bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors affecting the efficiency of molecular species delimitation in a species‐rich insect family
Authors: Magoga Giulia , Fontaneto Diego , Montagna Matteo 
Published: February 2021

AbstractIn the context of global biodiversity loss, molecular species delimitation approaches can be very useful for accelerating species discovery through DNA taxonomy and inventory through DNA metabarcoding. In this study, the effect of some intrinsic factors on the efficiency of various single‐marker species delimitation methods (fixed and variable nucleotide distance thresholds, ABGD, ASAP, GMYC, mPTP) was tested on more than 90 empirical data sets, derived from a set of 7,237 COI sequences attributed to 542 leaf beetles species (Coleoptera: Chrysomelidae). The considered factors were: (i) the number of haplotypes per species (as a proxy for genetic diversity), (ii) the geographic distance among conspecific collection localities (as a proxy of sampling width), (iii) the difficulty related to morphological identification of species, and (iv) the taxonomic rank. Distance‐based methods, with on average more than 70% of match with morphological identification, outperformed those relying on phylogenetic trees, with less than 59%. A high number of haplotypes per species was found to have a negative effect on delimitation efficiency, whereas large geographic distances within species had a positive effect. All methods delimitations (except for GMYC) were significantly affected by the presence of species that are difficult to be identified, decreasing their efficiency. Finally, the only method influenced by the taxonomic rank of the data set was GMYC, showing lower efficiency in data sets at the genus than at higher levels. The observed biases we highlighted affecting efficiency could be accounted for when developing input data sets for species delimitation analyses to obtain a more reliable representation of biological diversity.
Inhibition of longevity regulator PAPP‐A modulates tissue homeostasis via restraint of mesenchymal stromal cells
Authors: Mohrin Mary , Liu Justin , Zavala‐Solorio Jose , Bhargava Sakshi , Maxwell Trumble John , Brito Alyssa , Hu Dorothy , Brooks Daniel , Koukos Georgios , Alabdulaaly Lama , Paw Jonathan S. , Hake Kayley , Kolumam Ganesh , Bouxsein Mary L. , Baron Roland , Kutskova Yuliya , Freund Adam 
Published: February 2021

AbstractPregnancy‐associated plasma protein‐A (PAPP‐A) is a secreted metalloprotease that increases insulin‐like growth factor (IGF) availability by cleaving IGF‐binding proteins. Reduced IGF signaling extends longevity in multiple species, and consistent with this, PAPP‐A deletion extends lifespan and healthspan; however, the mechanism remains unclear. To clarify PAPP‐A’s role, we developed a PAPP‐A neutralizing antibody and treated adult mice with it. Transcriptomic profiling across tissues showed that anti‐PAPP‐A reduced IGF signaling and extracellular matrix (ECM) gene expression system wide. The greatest reduction in IGF signaling occurred in the bone marrow, where we found reduced bone, marrow adiposity, and myelopoiesis. These diverse effects led us to search for unifying mechanisms. We identified mesenchymal stromal cells (MSCs) as the source of PAPP‐A in bone marrow and primary responders to PAPP‐A inhibition. Mice treated with anti‐PAPP‐A had reduced IGF signaling in MSCs and dramatically decreased MSC number. As MSCs are (1) a major source of ECM and the progenitors of ECM‐producing fibroblasts, (2) the originating source of adult bone, (3) regulators of marrow adiposity, and (4) an essential component of the hematopoietic niche, our data suggest that PAPP‐A modulates bone marrow homeostasis by potentiating the number and activity of MSCs. We found that MSC‐like cells are the major source of PAPP‐A in other tissues also, suggesting that reduced MSC‐like cell activity drives the system‐wide reduction in ECM gene expression due to PAPP‐A inhibition. Dysregulated ECM production is associated with aging and drives age‐related diseases, and thus, this may be a mechanism by which PAPP‐A deficiency enhances longevity.
Senescent cells and the incidence of age‐related diseases
Authors: Katzir Itay , Adler Miri , Karin Omer , Mendelsohn‐Cohen Netta , Mayo Avi , Alon Uri 
Published: February 2021

