bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testing the accuracy of 3D automatic landmarking via genome-wide association studies
Authors: Savriama Yoland , Tautz Diethard 
Published: December 2021

Abstract
Various advances in 3D automatic phenotyping and landmark-based geometric morphometric methods have been made. While it is generally accepted that automatic landmarking compromises the capture of the biological variation, no studies have directly tested the actual impact of such landmarking approaches in analyses requiring a large number of specimens and for which the precision of phenotyping is crucial to extract an actual biological signal adequately. Here, we use a recently developed 3D atlas-based automatic landmarking method to test its accuracy in detecting QTLs associated with craniofacial development of the house mouse skull and lower jaws for a large number of specimens (circa 700) that were previously phenotyped via a semiautomatic landmarking method complemented with manual adjustment. We compare both landmarking methods with univariate and multivariate mapping of the skull and the lower jaws. We find that most significant SNPs and QTLs are not recovered based on the data derived from the automatic landmarking method. Our results thus confirm the notion that information is lost in the automated landmarking procedure although somewhat dependent on the analyzed structure. The automatic method seems to capture certain types of structures slightly better, such as lower jaws whose shape is almost entirely summarized by its outline and could be assimilated as a 2D flat object. By contrast, the more apparent 3D features exhibited by a structure such as the skull are not adequately captured by the automatic method. We conclude that using 3D atlas-based automatic landmarking methods requires careful consideration of the experimental question.
Genome assembly of Danaus chrysippus and comparison with the Monarch Danaus plexippus
Authors: Singh Kumar Saurabh , De-Kayne Rishi , Omufwoko Kennedy Saitoti , Martins Dino J , Bass Chris , ffrench-Constant Richard , Martin Simon H 
Published: December 2021

Abstract
Milkweed butterflies in the genus Danaus are studied in a diverse range of research fields including the neurobiology of migration, biochemistry of plant detoxification, host–parasite interactions, evolution of sex chromosomes, and speciation. We have assembled a nearly chromosomal genome for Danaus chrysippus (known as the African Monarch, African Queen, and Plain Tiger) using long-read sequencing data. This species is of particular interest for the study of genome structural change and its consequences for evolution. Comparison with the genome of the North American Monarch Danaus plexippus reveals generally strong synteny but highlights 3 inversion differences. The 3 chromosomes involved were previously found to carry peaks of intraspecific differentiation in D. chrysippus in Africa, suggesting that these inversions may be polymorphic and associated with local adaptation. The D. chrysippus genome is over 40% larger than that of D. plexippus, and nearly all of the additional ∼100 Megabases of DNA comprises repeats. Future comparative genomic studies within this genus will shed light on the evolution of genome architecture.
Sex-Specific Effect of Blood Oxygen-Carrying Capacity on Orthostatic Tolerance in Older Individuals
Authors: Diaz-Canestro Candela , Montero David 
Published: December 2021

Abstract
Blood oxygen (O2)-carrying capacity is reduced with aging and has been previously linked with the capacity to withstand the upright posture, that is, orthostatic tolerance (OT). This study experimentally tested the hypothesis that a definite reduction in blood O2-carrying capacity via hemoglobin manipulation differently affects the OT of older women and men as assessed by lower body negative pressure (LBNP). Secondary hemodynamic parameters were determined with transthoracic echocardiography throughout incremental LBNP levels for 1 hour or until presyncope in healthy older women and men (total n = 26) matched by age (64 ± 7 vs 65 ± 8 years, p &lt; .618) and physical activity levels. Measurements were repeated within a week period after a 10% reduction of blood O2-carrying capacity via carbon monoxide rebreathing and analyzed via 2-way analysis of covariance. In the assessment session, OT time was similar between women and men (53.5 ± 6.1 vs 56.4 ± 6.0 minutes, p = .238). Following a 10% reduction of blood O2-carrying capacity, OT time was reduced in women compared with men (51.3 ± 7.0 vs 58.2 ± 2.8 minutes, p = .003). The effect of reduced O2-carrying capacity on OT time differed between sexes (mean difference [MD] = −5.30 minutes, p = .010). Prior to presyncope, reduced O2-carrying capacity resulted in lower left ventricular end-diastolic volume (MD = −8.11 mL∙m−2, p = .043) and stroke volume (MD = −8.04 mL∙m−2, 95% confidence interval = −14.36, −1.71, p = .018) in women relative to men, even after adjusting for baseline variables. In conclusion, present results suggest that reduced blood O2-carrying capacity specifically impairs OT and its circulatory determinants in older women.
Assessment of a claimed ultra-low frequency electromagnetic (ULFEM) earthquake precursor
Authors: Wang Can , Christman Lilianna E , Klemperer Simon L , Glen Jonathan M , McPhee Darcy K , Chen Bin 
Published: December 2021

