bluuebunny/crossref_metadata_2025_split huggingface dataset:
New evidence about HW Vir’s circumbinary planets from Hipparcos-Gaia astrometry and a reanalysis of the eclipse timing variations using nested sampling
Authors: Baycroft Thomas A , Triaud Amaury H M J , Kervella Pierre 
Published: September 2023

ABSTRACT
The post common-envelope eclipsing binary HW Virginis (HW Vir) has had many circumbinary companions proposed based on eclipse timing variations. Each proposed solution has lacked in predictability and orbital stability, leaving the origin of the eclipse timing variations an active area of research. Leveraging the catalogue of Hipparcos and Gaia proper motion anomalies, we show there is slight evidence for a circumbinary companion orbiting HW Vir. We place an upper limit in mass for such a companion which excludes some previously claimed companions. We also apply this method to V471 Tauri and confirm the non-detection of a previously claimed brown dwarf. We adapt the kima nested sampling code to analyse eclipse timing variations and re-analyse archival data on HW Vir, varying the order of the ephemeris that we fit for and the amount of the data that we use. Although signals are clearly present, we find two signals around 2500 and 4000-d periods that are not coherent between different chunks of the data, so are likely to not be of planetary origin. We analyse the whole data set and find the best solution to contain four signals. Of these four we argue the outermost is the most compatible with astrometry and thus the most likely to be of planetary nature. We posit the other three pseudo-periodic signals are caused by physical processes on the white dwarf. The eventual release of the full Gaia epoch astrometry is a promising way to confirm whether circumbinary planets exist around HW Vir (and other similar systems), and explore white dwarf physics.
Evaluating the Accuracy of Methods for Detecting Correlated Rates of Molecular and Morphological Evolution
Authors: Asar Yasmin , Sauquet Hervé , Ho Simon Y W 
Published: September 2023

Abstract
Determining the link between genomic and phenotypic change is a fundamental goal in evolutionary biology. Insights into this link can be gained by using a phylogenetic approach to test for correlations between rates of molecular and morphological evolution. However, there has been persistent uncertainty about the relationship between these rates, partly because conflicting results have been obtained using various methods that have not been examined in detail. We carried out a simulation study to evaluate the performance of 5 statistical methods for detecting correlated rates of evolution. Our simulations explored the evolution of molecular sequences and morphological characters under a range of conditions. Of the methods tested, Bayesian relaxed-clock estimation of branch rates was able to detect correlated rates of evolution correctly in the largest number of cases. This was followed by correlations of root-to-tip distances, Bayesian model selection, independent sister-pairs contrasts, and likelihood-based model selection. As expected, the power to detect correlated rates increased with the amount of data, both in terms of tree size and number of morphological characters. Likewise, greater among-lineage rate variation in the data led to improved performance of all 5 methods, particularly for Bayesian relaxed-clock analysis when the rate model was mismatched. We then applied these methods to a data set from flowering plants and did not find evidence of a correlation in evolutionary rates between genomic data and morphological characters. The results of our study have practical implications for phylogenetic analyses of combined molecular and morphological data sets, and highlight the conditions under which the links between genomic and phenotypic rates of evolution can be evaluated quantitatively.
Two Notorious Nodes: A Critical Examination of Relaxed Molecular Clock Age Estimates of the Bilaterian Animals and Placental Mammals
Authors: Budd Graham E , Mann Richard P 
Published: September 2023

Abstract
The popularity of relaxed clock Bayesian inference of clade origin timings has generated several recent publications with focal results considerably older than the fossils of the clades in question. Here, we critically examine two such clades: the animals (with a focus on the bilaterians) and the mammals (with a focus on the placentals). Each example displays a set of characteristic pathologies which, although much commented on, are rarely corrected for. We conclude that in neither case does the molecular clock analysis provide any evidence for an origin of the clade deeper than what is suggested by the fossil record. In addition, both these clades have other features (including, in the case of the placental mammals, proximity to a large mass extinction) that allow us to generate precise expectations of the timings of their origins. Thus, in these instances, the fossil record can provide a powerful test of molecular clock methodology, and why it goes astray, and we have every reason to think these problems are general. [Cambrian explosion; mammalian evolution; molecular clocks.]
Cophylogeny Reconstruction Allowing for Multiple Associations Through Approximate Bayesian Computation
Authors: Sinaimeri Blerina , Urbini Laura , Sagot Marie-France , Matias Catherine 
Published: September 2023

