bluuebunny/crossref_metadata_2025_split huggingface dataset:
Technology Shocks and Predictable Minsky Cycles
Authors: L’Huillier Jean-Paul , Phelan Gregory , Wieman Hunter 
Published: October 2023

Abstract
Big technological improvements in a new, secondary sector lead to a period of excitement about the future prospects of the overall economy, generating boom-bust dynamics propagating through credit markets. Increased future capital prices relax collateral constraints today, leading to a boom before the realisation of the shock. But reallocation of capital toward the secondary sector when the shock hits leads to a bust going forward. These cycles are perfectly foreseen in our model, making them markedly different from the typical narrative about unexpected financial shocks used to explain crises. Our dynamics obtain without a departure from rational expectations. In fact, these cycles echo Minsky’s original narrative for financial cycles, according to which ‘financial trauma occur [sic] as normal functioning events in a capitalistic economy’ (Minsky, 1980, p. 21).
Parental Investments and Intra-household Inequality in Child Human Capital: Evidence from a Survey Experiment
Authors: Giannola Michele 
Published: October 2023

Abstract
Intra-household inequality explains 40% of child human capital variation in the developing world. I study how parents’ investment contributes to this inequality. To mitigate the identification problem posed by observational data, I design a survey experiment with parents in India that allows me to identify beliefs about the human capital production function, preferences for inequality in outcomes and the role of resources. I find that investments are driven by efficiency considerations: as parents perceive investment and ability as complements, they invest more in higher-achieving children and more so when constrained. Simulations indicate that interventions have intra-household distributional impacts through parental responses.
Mavacamten: a first-in-class myosin inhibitor for obstructive hypertrophic cardiomyopathy
Authors: Braunwald Eugene , Saberi Sara , Abraham Theodore P , Elliott Perry M , Olivotto Iacopo 
Published: October 2023

Abstract
Mavacamten is a first-in-class, targeted, cardiac-specific myosin inhibitor approved by the US Food and Drug Administration for the treatment of adults with symptomatic New York Heart Association Classes II and III obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten was developed to target the hyper-contractile phenotype, which plays a critical role in the pathophysiology of the disease. In Phase 2 and 3 clinical trials, mavacamten was well tolerated, reduced left ventricular outflow tract gradients, improved exercise capacity and symptoms, and was associated with improvements in other clinically relevant parameters, such as patient-reported outcomes and circulating biomarkers. In addition, treatment with mavacamten was associated with evidence of favourable cardiac remodelling in multi-modality imaging studies. Mavacamten substantially reduced guideline eligibility for septal reduction therapy candidates with oHCM and drug-refractory symptoms. In this article, the available efficacy and safety data from completed and ongoing clinical studies of mavacamten in patients with symptomatic oHCM are reviewed. Longer term extension studies may help address questions related to the positioning of mavacamten in current oHCM management algorithms, interactions with background therapy, as well as the potential for disease modification beyond symptomatic relief of left ventricular outflow tract obstruction.
Structural genomic variation and migratory behavior in a wild songbird
Authors: Delmore Kira E , Van Doren Benjamin M , Ullrich Kristian , Curk Teja , van der Jeugd Henk P , Liedvogel Miriam 
Published: October 2023

Abstract
Structural variants (SVs) are a major source of genetic variation; and descriptions in natural populations and connections with phenotypic traits are beginning to accumulate in the literature. We integrated advances in genomic sequencing and animal tracking to begin filling this knowledge gap in the Eurasian blackcap. Specifically, we (a) characterized the genome-wide distribution, frequency, and overall fitness effects of SVs using haplotype-resolved assemblies for 79 birds, and (b) used these SVs to study the genetics of seasonal migration. We detected &gt;15 K SVs. Many SVs overlapped repetitive regions and exhibited evidence of purifying selection suggesting they have overall deleterious effects on fitness. We used estimates of genomic differentiation to identify SVs exhibiting evidence of selection in blackcaps with different migratory strategies. Insertions and deletions dominated the SVs we identified and were associated with genes that are either directly (e.g., regulatory motifs that maintain circadian rhythms) or indirectly (e.g., through immune response) related to migration. We also broke migration down into individual traits (direction, distance, and timing) using existing tracking data and tested if genetic variation at the SVs we identified could account for phenotypic variation at these traits. This was only the case for 1 trait—direction—and 1 specific SV (a deletion on chromosome 27) accounted for much of this variation. Our results highlight the evolutionary importance of SVs in natural populations and provide insight into the genetic basis of seasonal migration.
Successful cultivation of black morel, Morchella sp. in Japan
Authors: Narimatsu Maki , Sato Shiho , Sakamoto Yuichi 
Published: October 2023

