bluuebunny/crossref_metadata_2025_split huggingface dataset:
Icarust, a real-time simulator for Oxford Nanopore adaptive sampling
Authors: Munro Rory , Wibowo Satrio , Payne Alexander , Loose Matthew 
Published: March 2024

Abstract

Motivation
Oxford Nanopore Technologies (ONT) sequencers enable real-time generation of sequence data, which allows for concurrent analysis during a run. Adaptive sampling leverages this real-time capability in extremis, rejecting or accepting reads for sequencing based on assessment of the sequence from the start of each read. This functionality is provided by ONT’s software, MinKNOW (Oxford Nanopore Technologies). Designing and developing software to take advantage of adaptive sampling can be costly in terms of sequencing consumables, using precious samples and preparing sequencing libraries. MinKNOW addresses this in part by allowing the replay of previously sequenced runs for testing. However, as we show, the sequencing output only partially changes in response to adaptive sampling instructions. Here we present Icarust, a tool enabling more accurate approximations of sequencing runs. Icarust recreates all the required endpoints of MinKNOW to perform adaptive sampling and writes output compatible with current base-callers and analysis pipelines. Icarust serves nanopore signal simulating a MinION or PromethION flow cell experiment from any reference genome using either R9 or R10 pore models. We show that simulating sequencing runs with Icarust provides a realistic testing and development environment for software exploiting the real-time nature of Nanopore sequencing.

Availability and implementation
All code is open source and freely available here—https://github.com/LooseLab/Icarust. Icarust is implemented in Rust, with a docker container also available. The data underlying this article will be shared on reasonable request to the corresponding author.
Simultaneous Determination of D and L Enantiomers of 2-Hydroxyglutarate by UHPLC–MS/MS Method in Human Biological Fluids and its Clinical Application
Authors: Li Xiaoqing , Bo Yunhai , Le Le , Yang Fen 
Published: March 2024

Abstract
2-hydroxyglutarate has limited abundance in normal tissues but a high level under certain pathologic conditions. To clarify the diagnostic value of two chiral isomers of 2-hydroxyglutarate in plasma and urine of Chinese cancer patients, an ultra-high performance liquid chromatography-tandem mass spectrometric method was developed for simultaneous quantification of D-/L-2-hydroxyglutarate. The selected D-/L-2-hydroxyglutarate-d5 as internal standards were added to samples before the SPE on Waters Oasis® MAX 96-Well plate (30 μm, 60 mg). A derivatization step with (+)-O,O′-diacetyl-L-tartaric anhydride permitted the chromatography separation of D-/L-2-hydroxyglutarate on an ACQUITY UPLC-HSS T3 column (50 × 2.1 mm, i.d. 1.8 μm) with acetonitrile and water (containing 0.1% formic acid and 10 mmol ammonium acetate) as the mobile phase. The calibration curves showed good linearity (R ≥ 0.99) over the concentration ranges of 200–5,000 ng/mL and 500–20,000 ng/mL for analysis of D-/L-2-hydroxyglutarate in plasma and urine samples, respectively. Intra- and inter-run precision were ≤ 12.33%, and the accuracy was within the range of −10.44 to 13.90%. This method was further successfully applied to clinical sample analysis in isocitrate dehydrogenase 1/2 mutated Chinese cancer patients.
The prognostic impact of follow-up cardiac metaiodobenzylguanidine imaging on left ventricular trajectory after acute decompensation
Authors: Kayama Kiyomi , Yamada Takahisa , Seo Masahiro , Watanabe Tetsuya , Morita Takashi , Kawasaki Masato , Kikuchi Atsushi , Kawai Tsutomu , Nakamura Jun , Fukunami Masatake 
Published: March 2024

Abstract

Aims
Cardiac metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with heart failure (HF). Recently, the trajectory of left ventricular ejection fraction (LVEF) has been a focus in patients with reduced LVEF admitted for acute decompensated HF (ADHF). We sought to investigate the prognostic value of follow-up cardiac MIBG imaging in ADHF patients with reduced LVEF in relation to LVEF trajectory.

