bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating Dermal Bone as a Novel Source of Endocrine Information in Ninespine and Threespine Stickleback Fish
Authors: Dillon D , Witten P E , Buck C L
Published: March 2023

Synopsis

Monitoring the physiology of small aquatic and marine teleost fish presents challenges. Blood samples, often the first choice for endocrinologists, can be difficult or even impossible to obtain and alternative matrices currently used for hormone analyses do not occur in fishes (e.g., hair, feathers etc.) or are not easily collected from small aquatic organisms (e.g., urine and feces). Some teleosts, however, have enlarged bony dermal elements that possibly accumulate and store steroid hormones in physiological relevant concentrations. Both threespine stickleback (Gasterosteus aculeatus) and ninespine stickleback (Pungitius pungitius) have a series of external, lateral bony plates, dorsal spines, and a pair of pelvic spines attached to the pelvic girdle. We investigated if cortisol, the primary circulating glucocorticoid in teleosts, could be extracted from stickleback dermal bone and quantified using a commercially available enzyme immunoassay (EIA). We successfully validated a cortisol EIA for dermal bone extracts, determined that cortisol was detectable in both species, and found that dermal bone cortisol levels significantly correlated with cortisol levels in whole body homogenate. Ninespine stickleback had significantly higher dermal bone cortisol concentrations than threespine stickleback and female threespine stickleback tended to have over twice the mean dermal bone cortisol concentration than males. Because both stickleback species are widely used for ecotoxicological studies, using dermal bone as a source of endocrine information, while leaving the body for contaminant, genomic, histological, and stable isotope analyses, could be a powerful and parsimonious tool. Further investigation and physiological validations are necessary to fully understand the utility of this new sample matrix.
Designing and Evaluating Aventura Marina: A Serious Game to Promote Visitors’ Engagement in a Science Museum Exhibition
Authors: Cordova-Rangel Jessica , Caro Karina
Published: March 2023

Museums have employed video games in their exhibitions to foster visitors’ participation and improve their learning process through a positive experience. In this work, we present Aventura Marina, a serious video game inspired by escape room game mechanics, composed of an app and an authoring tool, which aims to promote visitors’ engagement with the new exhibition Sea Hall of the Caracol Museo de Ciencias, a Mexican museum in the northwest of Mexico. To design Aventura Marina, we followed a user-centered design approach, based on the design thinking methodology. We evaluated the high-fidelity prototype of the game and the low-fidelity prototype of the authoring tool with museum staff and potential visitors. Our results indicate that Aventura Marina has the potential to promote visitors’ engagement with the Sea Hall exhibition as participants indicated having a positive experience, recognized that they were more interested in and less bored by the topics of the exhibition and that they were eager to play the game again. In relation to the authoring tool, museum staff mentioned how this project could be implemented in other halls of the museum. Finally, we discuss the improvements for a future iteration of the prototypes and how this kind of technology can complement the content of museum exhibitions.
Linking rare and common disease vocabularies by mapping between the human phenotype ontology and phecodes
Authors: McArthur Evonne , Bastarache Lisa , Capra John A
Published: March 2023

Enabling discovery across the spectrum of rare and common diseases requires the integration of biological knowledge with clinical data; however, differences in terminologies present a major barrier. For example, the Human Phenotype Ontology (HPO) is the primary vocabulary for describing features of rare diseases, while most clinical encounters use International Classification of Diseases (ICD) billing codes. ICD codes are further organized into clinically meaningful phenotypes via phecodes. Despite their prevalence, no robust phenome-wide disease mapping between HPO and phecodes/ICD exists. Here, we synthesize evidence using diverse sources and methods—including text matching, the National Library of Medicine’s Unified Medical Language System (UMLS), Wikipedia, SORTA, and PheMap—to define a mapping between phecodes and HPO terms via 38 950 links. We evaluate the precision and recall for each domain of evidence, both individually and jointly. This flexibility permits users to tailor the HPO–phecode links for diverse applications along the spectrum of monogenic to polygenic diseases.
Comprehensive Evaluation of an HPLC–MS-MS Method for Quantitation of Seven Anti-Coagulant Rodenticides and Dicoumarol in Animal Serum
Authors: Francis Kyle A , Tkachenko Andriy , Johnson Joseph T , Smith Lori L , Noonan Robyn T , Filigenzi Michael S , Gaskill Cynthia L , Romano Megan C
Published: March 2023

Anti-coagulant rodenticides (ARs) are commonly utilized for controlling rodent populations; however, non-target companion and wildlife animals are also exposed. A method was developed for quantitation of seven ARs (chlorophacinone, coumachlor, bromadiolone, brodifacoum, difethialone, diphacinone and warfarin) and dicoumarol (a naturally occurring anti-coagulant) in animal serum. Analytes were extracted with 10% (v/v) acetone in methanol and analyzed by reverse phase high-performance liquid chromatography–tandem mass spectrometry using electrospray ionization (negative mode) combined with multiple reaction monitoring. In-house method validation in the originating laboratory using non-blinded samples revealed method limits of quantitation at 2.5 ng/mL for all analytes. The inter-assay accuracy ranged from 99% to 104%, and the relative standard deviation ranged from 3.5% to 20.5%. Method performance was then verified in the originating laboratory during an exercise organized by an independent party using blinded samples. The method was successfully transferred to two naïve laboratories and further evaluated for reproducibility among three laboratories by means of Horwitz ratio (HorRat(R)) values. Such extensive validation provides a high degree of confidence that the method is rugged, robust, and will perform as expected if used by others in the future.
Technological and Organizational Change and the Careers of Workers
Authors: Battisti Michele , Dustmann Christian , Schönberg Uta
Published: March 2023

