bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intertemporal choice reflects value comparison rather than self-control: insights from confidence judgements
Authors: Bulley Adam , Lempert Karolina M. , Conwell Colin , Irish Muireann , Schacter Daniel L. 
Published: October 2022

Intertemporal decision-making has long been assumed to measure self-control, with prominent theories treating choices of smaller, sooner rewards as failed attempts to override immediate temptation. If this view is correct, people should be more confident in their intertemporal decisions when they ‘successfully’ delay gratification than when they do not. In two pre-registered experiments with built-in replication, adult participants (n= 117) made monetary intertemporal choices and rated their confidence in having made the right decisions. Contrary to assumptions of the self-control account, confidence was not higher when participants chose delayed rewards. Rather, participants were more confident in their decisions when possible rewards were further apart in time-discounted subjective value, closer to the present, and larger in magnitude. Demonstrating metacognitive insight, participants were more confident in decisions that better aligned with their separate valuation of possible rewards. Decisions made with less confidence were more prone to changes-of-mind and more susceptible to a patience-enhancing manipulation. Together, our results establish that confidence in intertemporal choice tracks uncertainty in estimating and comparing the value of possible rewards—just as it does in decisions unrelated to self-control. Our findings challenge self-control views and instead cast intertemporal choice as a form of value-based decision-making about future possibilities.This article is part of the theme issue ‘Thinking about possibilities: mechanisms, ontogeny, functions and phylogeny’.
What would have happened? Counterfactuals, hypotheticals and causal judgements
Authors: Gerstenberg Tobias 
Published: October 2022

How do people make causal judgements? In this paper, I show that counterfactual simulations are necessary for explaining causal judgements about events, and that hypotheticals do not suffice. In two experiments, participants viewed video clips of dynamic interactions between billiard balls. In Experiment 1, participants either made hypothetical judgements about whether ball Bwould gothrough the gate if ball A were not present in the scene, or counterfactual judgements about whether ball Bwould have gonethrough the gate if ball A had not been present. Because the clips featured a block in front of the gate that sometimes moved and sometimes stayed put, hypothetical and counterfactual judgements came apart. A computational model that evaluates hypotheticals and counterfactuals by running noisy physical simulations accurately captured participants’ judgements. In Experiment 2, participants judged whether ball A caused ball B to go through the gate. The results showed a tight fit between counterfactual and causal judgements, whereas hypotheticals did not predict causal judgements. I discuss the implications of this work for theories of causality, and for studying the development of counterfactual thinking in children.This article is part of the theme issue ‘Thinking about possibilities: mechanisms, ontogeny, functions and phylogeny’.
Verbal autopsy analysis of childhood deaths in rural Gambia
Authors: Wutor Baleng Mahama , Osei Isaac , Galega Lobga Babila , Ezeani Esu , Adefila Williams , Hossain Ilias , Sarwar Golam , Mackenzie Grant 
Published: October 2022