Methods and results
We prospectively studied 145 ADHF patients with a reduced LVEF of &lt;40%. The cardiac MIBG heart-to-mediastinum ratio (the late HMR) was measured on the delayed image at discharge and at the 6-month follow-up (6FUP). At 6 months after discharge, 54 (37%) patients had complete recovery of LVEF ≥50% (HFcorEF), and 43 (30%) patients had partial recovery of LVEF 40–50% (HFparEF), while the remaining 48 (33%) patients had no functional recovery of LVEF (HFnorEF). The late HMR at the 6FUP in HFcorEF patients was significantly greater than that in HFparEF and HFnorEF patients. During a follow-up period of 4.3 ± 2.6 years, 43 patients had cardiac events, defined as a composite of readmission for worsening HF and cardiac death. Patients with a lower late HMR at the 6FUP had a greater risk of cardiac events than those with a higher late HMR at the 6FUP in the group with recovered LVEF, especially HFparEF, which was not observed in the HFnorEF subgroup.

Conclusion
Follow-up MIBG imaging after discharge could provide additional prognostic information in ADHF patients with recovered left ventricular function.
Improving Administrative Data at Scale: Experimental Evidence on Digital Testing in Indian Schools
Authors: Singh Abhijeet 
Published: March 2024

AbstractLarge-scale student assessments are a cornerstone of proposed educational reforms to improve student achievement from very low levels in low- and middle-income countries. Yet, this promise relies on their presumed reliability. I use direct audit evidence from a large Indian state (Andhra Pradesh) to show that, as currently administered, official learning assessments substantially overstate proficiency and understate the ‘learning crisis’ of low student achievement. In an experiment covering over 2,400 schools, I evaluate whether digital tablet-based testing could reduce distortion. Although paper-based assessments proctored by teachers severely exaggerate achievement, tablet-based assessments closely match independent test data and are much less likely to be flagged for cheating. Furthermore, I use the direct audit-based retest to directly validate existing (indirect) statistical procedures for detecting cheating at scale and establish that it would be feasible to monitor data integrity cheaply and at scale with such methods. Overall, these results suggest that well-designed technology-aided interventions may improve data integrity at scale, without which these learning assessments are unlikely to serve as a catalyst for policy action.
Why High Incentives Cause Repugnance: a Framed Field Experiment
Authors: Stüber Robert 
Published: March 2024

Abstract
Why are high monetary payments prohibited for certain goods, thereby causing shortages in their supply? I conduct (i) a framed field experiment with a general population sample and (ii) a survey experiment with this sample and with ethics committees. In the experiment, participants can prohibit others from being offered money to register as stem-cell donors. I document that, whereas the majority of participants do not respond to changes in the incentives (63%) or become more in favour of the offer with higher incentives (20%), a minority of 17% prohibit high incentives. I show that this minority wants to protect individuals who are persuaded by high incentives. I also show that a lottery scheme reduces their objections to high incentives. Finally, I document that the public is much more supportive of high incentives than are ethics committees.
Exercise therapy for chronic symptomatic peripheral artery disease
Authors: Mazzolai Lucia , Belch Jill , Venermo Maarit , Aboyans Victor , Brodmann Marianne , Bura-Rivière Alessandra , Debus Sebastien , Espinola-Klein Christine , Harwood Amy E , Hawley John A , Lanzi Stefano , Madarič Juraj , Mahé Guillaume , Malatesta Davide , Schlager Oliver , Schmidt-Trucksäss Arno , Seenan Chris , Sillesen Henrik , Tew Garry A , Visonà Adriana 
Published: March 2024