This paper investigates the effects of technological and organizational change (T&O) on jobs and workers. We show that although T&O reduces firm demand for routine relative to abstract task-based jobs, affected workers do not face higher probability of non-employment or lower earnings growth than unaffected workers. Rather, firms that adopt T&O offer routine workers retraining opportunities to upgrade to more abstract jobs. Older workers form an important exception: T&O increases the risk that they permanently withdraw from the labor market and reduces their earnings, regardless of the tasks they performed in the firm prior to T&O.
A study of ionospheric impacts in the wireless electromagnetic exploration with the QWE method
Authors: Zhang Yilang , Gao Ya , Fu Changmin
Published: March 2023

The wireless electromagnetic method (WEM) is an emerging new method for deep resource exploration. This method, based on magnetotellurics and the controlled-source electromagnetic method, features advantages such as high signal strength and signal-to-noise ratio, large penetration depth, and easy survey geometry setups, which gives WEM potential for deployment in mineral exploration of large depths. As for now, there is little research into the controlling factors of the ionosphere in WEM exploration, and whether the ionosphere is related to the modeling result remains unclear. In this work, we first developed a modified quadrature with extrapolation (QWE) method to settle the oscillation in the calculation of a WEM response. Then we compared its performance and accuracy with other methods and find that our method has better numerical stability even with highly oscillated integral kernels, which is ideal for WEM emulation. With the emulation tools, we can further investigate how the ionosphere’s height and resistivity affect the ground-received signal. We compared signals obtained with different ionospheric properties under various earth resistivity models. The conclusion is that these ionospheric properties only impact the received signal’s strength and have no influence on the Cagniard resistivity or phase of impedance.
Bacterial DNA promoting inflammation via the Sgk1/Nedd4L/Syk pathway in mast cells contributes to antihistamine-nonresponsive CSU
Authors: Chen Bangtao , Song Yao , Yang Xiongbo , Yang Jing , Hao Fei
Published: March 2023

Inflammation centered on non-IgE-mediated mast cell activation characterizes chronic spontaneous urticaria resistant to nonsedating H1-antihistamines. We recently uncovered a strong positive association between inflammation and the fecal Escherichia. To further explore the actions of bacterial DNA derived from Escherichia on mast cells, intestinal permeability of patients with chronic spontaneous urticaria with or without nonsedating H1-antihistamine resistance and healthy controls were determined, and LAD2 cells with knockdown of Syk, Nedd4L, or Sgk1 or with incubation of inhibitors GS9973, GSK650394, and MG132 were posttreated with btDNA. We found that (i) serum intestinal permeability indices and bacterial DNA markedly increased in patients with chronic spontaneous urticaria with nonsedating H1-antihistamine resistance compared with those without (all P < 0.001), and bacterial DNA positively correlated with the degree of inflammation; (ii) IL-6 and TNF-α levels were time- and dose-dependently upregulated in bacterial DNA–stimulated LAD2 cells, which relied on unmethylated CpG in bacterial DNA and Toll-like receptor 9 protein in cells; (iii) Syk knockdown or inhibition of Syk Tyr525/526 phosphorylation blocked bacterial DNA–initiated cytokine production; (iv) Nedd4L interacted with Tyr525/526-phosphorylated Syk, and inhibition of Nedd4L Ser448 phosphorylation induced by bacterial DNA–activated Sgk1 was mandatory for bacterial DNA's proinflammatory property; and (v) Sgk1 suppression showed an inhibitory effect on bacterial DNA–induced inflammation by ensuring Nedd4L-mediated ubiquitination of Tyr525/526-phosphorylated Syk. Collectively, we identified previously unknown contributory roles of bacterial translocation and serum bacterial DNA on the inflammation phenotype in patients with chronic spontaneous urticaria with nonsedating H1-antihistamine resistance and further uncovered a vital negative regulatory role for the Sgk1/Nedd4L/Syk pathway in bacterial DNA–induced inflammation in LAD2 cells.
Association of metformin, aspirin, and cancer incidence with mortality risk in adults with diabetes
Authors: Orchard Suzanne G , Lockery Jessica E , Broder Jonathan C , Ernst Michael E , Espinoza Sara , Gibbs Peter , Wolfe Rory , Polekhina Galina , Zoungas Sophia , Loomans-Kropp Holli A , Woods Robyn L ,   ASPREE Investigator Group, McNeil John , Woods Robyn , Wolfe Rory , Murray Anne , Chan Andrew , Orchard Suzanne , Lockery Jessica , Nelson Mark , Reid Christorpher , Shah Raj , Newmann Anne , Storey Elsdon , Stocks Nigel , Tonkin Andrew , Espinoza Sara
Published: March 2023

Background

Metformin and aspirin are commonly co-prescribed to people with diabetes. Metformin may prevent cancer, but in older people (over 70 years), aspirin has been found to increase cancer mortality. This study examined whether metformin reduces cancer mortality and incidence in older people with diabetes; it used randomization to 100 mg aspirin or placebo in the ASPirin in Reducing Events in the Elderly (ASPREE) trial to quantify aspirin’s impact on metformin users.

