bluuebunny/crossref_metadata_2025 huggingface dataset:
High resolution inclination records from the Gulf of Alaska, IODP Expedition 341 Sites U1418 and U1419
Authors: Velle Julie Heggdal , Walczak Maureen H , Reilly Brendan , St-Onge Guillaume , Stoner Joseph S , Fallon Stewart , Mix Alan C , Belanger Christina , Forwick Matthias
Published: November 2021

International Ocean Drilling Program (IODP) Expedition 341 recovered sediments from the south Alaska continental slope that preserves a well resolved and dated inclination record over most of the past ∼43 000 yr. The Site U1419 chronology is among the highest resolution in the world, constrained by 173 radiocarbon dates, providing the ability to study Palaeomagnetic Secular Variation (PSV) on centennial to millennial timescales. This record has an exceptionally expanded late Pleistocene sedimentary record with sedimentation rates commonly exceeding 100 cm kyr–1, while also preserving a lower resolution Holocene PSV record at the top. Natural and laboratory-induced magnetic remanences of U1419 u-channels from the 112-m-long spliced record were studied using stepwise AF demagnetization. Hysteresis loops were obtained on 95 and IRM acquisition curves on 9 discrete samples to facilitate magnetic domain state, coercivity and magnetic mineralogical determinations. Due to complexities related to lithology, magnetic mineralogy, and depositional and post-depositional processes, Site U1419 sediments are not suitable for palaeointensity studies and declination could not be robustly reconstructed. Progressive (titano-)magnetite dissolution with depth results in decreasing NRM intensity and signal-to-noise that is exacerbated at higher demagnetization steps. As a result, inclination measured after the 20 mT AF demagnetization step provides the most reliable directional record. Inclination appears to be well resolved with removal of just a few intervals influenced by depositional and/or sampling and coring deformation. The shipboard inclination stack from nearby IODP Site U1418, on a new age model developed from 19 radiocarbon dates on U1418 and 18 magnetic susceptibility-based tie-points to site survey core EW0408-87JC, verifies centennial to millennial scale variations in inclination observed in U1419. Comparisons with other independently dated records from the NE Pacific and western North America suggest that these sites likely capture regional geomagnetic variability. As such, this new high-resolution and well-dated inclination record, especially robust between 15 and 30 cal kyr BP, offers new geomagnetic insights and a regional correlation tool to explore this generally understudied part of the world.
Assessing the eco-efficiency of industrial investment in China: a DEA approach
Authors: Zhu Chuanjin , Zhu Nan
Published: November 2021

Although the rapid growth of industrial investment has greatly contributed to Chinese socioeconomic development, the consequent resource depletion and environmental degradation have seriously restricted its potential for sustainability. Hence, the concept of eco-efficiency of industrial investment (EEII) is constructed under the comprehensive perspective of economic benefits, energy consumption and environmental impact. To assess the true EEII in China, a new super-efficient undesirable-outputs slacks-based measure DEA model is proposed by adding a new constraint condition to rebuild the reference set. The proposed model not only can consider the joint production of desirable and undesirable outputs, but also achieves full ranking of all decision-making units. Taking 30 provinces in China as an example, our empirical results indicate that the eco-efficiency of China’s industrial investment is generally low (0.643) in 2015–2020, and there exists significant regional disparity, in that the average value of EEII in the eastern regions (0.851) is the highest, followed by the central regions (0.594) and the western regions (0.469). Finally, this study provides some suggestions for policymakers to promote the EEII based on its influencing factors, analysed using panel-data Tobit regression.
Difference Sets and the Metric Theory of Small Gaps
Authors: Aistleitner Christoph , El-Baz Daniel , Munsch Marc
Published: November 2021