Abstract
All guidelines worldwide strongly recommend exercise as a pillar of the management of patients affected by lower extremity peripheral artery disease (PAD). Exercise therapy in this setting presents different modalities, and a structured programme provides optimal results. This clinical consensus paper is intended for clinicians to promote and assist for the set-up of comprehensive exercise programmes to best advice in patients with symptomatic chronic PAD. Different exercise training protocols specific for patients with PAD are presented. Data on patient assessment and outcome measures are narratively described based on the current best evidence. The document ends by highlighting disparities in access to supervised exercise programmes across Europe and the series of gaps for evidence requiring further research.
Fitness as the organismal performance measure guiding adaptive evolution
Authors: Fromhage Lutz , Jennions Michael D , Myllymaa Lauri , Henshaw Jonathan M 
Published: March 2024

Abstract
A long-standing problem in evolutionary theory is to clarify in what sense (if any) natural selection cumulatively improves the design of organisms. Various concepts, such as fitness and inclusive fitness, have been proposed to resolve this problem. In addition, there have been attempts to replace the original problem with more tractable questions, such as whether a given gene or trait is favored by selection. Here, we ask what theoretical properties the concept fitness should possess to encapsulate the improvement criterion required to talk meaningfully about adaptive evolution. We argue that natural selection tends to shape phenotypes based on the causal properties of individuals and that this tendency is, therefore, best captured by a fitness concept that focuses on these properties. We highlight a fitness concept that meets this role under broad conditions but requires adjustments in our conceptual understanding of adaptive evolution. These adjustments combine elements of Dawkinsian gene selectionism and Egbert Leigh’s “parliament of genes.”
Application and development of a TaqMan-based real-time PCR assay for rapid detection of snakehead vesiculovirus
Authors: Gong Cuiping , Zhu Panpan , Ye Jiaxin , Lou Jianfeng , Zhang Liwen , Liu Xiaodan , Kong Weiguang 
Published: March 2024

Abstract
Snakehead vesiculovirus (SHVV) is one of the primary pathogens responsible for viral diseases in the snakehead fish. A TaqMan-based real-time PCR assay was established for the rapid detection and quantification of SHVV in this study. Specific primers and fluorescent probes were designed for phosphoprotein (P) gene, and after optimizing the reaction conditions, the results indicated that the detection limit of this method could reach 37.1 copies, representing a 100-fold increase in detection sensitivity compared to RT-PCR. The specificity testing results revealed that this method exhibited no cross-reactivity with ISKNV, LMBV, RSIV, RGNNV, GCRV, and CyHV-2. Repetition experiments demonstrated that both intra-batch and inter-batch coefficients of variation were not higher than 1.66%. Through in vitro infection experiments monitoring the quantitative changes of SHVV in different tissues, the results indicated that the liver and spleen exhibited the highest viral load at 3 poi. The TaqMan-based real-time PCR method established in this study exhibits high sensitivity, excellent specificity, and strong reproducibility. It can be employed for rapid detection and viral load monitoring of SHVV, thus providing a robust tool for the clinical diagnosis and pathogen research of SHVV.
Interactions between commensal Enterococcus faecium and Enterococcus lactis and clinical isolates of Enterococcus faecium
Authors: Wagner Theresa Maria , Pöntinen Anna Kaarina , Fenzel Carolin Kornelia , Engi Daniel , Janice Jessin , Almeida-Santos Ana C , Tedim Ana P , Freitas Ana R , Peixe Luísa , van Schaik Willem , Johannessen Mona , Hegstad Kristin 
Published: March 2024

Abstract
Enterococcus faecium (Efm) is a versatile pathogen, responsible for multidrug-resistant infections, especially in hospitalized immunocompromised patients. Its population structure has been characterized by diverse clades (A1, A2, and B (reclassified as E. lactis (Ela)), adapted to different environments, and distinguished by their resistomes and virulomes. These features only partially explain the predominance of clade A1 strains in nosocomial infections. We investigated in vitro interaction of 50 clinical isolates (clade A1 Efm) against 75 commensal faecal isolates from healthy humans (25 clade A2 Efm and 50 Ela). Only 36% of the commensal isolates inhibited clinical isolates, while 76% of the clinical isolates inhibited commensal isolates. The most apparent overall differences in inhibition patterns were presented between clades. The inhibitory activity was mainly mediated by secreted, proteinaceous, heat-stable compounds, likely indicating an involvement of bacteriocins. A custom-made database targeting 76 Bacillota bacteriocins was used to reveal bacteriocins in the genomes. Our systematic screening of the interactions between nosocomial and commensal Efm and Ela on a large scale suggests that, in a clinical setting, nosocomial strains not only have an advantage over commensal strains due to their possession of AMR genes, virulence factors, and resilience but also inhibit the growth of commensal strains.
Parental thermal environment controls the offspring phenotype in Brook charr (Salvelinus fontinalis): insights from a transcriptomic study
Authors: Banousse Ghizlane , Normandeau Eric , Semeniuk Christina , Bernatchez Louis , Audet Céline 
Published: March 2024