Methods

Analysis included community-dwelling ASPREE participants (aged ≥70 years, or ≥65 years for members of US minority populations) with diabetes. Diabetes was defined as a fasting blood glucose level greater than 125 mg/dL, self-report of diabetes, or antidiabetic medication use. Cox proportional hazards regression models were used to analyze the association of metformin and a metformin-aspirin interaction with cancer incidence and mortality, with adjustment for confounders.

Results

Of 2045 participants with diabetes at enrollment, 965 were concurrently using metformin. Metformin was associated with a reduced cancer incidence risk (adjusted hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.51 to 0.90), but no conclusive benefit for cancer mortality (adjusted HR = 0.72, 95% CI = 0.43 to 1.19). Metformin users randomized to aspirin had greater risk of cancer mortality compared with placebo (HR = 2.53, 95% CI = 1.18 to 5.43), but no effect was seen for cancer incidence (HR = 1.11, 95% CI = 0.75 to 1.64). The possible effect modification of aspirin on cancer mortality, however, was not statistically significant (interaction P = .11).

Conclusions

In community-dwelling older adults with diabetes, metformin use was associated with reduced cancer incidence. Increased cancer mortality risk in metformin users randomized to aspirin warrants further investigation.

ASPREE Trial Registration

ClinicalTrials.gov ID NCT01038583
Functional and phylogenetic similarities of co-occurring invaders affect the growth of an invasive forb
Authors: Ren Jie , Chen Pengdong , Shen Changchao , Tao Zhibin , Huang Wei
Published: March 2023

Expansion of global trade and acceleration of climate change dramatically promote plant invasions. As a result, a large number of habitats harbor multiple invasive plant species. However, patterns of invasive interactions and the drivers mediating their interactions remain unclear. In this greenhouse, potted plant study, we tested the impacts of 18 invasive plant species on the growth of target invader Erigeron canadensis which is dominant in central China. Neighboring invasive species belong to three functional groups (grass, forb and legume) and have different levels of relatedness to E. canadensis. Growth of E. canadensis’ strongly depended on the identity of neighboring invaders. Some neighboring invasive species suppressed growth of E. canadensis, others had no effect, while some promoted growth of E. canadensis. Through analyses of functional and phylogenetic similarities between the target species and neighboring invaders, we showed that two factors probably play roles in determining the relative responses of E. canadensis. Generally, E. canadensis responded negatively to invasive grasses and forbs, while it responded positively to invasive legumes. Furthermore, the negative responses to neighboring invasive grasses and forbs increased with increasing phylogenetic distance between the neighbors and E. canadensis. In contrast, the positive responses to invasive legumes did not depend on phylogenetic distance from E. canadensis. Our results suggest that successful invasion of E. canadensis probably depends on the identity of co-occurring invasive plant species. Interactions between E. canadensis and other invasive species should help managers select management priorities.
Investigation of the effect of concurrently administered carvedilol, atorvastatin and bile salts on intestinal absorption of linagliptin
Authors: Embaby Muhammad A , El Maghraby Gamal M , Osman Mohamed A , Sultan Amal A
Published: March 2023

Objectives

The aim of this work was to investigate the regional difference in linagliptin intestinal membrane transport and to investigate the effects of carvedilol, atorvastatin and bile salts on intestinal absorption of linagliptin.

Methods

The study employed an in-situ rabbit intestinal absorption technique. The membrane transport parameters of linagliptin were determined through duodenum, jejunum, ileum and colon segments. The effect of carvedilol, atorvastatin and sodium cholate was investigated by co-perfusion of each with linagliptin through jejunum and ileum.

Key findings

The study reflected incomplete linagliptin absorption from the explored intestinal segments. The resulted rank indicated that the extent of absorption decreases as we move distally through the small intestine before increasing at the ascending colon. This behaviour suggests a role of P-glycoprotein (P-gp) efflux on reduced linagliptin intestinal absorption. Co-perfusion with carvedilol, atorvastatin or bile salts significantly enhanced linagliptin absorption. This elects P-gp efflux inhibition as one possible mechanism for enhanced linagliptin intestinal membrane transport.

Conclusions

The study confirmed the role of P-gp efflux transporters in reduced intestinal linagliptin absorption. Co-administration of linagliptin with either carvedilol or atorvastatin can modulate the oral bioavailability of linagliptin. Bile salts can be employed as a formulation excipient for enhanced oral absorption of linagliptin.
Semi-mechanistic Bayesian modelling of COVID-19 with renewal processes
Authors: Bhatt Samir , Ferguson Neil , Flaxman Seth , Gandy Axel , Mishra Swapnil , Scott James A
Published: March 2023