SUMMARY
The rate of occurrence of anomalous ultra-low frequency electromagnetic (ULFEM) pulses has been claimed to have increased days to weeks prior to the M5.4 2007 and M4.0 2010 Alum Rock earthquakes. We re-examine the previously reported ultra-low frequency (ULF: 0.01–10 Hz) magnetic data recorded at a QuakeFinder site located 9 km from the earthquake hypocentre, and compare to data from a nearby Stanford-USGS site located 42 km from the hypocentre, to analyse the characteristics of the pulses and assess their origin. Using pulse definitions and pulse-counting algorithms analogous to those previously reported, we corroborate the increase in pulse counts before the 2007 Alum Rock earthquake at the QuakeFinder station, but we note that the number of pulses depends on chosen temporal and amplitude detection thresholds. These thresholds are arbitrary because we lack a clear physical model or basis for their selection. We do not see the same increase in pulse counts before the 2010 Alum Rock earthquake at the QuakeFinder or Stanford-USGS stations. In addition, the majority of pulses in the QuakeFinder data and Stanford-USGS data do not match temporally, indicating the pulses lack a common origin and are not from lightning or solar-driven ionospheric/magnetospheric disturbances. Our assessment of the temporal distribution of pulse counts shows pulse counts increase during peak human activity hours, suggesting these pulses result from local cultural noise and are not tectonic in origin. The many unknowns about the character and even existence of precursory earthquake pulses means that standard numerical and statistical tests cannot easily be applied. Yet here we show that exhaustive investigation of many different aspects of ULFEM signals can be used to properly characterize their origin.
Paraquat sorption- and organic matter-induced modifications of soil spectral induced polarization (SIP) signals
Authors: Mellage Adrian , Zakai Gal , Efrati Bar , Pagel Holger , Schwartz Nimrod 
Published: December 2021

SUMMARY
Quantifying the capacity of soils to immobilize sorbing contaminants of concern relies on batch sorption experiments, typically performed at skewed solid-to-liquid ratios. The geophysical method spectral induced polarization (SIP) provides a powerful non-invasive monitoring alternative that can capture changes in soil electrical properties driven by contaminant sorption, yielding an approach whereby immobilization can be monitored in situ. Here, we present SIP signals obtained from a series of columns packed with a water saturated natural sandy-loam soil, with and without solid organic matter (SOM) amendment, contaminated with increasing concentrations of the herbicide paraquat. Our results highlight that soil polarization drops proportional to increasing amounts of sorbed paraquat in the SOM-free soil, exhibiting a Langmuir-type leveling-off behaviour. The addition of 8 percent-SOM yielded an increase in both the real ($\sigma ^{\prime}$) and imaginary ($\sigma ^{\prime\prime}$) conductivity of the uncontaminated treatment, driven by the contribution of charged sites in the SOM. Further, SOM modified the dependence between $\sigma ^{\prime\prime}$ and sorbed paraquat, likely driven by continued polarization within the polydisperse SOM with continued paraquat addition. However, the time constant ($\tau $), derived using the Cole–Cole model, shed light on a saturation-type dependence governed by a drop in ion mobility with increasing sorption. Thus, aiding the interpretation of sorption-driven SIP signals.
Abnormal activation of Yap/Taz contributes to the pathogenesis of tuberous sclerosis complex
Authors: Terry Bethany K , Park Raehee , Cho Seo-Hee , Crino Peter B , Kim Seonhee 
Published: December 2021