Abstract
True morels (Morchella spp.) are economically important edible fungi cultivated mainly in China. Japan is one of the top importers of morels, but there are no reports on the distribution of major cultivated species. To investigate the possibility of black morel cultivation in Japan, phylogenetic analysis, mating-type analysis, and field cultivation tests were conducted using domestically collected strains. A total of 172 strains were isolated from the spores of wild ascomata collected from 15 locations. Mating-type analysis for 118 strains revealed 28 strains had only MAT1-1-1, 40 strains had only MAT1-2-1, and 48 strains had both MAT genes. Seven strains were inoculated in March 2020 at the field cultivation test site. Mycelial growth and conidial layer formation were observed within a month. Ascomata were observed in April 2021 for one of the tested strains. Phylogenetic analysis revealed that both the observed ascomata and fruited strains were Morchella sp. Mel-21, which is one of the cultivated species in China. Moreover, no antagonism was observed in the somatic incompatibility test between strains isolated from observed ascomata and spawn strain. These results suggest that the ascomata originated in the inoculated spawn, a finding that will contribute to commercial morel cultivation in Japan.
Effect of BRAF mutation on the prognosis for patients with colorectal cancer undergoing cytoreductive surgery for synchronous peritoneal metastasis
Authors: Wu Zhijie , Qin Xiusen , Zhang Yuanxin , Luo Jian , Luo Rui , Cai Zonglu , Wang Hui 
Published: October 2023

Abstract

Background
KRAS/BRAF mutations (mutKRAS/mutBRAF) are unfavorable prognostic factors for colorectal cancer (CRC) metastases to the liver and lungs. However, their effects on the prognosis for patients with synchronous peritoneal metastasis (S-PM) of CRC after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are controversial. In the study, we aimed to determine the effects of mutKRAS/mutBRAF on the prognosis for patients with S-PM who received CRS.

Methods
A total of 142 patients diagnosed with S-PM between July 2007 and July 2019 were included in this study. The demographics, mutKRAS/mutBRAF status, overall survival (OS), and progression-free survival (PFS) of the patients were evaluated. The Kaplan–Meier method and log-rank test were used to estimate the difference in survival between groups.

Results
Among 142 patients, 68 (47.9%) showed mutKRAS and 42 (29.5%) showed mutBRAF. The median OS values were 8.4 and 34.3 months for patients with mutBRAF and BRAF wild-type, respectively (P &lt; 0.01). However, KRAS status was not significantly associated with median OS (P = 0.76). Multivariate analysis revealed carcinoembryonic antigen, CRS, HIPEC, and mutBRAF as independent predictors for OS. Based on these findings, a nomogram was constructed. The C-index was 0.789 (95% confidence interval, 0.742–0.836), indicating good predictive ability of the model. Furthermore, the 1- and 2-year survival calibration plots showed good agreement between the predicted and actual OS rates. The area under curves of the 1- and 2-year survival predictions based on the nomogram were 0.807 and 0.682, respectively. Additionally, mutBRAF was significantly associated with lower PFS (P &lt; 0.001).