We propose a general Bayesian approach to modelling epidemics such as COVID-19. The approach grew out of specific analyses conducted during the pandemic, in particular, an analysis concerning the effects of non-pharmaceutical interventions (NPIs) in reducing COVID-19 transmission in 11 European countries. The model parameterises the time-varying reproduction number Rt through a multilevel regression framework in which covariates can be governmental interventions, changes in mobility patterns, or other behavioural measures. Bayesian multilevel modelling allows a joint fit across regions, with partial pooling to share strength. This innovation was critical to our timely estimates of the impact of lockdown and other NPIs in the European epidemics: estimates from countries at later stages in their epidemics informed those of countries at earlier stages. Originally released as Imperial College Reports, the validity of this approach was borne out by the subsequent course of the epidemic. Our framework provides a fully generative model for latent infections and derived observations, including deaths, cases, hospitalizations, ICU admissions, and seroprevalence surveys. In this article, we additionally explore the confounded nature of NPIs and mobility. Versions of our model were used by New York State, Tennessee, and Scotland to estimate the current epidemic situation and make policy decisions.
Lipoprotein-Associated Phospholipase A2 Correlates with Reduced Left Ventricle Ejection Fraction in Hemodialysis Patients
Authors: Jun-Feng Chen , Xiao-Ping Jin , Juan Zhang , Man-Li Yang , Fan Liu , Peng Fu , Qi-Shun Wu , Yang Shu , Bo-Lin Si , Yu-Wen Hu , Liang Chen
Published: March 2023

Objective

Reduced left ventricular ejection fraction (LVEF) is common in hemodialysis (HD) patients. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered an important determinant of cardiovascular events. The aim of the study was to evaluate the relationship between Lp-PLA2 and LVEF in HD patients.

Methods

Fifty-seven HD patients with coronary heart disease were enrolled. Predialysis and postdialysis venous whole blood samples were collected. The patients were divided into preserved and reduced LVEF groups. The relationship between Lp-PLA2 and LVEF was assessed.

Results

A significant difference in C-reactive protein (CRP) and Lp-PLA2 was observed, with higher levels noted in patients with reduced LVEF (P ≤ .001). Both Lp-PLA2 and CRP were negatively correlated with LVEF in the HD patients. Only Lp-PLA2 remained associated with LVEF in multiple regression analysis.

Conclusion

Lipoprotein-associated phospholipase A2 levels are associated with LVEF and could potentially be used to evaluate chronic heart failure with reduced LVEF in HD patients for risk stratification management.
Hierarchical inhibition of mTORC1 by glucose starvation-triggered AXIN lysosomal translocation and by AMPK
Authors: Li Mengqi , Wei Xiaoyan , Xiong Jinye , Feng Jin-Wei , Zhang Chen-Song , Lin Sheng-Cai
Published: March 2023

When glucose is replete, mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is active and anchored to the lysosomal surface via the two GTPases, Ras-related GTPase (RAG) and Ras homolog enriched in brain (Rheb), which are regulated by Ragulator and tuberous sclerosis complex 2 (TSC2), respectively. When glucose is low, aldolase senses low fructose-1,6-bisphosphate level and promotes the translocation of AXIN−liver kinase B1 (LKB1) to the lysosomal surface, which leads to the activation of AMP-activated protein kinase (AMPK) and the inhibition of RAGs, sundering mTORC1 from the lysosome and causing its inactivation. AMPK can also inactivate mTORC1 by phosphorylating Raptor and TSC2. However, the hierarchy of AXIN- and AMPK-mediated inhibition of mTORC1 remains poorly defined. Here, we show that AXIN translocation does not require AMPK expression or activity. In glucose starvation conditions, knockout of AXIN extended the half-life of mTORC1 inhibition from 15 to 60 min, whereas knockout of AMPK only extended it to 30 min. RAGBGTP (constitutively active RAGB) almost entirely blocked the lysosomal dissociation and inhibition of mTORC1 under glucose starvation, but it did not inhibit AMPK, indicating that under these conditions, it is AXIN lysosomal translocation that inhibits mTORC1, and it does so via inhibition of RAGs. 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a mimetic of AMP, which activates both cytosolic AMPK and lysosomal AMPK, fully inhibited mTORC1 even when it is stably anchored to the lysosome by RAGBGTP, whereas glucose starvation mildly inhibited such anchored mTORC1. Together, we demonstrate that the lysosomal translocation of AXIN plays a primary role in glucose starvation-triggered inhibition of mTORC1 by inhibiting RAGs, and that AMPK activity inhibits mTORC1 through phosphorylating Raptor and TSC2, especially under severe stress.
Observation of Mott instability at the valence transition of f-electron system
Authors: Yang Haifeng , Gao Jingjing , Cao Yingying , Xu Yuanji , Liang Aiji , Xu Xiang , Chen Yujie , Liu Shuai , Huang Kui , Xu Lixuan , Wang Chengwei , Cui Shengtao , Wang Meixiao , Yang Lexian , Luo Xuan , Sun Yuping , Yang Yi-feng , Liu Zhongkai , Chen Yulin
Published: March 2023

Mott physics plays a critical role in materials with strong electronic correlations. Mott insulator-to-metal transition can be driven by chemical doping, external pressure, temperature and gate voltage, which is often seen in transition metal oxides with 3d electrons near the Fermi energy (e.g. cuprate superconductor). In 4f-electron systems, however, the insulator-to-metal transition is mostly driven by Kondo hybridization and the Mott physics has rarely been explored in experiments. Here, by combining the angle-resolved photoemission spectroscopy and strongly correlated band structure calculations, we show that an unusual Mott instability exists in YbInCu4 accompanying its mysterious first-order valence transition. This contrasts with the prevalent Kondo picture and demonstrates that YbInCu4 is a unique platform to explore the Mott physics in Kondo lattice systems. Our work provides important insight for the understanding and manipulation of correlated quantum phenomena in the f-electron system.
Effects of edge cracks on the thermomagnetic instabilities of type-II superconducting thin films
Authors: Jing Ze
Published: March 2023