AbstractThe multi-systemic genetic disorder tuberous sclerosis complex (TSC) impacts multiple neurodevelopmental processes including neuronal morphogenesis, neuronal migration, myelination and gliogenesis. These alterations contribute to the development of cerebral cortex abnormalities and malformations. Although TSC is caused by mTORC1 hyperactivation, cognitive and behavioral impairments are not improved through mTORC1 targeting, making the study of the downstream effectors of this complex important for understanding the mechanisms underlying TSC. As mTORC1 has been shown to promote the activity of the transcriptional co-activator Yap, we hypothesized that altered Yap/Taz signaling contributes to the pathogenesis of TSC. We first observed that the levels of Yap/Taz are increased in human cortical tuber samples and in embryonic cortices of Tsc2 conditional knockout (cKO) mice. Next, to determine how abnormal upregulation of Yap/Taz impacts the neuropathology of TSC, we deleted Yap/Taz in Tsc2 cKO mice. Importantly, Yap/Taz/Tsc2 triple conditional knockout (tcKO) animals show reduced cortical thickness and cortical neuron cell size, despite the persistence of high mTORC1 activity, suggesting that Yap/Taz play a downstream role in cytomegaly. Furthermore, Yap/Taz/Tsc2 tcKO significantly restored cortical and hippocampal lamination defects and reduced hippocampal heterotopia formation. Finally, the loss of Yap/Taz increased the distribution of myelin basic protein in Tsc2 cKO animals, consistent with an improvement in myelination. Overall, our results indicate that targeting Yap/Taz lessens the severity of neuropathology in a TSC animal model. This study is the first to implicate Yap/Taz as contributors to cortical pathogenesis in TSC and therefore as potential novel targets in the treatment of this disorder.
Integrin CD11b provides a new marker of pre-germinal center IgA+ B cells in murine Peyer’s patches
Authors: Gao Peng , Adachi Takahiro , Okai Shinsaku , Morita Naoki , Kitamura Daisuke , Shinkura Reiko 
Published: December 2021

Abstract
Activated B cells can enter germinal centers (GCs) for affinity maturation to produce high-affinity antibodies. However, which activated B cells will enter GCs remains unknown. Here, we found a small population of CD11b+IgA+ B cells located outside of GCs in murine Peyer’s patches (PPs). After injection of the CD11b+IgA+ PP B cells into a PP of a recipient mouse, they entered GCs forty hours later. They expressed GC surface markers and pre-GC B cell genes, suggesting that CD11b provides a novel surface marker of pre-GC IgA+ B cells in murine PPs. Furthermore, independently of dendritic cell activation, CD11b expression on B cells can be induced by bacterial antigens, such as pam3CSK4 and heat-killed Escherichia coli in vitro. In addition, mice orally administered with pam3CSK4 or heat-killed E. coli increased the number of PP GC B cells within two days, and enhanced the mucosal antigen-specific IgA response. Our results demonstrate that the induction of CD11b on B cells is a promising marker for selecting an effective mucosal vaccine adjuvant.
Molecular Biologic and Epidemiologic Insights for Preventability of Colorectal Cancer
Authors: Giovannucci Edward 
Published: December 2021

Abstract
The etiology of colorectal cancer (CRC) has been informed from both a molecular biology perspective, which concerns the study of the nature, timing, and consequences of mutations in driver genes, and epidemiology, which focuses on identifying risk factors for cancer. For the most part, these fields have developed independently, and it is thus important to consider them in a more integrated manner. The molecular mutational perspective has stressed the importance of mutations due to replication of adult stem cells, and the molecular fingerprint of most CRCs does not suggest the importance of direct carcinogens. Epidemiology has identified numerous modifiable risk factors that account for most CRCs, most of which are not direct mutagens. The distribution of CRCs across the large bowel is not uniform, which is possibly caused by regional differences in the microbiota. Some risk factors are likely to act through or interact with the microbiota. The mutational perspective informs when risk factors may begin to operate in life and when they may cease to operate. Evidence from the mutational model and epidemiology supports that CRC risk factors begin early in life and may contribute to the risk of early-onset CRC. Later in carcinogenesis, there may be a “point of no return” when sufficient mutations have accumulated, and some risk factors do not affect cancer risk. This period may be at least 5-15 years for some risk factors. A more precise knowledge of timing of risk factor to cancer is required to inform preventive efforts.
Self-Efficacy Among Caregivers of Children With Food Allergy: A Cohort Study
Authors: Pappalardo Andrea A , Herbert Linda , Warren Christopher , Lombard Lisa , Ramos Ashley , Asa’ad Amal , Sharma Hemant , Tobin Mary C , Choi Jonathan , Hultquist Haley , Jiang Jialing , Kulkarni Ashwin , Mahdavinia Mahboobeh , Vincent Eileen , Gupta Ruchi 
Published: December 2021

Abstract

Objective
The prevalence of pediatric food allergy (FA) is increasing and, due to early disease onset, requires significant caregiver management that is associated with psychosocial burden. Caregiver perception of how they cope and handle FA-related events (self-efficacy) has been linked to psychosocial outcomes in racially/geographically homogenous samples. This study explores FA-related caregiver self-efficacy and associations with FA-related caregiver quality of life (QoL) in a diverse cohort.