Abstract
Phylogenetic tree reconciliation is extensively employed for the examination of coevolution between host and symbiont species. An important concern is the requirement for dependable cost values when selecting event-based parsimonious reconciliation. Although certain approaches deduce event probabilities unique to each pair of host and symbiont trees, which can subsequently be converted into cost values, a significant limitation lies in their inability to model the invasion of diverse host species by the same symbiont species (termed as a spread event), which is believed to occur in symbiotic relationships. Invasions lead to the observation of multiple associations between symbionts and their hosts (indicating that a symbiont is no longer exclusive to a single host), which are incompatible with the existing methods of coevolution. Here, we present a method called AmoCoala (an enhanced version of the tool Coala) that provides a more realistic estimation of cophylogeny event probabilities for a given pair of host and symbiont trees, even in the presence of spread events. We expand the classical 4-event coevolutionary model to include 2 additional outcomes, vertical and horizontal spreads, that lead to multiple associations. In the initial step, we estimate the probabilities of spread events using heuristic frequencies. Subsequently, in the second step, we employ an approximate Bayesian computation approach to infer the probabilities of the remaining 4 classical events (cospeciation, duplication, host switch, and loss) based on these values. By incorporating spread events, our reconciliation model enables a more accurate consideration of multiple associations. This improvement enhances the precision of estimated cost sets, paving the way to a more reliable reconciliation of host and symbiont trees. To validate our method, we conducted experiments on synthetic datasets and demonstrated its efficacy using real-world examples. Our results showcase that AmoCoala produces biologically plausible reconciliation scenarios, further emphasizing its effectiveness.
Assessing the potential molecular mechanism of arsenite-induced skin cell senescence
Authors: Du Sufei , Yang Fan , Wu Liping , Hu Dexiu , Zhang Yuhong , Gong Maoyuan , Yang Yang , Yang Xingcan , Zeng Qibing 
Published: September 2023

Abstract
Arsenic exposure is a public health concern worldwide. Skin damage, as a typical lesion of arsenic exposure, the mechanism is still unknown. Studies have found that cellular senescence plays a key role in arsenic-induced skin damage, and the previous research found that the ERK/CEBPB signaling pathway may be an important molecular event of arsenic-induced skin cell senescence, but its specific mechanism is unknown. In this study, genetic engineering technology was used to construct stable HaCaT cell lines, and the role and mechanism of ERK/CEBPB signaling pathway in arsenic-induced HaCaT cell senescence were verified by knockdown and overexpression of ERK and CEBPB in both forward and backward. It was found that knockdown of CEBPB or ERK can downregulate the ERK/CEBPB signaling pathway and reduce arsenic-induced skin cell senescence. In contrast to knockdown, overexpression of CEBPB or ERK can upregulate the ERK/CEBPB signaling pathway and aggravate the senescence of skin cells caused by arsenic. These findings suggest that sodium arsenite can further promote SASP secretion and the expression of p53, p21 and p16 INK4a by activating the ERK/CEBPB signaling pathway, induce cell cycle arrest and trigger cellular senescence.
Gestational ozone inhalation elicits maternal cardiac dysfunction and transcriptional changes to placental pericytes and endothelial cells
Authors: Hunter Russell , Baird Brenna , Garcia Marcus , Begay Jessica , Goitom Siem , Lucas Selita , Herbert Guy , Scieszka David , Padilla Jamie , Brayer Kathryn , Ottens Andrew K , Suter Melissa A , Barrozo Enrico R , Hines Curt , Bleske Barry , Campen Matthew J 
Published: September 2023