Thermomagnetic instability is a crucial issue for the application of superconductors. Effects of edge cracks on the thermomagnetic instability of superconducting thin films are systematically investigated in this work. Dendritic flux avalanches in thin films are well reproduced through electrodynamics simulations, and relevant physical mechanisms are revealed from dissipative vortex dynamics simulations. It is found that edge cracks sharply decrease the threshold field for the thermomagnetic instability of superconducting films. Spectrum analysis shows that the time series of magnetization jumping displays scale-invariance and follows a power law with an exponent around 1.9. In a cracked film, flux jumps more frequently with lower amplitudes compared with its crack-less counterpart. As the crack extends, the threshold field decreases, the jumping frequency gets lower, while its magnitude gets larger. When the crack has extended long enough, the threshold field increases to even larger than that of the crack-less film. This counterintuitive result originates from the transition of the thermomagnetic instability triggered at the crack tip to the one triggered at the center of the crack edges, which is validated by the multifractal spectrum of magnetization jumping sequences. In addition, with the variation of crack lengths, three different modes of vortex motion are found, which explains the different flux patterns formed in the avalanche process.
Viral Etiology and Clinical Characteristics of Acute Respiratory Tract Infections in Hospitalized Children in Southern Germany (2014–2018)
Authors: Tabatabai Julia , Ihling Clara M , Manuel Britta , Rehbein Rebecca M , Schnee Sarah V , Hoos Johannes , Pfeil Johannes , Grulich-Henn Juergen , Schnitzler Paul
Published: March 2023

Background

Viral acute respiratory tract infections (ARTIs) are a leading cause of hospitalization in infants and young children.

Methods

During the winter seasons of 2014–2018, hospitalized children (<18 years) with symptoms of ARTI were prospectively included at the University Hospital Heidelberg, Germany. Nasopharyngeal swabs were obtained for multiplex molecular analysis of 10 groups of respiratory viruses, and clinical data were obtained using a standardized questionnaire.

Results

Of 1353 children included in this study, 1142 (84.4%) were positive for ≥1 viral pathogen. Virus monoinfection was detected in 797 (69.8%) children, whereas 345 (30.2%) children had coinfections with 2–4 viral pathogens. Respiratory syncytial virus (RSV), rhinovirus, and influenza virus were the main pathogens detected. RSV-positive children had significantly more often lower ARTIs, including symptoms of severe cough, wheezing, chest indrawing, tachypnea, and pulmonary rales. Hospitalized children aged <6 months represented the largest age group with detection of ≥1 viral pathogen (455/528 [86.2%] children). Coinfection was more frequent in younger children and, particularly for RSV with rhinovirus, significantly associated with more severe respiratory symptoms (P = .01).

Conclusions

A better understanding of the etiology of viral ARTIs among hospitalized children plays a key role for future strategies in prevention, control, and treatment of respiratory viral infections.
The Humoral Response of Patients With Cancer to Breakthrough COVID-19 Infection or the Fourth BNT162b2 Vaccine Dose
Authors: Cohen Idan , Campisi-Pfinto Salvatore , Rozenberg Orit , Colodner Raul , Bar-Sela Gil
Published: March 2023

Since January 2022 in Israel, high-risk populations with underlying health conditions were advised to receive a fourth dose of the BNT162b2 vaccine (Pfizer-BioNTech) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We monitored vaccine-induced immunity among oncology patients undergoing systemic anti-cancer therapy before and after the 4th-BNT162b2-dose. Three groups of patients were included in the study: those who received 3rd-BNT162b2-dose and had no breakthrough infection (control), those who received 3rd-BNT162b2-dose and had the breakthrough infection, and those who received the 4th-BNT162b2-dose and had no breakthrough infection. Anti-SARS-CoV-2 immunoglobulin-G (IgG) levels of the control group exhibited a rapid decrease over time, whereas IgG titers of patients with breakthrough-infections or patients vaccinated with the 4th-BNT162b2-dose were considerably elevated, consistent with the capacity of the second booster to induce anti-SARS-CoV-2 IgG levels. Additionally, oncology patients’ humoral immune response was significantly greater after breakthrough-infection than in response to the 4th dose of BNT162b2.
SWEET11b transports both sugar and cytokinin in developing barley grains
Authors: Radchuk Volodymyr , Belew Zeinu M , Gündel Andre , Mayer Simon , Hilo Alexander , Hensel Goetz , Sharma Rajiv , Neumann Kerstin , Ortleb Stefan , Wagner Steffen , Muszynska Aleksandra , Crocoll Christoph , Xu Deyang , Hoffie Iris , Kumlehn Jochen , Fuchs Joerg , Peleke Fritz F , Szymanski Jedrzej J , Rolletschek Hardy , Nour-Eldin Hussam H , Borisjuk Ljudmilla
Published: March 2023