AbstractAge‐related diseases such as cancer, cardiovascular disease, kidney failure, and osteoarthritis have universal features: Their incidence rises exponentially with age with a slope of 6–8% per year and decreases at very old ages. There is no conceptual model which explains these features in so many diverse diseases in terms of a single shared biological factor. Here, we develop such a model, and test it using a nationwide medical record dataset on the incidence of nearly 1000 diseases over 50 million life‐years, which we provide as a resource. The model explains incidence using the accumulation of senescent cells, damaged cells that cause inflammation and reduce regeneration, whose level rise stochastically with age. The exponential rise and late drop in incidence are captured by two parameters for each disease: the susceptible fraction of the population and the threshold concentration of senescent cells that causes disease onset. We propose a physiological mechanism for the threshold concentration for several disease classes, including an etiology for diseases of unknown origin such as idiopathic pulmonary fibrosis and osteoarthritis. The model can be used to design optimal treatments that remove senescent cells, suggeting that treatment starting at old age can sharply reduce the incidence of all age‐related diseases, and thus increase the healthspan.
Leverage constraints and corporate financing decisions
Authors: Yang Liu , Zhou Qing 
Published: February 2021

AbstractWe examine the impact of investors’ leverage constraints on corporate financing decisions. We use mutual fund flow to capture the net buying pressure from leverage‐constrained investors’ demand for high‐beta stocks. We show that firms confronted by the constrained funds’ excessive trading pressure are more likely to issue a seasoned equity offering and conduct stock‐based mergers and acquisitions, and their managers engage in more insider sales than those facing low or little trading pressure. Our results are robust to controlling for the short‐sales constraints of mutual funds and are consistent across different stages of the business cycle.
Sugar, a powerful substitute for ethanol in ethanol postdependent rats: Relevance for clinical consideration?
Authors: Alaux‐Cantin Stéphanie , Alarcon Régis , Audegond Clément , Simon O'Brien Emmanuelle , Martinetti Margaret P. , Ahmed Serge H. , Nalpas Bertrand , Perney Pascal , Naassila Mickael 
Published: February 2021

AbstractSugar has been shown to be a powerful substitute for drugs in preclinical studies on addiction. However, the link between sugar intake and alcohol use disorder (AUD) is poorly understood. We assessed the influence of sucrose on ethanol drinking in both nondependent (ND) and dependent (D) Long–Evans rats during acute withdrawal using the postdependent state model. Ethanol (10%–40%) and sucrose (1%–4%) solutions were offered in an operant paradigm either independently or concurrently under ratio schedules of reinforcement. We showed that D rats displayed an enhanced motivation for both 10% ethanol solution (10E) and 4% sucrose solution (4S) as compared with ND rats, and a clear preference for 4S was observed in both groups. During acute withdrawal, D rats showed a strong motivation for 30% ethanol (30E), even when adulterated with quinine, but still preferred 4S despite the fact that a high level of negative reinforcement could be expected. However, when a premix solution (30E4S) was offered concurrently with 4S, the preference for 4S was lost in D animals, which consumed as much premix as 4S, whereas ND animals displayed preference for 4S. Altogether, those results suggest that reinforcing properties of sucrose surpass those of ethanol in D rats under acute withdrawal, which indicates that sugar is a powerful substitute for ethanol. Our results suggest that craving for sugar may be increased in AUD patients during withdrawal and raise the issue of dependence transfer from alcohol to sugar.
Availability of medical cannabis dispensaries and cannabis abuse/dependence‐related hospitalizations in California
Authors: Mair Christina , Sumetsky Natalie , Kranich Christiana , Freisthler Bridget 
Published: February 2021

ABSTRACTAimsTo estimate associations between both current‐ and prior‐year medical cannabis dispensary densities and hospitalizations for cannabis use disorder in California, USA between 2013 and 2016.DesignSpatial analysis of ZIP code‐level hospitalization discharge data using Bayesian Poisson hierarchical space–time models over 4 years.Setting and casesCalifornia, USA from 2013 to 2016 (6832 space–time ZIP code units).MeasurementsWe assessed associations of annual hospitalizations for cannabis use disorder [assignment of a primary or secondary code for cannabis abuse and/or dependence using ICD‐9‐CM or ICD‐10‐CM (outcome)] with the total number of medical cannabis dispensaries per square mile in a ZIP code as well as dispensary temporal and spatial lags (primary exposures). Other exposure covariates included alcohol outlet densities, manual labor and retail sales densities and ZIP code‐level economic and demographic conditions.FindingsOne additional dispensary per square mile was associated with a median risk ratio of 1.021 (95% credible interval 1.001, 1.041). Prior‐year dispensary density did not appear to be associated with hospitalizations (median risk ratio = 1.006, 95% CrI = 0.986, 1.026). Higher median household income, higher unemployment, greater off‐premises alcohol outlet density and lower on‐premises alcohol outlet density and poverty were all associated with decreased ZIP code‐level risk of cannabis abuse/dependence hospitalizations.ConclusionsIn California, USA, the increasing density of medical cannabis dispensaries appears to be positively associated with same‐year but not next‐year hospitalizations for cannabis use disorder.
Do alcohol product labels stating lower strength verbal description, percentage alcohol‐by‐volume, or their combination affect wine consumption? A bar laboratory adaptive randomised controlled trial
Authors: Vasiljevic Milica , Frings Daniel , Pilling Mark , Marteau Theresa M. 
Published: February 2021