Let $(a_n)_{n \geq 1}$ be a sequence of distinct positive integers. In a recent paper, Rudnick established asymptotic upper bounds for the minimal gaps of $\{a_n \alpha \mod 1, ~1 \leq n \leq N\}$ as $N \to \infty $, valid for Lebesgue-almost all $\alpha $ and formulated in terms of the additive energy of $\{a_1, \dots , a_N\}$. In the present paper, we argue that the metric theory of minimal gaps of such sequences is not controlled by the additive energy, but rather by the cardinality of the difference set of $\{a_1, \dots , a_N\}$. We establish a (complicated) sharp convergence/divergence test for the typical asymptotic order of the minimal gap and prove (slightly weaker) general upper and lower bounds that allow for a direct application. A major input for these results comes from the recent proof of the Duffin–Schaeffer conjecture by Koukoulopoulos and Maynard. We show that our methods give very precise results for slowly growing sequences whose difference set has relatively high density, such as the primes or the squares. Furthermore, we improve a metric result of Blomer, Bourgain, Rudnick, and Radziwiłł on the order of the minimal gap in the eigenvalue spectrum of a rectangular billiard.
Immune Responses to the ChAdOx1 nCoV-19 and BNT162b2 Vaccines and to Natural Coronavirus Disease 2019 Infections Over a 3-Month Period
Authors: Kim Ji Yeun , Lim So Yun , Park Soonju , Kwon Ji-Soo , Bae Seongman , Park Ji Young , Cha Hye Hee , Seo Mi Hyun , Lee Hyun Jung , Lee Nakyung , Kim Kideok , Shum David , Jee Youngmee , Kim Sung-Han
Published: November 2021

Background

There are limited data directly comparing immune responses to vaccines and to natural infections with coronavirus disease 2019 (COVID-19). This study assessed the immunogenicity of the BNT162b2 and ChAdOx1 nCoV-19 vaccines over a 3-month period and compared the immune responses with those to natural infections.

Method

We enrolled healthcare workers who received BNT162b2 or ChAdOx1 nCoV-19 vaccines and patients with confirmed COVID-19 and then measured S1 immunoglobulin (Ig) G and neutralizing antibodies and T-cell responses.

Results

A total of 121 vaccinees and 26 patients with confirmed COVID-19 were analyzed. After the second dose, the BNT162b2 vaccine yielded S1 IgG antibody responses similar to those achieved with natural infections (mean IgG titer [standard deviation], 2241 [899] vs 2601 [5039]; P = .68) but significantly stronger than responses to the ChAdOx1 vaccine (174 [96]; P < .001). The neutralizing antibody titer generated by BNT162b2 was 6-fold higher than that generated by ChAdOx1 but lower than that by natural infection. T-cell responses persisted for 3 months with BNT162b2 and natural infection but decreased with ChAdOx1.

Conclusions

Antibody responses after the second dose of BNT162b2 are higher than after the second dose of ChAdOx1 and like those occurring after natural infection. T-cell responses are maintained longer in BNT162b2 vaccinees than in ChAdOx1 vaccinees.
Curating a longitudinal research resource using linked primary care EHR data—a UK Biobank case study
Authors: Darke Philip , Cassidy Sophie , Catt Michael , Taylor Roy , Missier Paolo , Bacardit Jaume
Published: November 2021

Primary care EHR data are often of clinical importance to cohort studies however they require careful handling. Challenges include determining the periods during which EHR data were collected. Participants are typically censored when they deregister from a medical practice, however, cohort studies wish to follow participants longitudinally including those that change practice. Using UK Biobank as an exemplar, we developed methodology to infer continuous periods of data collection and maximize follow-up in longitudinal studies. This resulted in longer follow-up for around 40% of participants with multiple registration records (mean increase of 3.8 years from the first study visit). The approach did not sacrifice phenotyping accuracy when comparing agreement between self-reported and EHR data. A diabetes mellitus case study illustrates how the algorithm supports longitudinal study design and provides further validation. We use UK Biobank data, however, the tools provided can be used for other conditions and studies with minimal alteration.
Monadic NM-algebras: an algebraic approach to monadic predicate nilpotent minimum logic
Authors: Wang Juntao , He Pengfei , Yang Jiang , Wang Mei , He Xiaoli
Published: November 2021