Even though Sugars Will Eventually be Exported Transporters (SWEETs) have been found in every sequenced plant genome, a comprehensive understanding of their functionality is lacking. In this study, we focused on the SWEET family of barley (Hordeum vulgare). A radiotracer assay revealed that expressing HvSWEET11b in African clawed frog (Xenopus laevis) oocytes facilitated the bidirectional transfer of not only just sucrose and glucose, but also cytokinin. Barley plants harboring a loss-of-function mutation of HvSWEET11b could not set viable grains, while the distribution of sucrose and cytokinin was altered in developing grains of plants in which the gene was knocked down. Sucrose allocation within transgenic grains was disrupted, which is consistent with the changes to the cytokinin gradient across grains, as visualized by magnetic resonance imaging and Fourier transform infrared spectroscopy microimaging. Decreasing HvSWEET11b expression in developing grains reduced overall grain size, sink strength, the number of endopolyploid endosperm cells, and the contents of starch and protein. The control exerted by HvSWEET11b over sugars and cytokinins likely predetermines their synergy, resulting in adjustments to the grain's biochemistry and transcriptome.
Functional importance and divergence of plant apurinic/apyrimidinic endonucleases in somatic and meiotic DNA repair
Authors: Li Jinchao , Wang Cong , Liang Wenjie , Zhang Jun , Jiang Chen-Kun , Liu Yi , Ren Zhitong , Ci Dong , Chang Jinjie , Han Shangling , Deng Xing Wang , Wang Yingxiang , Qian Weiqiang
Published: March 2023

Apurinic/apyrimidinic (AP) sites are one of the most abundant DNA lesions and are mainly repaired by AP endonucleases (APEs). While most eukaryotic genomes encode two APEs, plants usually possess three APEs, namely APE1L, APE2, and ARP. To date, the biological relevance and functional divergence of plant APEs are unclear. Here, we show that the three plant APEs have ancient origins, with the APE1L clade being plant-specific. In Arabidopsis thaliana, simultaneously mutating APE1L and APE2, but not ARP alone or in combination with either APE1L or APE2, results in clear developmental defects linked to genotoxic stress. Genetic analyses indicated that the three plant APEs have different substrate preferences in vivo. ARP is mainly responsible for AP site repair, while APE1L and APE2 prefer to repair 3′-blocked single-stranded DNA breaks. We further determined that APEs play an important role in DNA repair and the maintenance of genomic integrity in meiotic cells. The ape1l ape2 double mutant exhibited a greatly enhanced frequency of sporulation 1 (SPO11-1)-dependent and SPO11-1-independent double-stranded DNA breaks. The DNA damage response (DDR) was activated in ape1l ape2 to trigger pollen abortion. Our findings suggest functional divergence of plant APEs and reveal important roles of plant APEs during vegetative and reproductive development.
Low-elevation conifers in California’s Sierra Nevada are out of equilibrium with climate
Authors: Hill Avery P , Nolan Connor J , Hemes Kyle S , Cambron Trevor W , Field Christopher B
Published: March 2023

Since the 1930s, California’s Sierra Nevada has warmed by an average of 1.2∘C. Warming directly primes forests for easier wildfire ignition, but the change in climate also affects vegetation species composition. Different types of vegetation support unique fire regimes with distinct probabilities of catastrophic wildfire, and anticipating vegetation transitions is an important but undervalued component of long-term wildfire management and adaptation. Vegetation transitions are more likely where the climate has become unsuitable but the species composition remains static. This vegetation climate mismatch (VCM) can result in vegetation conversions, particularly after a disturbance like wildfire. Here we produce estimates of VCM within conifer-dominated forests in the Sierra Nevada. Observations from the 1930s Wieslander Survey provide a foundation for characterizing the historical relationship between Sierra Nevada vegetation and climate before the onset of recent, rapid climate change. Based on comparing the historical climatic niche to the modern distribution of conifers and climate, ∼19.5% of modern Sierra Nevada coniferous forests are experiencing VCM, 95% of which is below an elevation of 2356 m. We found that these VCM estimates carry empirical consequences: likelihood of type-conversion increased by 9.2% for every 10% decrease in habitat suitability. Maps of Sierra Nevada VCM can help guide long-term land management decisions by distinguishing areas likely to transition from those expected to remain stable in the near future. This can help direct limited resources to their most effective uses—whether it be protecting land or managing vegetation transitions—in the effort to maintain biodiversity, ecosystem services, and public health in the Sierra Nevada.
Misspecified Moment Inequality Models: Inference and Diagnostics
Authors: Andrews Donald W K , Kwon Soonwoo
Published: March 2023

This paper is concerned with possible model misspecification in moment inequality models. Two issues are addressed. First, standard tests and confidence sets for the true parameter in the moment inequality literature are not robust to model misspecification in the sense that they exhibit spurious precision when the identified set is empty. This paper introduces tests and confidence sets that provide correct asymptotic inference for a pseudo-true parameter in such scenarios, and hence, do not suffer from spurious precision. Second, specification tests have relatively low power against a range of misspecified models. Thus, failure to reject the null of correct specification does not necessarily provide evidence of correct specification. That is, model specification tests are subject to the problem that absence of evidence is not evidence of absence. This paper develops new diagnostics for model misspecification in moment inequality models that do not suffer from this problem.
Beyond Biological Essentialism: White Nationalism, Health Disparities Data, and the Cultivation of Lay Agnotology
Authors: Dasgupta Kushan , Iturriaga Nicole , Panofsky Aaron
Published: March 2023