Conclusions
mutBRAF is an independent prognostic risk factor for S-PM. The established nomogram predicted the OS of patients with CRC having S-PM with high accuracy, indicating its usefulness as a valuable prognostic tool for the designated patient cohort.
Incidence of Dementia and Alzheimer’s Disease, Genetic Susceptibility, and Grip Strength Among Older Adults
Authors: Kim Youngwon , Wang Mengyao , Sharp Stephen J , Au Yeung Shiu Lun , Luo Shan , Jang Haeyoon , Jiesisibieke Zhu Liduzi , Shi Qiaoxin , Chen Ziyuan , Brage Soren 
Published: October 2023

Abstract

Background
Grip strength has prognostic value for aging-related health outcomes. Whether the associations of grip strength with the risk of dementia and Alzheimer’s disease (AD) vary by the genetic risk of AD and related dementias (ADD) is unknown.

Methods
This study included 148 659 older adults of white British ancestry (aged ≥60 years) participating in UK Biobank with no dementia, and self-reported poor health status at baseline. Polygenic risk scores (PRS) for ADD were calculated based on 64 genetic variants. Grip strength was measured by hand dynamometers.

Results
The hazard ratios (HR) of dementia (n = 4 963) and AD (n = 2 373) for high genetic risk of ADD were 2.36 (95% confidence interval [CI]: 2.15–2.59) and 3.00 (95% CI: 2.61–3.44), respectively, compared with low genetic risk. Compared with the bottom tertile of grip strength, the top tertile of grip strength had a hazard ratio (HR) of 0.69 (95% CI: 0.64–0.74) for incident dementia, and 0.74 (95% CI: 0.66–0.82) for incident AD, after adjustment for confounders and PRS for ADD. The risk of dementia and AD was lower with the top grip strength tertile within each level of genetic susceptibility to ADD. There was no evidence of multiplicative interaction between grip strength and genetic susceptibility to ADD for both dementia (p value: .241) and AD (p value: .314).

Conclusions
Older adults with higher PRS for ADD are at higher risk of developing dementia and AD. The risk of dementia and AD was lower in individuals with higher grip strength, regardless of their level of genetic susceptibility to ADD.
The Third Annual Symposium of the Midwest Aging Consortium
Authors: Keller Andrea , Bai Hua , Budinger Scott , Eliazer Susan , Hansen Malene , Konopka Adam R , Morales-Nebreda Luisa , Najt Charles P , Prahlad Veena , Victorelli Stella , Vorland Colby J , Yuan Rong , Rhoads Timothy W , Mihaylova Maria M 
Published: October 2023

Abstract
The geroscience hypothesis suggests that addressing the fundamental mechanisms driving aging biology will prevent or mitigate the onset of multiple chronic diseases, for which the largest risk factor is advanced age. Research that investigates the root causes of aging is therefore of critical importance given the rising healthcare burden attributable to age-related diseases. The third annual Midwest Aging Consortium symposium was convened as a showcase of such research performed by investigators from institutions across the Midwestern United States. This report summarizes the work presented during a virtual conference across topics in aging biology, including immune function in the lung—particularly timely given the Corona Virus Immune Disease-2019 pandemic—along with the role of metabolism and nutrient-regulated pathways in cellular function with age, the influence of senescence on stem cell function and inflammation, and our evolving understanding of the mechanisms underlying observation of sex dimorphism in aging-related outcomes. The symposium focused on early-stage and emerging investigators, while including keynote presentations from leaders in the biology of aging field, highlighting the diversity and strength of aging research in the Midwest.
How, why and for whom does a basic income contribute to health and wellbeing: a systematic review
Authors: McKay Fiona H , Bennett Rebecca , Dunn Matthew 
Published: October 2023

AbstractEnsuring that people have a sufficient income to meet their basic needs and that it keeps pace with costs of living are important when considering ways to reduce health inequities. Many have argued that providing a basic income is one way to do this. The aim of this review is to provide an overview of the existing peer reviewed evidence on the health and wellbeing impacts of basic income interventions. A systematic search of ten electronic databases was conducted in June 2022. Eligible publications examined any effect on health and wellbeing from unconditional cash transfers. All study designs were included, and no limitations were placed on duration of cash transfer trials, location of study, study population or on amount of money provided through the cash transfer. Ten studies were included in this review. Studies employed a range of methods. All studies reported on a trial of Universal Basic Income in either a region or a town. Studies explored a range of health and wellbeing related outcomes including crime, quality of life, employment, subjective wellbeing, tuberculosis and hospitalization. Basic income programs can mitigate poverty in a time of economic upheaval and have the potential to become a powerful policy tool to act upon the determinants of health and reduce health inequality. This review found a small number of trials indicating a positive impact on health and wellbeing. More trials which track recipients over a longer period are needed to provide more robust evidence for the impact of basic income programs.
Dysregulation of alternative splicing in spinocerebellar ataxia type 1
Authors: Olmos Victor , Thompson Evrett N , Gogia Neha , Luttik Kimberly , Veeranki Vaishnavi , Ni Luhan , Sim Serena , Chen Kelly , Krause Diane S , Lim Janghoo 
Published: October 2023