In this paper, we further study the variety of monadic nilpotent minimum (NM)-algebras and their corresponding logic. In order to solve the drawback of monadic NM-algebras, we review some well-known classes of monadic t-norm-based fuzzy logical algebras and then revise the axiomatic system of monadic NM-algebras. Then we show that the variety of monadic NM-algebras is the equivalent algebraic semantics of monadic predicate fuzzy logic $\textbf {mNM}_{\forall }$, which is equivalent to the modal fuzzy logic $\textbf {S5(NM)}$. Moreover, we show that the propositional case of the modal fuzzy logic $\textbf {S5(NM)}$, which is $\textbf{S5}^{\prime}\textbf{(NM),}$ is also complete with respect to the variety of monadic NM-algebras in the sense of Blok and Pigozzi and obtain a necessary and sufficient condition for this logic to be semilinear. Finally, we give some representations of monadic NM-algebras. In particular, we give some characterizations of representable and directly indecomposable monadic NM-algebras.
Gravitational instability in radiative molecular clouds including cosmic ray diffusion and ion Larmor radius corrections
Authors: Prajapati Ram Prasad
Published: November 2021

The effects of cosmic ray (CR) diffusion and finite Larmor radius (FLR) corrections have been studied on the linear gravitational instability of thermally conducting plasmas typically in the H ii regions of molecular clouds. The hydrodynamic fluid–fluid approach is considered for interacting CRs with gravitating, magnetized, and thermally conducting gas in molecular clouds. The magnetohydrodynamic fluid model is formulated considering CR pressure gradients, CR diffusion, and radiative and FLR effects in terms of particle Larmor radius. The dispersion relation of the gravitational instability is analytically derived using the normal mode analysis, and the effects of CRs and FLR corrections have been discussed in longitudinal and transverse modes. It is observed that in the absence of CRs, the FLR effects (magnetic viscosity) reduce the growth rate for wavenumber smaller than a critical value, and above it gets increased. However, the growth rate is strongly suppressed in the presence of combined CRs and FLR effects. The individual behaviour of FLR effects is observed to destabilize the growth rate of the gravitational instability in the presence of CR effects. The CR pressure decreases the growth rates of the gravitational and thermal instabilities, whereas parallel CR diffusion enhances the growth rate of the gravitational instability. The Jeans length of the gravitating gas cloud gets increased due to an increase in the CR-to-gas pressure ratio. It is found that the gravitational collapse of the system is supported by high-energy (above knee) CR particles with the Larmor radii comparable to the cloud size. The present results have been applied to understand the role of CRs and FLR corrections on the gravitational collapse in the H ii regions of molecular clouds.
Large-scale atomic data calculations in Ce V – X ions for application to early kilonova emission from neutron star mergers
Authors: Carvajal Gallego H , Berengut J C , Palmeri P , Quinet P
Published: November 2021

New radiative parameters (wavelengths, transition probabilities, and oscillator strengths) are reported in the present paper for a large number of spectral lines in moderately charged cerium ions, from Ce V to Ce X. These results were obtained through large-scale atomic structure calculations carried out using three different and independent theoretical approaches, namely the relativistic Hartree–Fock method, including core-polarization corrections (HFR + CPOL), the multiconfiguration Dirac–Hartree–Fock method, and the Particle-Hole Configuration Interaction (PH-CI) method implemented in the AMBiT code. The accuracy of the results was assessed through detailed comparisons between the data deduced from these methods and with the few theoretical and experimental data previously published. For the six cerium ions considered, the most complete and reliable sets of transition wavelengths and rates were then used to calculate the expansion opacities characterizing the early phases of kilonovae following neutron star mergers, i.e. for typical conditions corresponding to temperatures T > 20 000 K, a density ρ  = 10−10 g cm−3 and a time after the merger t  = 0.1 d.
MirGeneDB 2.1: toward a complete sampling of all major animal phyla
Authors: Fromm Bastian , Høye Eirik , Domanska Diana , Zhong Xiangfu , Aparicio-Puerta Ernesto , Ovchinnikov Vladimir , Umu Sinan U , Chabot Peter J , Kang Wenjing , Aslanzadeh Morteza , Tarbier Marcel , Mármol-Sánchez Emilio , Urgese Gianvito , Johansen Morten , Hovig Eivind , Hackenberg Michael , Friedländer Marc R , Peterson Kevin J
Published: November 2021