ABSTRACTBackground and AimsA previous research study concluded that wine and beer labelled as lower in strength increase consumption compared with the same drinks labelled as regular strength. The label included both a verbal and numerical descriptor of strength. The present study aimed to estimate the effect of each of these label components.DesignAdaptive, parallel group randomised controlled trial, comprising an internal pilot sample (n1 = 90) and a confirmatory sample (n2 = 57).SettingUniversity bar laboratory in London, United Kingdom (UK).ParticipantsA total of 147 weekly wine drinkers were sampled from a nationally representative English panel.InterventionParticipants were randomised to one of three groups to taste test wine in a bar‐laboratory, varying only in the label displayed: (i) verbal descriptor only (Super Low); (ii) numerical descriptor only (4% alcohol by volume (ABV)); and (iii) verbal descriptor and numerical descriptor combined (Super Low 4%ABV) (each group n = 49).MeasurementsThe primary outcome was total volume (ml) of wine consumed.FindingsParticipants randomised to the numerical descriptor label group (4%ABV: M = 155.12 ml, B = 20.30; 95% CI = 3.92, 36.69; P value = 0.016) and combined verbal and numerical descriptor label group (Super Low 4%ABV: M = 154.59 ml, B = 20.68; 95% CI = 4.32, 37.04; P value = 0.014) drank significantly greater amounts than those randomised to the verbal descriptor label group (Super Low: M = 125.65 ml).ConclusionsThis bar laboratory study estimated that a greater quantity of ‘lower’ strength wine was consumed when the label included a numerical strength descriptor compared with a verbal only strength descriptor.
United colours of the city: A review about urbanisation impact on animal colours
Authors: Leveau Lucas 
Published: February 2021

AbstractHabitat colour gradients characterise urban areas: from green prevailing in the least urbanised areas dominated by lawn, shrubs and trees, to grey characteristic of heavily urbanised areas dominated by impervious surfaces. These changes may promote modifications in community composition and intraspecific colour changes in species occurring in urban areas. This review's objectives were: (1) to analyse reported patterns of animal colour change between urban and non‐urban areas; (2) to identify the main mechanisms underlying those patterns; and (3) to determine research bias and suggest future research directions. A bibliometric on animal colour patterns using Scopus resulted in 62 studies being found and their findings assessed. Most studies were focused on birds (N = 38) and were conducted in the Northern Hemisphere (N = 55), with 90% analysing intraspecific colour changes. Intraspecific studies found three main patterns: (1) urban melanism, with polymorphic species of insects, birds and reptiles showing darker colouration in urban areas than in non‐urban areas; (2) urban dullness, with carotenoid‐based plumage colours being duller in urban than in rural areas; and (3) a reduction in conspicuousness of sexually selected plumages in urban areas. Interspecific studies suggested that urban areas are filters for animal colours, promoting the colonisation of those species that increase camouflage or exhibit warning colours to predators. More studies are needed in the Southern Hemisphere and at the interspecific level to determine the role of animal colours in urban colonisation.
DNA damage contributes to transcriptional and immunological dysregulation of testicular cells during Chlamydia infection
Authors: Bryan Emily R. , Barrero Roberto A. , Cheung Eddie , Tickner Jacob A. D. , Trim Logan K. , Richard Derek , McLaughlin Eileen A. , Beagley Kenneth W. , Carey Alison J. 
Published: February 2021