AbstractBackgroundIn low-resource settings, it is challenging to ascertain the burden and causes of under-5 mortality as many deaths occur outside health facilities. Verbal autopsy (VA) is an important tool that provides data on causes of death in communities with limited access to health care. We aimed to determine the causes of childhood deaths by VA in rural Gambia.MethodologyWe used WHO standard questionnaires to conduct VAs for deaths under-5 years of age in the Basse and Fuladu West Health and Demographic Surveillance Systems in rural Gambia between September 01, 2019, and December 31, 2021. Two physicians assigned a cause of death and discordant diagnoses were resolved by consensus. Causes of death were classified using the International Classification of Disease 10th edition codes.ResultsVAs were conducted for 89% (647/727) of deaths. Of these deaths, 49.5% (n=319) occurred at home, 50.1% (n=324) in females, 37.1% (n=240) in neonates, and 27.1% (n=175) in infants aged 1-11 months. Outside the neonatal period, pneumonia (27.0%, n=110), diarrhoeal diseases (23.3%, n=95), and sepsis (21.6%, n=88) were the commonest primary causes of death. In the neonatal period, unspecified perinatal causes of death (29.6%, n=71), birth asphyxia (23.8%, n=57) and prematurity/low birth weight (17.1%, n=41) were the commonest causes. Severe malnutrition (28.6%, n=185), unspecified perinatal deaths (10.7%, n=69), pneumonia (10.2%, n=66), and prematurity/low birth weight (10.2%, n=66) were the commonest underlying causes of death.ConclusionAccording to VA analysis, half of deaths amongst children under-5 in rural Gambia occur at home. Pneumonia, diarrhoea, and sepsis, and the underlying cause of severe malnutrition, as well as birth asphyxia in neonates, remain the predominant causes of child mortality in rural Gambia. Improved health care and health-seeking behaviour may reduce childhood deaths in rural Gambia.
The relative contribution of COVID-19 infection versus COVID-19 related occupational stressors to insomnia in healthcare workers
Authors: Hendrickson Rebecca C. , McCall Catherine A. , Rosser Aaron F. , Pagulayan Kathleen F. , Chang Bernard P. , Sano Ellen D. , Thomas Ronald G. , Raskind Murray A. 
Published: October 2022

AbstractObjective/BackgroundHealthcare workers have experienced high rates of psychiatric symptom burden and occupational attrition during the COVID-19 pandemic. Identifying contributory factors can inform prevention and mitigation measures. Here, we explore the potential contributions of occupational stressors vs COVID-19 infection to insomnia symptoms in US healthcare workers.Patients/MethodsAn online self-report survey was collected between September 2020 and July 2022 from N=594 US healthcare workers, with longitudinal follow-up up to 9 months. Assessments included the Insomnia Severity Index (ISI), the PTSD Checklist for DSM-5 (PCL-5), and a 13-item scale assessing COVID-19 related occupational stressors.ResultsInsomnia was common (45% of participants reported at least moderate and 9.2% reported severe symptoms at one or more timepoint) and significantly associated with difficulty completing work-related tasks, increased likelihood of occupational attrition, and thoughts of suicide or self-harm (all p<.0001). In multivariable regression with age, gender, and family COVID-19 history as covariates, past two-week COVID-related occupational stressors, peak COVID-related occupational stressors, and personal history of COVID-19 infection were all significantly related to past two-week ISI scores (β=1.7±0.14SE, β=0.08±0.03, and β=0.69±0.22 respectively). Although similar results were found for the PCL-5, when ISI and PCL-5 items were separated by factor, COVID-19 infection was significantly related only to the factor consisting of sleep-related items.ConclusionsBoth recent occupational stress and personal history of COVID-19 infection were significantly associated with insomnia in healthcare workers. These results suggest that both addressing occupational stressors and reducing rates of COVID-19 infection are important to protect healthcare workers and the healthcare workforce.
Confinement or internment? Aeromedical retrieval of pregnant people in labour: A retrospective observational study
Authors: Honan Bridget , Spring Breeanna , Gardiner Fergus William , Durup Cheryl , Venkatesh Ajay , McInnes Jessica , Schultz Rebecca , Ullah Shahid , Johnson Richard 
Published: October 2022

AbstractIntroductionThe aim of this study was to describe the characteristics and outcomes of remote-dwelling pregnant people with threatened labour referred for aeromedical retrieval to a regional birthing centre, as well as factors associated with birth within 48 hours.MethodsThis was a retrospective observational study of all pregnant people in the remote Central Australian region referred to the Medical Retrieval Consultation and Coordination Centre for labour >23 weeks gestation, between 12 February 2018 – 12 February 2020. Data was extracted manually from written medical records on maternal, neonatal and retrieval mission characteristics. Univariate and multivariate statistical analysis was performed.ResultsThere were 116 people referred for retrieval for labour. There were no births during transport and less than half of the cases in this cohort resulted in birth within 48 hours of retrieval. Tocolysis was frequently used. Predictors of birth with 48 hours were cervical dilatation 5cm or more, preterm gestational age and ruptured membranes in the univariate analysis. Nearly one-third of this cohort required intervention or had complications during birth.DiscussionBirth during transport for threatened labour did not occur in this cohort, and more than half of retrievals did not result in birth within 48 hours, however the high risk of birth complications may offset any benefit of avoiding aeromedical transport from remote regions. Retrieval clinicians should have a lower threshold for urgent transfer in cases of ruptured membranes, cervical dilatation of 5cm or more, or gestational age is less than 37 weeks.
Toblerone: detecting exon deletion events in cancer using RNA-seq
Authors: Lonsdale Andrew , Halman Andreas , Brown Lauren M , Kosasih Hansen J , Ekert Paul G , Oshlack Alicia 
Published: October 2022

