bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prioritization and functional analysis of GWAS risk loci for Barrett’s esophagus and esophageal adenocarcinoma
Authors: Chen Jianhong , Ali Mourad Wagdy , Yan Li , Dighe Shruti G , Dai James Y , Vaughan Thomas L , Casey Graham , Buas Matthew F 
Published: September 2021

Abstract
Genome-wide association studies (GWAS) have identified ~20 genetic susceptibility loci for esophageal adenocarcinoma (EAC), and its precursor, Barrett’s esophagus (BE). Despite such advances, functional/causal variants and gene targets at these loci remain undefined, hindering clinical translation. A key challenge is that most causal variants map to non-coding regulatory regions such as enhancers, and typically, numerous potential candidate variants at GWAS loci require testing. We developed a systematic informatics pipeline for prioritizing candidate functional variants via integrative functional potential scores (FPS) consolidated from multi-omics annotations, and used this pipeline to identify two high-scoring variants for experimental interrogation: chr9q22.32/rs11789015 and chr19p13.11/rs10423674. Minimal candidate enhancer regions spanning these variants were evaluated using luciferase reporter assays in two EAC cell lines. One of the two variants tested (rs10423674) exhibited allele-specific enhancer activity. CRISPR-mediated deletion of the putative enhancer region in EAC cell lines correlated with reduced expression of two genes—CREB-regulated transcription coactivator 1 (CRTC1) and Cartilage oligomeric matrix protein (COMP); expression of five other genes remained unchanged (CRLF1, KLHL26, TMEM59L, UBA52, RFXANK). Expression quantitative trait locus mapping indicated that rs10423674 genotype correlated with CRTC1 and COMP expression in normal esophagus. This study represents the first experimental effort to bridge GWAS associations to biology in BE/EAC and supports the utility of FPS to guide variant prioritization. Our findings reveal a functional variant and candidate risk enhancer at chr19p13.11 and implicate CRTC1 and COMP as putative gene targets, suggesting that altered expression of these genes may underlie the BE/EAC risk association.
CFTR corrector C17 is effective in muscular dystrophy, in vivo proof of concept in LGMDR3
Authors: Scano Martina , Benetollo Alberto , Nogara Leonardo , Bondì Michela , Dalla Barba Francesco , Soardi Michela , Furlan Sandra , Akyurek Eylem Emek , Caccin Paola , Carotti Marcello , Sacchetto Roberta , Blaauw Bert , Sandonà Dorianna 
Published: September 2021

Abstract
Limb-girdle muscular dystrophy R3 (LGMDR3) is caused by mutations in the SGCA gene coding for α-sarcoglycan (SG). Together with β- γ- and δ-SG, α-SG forms a tetramer embedded in the dystrophin associated protein complex crucial for protecting the sarcolemma from mechanical stresses elicited by muscle contraction. Most LGMDR3 cases are due to missense mutations, which result in non-properly folded, even though potentially functional α-SG. These mutants are prematurely discarded by the cell quality control. Lacking one subunit, the SG-complex is disrupted. The resulting loss of function leads to sarcolemma instability, muscle fiber damage and progressive limb muscle weakness. LGMDR3 is severely disabling and, unfortunately, still incurable. Here, we propose the use of small molecules, belonging to the class of cystic fibrosis transmembrane regulator (CFTR) correctors, for recovering mutants of α-SG defective in folding and trafficking. Specifically, CFTR corrector C17 successfully rerouted the SG-complex containing the human R98H-α-SG to the sarcolemma of hind-limb muscles of a novel LGMDR3 murine model. Notably, the muscle force of the treated model animals was fully recovered. To our knowledge, this is the first time that a compound designated for cystic fibrosis is successfully tested in a muscular dystrophy and may represent a novel paradigm of treatment for LGMDR3 as well as different other indications in which a potentially functional protein is prematurely discarded as folding-defective. Furthermore, the use of small molecules for recovering the endogenous mutated SG has an evident advantage over complex procedures such as gene or cell transfer.
Liquid biopsy: state of reproductive medicine and beyond
Authors: Schobers Gaby , Koeck Rebekka , Pellaers Dominique , Stevens Servi J C , Macville Merryn V E , Paulussen Aimée D C , Coonen Edith , van den Wijngaard Arthur , de Die-Smulders Christine , de Wert Guido , Brunner Han G , Zamani Esteki Masoud 
Published: September 2021