Abstract
Brook charr is a cold-water species which is highly sensitive to increased water temperatures, such as those associated with climate change. Environmental variation can potentially induce phenotypic changes that are inherited across generations, for instance, via epigenetic mechanisms. Here, we tested whether parental thermal regimes (intergenerational plasticity) and offspring-rearing temperatures (within-generational plasticity) modify the brain transcriptome of Brook charr progeny (fry stage). Parents were exposed to either cold or warm temperatures during final gonad maturation and their progeny were reared at 5 or 8 °C during the first stages of development. Illumina Novaseq6000 was used to sequence the brain transcriptome at the yolk sac resorption stage. The number of differentially expressed genes was very low when comparing fry reared at different temperatures (79 differentially expressed genes). In contrast, 9,050 differentially expressed genes were significantly differentially expressed between fry issued from parents exposed to either cold or warm temperatures. There was a significant downregulation of processes related to neural and synaptic activity in fry originating from the warm parental group vs fry from the cold parental one. We also observed significant upregulation of DNA methylation genes and of the most salient processes associated with compensation to warming, such as metabolism, cellular response to stress, and adaptive immunity.
Early-Life Exposure to War and Later-Life Physical Functional Health
Authors: Haas Steven A , Ramirez Daniel 
Published: March 2024

Abstract

Objectives
A growing body of research shows that early-life exposure to war has adverse effects on later-life health. Research has emphasized the importance of exposure timing implicating domain-specific developmental processes and associated critical/sensitive periods. This study looks at the impacts of early childhood war exposure and the repercussions for later-life physical and functional health, with a focus on time of exposure as a source of variability.

Methods
We use residential histories from the Survey of Health Ageing, and Retirement in Europe linked to external data on the location and timing of hostilities to examine the impact of early-life exposure to World War II on later-life physical and functional health.

Results
Exposure to war increases the risk of objective (grip strength, chair rise, and peak expiratory flow) and self-reported (mobility limitations and activities of daily living) measures of functional health. Effects are especially pronounced for those born during the war and for those with more prolonged exposures. There is little evidence that the impact of war is mediated by war-related hardships, socioeconomic conditions, health behaviors, or adult chronic disease.

Discussion
Our results suggest early-life exposure to war has a lasting impact on physical functional health. Exposure appears to largely operate via direct effects, indicative of altered initial development of physical capacity in early life. Because exposure was so pervasive among some cohorts of older individuals, understanding the health of present older European populations requires wrestling with the residual consequences of wartime exposure at the start of their lives.
New Genomic Techniques and Intellectual Property Law: Challenges and Solutions for the Plant Breeding Sector ‒ Position Statement of the Max Planck Institute for Innovation and Competition
Authors: Kim Daria , Kock Michael A , Lamping Matthias , Batista Pedro Henrique D , Hilty Reto M , Slowinski Peter R , Steinhart Miriam 
Published: March 2024

Abstract
On 5 July 2023, the European Commission proposed a regulation aiming to ease the requirements for the marketing authorisation of plants obtained through certain new genomic techniques (NGTs) within the European Union (EU). While NGTs are expected to become more attractive to breeders and farmers, the complexity of the intellectual property (IP) landscape surrounding these techniques and resulting products may negatively impact technology diffusion and innovation. Given numerous concerns related to IP protection for NGTs and NGT-derived plants, this Position Statement from the Max Planck Institute for Innovation and Competition presents a set of policy recommendations for facilitating access to and utilisation of IP-protected NGTs and NGT-derived products in the breeding sector.
Microfluidic sperm sorting selects a subpopulation of high-quality sperm with a higher potential for fertilization
Authors: Sheibak Nadia , Amjadi Fatemehsadat , Shamloo Amir , Zarei Fatemeh , Zandieh Zahra 
Published: March 2024

Abstract

STUDY QUESTION
Is a microfluidic sperm sorter (MSS) able to select higher quality sperm compared to conventional methods?