Abstract
Spinocerebellar ataxia type 1 is caused by an expansion of the polyglutamine tract in ATAXIN-1. Ataxin-1 is broadly expressed throughout the brain and is involved in regulating gene expression. However, it is not yet known if mutant ataxin-1 can impact the regulation of alternative splicing events. We performed RNA sequencing in mouse models of spinocerebellar ataxia type 1 and identified that mutant ataxin-1 expression abnormally leads to diverse splicing events in the mouse cerebellum of spinocerebellar ataxia type 1. We found that the diverse splicing events occurred in a predominantly cell autonomous manner. A majority of the transcripts with misregulated alternative splicing events were previously unknown, thus allowing us to identify overall new biological pathways that are distinctive to those affected by differential gene expression in spinocerebellar ataxia type 1. We also provide evidence that the splicing factor Rbfox1 mediates the effect of mutant ataxin-1 on misregulated alternative splicing and that genetic manipulation of Rbfox1 expression modifies neurodegenerative phenotypes in a Drosophila model of spinocerebellar ataxia type 1 in vivo. Together, this study provides novel molecular mechanistic insight into the pathogenesis of spinocerebellar ataxia type 1 and identifies potential therapeutic strategies for spinocerebellar ataxia type 1.
CYP2A6associates with respiratory disease risk and younger age of diagnosis: a phenome-wide association Mendelian Randomization study
Authors: Giratallah Haidy , Chenoweth Meghan J , Pouget Jennie G , El-Boraie Ahmed , Alsaafin Alaa , Lerman Caryn , Knight Jo , Tyndale Rachel F 
Published: October 2023

AbstractCYP2A6, a genetically variable enzyme, inactivates nicotine, activates carcinogens, and metabolizes many pharmaceuticals. Variation in CYP2A6 influences smoking behaviors and tobacco-related disease risk. This phenome-wide association study examined associations between a reconstructed version of our weighted genetic risk score (wGRS) for CYP2A6 activity with diseases in the UK Biobank (N = 395 887). Causal effects of phenotypic CYP2A6 activity (measured as the nicotine metabolite ratio: 3′-hydroxycotinine/cotinine) on the phenome-wide significant (PWS) signals were then estimated in two-sample Mendelian Randomization using the wGRS as the instrument. Time-to-diagnosis age was compared between faster versus slower CYP2A6 metabolizers for the PWS signals in survival analyses. In the total sample, six PWS signals were identified: two lung cancers and four obstructive respiratory diseases PheCodes, where faster CYP2A6 activity was associated with greater disease risk (Ps &lt; 1 × 10−6). A significant CYP2A6-by-smoking status interaction was found (Psinteraction &lt; 0.05); in current smokers, the same six PWS signals were found as identified in the total group, whereas no PWS signals were found in former or never smokers. In the total sample and current smokers, CYP2A6 activity causal estimates on the six PWS signals were significant in Mendelian Randomization (Ps &lt; 5 × 10−5). Additionally, faster CYP2A6 metabolizer status was associated with younger age of disease diagnosis for the six PWS signals (Ps &lt; 5 × 10−4, in current smokers). These findings support a role for faster CYP2A6 activity as a causal risk factor for lung cancers and obstructive respiratory diseases among current smokers, and a younger onset of these diseases. This research utilized the UK Biobank Resource.
Relationship between deprivation, and the uptake and use of the common ailments service in community pharmacies in Wales
Authors: Thayer Nick , Mackridge Adam John , White Simon 
Published: October 2023

Abstract

Objectives
Since 2013 community pharmacies in Wales have been commissioned to provide a common ailments service (CAS), providing pharmacy medicine without charge to patients. In the first review of national pharmacy data, this study aimed to describe the relationship between provision of CAS and deprivation.