ABSTRACT
Liquid biopsy is the process of sampling and analyzing body fluids, which enables non-invasive monitoring of complex biological systems in vivo. Liquid biopsy has myriad applications in health and disease as a wide variety of components, ranging from circulating cells to cell-free nucleic acid molecules, can be analyzed. Here, we review different components of liquid biopsy, survey state-of-the-art, non-invasive methods for detecting those components, demonstrate their clinical applications and discuss ethical considerations. Furthermore, we emphasize the importance of artificial intelligence in analyzing liquid biopsy data with the aim of developing ethically-responsible non-invasive technologies that can enhance individualized healthcare. While previous reviews have mainly focused on cancer, this review primarily highlights applications of liquid biopsy in reproductive medicine.
Teaching Empire and War: Animating Marginalized Histories in the Classroom
Authors: Maguire Anna , Gupta Diya 
Published: September 2021

Abstract
How can we teach ‘forgotten’ histories of war and empire in the classroom, responding to urgent needs to ‘decolonize’ the curriculum and pedagogic practice? This article reflects on an exercise in pedagogical experimentation – a ‘widening participation’ project based upon a series of workshops – to demonstrate a more global and ‘messy’ understanding of the role of empire in the First and Second World Wars and their commemoration. We discuss the role of students and teachers as co-producers of knowledge, engaging with race and colonialism in the classroom, and the intervention of such work in the project of ‘decolonizing’ curricula.
Personality characteristics and the decision to hire
Authors: Caliendo Marco , Fossen Frank M , Kritikos Alexander S 
Published: September 2021

Abstract
As the policy debate on entrepreneurship increasingly centers on firm growth in terms of job creation, it is important to understand whether the personality of entrepreneurs drives the first hiring in their firms. Using the German Socio-Economic Panel (SOEP), we analyze to what extent personality traits influence the probability of becoming an employer. The results indicate that personality matters. Risk tolerance unfolds the strongest influence on hiring, shortening the time until entrepreneurs hire their first employee; the effect size of a one-standard-deviation increase in risk tolerance is similar to that of having a university degree. Moreover, individuals who are more open to experience, more conscientious, and more trustful are more likely to hire upon establishing their business.
The long-term economic effects of pandemics: toward an evolutionary approach
Authors: Callegari Beniamino , Feder Christophe 
Published: September 2021

AbstractCOVID-19 has brought to the forefront of academic debates the consequences of pandemics and their appropriate policy responses. Using the PRISMA methodology, we provide a comprehensive review of the economic and historical analysis of the long-term economic consequences of pandemics. Mainstream economists focus on the impact of pandemics on production factors, finding a rich but contrasting set of mechanisms with overall negative or insignificant effects. Historians focus on the institutional impact, finding positive effects of pandemics when they trigger new socioeconomic arrangements. Evolutionary economists can integrate into the economic debate both historical elements and the complex biological characteristics of pandemics. We argue that the evolutionary approach provides new and fertile theoretical foundations to understand the phenomenon and develop effective policies.
Economic impact of public R&D: an international perspective
Authors: Soete Luc , Verspagen Bart , Ziesemer Thomas H W 
Published: September 2021