AbstractCancer is driven by mutations of the genome that can result in the activation of oncogenes or repression of tumour suppressor genes. In acute lymphoblastic leukemia (ALL) focal deletions in IKAROS family zinc finger 1 (IKZF1) result in the loss of zinc-finger DNA-binding domains and a dominant negative isoform that is associated with higher rates of relapse and poorer patient outcomes. Clinically, the presence of IKZF1 deletions informs prognosis and treatment options. In this work we developed a method for detecting exon deletions in genes using RNA-seq with application to IKZF1. We developed a pipeline that first uses a custom transcriptome reference consisting of transcripts with exon deletions. Next, RNA-seq reads are mapped using a pseudoalignment algorithm to identify reads that uniquely support deletions. These are then evaluated for evidence of the deletion with respect to gene expression and other samples. We applied the algorithm, named Toblerone, to a cohort of 99 B-ALL paediatric samples including validated IKZF1 deletions. Furthermore, we developed a graphical desktop app for non-bioinformatics users that can quickly and easily identify and report deletions in IKZF1 from RNA-seq data with informative graphical outputs.
Comprehensive investigation and regulatory function of lncRNAs engaged in western honey bee larval immune response toAscosphaera apisinvasion
Authors: Ye Yaping , Fan Xiaoxue , Long Qi , Wang Jie , Zhang Wende , Cai Zongbing , Sun Minghui , Gu Xiaoyu , Zou Peiyuan , Chen Dafu , Guo Rui 
Published: October 2022

ABSTRACTAscosphaera apisis a fungal pathogen that exclusively infects bee larvae, causing chalkbrood disease, which results in severe damage for beekeeping industry. Long non-coding RNAs (lncRNAs) are versatile regulators in various biological processes such as immune defense and host-pathogen interaction. However, expression pattern and regulatory role of lncRNAs involved in immune response of bee host toA. apisinvasion is still very limited. Here,Apis mellifera ligustica4-, 5-, and 6-day-old larvae inoculated byA. apisspores (AmT1, AmT2, and AmT3 groups) and corresponding un-inoculated larval guts (AmCK1, AmCK2, and AmCK3 groups) were prepared and subjected to deep sequencing, followed by identification of lncRNAs, analysis of differentially expressed lncRNAs (DElncRNAs), and investigation of DElncRNA-regulated host immune responses. In total, 3 746A. m. ligusticalncRNAs were identified, including 78 sense lncRNAs, 891 antisense lncRNAs, 1 893 intergenic lncRNAs, 346 bidirectional lncRNAs, and 210 intronic lncRNAs. Compared with corresponding un-inoculated larval guts, 357, 236, and 505 DElncRNAs were discovered in theA. apis-inoculated 4-, 5-, and 6-day-old larval guts. Additionally, there were 32 shared DElncRNAs. In AmCK1 vs AmT1, AmCK2 vs AmT2, and AmCK3 vs AmT3 comparison groups, 217, 129, and 272 DElncRNAs were respectively predicted to regulate neighboring genes viacis-acting manner, and these targets were associated with a series of GO terms and KEGG pathways of great importance, such as response to stimulus and Jak-STAT signal pathway. Moreover, competing endogenous RNA (ceRNA) network analysis indicated that 197, 95, and 356 DElncRNAs in the aforementioned three comparison groups could target 10, eight, and 21 DEmiRNAs and further target 147, 79, and 315 DEmRNAs, forming complex regulatory networks. Further investigation suggested that these targets were relevant to several key cellular and humoral immune pathways, such as phagosome and MAPK signaling pathway. Ultimately, the expression trends of nine randomly selected DElncRNAs were verified by RT-qPCR, indicative of the authenticity and reliability of our transcriptome data. Findings in this current work not only provide candidate DElncRNAs for functional study, but also lay a foundation for unclosing the mechanism underlying DElncRNA-regulated larval immune responses toA. apisinfection.
Structural variations in the phytoene synthase 1 gene affect carotenoid accumulation in tomato fruits and result in bicolor and yellow phenotypes
Authors: Bulot Blandine , Isabelle Sébastien , Montoya Roberto , Nadeau Louis Félix , Tremblay Jonathan , Goulet Charles 
Published: October 2022