Scholars and practitioners position health disparities research as an important tool for redressing race-based inequities and re-conceptualizing racialized health outcomes in non-essentialist terms. Given this context, we explore a peculiar phenomenon, which is the circulation of such research among white nationalists. We discover that white nationalists incorporate and respond to health disparities research not solely to defend racist and essentialist reasoning, but also to project a discourse that indicts the science establishment for ostensibly incorporating liberal politics, corrupting inquiry, and obfuscating understanding of biology in the name of anti-racism or social constructionism. We term this practice “lay agnotology,” as it involves white nationalists capitalizing on their role as non-specialists to charge the health disparities field and its expert contributors with an alleged set of institutionalized biases that produce ignorance about the “truth” of race. We connect this finding to the literature on racialized ignorance, as it demonstrates how stories about the institutional nature of science can be as central to myth-making about race as stories about the scientific nature of people.
Excretion of polybrominated diphenyl ethers and AhR activation in breastmilk among firefighters
Authors: Jung Alesia M , Beitel Shawn C , Gutenkunst Shannon L , Billheimer Dean , Jahnke Sara A , Littau Sally R , White Mandie , Hoppe-Jones Christiane , Cherrington Nathan J , Burgess Jefferey L
Published: March 2023

Excretion of toxicants accumulated from firefighter exposures through breastmilk represents a potential hazard. We investigated if firefighting exposures could increase the concentration of polybrominated diphenyl ethers (PBDEs) and aryl hydrocarbon receptor (AhR) activation in excreted breastmilk. Firefighters and nonfirefighters collected breastmilk samples prior to any firefighting responses (baseline) and at 2, 8, 24, 48, and 72 h after a structural fire (firefighters only). Five PBDE analytes (BDEs 15, 28, 47, 99, and 153) detected in at least 90% of samples were summed for analyses. The AhR in vitro DR CALUX bioassay assessed the mixture of dioxin-like compounds and toxicity from breastmilk extracts. Baseline PBDEs and AhR responses were compared between firefighters and nonfirefighters. Separate linear mixed models assessed changes in sum of PBDEs and AhR response among firefighters over time and effect modification by interior or exterior response was assessed. Baseline PBDE concentrations and AhR responses did not differ between the 21 firefighters and 10 nonfirefighters. There were no significant changes in sum of PBDEs or AhR response among firefighters over time postfire, and no variation by interior or exterior response. Plots of sum of PBDEs and AhR response over time demonstrated individual variation but no consistent pattern. Currently, our novel study results do not support forgoing breastfeeding after a fire exposure. However, given study limitations and the potential hazard of accumulated toxicants from firefighter exposures excreted via breastfeeding, future studies should consider additional contaminants and measures of toxicity by which firefighting may impact maternal and child health.
Glyphosate toxicity:in vivo, in vitro, and epidemiological evidence
Authors: Lacroix Rachel , Kurrasch Deborah M
Published: March 2023

Glyphosate is the most applied agricultural chemical worldwide and has become nearly ubiquitous throughout the environment. Glyphosate is an effective herbicide because it disrupts the shikimate pathway, which is responsible for the synthesis of essential amino acids in plants and microorganisms. Given that there is no known target for glyphosate in higher animals, its toxicity to humans and other animals is heavily debated, especially after the 2015 IARC ruling that glyphosate is carcinogenic. Today, a growing body of literature shows in vitro, in vivo, and epidemiological evidence for the toxicity of glyphosate across animal species. With the application of glyphosate increasing globally, it is important to discuss these reports to enable a broader conversation on glyphosate toxicity and its impact on human and environmental health. Here, we summarize the recent glyphosate literature and discuss its implications.
The Use of Synthetic Microbial Communities to Improve Plant Health
Authors: Martins Samuel J. , Pasche Josephine , Silva Hiago Antonio O. , Selten Gijs , Savastano Noah , Abreu Lucas Magalhães , Bais Harsh P. , Garrett Karen A. , Kraisitudomsook Nattapol , Pieterse Corné M. J. , Cernava Tomislav
Published: March 2023

Despite the numerous benefits plants receive from probiotics, maintaining consistent results across applications is still a challenge. Cultivation-independent methods associated with reduced sequencing costs have considerably improved the overall understanding of microbial ecology in the plant environment. As a result, now, it is possible to engineer a consortium of microbes aiming for improved plant health. Such synthetic microbial communities (SynComs) contain carefully chosen microbial species to produce the desired microbiome function. Microbial biofilm formation, production of secondary metabolites, and ability to induce plant resistance are some of the microbial traits to consider when designing SynComs. Plant-associated microbial communities are not assembled randomly. Ecological theories suggest that these communities have a defined phylogenetic organization structured by general community assembly rules. Using machine learning, we can study these rules and target microbial functions that generate desired plant phenotypes. Well-structured assemblages are more likely to lead to a stable SynCom that thrives under environmental stressors as compared with the classical selection of single microbial activities or taxonomy. However, ensuring microbial colonization and long-term plant phenotype stability is still one of the challenges to overcome with SynComs, as the synthetic community may change over time with microbial horizontal gene transfer and retained mutations. Here, we explored the advances made in SynCom research regarding plant health, focusing on bacteria, as they are the most dominant microbial form compared with other members of the microbiome and the most commonly found in SynCom studies.
Leaf Microbiome Data for European Cultivated Grapevine (Vitis vinifera) During Downy Mildew (Plasmopara viticola) Epidemics in Three Wine-Producing Regions in France
Authors: Barroso-Bergadà Didac , Delmotte François , Faivre d'Arcier Julie , Massot Marie , Chancerel Emilie , Demeaux Isabelle , Guimier Soizic , Guichoux Erwan , Bohan David A. , Vacher Corinne
Published: March 2023