AbstractDespite the fact that research and development (R&D) activities are carried out in most countries in public research institutes such as universities and public research organizations, there have been few studies that attempted to estimate the economic impact of such public investment in R&D. In this paper, we analyze the relations between total factor productivity (TFP) and public and private R&D as well as gross domestic product for a set of 17 Organisation for Economic Cooperation and Development (OECD) countries using a vector-error-correction model. We find that for the period 1975–2014, investment in public R&D has had a clearly positive effect on TFP growth in the majority of countries analyzed. In simulations allowing for a permanent positive shock to public R&D, we observe a strong dynamic complementarity between the public and private (domestic) stocks of R&D for several countries. In countries where this complementarity is strong, the TFP effect of extra public R&D investments is also strong. A discriminant analysis shows that in countries with high complementarity between private and public R&D, the share of foreign funding of R&D performed in the business sector combined with a high business R&D intensity tends to be low. At the same time, the share of basic R&D in business R&D combined with a higher public R&D intensity tends to be higher in countries with strong complementarity.
Impact of sourcing from the informal economy on the export likelihood and performance of emerging economy firms
Authors: Escobar Octavio , Lamotte Olivier , Colovic Ana , Meschi Pierre-Xavier 
Published: September 2021

AbstractBuilding on the institutional economics perspective, we study how local firms in an emerging economy exploit institutional voids by sourcing inputs from industries with a large informal economy. We argue that this allows them to build a cost-related competitive advantage and leverage it both to export and to enhance export performance. The empirical study uses a unique dataset compiled by the Mexican authorities covering manufacturing plants between 2005 and 2012. Our results indicate that firms operating in industries that procure from industries with an extensive informal economy are more likely to export and to have better export performance.
Within-firm inequality in workdays and labor productivity: evidence from linked employer–employee Italian data
Authors: Bloise Francesco , Cirillo Valeria , Raitano Michele , Ricci Andrea 
Published: September 2021

Abstract
Using a longitudinal dataset built merging survey and administrative datasets on Italian firms, we investigate the association between productivity growth and labor flexibility focusing on the role of inequality of yearly workdays within firms. In addition to a negative association between productivity growth and the share of fixed-term employment, we find a further negative association between this type of within-firm inequality and labor productivity growth. This finding suggests that higher inequality in workdays may weaken cooperation among workers, affecting productivity.
Non-stationary effects of growth on the survival of North American Atlantic salmon (Salmo salar)
Authors: Tillotson Michael D , Sheehan Timothy F , Ellingson Brandon , Haas-Castro Ruth E , Olmos Maxime , Mills Katherine E 
Published: September 2021

Abstract
The productivity of Atlantic salmon (Salmo salar) has declined markedly since the 1980s, in part because of changing ocean conditions, but mechanisms driving this decline remain unclear. Previous research has suggested differential recruitment dynamics between the continental stock groups, with post-smolt growth influencing the survival of populations in Europe, but not North America. We used a large, representative archive of North American, multi sea-winter salmon scales to reconstruct long-term changes in growth between 1968 and 2018. We then modeled relationships between annual growth indices, estimates of maturation rates, and post-smolt survival, while allowing for the possibility of non-stationary dynamics. We found that marine growth of MSW salmon has changed over the past 50 years, generally increasing despite declining survival. However, we found strong evidence of a non-stationary influence of post-smolt growth on survival. Prior to a period of rapid change in the ocean environment during the late 1980s, post-smolt growth was positively related with survival, similar to the pattern observed in European populations. These findings suggest that the mechanisms determining marine survival of North American and European salmon populations may have diverged around 1990. More generally, our results highlight the importance of considering non-stationary dynamics when evaluating linkages between the environment, growth, and survival of Atlantic salmon.
Environmental drivers of a decline in a coastal zooplankton community
Authors: Wells Seòna R , Bresnan Eileen , Cook Kathryn , Eerkes-Medrano Dafne , Machairopoulou Margarita , Mayor Daniel J , Rabe Berit , Wright Peter J 
Published: September 2021