Abstract
Ozone (O3) is a criteria air pollutant with the most frequent incidence of exceeding air quality standards. Inhalation of O3 is known to cause lung inflammation and consequent systemic health effects, including endothelial dysfunction. Epidemiologic data have shown that gestational exposure to air pollutants correlates with complications of pregnancy, including low birth weight, intrauterine growth deficiency, preeclampsia, and premature birth. Mechanisms underlying how air pollution may facilitate or exacerbate gestational complications remain poorly defined. The current study sought to uncover how gestational O3 exposure impacted maternal cardiovascular function, as well as the development of the placenta. Pregnant mice were exposed to 1PPM O3 or a sham filtered air (FA) exposure for 4 h on gestational day (GD) 10.5, and evaluated for cardiac function via echocardiography on GD18.5. Echocardiography revealed a significant reduction in maternal stroke volume and ejection fraction in maternally exposed dams. To examine the impact of maternal O3 exposure on the maternal-fetal interface, placentae were analyzed by single-cell RNA sequencing analysis. Mid-gestational O3 exposure led to significant differential expression of 4021 transcripts compared with controls, and pericytes displayed the greatest transcriptional modulation. Pathway analysis identified extracellular matrix organization to be significantly altered after the exposure, with the greatest modifications in trophoblasts, pericytes, and endothelial cells. This study provides insights into potential molecular processes during pregnancy that may be altered due to the inhalation of environmental toxicants.
Postoperative Discharge to Acute Rehabilitation or Skilled Nursing Facility Compared With Home Does Not Reduce Hospital Readmissions, Return to Surgery, or Improve Outcomes Following Adult Spine Deformity Surgery
Authors: Bess Shay , Line Breton G. , Nunley Pierce , Ames Christopher , Burton Douglas , Mundis Gregory , Eastlack Robert , Hart Robert , Gupta Munish , Klineberg Eric , Kim Han Jo , Kelly Michael , Hostin Richard , Kebaish Khaled , Lafage Virgine , Lafage Renaud , Schwab Frank , Shaffrey Christopher , Smith Justin S. ,   International Spine Study Group
Published: September 2023

Study Design.
Retrospective review of a prospective multicenter adult spinal deformity (ASD) study.

Objective.
The aim of this study was to evaluate 30-day readmissions, 90-day return to surgery, postoperative complications, and patient-reported outcomes (PROs) for matched ASD patients receiving nonhome discharge (NON), including acute rehabilitation (REHAB), and skilled nursing facility (SNF), or home (HOME) discharge following ASD surgery.

Summary of Background Data.
Postoperative disposition following ASD surgery frequently involves nonhome discharge. Little data exists for longer term outcomes for ASD patients receiving nonhome discharge versus patients discharged to home.

Materials and Methods.
Surgically treated ASD patients prospectively enrolled into a multicenter study were assessed for NON or HOME disposition following hospital discharge. NON was further divided into REHAB or SNF. Propensity score matching was used to match for patient age, frailty, spine deformity, levels fused, and osteotomies performed at surgery. Thirty-day hospital readmissions, 90-day return to surgery, postoperative complications, and 1-year and minimum 2-year postoperative PROs were evaluated.

Results.
A total of 241 of 374 patients were eligible for the study. NON patients were identified and matched to HOME patients. Following matching, 158 patients remained for evaluation; NON and HOME had similar preoperative age, frailty, spine deformity magnitude, surgery performed, and duration of hospital stay (P>0.05). Thirty-day readmissions, 90-day return to surgery, and postoperative complications were similar for NON versus HOME and similar for REHAB (N=64) versus SNF (N=42) versus HOME (P>0.05). At 1-year and minimum 2-year follow-up, HOME demonstrated similar to better PRO scores including Oswestry Disability Index, Short-Form 36v2 questionnaire Mental Component Score and Physical Component Score, and Scoliosis Research Society scores versus NON, REHAB, and SNF (P<0.05).

Conclusions.
Acute needs must be considered following ASD surgery, however, matched analysis comparing 30-day hospital readmissions, 90-day return to surgery, postoperative complications, and PROs demonstrated minimal benefit for NON, REHAB, or SNF versus HOME at 1- and 2-year follow-up, questioning the risk and cost/benefits of routine use of nonhome discharge.