We describe an update of MirGeneDB, the manually curated microRNA gene database. Adhering to uniform and consistent criteria for microRNA annotation and nomenclature, we substantially expanded MirGeneDB with 30 additional species representing previously missing metazoan phyla such as sponges, jellyfish, rotifers and flatworms. MirGeneDB 2.1 now consists of 75 species spanning over ∼800 million years of animal evolution, and contains a total number of 16 670 microRNAs from 1549 families. Over 6000 microRNAs were added in this update using ∼550 datasets with ∼7.5 billion sequencing reads. By adding new phylogenetically important species, especially those relevant for the study of whole genome duplication events, and through updating evolutionary nodes of origin for many families and genes, we were able to substantially refine our nomenclature system. All changes are traceable in the specifically developed MirGeneDB version tracker. The performance of read-pages is improved and microRNA expression matrices for all tissues and species are now also downloadable. Altogether, this update represents a significant step toward a complete sampling of all major metazoan phyla, and a widely needed foundation for comparative microRNA genomics and transcriptomics studies. MirGeneDB 2.1 is part of RNAcentral and Elixir Norway, publicly and freely available at http://www.mirgenedb.org/.
The European Bioinformatics Institute (EMBL-EBI) in 2021
Authors: Cantelli Gaia , Bateman Alex , Brooksbank Cath , Petrov Anton I , Malik-Sheriff Rahuman S , Ide-Smith Michele , Hermjakob Henning , Flicek Paul , Apweiler Rolf , Birney Ewan , McEntyre Johanna
Published: November 2021

The European Bioinformatics Institute (EMBL-EBI) maintains a comprehensive range of freely available and up-to-date molecular data resources, which includes over 40 resources covering every major data type in the life sciences. This year's service update for EMBL-EBI includes new resources, PGS Catalog and AlphaFold DB, and updates on existing resources, including the COVID-19 Data Platform, trRosetta and RoseTTAfold models introduced in Pfam and InterPro, and the launch of Genome Integrations with Function and Sequence by UniProt and Ensembl. Furthermore, we highlight projects through which EMBL-EBI has contributed to the development of community-driven data standards and guidelines, including the Recommended Metadata for Biological Images (REMBI), and the BioModels Reproducibility Scorecard. Training is one of EMBL-EBI’s core missions and a key component of the provision of bioinformatics services to users: this year's update includes many of the improvements that have been developed to EMBL-EBI’s online training offering.
High throughput single-cell genome sequencing gives insights into the generation and evolution of mosaic aneuploidy inLeishmania donovani
Authors: Negreira Gabriel H , Monsieurs Pieter , Imamura Hideo , Maes Ilse , Kuk Nada , Yagoubat Akila , Van den Broeck Frederik , Sterkers Yvon , Dujardin Jean-Claude , Domagalska Malgorzata A
Published: November 2021

