rahul , Antony Edwin , Hedglin Mark , Freudenthal Bret D 
Published: June 2023

Abstract
Many types of damage, including abasic sites, block replicative DNA polymerases causing replication fork uncoupling and generating ssDNA. AP-Endonuclease 1 (APE1) has been shown to cleave abasic sites in ssDNA. Importantly, APE1 cleavage of ssDNA at a replication fork has significant biological implications by generating double strand breaks that could collapse the replication fork. Despite this, the molecular basis and efficiency of APE1 processing abasic sites at replication forks remain elusive. Here, we investigate APE1 cleavage of abasic substrates that mimic APE1 interactions at stalled replication forks or gaps. We determine that APE1 has robust activity on these substrates, like dsDNA, and report rates for cleavage and product release. X-ray structures visualize the APE1 active site, highlighting an analogous mechanism is used to process ssDNA substrates as canonical APE1 activity on dsDNA. However, mutational analysis reveals R177 to be uniquely critical for the APE1 ssDNA cleavage mechanism. Additionally, we investigate the interplay between APE1 and Replication Protein A (RPA), the major ssDNA-binding protein at replication forks, revealing that APE1 can cleave an abasic site while RPA is still bound to the DNA. Together, this work provides molecular level insights into abasic ssDNA processing by APE1, including the presence of RPA.
Using Typhoid Conjugate Vaccines to Prevent Disease, Promote Health Equity, and Counter Drug-Resistant Typhoid Fever
Authors: Nampota-Nkomba Nginache , Carey Megan E , Jamka Leslie P , Fecteau Natalie , Neuzil Kathleen M 
Published: June 2023

Abstract
Typhoid fever is a serious disease that disproportionately impacts children in low-resource settings in sub-Saharan Africa, South and Southeast Asia, and the Western Pacific. The prevalence of antimicrobial-resistant strains of S. Typhi continue to increase worldwide. Two safe, effective, and cost-effective typhoid conjugate vaccines (TCVs) are World Health Organization-prequalified for the prevention of typhoid fever in children as young as 6 months. Typhoid conjugate vaccines have proven effectiveness in preventing drug-resistant S. Typhi and have been deployed successfully in outbreak response and routine immunization scenarios. Broad and equitable distribution of TCVs is essential to combat the spread and potentially devastating consequences of typhoid fever. It is vital to empower decision-makers in typhoid-endemic countries to introduce TCVs and for leaders to embrace this critical tool to prevent typhoid fever, slow the spread of drug-resistant S. Typhi strains, promote health equity, and save lives.
Informed consent practices in clinical research: present and future
Authors: Jawa Natasha A , Boyd J Gordon , Maslove David M , Scott Stephen H , Silver Samuel A 
Published: June 2023

Abstract
Clinical research must balance the need for ambitious recruitment with protecting participants’ autonomy; a requirement of which is informed consent. Despite efforts to improve the informed consent process, participants are seldom provided sufficient information regarding research, hindering their ability to make informed decisions. These issues are particularly pervasive among patients experiencing acute illness or neurological impairment, both of which may impede their capacity to provide consent. There is a critical need to understand the components, requirements, and methods of obtaining true informed consent to achieve the vast numbers required for meaningful research. This paper provides a comprehensive review of the tenets underlying informed consent in research, including the assessment of capacity to consent, considerations for patients unable to consent, when to seek consent from substitute decision-makers, and consent under special circumstances. Various methods for obtaining informed consent are addressed, along with strategies for balancing recruitment and consent.