Grapevine downy mildew ( Plasmopara viticola) is a major disease of European cultivated grapevine ( Vitis vinifera L.) against which a large amount of synthetic pesticides are used. Developing microbial biocontrol of P. viticola could reduce the use of pesticides in viticulture and preserve human and environmental health. To achieve this goal, the ecological interactions that develop during infection between P. viticola and the vine foliar microbiome need to be explored. Here, we present metabarcoding datasets describing the bacterial and fungal communities of pairs of symptomatic and asymptomatic leaf samples collected during downy mildew epidemics in three major wine-producing regions of France. Fungal and bacterial communities were sequenced on a MiSeq Illumina platform, and the abundance of the oomycete P. viticola was quantified using qPCR. We provide the raw metabarcoding datasets, the amplicon sequence variant tables obtained after bioinformatic processing, the metadata describing sampling sites and tissue health conditions, and the code used for bioinformatic analysis. These datasets will enable microbiome comparison within pairs of symptomatic and asymptomatic samples collected at the same time on the same leaf. Such a comparison could help describe the ecological interactions between P. viticola and the grapevine foliar microbiome.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Assessment of the antidiabetic potential of extract and novel phytoniosomes formulation ofTradescantia pallidaleaves in the alloxan‐induced diabetic mouse model
Authors: Imtiaz Fariha , Islam Muhammad , Saeed Hamid , Ahmed Abrar , Rathore Hassaan Anwer
Published: March 2023

Diabetes inflicts health and economic burdens on communities and the present antidiabetic therapies have several drawbacks.Tradescantia pallidaleaves have been used as a food colorant and food preservative; however, to our knowledge antidiabetic potential of the leaves ofT. pallidahas not been explored yet. The current study aimed to investigate the antidiabetic potential ofT. pallidaleaves extract and its comparison with the novel nisosome formulation of the extract. The leaves extract and phytoniosomes ofT. pallidain doses of 15, 25 and 50 mg/kg were used to assess the oral glucose loaded, and alloxan‐induced diabetic mice models. The biological parameters evaluated were; change in body weight, blood biochemistry, relative organ to body weight ratio and histopathology of the liver, pancreas and kidney. Results revealed that the extract 50 mg/kg and phytoniosomes 25 and 50 mg/kg remarkably reduced the blood glucose level in all hyperglycemic mice by possibly inhibiting α‐amylase and α‐glucosidase production. Body weight and blood biochemical parameters were considerably improved in phytoniosomes 50 mg/kg treated group. The relative body weight was similar to those of healthy mice in extract 50 mg/kg, phytoniosomes 25 mg/kg, and phytoniosomes 50 mg/kg treated groups. Histopathology showed the regeneration of cells in the CHN50 treated group. Hyphenated chromatographic analysis revealed potent metabolites, which confirmed the antidiabetic potential of the extract by inhibiting α‐amylase and α‐glucosidase using in silico analysis. The present data suggested that phytoniosomes have shown better antidiabetic potential than crude extract of these leaves.
Randomized Pilot Test of a Decision Support Tool for Acute Appendicitis
Authors: Rosen Joshua E. , Flum David R. , Davidson Giana H. , Liao Joshua M.
Published: March 2023

Objective:

To test the effect of a new decision support tool for acute appendicitis and assess its efficacy and acceptability.

Background:

Mounting evidence from randomized controlled trials have shown that antibiotics can be a safe and effective treatment for appendicitis. Patients and surgeons must work together to choose the optimal treatment approach for each patient based on their own preferences and values. We developed a decision support tool to facilitate shared decision-making for appendicitis and its effect on decisional outcomes remains unknown.

Methods:

We conducted an online randomized field test in at-risk individuals comparing the decision support tool to a standard infographic. Individuals were randomized 3:1 to view the decision support tool or infographic. The primary outcome was the total decisional conflict scale (DCS) score measured before and after exposure to the decision support tool. Secondary outcomes included between-group DCS scores, and between-group comparisons of the acceptability.

Results:

One hundred eighty individuals were included in the study. Total DCS scores decreased significantly after viewing the decision support tool (59 [95% confidence interval (CI): 55–63] to 15 [95% CI: 12–17], P < 0.001) representing movement from a state of high to low decisional conflict. Individuals exposed to the decision support tool reported higher acceptability ratings (3.7 [95% CI: 3.6–3.8] vs 3.3 [95% CI: 3.2–3.5] out of 4) and demonstrated increased willingness to consider both treatment options.

Conclusions:

These data support the further use and testing of this novel decision support tool in patients with acute appendicitis.