Leishmania, a unicellular eukaryotic parasite, is a unique model for aneuploidy and cellular heterogeneity, along with their potential role in adaptation to environmental stresses. Somy variation within clonal populations was previously explored in a small subset of chromosomes using fluorescence hybridization methods. This phenomenon, termed mosaic aneuploidy (MA), might have important evolutionary and functional implications but remains under-explored due to technological limitations. Here, we applied and validated a high throughput single-cell genome sequencing method to study for the first time the extent and dynamics of whole karyotype heterogeneity in two clonal populations of Leishmania promastigotes representing different stages of MA evolution in vitro. We found that drastic changes in karyotypes quickly emerge in a population stemming from an almost euploid founder cell. This possibly involves polyploidization/hybridization at an early stage of population expansion, followed by assorted ploidy reduction. During further stages of expansion, MA increases by moderate and gradual karyotypic alterations, affecting a defined subset of chromosomes. Our data provide the first complete characterization of MA in Leishmania and pave the way for further functional studies.
Identification and classification of reverse transcriptases in bacterial genomes and metagenomes
Authors: Sharifi Fatemeh , Ye Yuzhen
Published: November 2021

Reverse transcriptases (RTs) are found in different systems including group II introns, Diversity Generating Retroelements (DGRs), retrons, CRISPR-Cas systems, and Abortive Infection (Abi) systems in prokaryotes. Different classes of RTs can play different roles, such as template switching and mobility in group II introns, spacer acquisition in CRISPR-Cas systems, mutagenic retrohoming in DGRs, programmed cell suicide in Abi systems, and recently discovered phage defense in retrons. While some classes of RTs have been studied extensively, others remain to be characterized. There is a lack of computational tools for identifying and characterizing various classes of RTs. In this study, we built a tool (called myRT) for identification and classification of prokaryotic RTs. In addition, our tool provides information about the genomic neighborhood of each RT, providing potential functional clues. We applied our tool to predict RTs in all complete and draft bacterial genomes, and created a collection that can be used for exploration of putative RTs and their associated protein domains. Application of myRT to metagenomes showed that gut metagenomes encode proportionally more RTs related to DGRs, outnumbering retron-related RTs, as compared to the collection of reference genomes. MyRT is both available as a standalone software (https://github.com/mgtools/myRT) and also through a website (https://omics.informatics.indiana.edu/myRT/).
Smoking Patterns Among Urban Alaska Native and American Indian Adults: The Alaska EARTH 10-Year Follow-up Study
Authors: Patten Christi A , Hiratsuka Vanessa Y , Nash Sarah H , Day Gretchen , Redwood Diana G , Beans Julie A , Howard Barbara V , Umans Jason G , Koller Kathryn R
Published: November 2021

Introduction

Data on cigarette smoking prevalence among Alaska Native and American Indian (ANAI) people are limited to cross-sectional studies or specific subpopulations. Using data from the Alaska Education and Research toward Health (EARTH) Study 10-year follow-up, this study assessed patterns of smoking from baseline and factors associated with current use.

Aims and Methods

EARTH Study urban south central ANAI participants (N = 376; 73% women) provided questionnaire data on smoking at baseline and 10-year follow-up. Multivariable-adjusted logistic regression assessed whether gender, cultural factors (Tribal identity, language spoken in the home), depressive symptoms (PHQ-9), baseline smoking status, and baseline cigarettes per day (CPD) were associated with current smoking at follow-up.

Results

Current smoking was 27% and 23% at baseline and follow-up, respectively. Of baseline smokers, 60% reported smoking at follow-up (77% men, 52% women). From multivariable-adjusted analyses, the odds of current smoking at follow-up were lower among women than men, those who never or formerly smoked versus currently smoked at baseline, and smoking <10 CPD compared with ≥10 CPD at baseline. PHQ-9 score or cultural variables were not associated with smoking at follow-up. Smoking fewer baseline CPD was associated with former smoking status (ie, quitting) at follow-up among women, but not men.

Conclusions

Our project is among the first to longitudinally explore smoking within an ANAI cohort. While we observed persistent smoking during a 10-year period, there were important differences by gender and CPD in quitting. These differences may be important to enhance the reach and efficacy of cessation interventions for ANAI people.