AbstractChlamydia is the most commonly reported sexually transmitted bacterial infection, with 127 million notifications worldwide each year. Both males and females are susceptible to the pathological impacts on fertility that Chlamydia infections can induce. However, male chlamydial infections, particularly within the upper reproductive tract, including the testis, are not well characterized. In this study, using mouse testicular cell lines, we examined the impact of infection on testicular cell lineage transcriptomes and potential mechanisms for this impact. The somatic cell lineages exhibited significantly fragmented genomes during infection. Likely resulting from this, each of the Leydig, Sertoli and germ cell lineages experienced extensive transcriptional dysregulation, leading to significant changes in cellular biological pathways, including interferon and germ‐Sertoli cell signalling. The cell lineages, as well as isolated spermatozoa from infected mice, also contained globally hypomethylated DNA. Cumulatively, the DNA damage and epigenetic‐mediated transcriptional dysregulation observed within testicular cells during chlamydial infection could result in the production of spermatozoa with abnormal epigenomes, resulting in previously observed subfertility in infected animals and congenital defects in their offspring.
Improved estimates of mean pharmacokinetic parameters for increased accuracy in dosing and reduced risk to patients
Authors: Scutt Greg , Waxman David 
Published: February 2021

AimsPharmacokinetic equations, which relate different parameters of a single individual, are often applied to reported mean parameter‐values, with the aim of estimating the mean value of an unreported parameter. Due to population heterogeneity this approach generally leads to errors in their estimation. We provide details of this source of error. Our aim is to take into account the effects of population heterogeneity in commonly used pharmacokinetic models. This provides improved estimates and knowledge of the concentration of a drug in the plasma over time.MethodsInequalities and approximations for corrected mean estimates are derived. These results are then applied to published clinical‐trial data to illustrate their accuracy in practical situations.ResultsBy using mean values within the pharmacokinetic equations for a single individual, we show that estimates of mean parameter values, for a variety of dosing regimens, generally have errors. Using published clinical trial data, we show that such estimates can systematically deviate from the exact mean value by up to 19%. We provide analytical results, which amount to inequalities when there are systematic deviations from exact results, along with approximate results that improve the accuracy of estimates.ConclusionsMedical, pharmacy and nursing students should be educated about errors and inequalities that can arise when transforming reported mean values of pharmacokinetic parameters into the mean values of parameters that are required, but not reported. Using approximate results, that correct estimates of mean parameter values so that they more accurately reflect actual average values, may provide a practical solution.
A kernel regression model for panel count data with nonparametric covariate functions
Authors: Wang Yang , Yu Zhangsheng 
Published: February 2021

AbstractThe local kernel pseudo‐partial likelihood is employed for estimation in a panel count model with nonparametric covariate functions. An estimator of the derivative of the nonparametric covariate function is derived first, and the nonparametric function estimator is then obtained by integrating the derivative estimator. Uniform consistency rates and pointwise asymptotic normality are obtained for the local derivative estimator under some regularity conditions. Moreover, the baseline function estimator is shown to be uniformly consistent. Demonstration of the asymptotic results strongly relies on the modern empirical theory, which generally does not require the Poisson assumption. Simulation studies also illustrate that the local derivative estimator performs well in a finite‐sample regardless of whether the Poisson assumption holds. We also implement the proposed methodology to analyze a clinical study on childhood wheezing.
The Tukey trend test: Multiplicity adjustment using multiple marginal models
Authors: Schaarschmidt Frank , Ritz Christian , Hothorn Ludwig A. 
Published: February 2021

AbstractIn dose–response analysis, it is a challenge to choose appropriate linear or curvilinear shapes when considering multiple, differently scaled endpoints. It has been proposed to fit several marginal regression models that try sets of different transformations of the dose levels as explanatory variables for each endpoint. However, the multiple testing problem underlying this approach, involving correlated parameter estimates for the dose effect between and within endpoints, could only be adjusted heuristically. An asymptotic correction for multiple testing can be derived from the score functions of the marginal regression models. Based on a multivariate t‐distribution, the correction provides a one‐step adjustment of p‐values that accounts for the correlation between estimates from different marginal models. The advantages of the proposed methodology are demonstrated through three example datasets, involving generalized linear models with differently scaled endpoints, differing covariates, and a mixed effect model and through simulation results. The methodology is implemented in an R package.
Measuring adolescents’ beliefs in conspiracy theories: Development and validation of the Adolescent Conspiracy Beliefs Questionnaire (ACBQ)
Authors: Jolley Daniel , Douglas Karen M. , Skipper Yvonne , Thomas Eleanor , Cookson Darel 
Published: February 2021