Level of Evidence.
Level III—prognostic.
Cognition, Academic Achievement, Adaptive Behavior, and Quality of Life in Child and Adolescent Boys with Klinefelter Syndrome
Authors: Jordan Tracy L. , Foland-Ross Lara C. , Wun Vanessa L. , Ross Judith L. , Reiss Allan L. 
Published: September 2023

Abstract:

Objective:
Klinefelter syndrome (KS; 47, XXY), the most common sex chromosome aneuploidy in males, is characterized by testicular failure and testosterone deficiency as well as a variety of cognitive, social, and emotional challenges. In the current study, we aimed to clarify the cognitive-behavioral profile of peripubertal boys with KS using measures of cognition, academic achievement, adaptive behavior, and quality of life.

Method:
We compared 47 boys with KS (7–16 years of age) with 55 performance IQ-matched boys without KS on measures of cognition (WISC-V), executive function (BRIEF-2), academic achievement (KTEA-3), adaptive behavior (Vineland-3), and quality of life (PROMIS). In exploratory analyses, we examined associations among these measures and potential associations with pubertal metrics.

Results:
Boys with KS demonstrated a significantly different profile of cognition, behavioral ratings of executive function, academic achievement, adaptive behavior, and quality of life compared with their typically developing peers, with, on average, lower functioning. The groups showed significantly different correlations between cognition and aspects of quality of life. No associations were observed between behavior and pubertal development.

Conclusion:
Taken together, these findings indicated that boys with KS are at increased risk for cognitive difficulties, which may affect academic achievement, adaptive behavior, and quality of life. Although initial exploratory analyses indicated that the magnitude of these alterations was not correlated with severity of testicular failure, longitudinal analyses currently being conducted by our group may help clarify the trajectory of these difficulties through the pubertal transition and testosterone replacement.
Complex Attention-Deficit/Hyperactivity Disorder in a Bilingual Child with Down Syndrome and Intellectual Disability
Authors: Moore Trevena , Soccorso Cara , Fogler Jason , Carroll Gretchen , Froehlich Tanya , Nyp Sarah S. 
Published: September 2023

CASE:
Maria is an 8-year-old girl with Down syndrome, described by her mother as an affectionate and social child, who was referred to developmental-behavioral pediatrics by her pediatrician because of increasing aggressive behaviors and inattention.
Maria was 5 pounds at birth, delivered full-term by cesarean section, and hospitalized for 1 month after delivery because of feeding issues that required a nasogastric (NG) tube. Maternal age was 24 years, pregnancy was uncomplicated, and there were no reported prenatal exposures to substances. Additional medical history includes corrective cardiac surgery at age 11 months, mild-to-moderate hearing loss in 1 ear, and myopia.
At the time of Maria's presentation to developmental-behavioral pediatrics, she was in third grade and had an IEP with placement in a substantially separate multigrade classroom and inclusion for special classes such as music and art. She had multiple academic goals and accommodations for behaviors such as eloping from class, shoving, and growling at adults; communication Picture Exchange Communication System (PECS); and extended time to complete assignments. Previously, she had attended an inclusion setting with a 1:1 aide. Maria is followed annually at a specialty clinic that focuses on the health needs of children with Down syndrome. At home, Maria's parents speak primarily Spanish, while her 2 older brothers speak primarily English. Maria has been using 3-word phrases since she was 6 years old and understands some American Sign Language. She also uses a PECS book for communication.
During the visit, Maria was notably fidgety, frequently interrupted the parent interview despite having toys to play with, and became aggressive—hitting, kicking, pushing, and shoving—when she did not want to comply with directives. She used mostly single words and a variety of gestures to communicate. Both the parent-completed and teacher-completed Conners-3 (Long Version) produced elevated T-scores (>70) in the domains of inattention, hyperactivity/impulsivity, defiance/aggression, peer relations, Global Index scale, DSM-5 Hyperactive/Impulsive symptom scale, and DSM-5 Conduct Disorder symptom scale. The teacher endorsed full criteria for attention-deficit/hyperactivity disorder, consistent with combined presentation, and the parent endorsed symptoms in a similar pattern. Methylphenidate (2.5 mg) was trialed but tolerated poorly when it was titrated to 5 mg. Maria's mother reported that Maria's focus was somewhat better, but she was easily brought to tears and “not herself.”
What would be the next steps in Maria's evaluation/treatment? Could there be reasons for her worsening behavior other than a primary attention disorder?
Hepatic farnesoid X receptor is necessary to facilitate ductular reaction and expression of heme biosynthetic genes
Authors: Dean Angela E. , Jungwirth Emilian , Panzitt Katrin , Wagner Martin , Anakk Sayeepriyadarshini 
Published: September 2023