Implications

This study contributes novel longitudinal information on cigarette smoking prevalence during a 10-year period among Alaska Native and American Indian (ANAI) people. Prior data on smoking prevalence among ANAI people are limited to cross-sectional studies or specific subpopulations. Our project is among the first to longitudinally explore smoking prevalence within an ANAI cohort. We observed persistent smoking during a 10-year period. The study also contributes information on differences by gender and cigarettes smoked per day in quitting. These findings have implications for enhancing the reach and efficacy of cessation interventions for ANAI people.
Effect of Electronic Nicotine Delivery Systems on Cigarette Abstinence in Smokers With No Plans to Quit: Exploratory Analysis of a Randomized Placebo-Controlled Trial
Authors: Foulds Jonathan , Cobb Caroline O , Yen Miao-Shan , Veldheer Susan , Brosnan Phoebe , Yingst Jessica , Hrabovsky Shari , Lopez Alexa A , Allen Sophia I , Bullen Christopher , Wang Xi , Sciamanna Chris , Hammett Erin , Hummer Breianna L , Lester Courtney , Richie John P , Chowdhury Nadia , Graham Jacob T , Kang Le , Sun Shumei , Eissenberg Thomas
Published: November 2021

Introduction

The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking is unclear. This exploratory analysis examined the effects of ENDS delivering different amounts of nicotine on cigarette abstinence up to 24-week follow-up, in comparison to placebo or a behavioral substitute.

Methods

This four-arm parallel-group, randomized, placebo-controlled trial took place at two academic medical centers in the United States (Penn State Hershey and Virginia Commonwealth University). Participants were current adult smokers (N = 520) interested in reducing but not planning to quit. They received brief advice and were randomized to one of four 24-week conditions, receiving either an eGo-style ENDS paired with 0, 8, or 36 mg/ml nicotine liquid (double-blind) or a cigarette-shaped tube, as a cigarette substitute (CS). Self-reported daily cigarette consumption and exhaled carbon monoxide (CO) were measured at all study visits. Outcomes included intent-to-treat, self-reported 7-day cigarette abstinence, biochemically confirmed by exhaled CO at 24 weeks after randomization.

Results

At 24 weeks, significantly more participants in the 36 mg/ml condition (14/130, 10.8%) than in the 0 mg/ml condition (1/130, 0.8%) and the CS condition (4/130, 3.1%) were abstinent (relative risk = 14 [95% CI = 1.9–104.9] and 3.5 [95% CI = 1.2–10.4], respectively). The abstinence rate in the 8 mg/ml condition was 4.6% (6/130).

Conclusions

When smokers seeking to reduce smoking tried ENDS, few quit smoking in the short term. However, if smokers continued to use an ENDS with cigarette-like nicotine delivery, a greater proportion completely switched to ENDS, as compared with placebo or a cigarette substitute.

Implications

The extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking was unclear. This randomized trial found that ENDS with nicotine delivery approaching that of a cigarette are more effective in helping ambivalent smokers to quit cigarette smoking.
Papering Over Protest: Contentious Politics and Archival Suppression in Early Modern Venice
Authors: van Gelder Maartje , de Vivo Filippo
Published: November 2021

This article studies the intertwined processes of popular protest and archival suppression in early modern Venice. It concentrates on a cycle of contention extending over several months in 1569, including a labour protest that started among the workers of the state shipyard and turned into a large revolt, anonymous placards and food riots. Such was the extent of the unrest that a major explosion in the shipyard raised suspicion of sabotage. Eventually, the government had to capitulate to the workers’ demands. This cycle of protests in Venice, a city normally renowned for peace and concord, has left minimal traces in the official records: the government tried to suppress the protests not only in practice but also on paper. It carried out convictions in secret, obliterated the revolt from its archives, buried any mention of protest under countless other records, and elided dissent from published histories. By using a variety of non-governmental sources, it is possible to investigate how contentious politics were written out of government records, and hence of history. Manipulating archives was always easier than subduing people: the more power was contested in the streets, the more it needed to be asserted in the archive.
The Effects of Benoxacor on the Liver and Gut Microbiome of C57BL/6 Mice
Authors: Simonsen Derek , Cady Nicole , Zhang Chunyun , Shrode Rachel L , McCormick Michael L , Spitz Douglas R , Chimenti Michael S , Wang Kai , Mangalam Ashutosh , Lehmler Hans-Joachim
Published: November 2021