Methods
Caregivers of children, diagnosed with IgE-mediated FA who identified as non-Hispanic Black or White, were recruited from U.S. academic allergy clinics. Caregivers completed demographic and medical questionnaires, the Food Allergy Self-Efficacy Scale for Parents (FASE-P), Food Allergy Independent Measure—Parent Form (FAIM), and the Food Allergy Quality of Life—Parental Burden (FAQL-PB). Bivariate and multivariate associations estimated relationships between study variables.

Results
Caregivers of 365 children (Mage = 5.8 years, 62.2% male, 31.1% Black) were enrolled. Caregivers reported high FA self-efficacy (M = 82.06/100), moderate perceptions of risk/FA severity (FAIM: M = 3.9/7), and some limitations on the FAQL-PB (M = 3.9/7). Self-efficacy was related to lower perceptions of risk/FA severity across all demographic groups (r = −.42, p &lt; .001). Caregivers who reported higher self-efficacy reported better QoL, particularly Black caregivers (r = .67).

Conclusions
In this sample of caregivers of children with FA, greater self-efficacy was related to improved QoL regardless of sociodemographic factors. Caregivers’ perception of risk was lower for those with greater self-efficacy. Future research into the impact of FA management on QoL among diverse caregivers is needed.
Study on the protective effect and mechanism of Liriodendrin on radiation enteritis in mice
Authors: Li Jiajun , Zheng Xin , Li Xiong , Yang Jing , Liu Wei , Yang Lei , Liu Bin 
Published: December 2021

Abstract
Patients receiving pelvic or abdominal radiotherapy may experience acute and/or chronic side effects due to gastrointestinal changes. However, effective medicine for treating radiation enteritis has not been found yet. Sargentodoxa cuneata is a famous Chinese medicine used to treat intestinal inflammation, and our research team has found the main biologically active compound through its extraction, which is Liriodendrin. In this study, we found that Liriodendrin can reduce the expression of Cer, Cer1P and S1P in the sphingolipid pathway, thereby reducing the histological damage to the intestinal tract of mice and inhibiting the apoptosis of intestinal tissue cells. In addition, Liriodendrin can reduce the levels of pro-inflammatory cytokines (IL-6 and TNF-α), and it is suggested through flow cytometry that the proportion of neutrophils in the intestinal tissue can decrease due to the existence of Liriodendrin. At the same time, the western blot evaluation revealed that Liriodendrin significantly inhibited the activation of Bcl-2/Bax/Caspase-3 and NF-κB signaling pathways. The results show that Liriodendrin can inhibit intestinal inflammation and intestinal cell apoptosis through the sphingolipid pathway. Therefore, the aforementioned results demonstrated that Liriodendrin may be a promising drug for the treatment of radiation enteritis.
Metabolite shift in Medicago truncatula occurs in phosphorus deprivation
Authors: Dokwal Dhiraj , Cocuron Jean-Christophe , Alonso Ana Paula , Dickstein Rebecca 
Published: December 2021

Abstract
Symbiotic nitrogen (N) fixation entails successful interaction between legume hosts and rhizobia that occur in specialized organs called nodules. N-fixing legumes have a higher demand for phosphorus (P) than legumes grown on mineral N. Medicago truncatula is an important model plant for characterization of effects of P deficiency at the molecular level. Hence, a study was carried out to address the alteration in metabolite levels of M. truncatula grown aeroponically and subjected to 4 weeks of P stress. First, GC-MS-based untargeted metabolomics initially revealed changes in the metabolic profile of nodules, with increased levels of amino acids and sugars and a decline in amounts of organic acids. Subsequently, LC-MS/MS was used to quantify these compounds including phosphorylated metabolites in the whole plant. Our results showed a drastic reduction in levels of organic acids and phosphorylated compounds in –P leaves, with a moderate reduction in –P roots and nodules. Additionally, sugars and amino acids were elevated in the whole plant under P deprivation. These findings provide evidence that N fixation in M. truncatula is mediated through a N feedback mechanism that in parallel is related to carbon and P metabolism.
Precision Medicine—A Demand Signal for Genomics Education
Authors: Doll Bruce , De Castro Mauricio J , Fries Melissa H , Pock Arnyce R , Seibert Diane , Yang Wendy 
Published: December 2021