Abstract
Major changes in North Atlantic zooplankton communities in recent decades have been linked to climate change but the roles of environmental drivers are often complex. High temporal resolution data is required to disentangle the natural seasonal drivers from additional sources of variability in highly heterogeneous marine systems. Here, physical and plankton abundance data spanning 2003–2017 from a weekly long-term monitoring site on the west coast of Scotland were used to investigate the cause of an increasing decline to approximately -80± 5% in annual average total zooplankton abundance from 2011 to 2017. Generalized additive mixed models (GAMMs), with an autoregressive correlation structure, were used to examine seasonal and inter-annual trends in zooplankton abundance and their relationship with environmental variables. Substantial declines were detected across all dominant taxa, with ∼ 30–70% of the declines in abundance explained by a concurrent negative trend in salinity, alongside the seasonal cycle, with the additional significance of food availability found for some taxa. Temperature was found to drive seasonal variation but not the long-term trends in the zooplankton community. The reduction in salinity had the largest effect on several important taxa. Salinity changes could partly be explained by locally higher freshwater run-off driven by precipitation as well as potential links to changes in offshore water masses. The results highlight that changes in salinity, caused by either freshwater input (expected from climate predictions) or fresher offshore water masses, may adversely impact coastal zooplankton communities and the predators that depend on them.
The Use of the UNIDROIT Principles and Other Transnational Principles of Commercial Law in Treaty Arbitration: Hazards and Opportunities
Authors: Carlevaris Andrea 
Published: September 2021

Abstract
The UNIDROIT Principles of International Commercial Contracts and more generally transnational principles of commercial law are often relied on, not only by international commercial arbitral tribunals, but also by investment tribunals. In rare cases, investment tribunals have relied on such principles as applicable law per se. More frequently, transnational principles have been relied on to supplement the tribunal’s findings based on the applicable domestic or international law as ‘general principles of law recognized by civilized nations’ in the meaning of Article 38(1)(c) of the Statute of the International Court of Justice. In commercial arbitration, reliance on transnational principles aims at strengthening the tribunal’s conclusions and enhancing their acceptance by the parties, whereas in investment arbitration reliance on transnational commercial principles shows growing convergence between the ways in which general principles are understood and applied in domestic private law and public international law. Transnational principles of commercial law serve a useful purpose in corroborating tribunals’ conclusions based on domestic or international law. However, their use requires an appropriate choice-of-law methodology to avoid risks for the enforceability of awards.
Density of aortopulmonary collaterals predicts in-hospital outcome in tetralogy of Fallot with pulmonary stenosis
Authors: Fang Yibing , Xiong Ziqing , Wang Yue , Li Bo , Wang Zetao , Kang Deying , An Qi , Lin Ke , Luo Shuhua 
Published: September 2021

Abstract

OBJECTIVES
The aim of this study was to characterize the anatomy of aortopulmonary collateral (APC) arteries in tetralogy of Fallot and pulmonary stenosis and to determine whether APC density identified on preoperative multidetector cardiac computed tomography predicts in-hospital outcome.

METHODS
The retrospective single-centre study includes consecutive 135 (2015–2019) patients who underwent one-stage repair. Preoperative multidetector cardiac computed tomography, echocardiography and clinical outcomes were reviewed. The cut-off value of indexed total distal APC cross-sectional area (APC-CSA) was identified by receiver operating characteristic curve. Logistic regression was used for predictors analysis.

RESULTS
The median age and body weight were 19.7 (10.1–89.7) months and 10 (8.3–18) kg. A total of 337 APCs were detected with only one demonstrating severe stenosis. There was a strong and significant correlation between mean APC diameter per patient and age (r = 0.70, P &lt; 0.001). APCs were imaged but mainly received no interventions. In-hospital mortality was similar between patients with high (indexed APC-CSA ≥3.0 mm2/m2) and low (&lt;3.0 mm2/m2) APC density (P = 0.642). Significantly greater patients with high indexed APC-CSA experienced the in-hospital composite outcome of death, arrest, renal/hepatic injury, lactic acidosis or extracorporeal membrane oxygenation (P = 0.007). High APC density was associated with greater dosing (P = 0.008) and longer (P = 0.01) use of inotropic support, prolonged pleural drainage (P = 0.013), longer ventilation (P = 0.042), intensive care unit (P = 0.014) and hospital (P = 0.027) duration. No reintervention and death occurred in the follow-up with the median duration of 24.4 (11–36.6) months. Multivariable analysis showed the Nakata index (P = 0.05) and high APC density (P = 0.02) independently predicted the composite outcome.