SUMMARY ANSWER
The MSS selects sperm with improved parameters, lower DNA fragmentation, and higher fertilizing potential.

WHAT IS KNOWN ALREADY
To date, the few studies that have compared microfluidics sperm selection with conventional methods have used heterogeneous study population and have lacked molecular investigations.

STUDY DESIGN, SIZE, DURATION
The efficiency of a newly designed MSS in isolating high-quality sperm was compared to the density-gradient centrifugation (DGC) and swim-up (SU) methods, using 100 semen samples in two groups, during 2023–2024.

PARTICIPANTS/MATERIALS, SETTING, METHODS
Semen specimens from 50 normozoospermic and 50 non-normozoospermic men were sorted using MSS, DGC, and SU methods to compare parameters related to the quality and fertilizing potential of sperm. The fertilizing potential of sperm was determined by measurement of phospholipase C zeta (PLCζ) and post-acrosomal sheath WW domain-binding protein (PAWP) expression using flow cytometry, and the chromatin dispersion test was used to assess sperm DNA damage.

MAIN RESULTS AND THE ROLE OF CHANCE
In both normozoospermic and non-normozoospermic groups, the MSS-selected sperm with the highest progressive motility, PLCζ positive expression and PLCζ and PAWP fluorescence intensity the lowest non-progressive motility, and minimal DNA fragmentation, compared to sperm selected by DGC and SU methods (P &lt; 0.05).

LIMITATION, REASONS FOR CAUTION
The major limitations of our study were the low yield of sperm in the MSS chips and intentional exclusion of severe male factor infertility to yield a sufficient sperm count for molecular experiments; thus testing with severe oligozoospermic semen and samples with low count and motility is still required. In addition, due to ethical considerations, at present, it was impossible to use the sperm achieved from MSS in the clinic to assess the fertilization rate and further outcomes.

WIDER IMPLICATIONS OF THE FINDINGS
Our research presents new evidence that microfluidic sperm sorting may result in the selection of high-quality sperm from raw semen. This novel technology might be a key to improving clinical outcomes of assisted reproduction in infertile patients.

STUDY FUNDING/COMPETING INTEREST(S)
The study is funded by the Iran University of Medical Sciences and no competing interest exists.

TRIAL REGISTRATION NUMBER
N/A.
Crisis Leadership in the Time of Covid: Effects of Personality Traits on Response Speed
Authors: Oktay Sibel 
Published: March 2024

Abstract
Why were some countries faster than others at introducing COVID-19 mitigation policies? Existing research shows that leaders are central to defining and making sense of crises, which then shapes their governments’ crisis response. I argue that crisis-sense-making depends on leaders’ personality traits pertaining to how they perceive their power status, collect and process information, and interact with their environment, subsequently influencing their governments’ crisis response speed. I test this argument in the context of the European experience with COVID-19, combining an original Leadership Traits Analysis dataset of thirty-two leaders with the Oxford COVID-19 Government Response Tracker data. I show that leaders who were highly self-confident or exhibited a tendency to challenge constraints were significantly slower at introducing pandemic mitigation policies. Leaders who were open to information were significantly faster to do so. I also show that policy emulation between countries over time dissipated the slowing effects of the leaders’ need for power and conceptual complexity on response speed. The results present new and systematic evidence on how leader personality shaped pandemic policy-making, contributing to the literature on crisis policy-making and political leadership. They also offer science advisors food for thought on how to communicate with leaders.