Methods
A retrospective observational study, using CAS claims data from April 2022 to March 2023 collected as part of routine service delivery. Consultation data were matched to the index of multiple deprivation (IMD) decile of the providing pharmacy. Linear regression was used to describe the correlation between CAS claims data and IMD deciles of the pharmacy postcode.

Key findings
In the study period, 239 028 consultations were recorded. More than twice as many consultations were carried out in pharmacies located in the most deprived decile (33 950) than in pharmacies in the least deprived decile (14 465). Linear regression demonstrated a significant correlation r(10) = −0.927, P &lt; 0.001. There was a strong relationship between greater numbers of consultations and greater deprivation of the pharmacy postcode (R2 = 0.887). This significant correlation with deprivation was also found in the majority of individual conditions. There was no significant correlation between deprivation decile and the number of consultations per patient.

Conclusions
Community pharmacies offer a key resource for tackling health inequalities. Patients in those areas with the greatest need are those most likely to use the CAS in pharmacies and receive the care they need. Commissioning services like this naturally supports deprived communities, through a combination of patient behaviours, location, and accessibility.
Immunoinformatic Approach for Rational Identification of Immunogenic Peptides Against Host Entry and/or Exit Mpox Proteins and Potential Multiepitope Vaccine Construction
Authors: de Araújo Leonardo Pereira , de Melo Santos Natália Cristina , Corsetti Patrícia Paiva , de Almeida Leonardo Augusto 
Published: October 2023

Abstract
COVID-19 has intensified humanity's concern about the emergence of new pandemics. Since 2018, epidemic outbreaks of the mpox virus have become worrisome. In June 2022, the World Health Organization declared the disease a global health emergency, with 14 500 cases reported by the Centers for Disease Control and Prevention in 60 countries. Therefore, the development of a vaccine based on the current virus genome is paramount in combating new cases. In view of this, we hypothesized the obtainment of rational immunogenic peptides predicted from proteins responsible for entry of the mpox virus into the host (A17L, A26L/A30L, A33R, H2R, L1R), exit (A27L, A35R, A36R, C19L), and both (B5R). To achieve this, we aligned the genome sequencing data of mpox virus isolated from an infected individual in the United States in June 2022 (ON674051.1) with the reference genome dated 2001 (NC_003310.1) for conservation analysis. The Immune Epitope Database server was used for the identification and characterization of the epitopes of each protein related to major histocompatibility complex I or II interaction and recognition by B-cell receptors, resulting in 138 epitopes for A17L, 233 for A28L, 48 for A33R, 77 for H2R, 77 for L1R, 270 for A27L, 72 for A35R, A36R, 148 for C19L, and 276 for B5R. These epitopes were tested in silico for antigenicity, physicochemical properties, and allergenicity, resulting in 51, 40, 10, 34, 38, 57, 25, 7, 47, and 53 epitopes, respectively. Additionally, to select an epitope with the highest promiscuity of binding to major histocompatibility complexes and B-cell receptor simultaneously, all epitopes of each protein were aligned, and the most repetitive and antigenic regions were identified. By classifying the results, we obtained 23 epitopes from the entry proteins, 16 from the exit proteins, and 7 from both. Subsequently, 1 epitope from each protein was selected, and all 3 were fused to construct a chimeric protein that has potential as a multiepitope vaccine. The constructed vaccine was then analyzed for its physicochemical, antigenic, and allergenic properties. Protein modeling, molecular dynamics, and molecular docking were performed on Toll-like receptors 2, 4, and 8, followed by in silico immune simulation of the vaccine. Finally, the results indicate an effective, stable, and safe vaccine that can be further tested, especially in vitro and in vivo, to validate the findings demonstrated in silico.