AbstractTomato fruits normally accumulate large amounts of the red pigment lycopene in their chromoplasts. Some tomato cultivars (Solanum lycopersicum) show however distinct phenotypes, from a pure yellow hue to bicolor fruits with red and yellow sections. In this study, we show that alleles of the phytoene synthase 1 gene (PSY1), the first gene of carotenoid synthesis pathway, are responsible for the yellow, but also the bicolor phenotype. Introgression lines with thePSY1allele from the green-fruited speciesS. habrochaitesexpress less the enzyme, resulting in a bicolor phenotype. On the other hand, in tomato bicolor cultivars, the same coloration pattern is caused by a 3789 bp-deletion in the promoter region ofPSY1. Since the deletion contains part of the 5’UTR region ofPSY1, translation efficiency is likely decreased resulting in a reduction of lycopene accumulation. Furthermore, we identified that the yellowryphenotype is caused by a duplication and an inversion implicatingPSY1and the downstream neighbor gene. The genomic rearrangement change the end of PSY1 amino acid sequence. The fruits of yellowrycultivars are still able in certain conditions to accumulate lycopene near the blossom-end of the fruit, though to a lesser extent than in bicolor cultivars. In contrast, fruits of the yellowrcultivars never present fleshy red sections. These cultivars have an insertion of a single long terminal repeat from the Rider transposon in the first exon of PSY1 resulting in a non-functional protein. These results demonstrate how multiple phenotypes can arise from structural variations in a key gene.
Developing Novel Biologicals with Multiple Modes of Action (BM) to Combat the Early Blight Disease in Tomato (Solanum lycopersicum), Potato (Solanum tuberosum), and Bell Pepper (Capsicum annuum)
Authors: Patel Shloke , Aglave Balaji 
Published: October 2022

AbstractEarly blight, a fungal disease, leads to annual crop losses of up to 79% in tomato, potato, and bell pepper crops. Current treatment requires repeated application of chemical fungicides, resulting in fungicidal resistance. Previous studies have identified microorganisms that enhance plant growth or prevent the growth of early blight spores. This study aims to develop a biological fungicide with multiple modes of action (BM) that can be used in fungicide rotation. The average area under the disease progress curve (AUDPC) values were calculated to quantify the disease progression; formulation 2, formulation 3, and formulation 3 produced the lowest AUDPC value for the tomato, potato, and bell pepper crops, respectively. All the treatments were compared with the current industry standard used to treat early blight, and analysis of variance (ANOVA) tests, with 95% confidence intervals (CIs), of the disease severity were conducted to determine the efficacy of the treatments.
The epidemic dynamics of three childhood infections and the impact of first vaccination in 18thand 19thcentury Finland
Authors: Briga Michael , Ketola Tarmo , Lummaa Virpi 
Published: October 2022

