bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract
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

Abstract

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

AbstractWhen 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

ABSTRACT
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

ABSTRACTThermomagnetic 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

AbstractBackgroundViral acute respiratory tract infections (ARTIs) are a leading cause of hospitalization in infants and young children.MethodsDuring the winter seasons of 2014–2018, hospitalized children (&lt;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.ResultsOf 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 &lt;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).ConclusionsA 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

AbstractSince 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

ABSTRACT
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

AbstractExcretion 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

AbstractGlyphosate 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.