ABSTRACT
Pressed by the accumulating knowledge in genomics and the proven success of the translation of cancer genomics to clinical practice in oncology, the Obama administration unveiled a $215 million commitment for the Precision Medicine Initiative (PMI) in 2016, a pioneering research effort to improve health and treat disease using a new model of patient-powered research. The objectives of the initiative include more effective treatments for cancer and other diseases, creation of a voluntary national research cohort, adherence to privacy protections for maintaining data sharing and use, modernization of the regulatory framework, and forging public–private partnerships to facilitate these objectives. Specifically, the DoD Military Health System joined other agencies to execute a comprehensive effort for PMI. Of the many challenges to consider that may contribute to the implementation of genomics—lack of familiarity and understanding, poor access to genomic medicine expertise, needs for extensive informatics and infrastructure to integrate genomic results, privacy and security, and policy development to address the unique requirements of military medical practice—we will focus on the need to establish education in genomics appropriate to the provider’s responsibilities. Our hypothesis is that there is a growing urgency for the development of educational experiences, formal and informal, to enable clinicians to acquire competency in genomics commensurate with their level of practice. Several educational approaches, both in practice and in development, are presented to inform decision-makers and empower military providers to pursue courses of action that respond to this need.
Polarization signatures of the head-on collision model for Type Ia supernovae: how much asymmetry is too much?
Authors: Livneh Ran , Katz Boaz 
Published: December 2021

ABSTRACT
In a previous paper, we showed that the asymmetric ejecta produced by (zero impact parameter) head-on collisions of carbon–oxygen white dwarfs allow these progenitor models for Type Ia supernovae (SNe Ia) to cover the observed 2D distribution of Si ii line depths (Branch plot). In this paper, we study the polarization signature associated with the 2D asymmetric ejecta of the collision model and a double-detonation model using similar tardis radiative transfer simulations along different lines of sight with a spherical photosphere, combined with a new 3D Monte Carlo polarization code. We show that the polarization Q can be parametrized as a product Q = QmaxQx of a radial structure component Qmax , which is insensitive to the model specifics and is shown to be universally around $Q_{\max }\sim 5\,{{\mathrm{ per\,cent}}}$, and a cancellation component Qx, which depends on the asymmetry details. The continuum polarization is found to be low for both the collision and double-detonation models with $Q\sim 0.5\,{{\mathrm{ per\,cent}}}$. However, the irregular Si distribution in the 2D head-on collision model results in the Si ii line polarization reaching $Q\sim 3\,{{\mathrm{ per\,cent}}}$ ($Q_{{x}} \lesssim 50\,{{\mathrm{ per\,cent}}}$) in tension with observations (mostly $\lesssim 1.2\,{{\mathrm{ per\,cent}}}$). In contrast, we show that the double-detonation model also covers the Branch plot, and yet results in low line polarization $Q\lesssim 0.7\,{{\mathrm{ per\,cent}}}$ ($Q_{ {x}} \sim 10\,{{\mathrm{ per\,cent}}}$) consistent with previous results and most SNe Ia. These results strengthen the case for asymmetric explosions as progenitors of SNe Ia, emphasizing an additional requirement for large polarization cancellations to account for the low observed line polarizations.
Epstein-Barr virus encephalitis in a patient with rheumatoid arthritis
Authors: Nakamura Jun , Yanagida Mai , Saito Keisuke , Kamata Yasuyuki , Nagashima Takao , Iwamoto Masahiro , Sato Takeo , Sato Kojiro 
Published: December 2021

ABSTRACT
A 53-year-old woman with a 6-year history of rheumatoid arthritis (RA) presented with pharyngeal pain, fever, and altered mental status. The patient had been treated with methotrexate (MTX) 12 mg/week, baricitinib 4 mg/day, and tacrolimus 2 mg/day. Magnetic resonance imaging of the brain revealed diffuse high-intensity lesions in the cerebral white matter, basal ganglia, brainstem, and right cerebellar hemisphere. She was diagnosed with Epstein-Barr virus (EBV) encephalitis due to elevated levels of EBV-DNA in the cerebrospinal fluid and serum. Although MTX-associated lymphoproliferative disorders are well-known complications in patients with RA, EBV encephalitis requires careful attention for such patients undergoing treatment with multiple potent immunosuppressants.