CONCLUSIONS
In tetralogy of Fallot and pulmonary stenosis, APCs are likely to be dilated bronchial arteries. Preoperative multidetector cardiac computed tomography-derived APC density was as important as Nakata index in predicting the occurrence of in-hospital composite outcome. The APC-CSA of 3.0 mm2/m2 maybe considered as a threshold for risk stratification.
Bilateral endoscopic technique for left atrial appendectomy and robot-assisted mitral valve repair
Authors: Seguchi Ryuta , Ohtsuka Toshiya , Ishikawa Norihiko , Watanabe Go 
Published: September 2021

Abstract
We report a bilateral thoracoscopic technique in which robot-assisted mitral valve repair was achieved concomitantly with stapler division of the large left atrial appendage. The patient was a 65-year-old male with severe mitral regurgitation, paroxysmal atrial fibrillation and a large-sized atrial appendage. Closure of the appendage was completed off-pump using a left thoracoscopic stapler-division technique previous to right thoracoscopic robot-assisted mitral valve repair and cryoablation. Complete closure of the appendage was confirmed in thoracoscopic views. The bilateral thoracoscopic technique could be preferable for the minimally invasive treatment of mitral valvular disease and concomitant large-sized atrial appendage management.
Common maternal infections during pregnancy and childhood leukaemia in the offspring: findings from six international birth cohorts
Authors: He Jian-Rong , Hirst Jane E , Tikellis Gabriella , Phillips Gary S , Ramakrishnan Rema , Paltiel Ora , Ponsonby Anne-Louise , Klebanoff Mark , Olsen Jørn , Murphy Michael F G , Håberg Siri E , Lemeshow Stanley , F Olsen Sjurdur , Qiu Xiu , Magnus Per , Golding Jean , Ward Mary H , Wiemels Joseph L , Rahimi Kazem , Linet Martha S , Dwyer Terence ,   the International Childhood Cancer Cohort Consortium
Published: September 2021

AbstractBackgroundPrevious epidemiological studies have found positive associations between maternal infections and childhood leukaemia; however, evidence from prospective cohort studies is scarce. We aimed to examine the associations using large-scale prospective data.MethodsData were pooled from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA (recruitment 1950s-2000s). Primary outcomes were any childhood leukaemia and acute lymphoblastic leukaemia (ALL); secondary outcomes were acute myeloid leukaemia (AML) and any childhood cancer. Exposures included maternal self-reported infections [influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections and urinary tract infection (including cystitis)] and infection-associated symptoms (fever and diarrhoea) during pregnancy. Covariate-adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using multilevel Cox models.ResultsAmong 312 879 children with a median follow-up of 13.6 years, 167 leukaemias, including 129 ALL and 33 AML, were identified. Maternal urinary tract infection was associated with increased risk of any leukaemia [HR (95% CI) 1.68 (1.10–2.58)] and subtypes ALL [1.49 (0.87–2.56)] and AML [2.70 ([0.93–7.86)], but not with any cancer [1.13 (0.85–1.51)]. Respiratory tract infection was associated with increased risk of any leukaemia [1.57 (1.06–2.34)], ALL [1.43 (0.94–2.19)], AML [2.37 (1.10–5.12)] and any cancer [1.33 (1.09–1.63)]; influenza-like illness showed a similar pattern but with less precise estimates. There was no evidence of a link between other infections and any outcomes.ConclusionsUrinary tract and respiratory tract infections during pregnancy may be associated with childhood leukaemia, but the absolute risk is small given the rarity of the outcome.