Four studies (total n = 961) developed and validated the Adolescent Conspiracy Beliefs Questionnaire (ACBQ). Initial items were developed in collaboration with teachers. An exploratory factor analysis (Study 1, n = 208, aged 11–14) and a student focus group (N = 3, aged 11) enabled us to establish the factor structure of a 9‐item scale. This was replicated via confirmatory factor analysis in Study 2 (N = 178, aged 11–17), and the scale displayed good convergent (i.e., relationship with paranoia and mistrust) and discriminant validity (i.e., no relationship with extraversion). Study 3a (N = 257) further tested convergent validity with a sample of 18‐year‐olds (i.e., relationship with adult‐validated measures of conspiracy beliefs) and demonstrated strong test–retest reliability. Study 3b (N = 318) replicated these findings with a mixed‐age adult sample. The ACBQ will allow researchers to explore the psychological antecedents and consequences of conspiracy thinking in young populations.
Immune checkpoint inhibitors in advanced upper and lower tract urothelial carcinoma: a comparison of outcomes
Authors: Esagian Stepan M. , Khaki Ali Raza , Diamantopoulos Leonidas N. , Carril‐Ajuria Lucia , Castellano Daniel , De Kouchkovsky Ivan , Park Joseph J. , Alva Ajjai , Bilen Mehmet A. , Stewart Tyler F. , McKay Rana R. , Santos Victor S. , Agarwal Neeraj , Jain Jayanshu , Zakharia Yousef , Morales‐Barrera Rafael , Devitt Michael E. , Nelson Ariel , Hoimes Christopher J. , Shreck Evan , Gartrell Benjamin A. , Sankin Alex , Tripathi Abhishek , Zakopoulou Roubini , Bamias Aristotelis , Rodriguez‐Vida Alejo , Drakaki Alexandra , Liu Sandy , Kumar Vivek , Lythgoe Mark P. , Pinato David J. , Murgic Jure , Fröbe Ana , Joshi Monika , Isaacsson Velho Pedro , Hahn Noah , Alonso Buznego Lucia , Duran Ignacio , Moses Marcus , Barata Pedro , Galsky Matthew D. , Sonpavde Guru , Yu Evan Y. , Msaouel Pavlos , Koshkin Vadim S. , Grivas Petros 
Published: February 2021

ObjectivesTo compare clinical outcomes between patients with locally advanced (unresectable) or metastatic urothelial carcinoma (aUC) in the upper and lower urinary tract receiving immune checkpoint inhibitors (ICIs).Patients and MethodsWe performed a retrospective cohort study collecting clinicopathological, treatment, and outcome data for patients with aUC receiving ICIs from 2013 to 2020 across 24 institutions. We compared the objective response rate (ORR), overall survival (OS), and progression‐free survival (PFS) between patients with upper and lower tract UC (UTUC, LTUC). Uni‐ and multivariable logistic and Cox regression were used to assess the effect of UTUC on ORR, OS, and PFS. Subgroup analyses were performed stratified based on histology (pure, mixed) and line of treatment (first line, subsequent line).ResultsOut of a total of 746 eligible patients, 707, 717, and 738 were included in the ORR, OS, and PFS analyses, respectively. Our results did not contradict the hypothesis that patients with UTUC and LTUC had similar ORRs (24% vs 28%; adjusted odds ratio [aOR] 0.73, 95% confidence interval [CI] 0.43–1.24), OS (median 9.8 vs 9.6 months; adjusted hazard ratio [aHR] 0.93, 95% CI 0.73–1.19), and PFS (median 4.3 vs 4.1 months; aHR 1.01, 95% CI 0.81–1.27). Patients with mixed‐histology UTUC had a significantly lower ORR and shorter PFS vs mixed‐histology LTUC (aOR 0.20, 95% CI 0.05–0.91 and aHR 1.66, 95% CI 1.06–2.59), respectively).ConclusionOverall, patients with UTUC and LTUC receiving ICIs have comparable treatment response and outcomes. Subgroup analyses based on histology showed that those with mixed‐histology UTUC had a lower ORR and shorter PFS compared to mixed‐histology LTUC. Further studies and evaluation of molecular biomarkers can help refine patient selection for immunotherapy.