AbstractChildhood infectious such as smallpox or measles have devasted human populations, but our knowledge on the history of public health interventions remains limited. Here, we use 100 years of newly available records in 18thand 19thcentury Finland to investigate the epidemic dynamics of three infections, smallpox, pertussis and measles and the impact of the country’s first nationwide vaccination programme. Between 1750 and 1850, we found over 40 epidemics of smallpox, pertussis and measles, which together were responsible for almost 20% of all registered deaths under age 10. The start of the first vaccination programme against smallpox in 1802 promptly triggered five major changes in smallpox epidemiology: (i) decreasing mortality, (ii) increasing age at infection, (iii) increasing time between epidemics, (iv) increasing fade-outs, which all result from (v) decreased pathogen transmission. In contrast, most epidemic characteristics of the childhood infections without vaccines, pertussis and measles, changed in the opposite direction to that of smallpox: their death toll almost doubled, their reproduction number increased and pertussis, but not measles, showed a decreasing age at infection and accelerating epidemics. Our study captures a rare glimpse of the epidemiology of childhood infections in historical populations and the possible long-term impact of major public health interventions.
Simultaneous global labeling (SiGL) of 5-methylcytosine and 5-hydroxymethylcytosine by DNA alkylation with a synthetic cofactor and engineered methyltransferase
Authors: Avraham Sigal , Schütz Leonie , Käver Larissa , Dankers Andreas , Margalit Sapir , Michaeli Yael , Zirkin Shahar , Torchinsky Dmitry , Gilat Noa , Bahr Omer , Nifker Gil , Koren-Michowitz Maya , Weinhold Elmar , Ebenstein Yuval 
Published: October 2022

Abstract5-methylcytosine and 5-hydroxymethylcytosine are epigenetic modifications involved in gene regulation and cancer. Here, we describe a new, simple, and high-throughput platform for multi-colour epigenetic analysis. The novelty of our approach is the ability to multiplex methylation and de-methylation signals in the same assay. We utilize an engineered methyltransferase enzyme that recognizes and labels all unmodified CpG sites with a fluorescent cofactor. In combination with the already established labelling of the de-methylation mark 5-hydroxymethylcytosine via enzymatic glycosylation, we obtained a robust platform for simultaneous epigenetic analysis of these marks. We assessed the global epigenetic levels in multiple samples of colorectal cancer and observed a reduction in 5-hydroxymethylcytosine levels, but no change in DNA methylation levels between sick and healthy individuals. We also measured epigenetic modifications in chronic lymphocytic leukaemia and observed a decrease in both modification levels. Our results indicate that this assay may be used for the epigenetic characterization of clinical samples for research and patient management.
Regulatory effects of miRNA-19a on MAD2 expression and tumorigenesis in gastric cancer
Authors: Bargiela-Iparraguirre J. , Herrero J.M. , Pajuelo-Lozano N. , Perez M. , Cales C. , Perona R. , Quiroga A.G. , Sanchez-Perez I. 
Published: October 2022

AbstractMAD2 is a key mitotic checkpoint protein that when overexpressed provokes chromosomal instability in gastric cancer. In this work, we usedin silicoanalysis in combination within vitrostudies and clinical data to explore if miRNAs can regulate MAD2 at post-transcriptional level. Byin silicoanalysis, we discriminate the expression of miRNAs between tumor and normal tissue, finding miR-19a and miR-203 targeted to 3’UTRMAD2L1. Luciferase Assays proved that those miR’s are specific toMAD2L1in human cells. RT-qPCR showed an inverse correlation between the expression miRNA19 and 203 andMAD2L1in a panel of gastric cancer cell lines and in a pilot series of patients’ study. The miR-19a expression reduces the migration ability of AGS cells and invasion in MKN45 cells. Furthermore, the expression of the miRNA in combination with mitotic checkpoint drugs increase apoptosis. Finally, the TCGA analysis showed that Gastric Cancer patients with overexpression of MAD2, showed higher overall survival when miR-19a was overexpressed. Together, our results defined miR-19a as a critical regulator of MAD2 protein in Gastric Cancer and could potentially be used as a prognostic biomarker in clinical use.