Background:
Bile, which contains bile acids, the natural ligands for farnesoid x receptor (FXR), moves from the liver to the intestine through bile ducts. Ductular reaction often occurs during biliary obstruction. A subset of patients with erythropoietic protoporphyria, an inherited genetic mutation in heme biosynthetic enzyme ferrochelatase, accumulate porphyrin-containing bile plugs, leading to cholestasis. Here, we examined the link between FXR, bile plug formation, and how heme biosynthesis relates to this connection.

Methods:
We treated female and male wild-type and global and tissue-specific Fxr knockout mice with a diet containing 3,5-diethoxycarbonyl-1,4-dihydrocollidine, an inhibitor of ferrochelatase, and examined the expression of heme biosynthetic genes. We mined FXR mouse ChIP-Seq data, performed biochemical and histological analysis, and tested HepG2 and primary human hepatocytes after treatment with obeticholic acid, an FXR agonist.

Results:
We observed that hepatic but not intestinal Fxr loss resulted in reduced bile plugs and ductular reaction in the liver. Then, we examined if FXR plays a regulatory role in heme biosynthesis and found significantly lower porphyrin accumulation in 3,5-diethoxycarbonyl-1, 4-dihydrocollidine–fed Fxr knockout mice. Gene expression and FXR mouse ChIP-Seq atlas analysis revealed that FXR orchestrates the expression of multiple heme biosynthetic enzymes. Finally, human HepG2 cells and primary human hepatocytes treated with obeticholic acid, showed increased expression of several heme biosynthetic genes.

Conclusions:
Overall, our data show that hepatic Fxr is necessary to maintain ductular reaction and accumulation of bile plugs. FXR can direct the expression of multiple heme biosynthetic genes. Thus, modulating FXR activity in EPP patients may help alleviate its associated liver disease.
Single-cell immune profiling of mouse liver aging reveals Cxcl2 + macrophages recruit neutrophils to aggravate liver injury
Authors: Liu Yasong , Xiao Jiaqi , Cai Jianye , Li Rong , Sui Xin , Zhang Jiebin , Lu Tongyu , Chen Haitian , Chen Guihua , Li Haibo , Jiang Chenhao , Zhao Xuegang , Xiao Cuicui , Lei Yunguo , Yao Jia , Lv Guo , Liang Jinliang , Zhang Yingcai , Yang Jian-Rong , Zheng Jun , Yang Yang 
Published: September 2023

Background and Aims:
Immune cells play a crucial role in liver aging. However, the impact of dynamic changes in the local immune microenvironment on age-related liver injury remains poorly understood. We aimed to characterize intrahepatic immune cells at different ages to investigate key mechanisms associated with liver aging.

Approach and Results:
We carried out single-cell RNA sequencing on mouse liver tissues at 4 different ages, namely, the newborn, suckling, young, and aged stages. The transcriptomic landscape, cellular classification, and intercellular communication were analyzed. We confirmed the findings by multiplex immunofluorescence staining, flow cytometry, in vitro functional experiments, and chimeric animal models. Nine subsets of 89,542 immune cells with unique properties were identified, of which Cxcl2
+ macrophages within the monocyte/macrophage subset were preferentially enriched in the aged liver. Cxcl2
+ macrophages presented a senescence-associated secretory phenotype and recruited neutrophils to the aged liver through the CXCL2-CXCR2 axis. Through the secretion of IL-1β and TNF-α, Cxcl2
+ macrophages stimulated neutrophil extracellular traps formation. Targeting the CXCL2-CXCR2 axis limited the neutrophils migration toward the liver and attenuated age-related liver injury. Moreover, the relationship between Cxcl2
+ macrophages and neutrophils in age-related liver injury was further validated by human liver transplantation samples.

Conclusions:
This in-depth study illustrates that the mechanism of Cxcl2
+ macrophage-driven neutrophil activation involves the CXCL2-CXCR2 axis and provides a potential therapeutic strategy for age-related liver injury.