The toxicity of many “inert” ingredients of pesticide formulations, such as safeners, is poorly characterized, despite evidence that humans may be exposed to these chemicals. Analysis of ToxCast data for dichloroacetamide safeners with the ToxPi tool identified benoxacor as the safener with the highest potential for toxicity, especially liver toxicity. Benoxacor was subsequently administered to mice via oral gavage for 3 days at concentrations of 0, 0.5, 5, and 50 mg/kg bodyweight (b.w.). Bodyweight-adjusted liver and testes weights were significantly increased in the 50 mg/kg b.w. group. There were no overt pathologies in either the liver or the intestine. 16S rRNA analysis of the cecal microbiome revealed no effects of benoxacor on α- or β-diversity; however, changes were observed in the abundance of certain bacteria. RNAseq analysis identified 163 hepatic genes affected by benoxacor exposure. Benoxacor exposure expressed a gene regulation profile similar to dichloroacetic acid and the fungicide sedaxane. Metabolomic analysis identified 9 serum and 15 liver metabolites that were affected by benoxacor exposure, changes that were not significant after correcting for multiple comparisons. The activity of antioxidant enzymes was not altered by benoxacor exposure. In vitro metabolism studies with liver microsomes and cytosol from male mice demonstrated that benoxacor is enantioselectively metabolized by cytochrome P450 enzymes, carboxylesterases, and glutathione S-transferases. These findings suggest that the minor toxic effects of benoxacor may be due to its rapid metabolism to toxic metabolites, such as dichloroacetic acid. This result challenges the assumption that inert ingredients of pesticide formulations are safe.
Comparative Toxicogenomics of Glyphosate and Roundup Herbicides by Mammalian Stem Cell-Based Genotoxicity Assays and Molecular Profiling in Sprague-Dawley Rats
Authors: Mesnage Robin , Ibragim Mariam , Mandrioli Daniele , Falcioni Laura , Tibaldi Eva , Belpoggi Fiorella , Brandsma Inger , Bourne Emma , Savage Emanuel , Mein Charles A , Antoniou Michael N
Published: November 2021

Whether glyphosate-based herbicides (GBHs) are more potent than glyphosate alone at activating cellular mechanisms, which drive carcinogenesis remain controversial. As GBHs are more cytotoxic than glyphosate, we reasoned they may also be more capable of activating carcinogenic pathways. We tested this hypothesis by comparing the effects of glyphosate with Roundup GBHs both in vitro and in vivo. First, glyphosate was compared with representative GBHs, namely MON 52276 (European Union), MON 76473 (United Kingdom), and MON 76207 (United States) using the mammalian stem cell-based ToxTracker system. Here, MON 52276 and MON 76473, but not glyphosate and MON 76207, activated oxidative stress and unfolded protein responses. Second, molecular profiling of liver was performed in female Sprague-Dawley rats exposed to glyphosate or MON 52276 (at 0.5, 50, and 175 mg/kg bw/day glyphosate) for 90 days. MON 52276 but not glyphosate increased hepatic steatosis and necrosis. MON 52276 and glyphosate altered the expression of genes in liver reflecting TP53 activation by DNA damage and circadian rhythm regulation. Genes most affected in liver were similarly altered in kidneys. Small RNA profiling in liver showed decreased amounts of miR-22 and miR-17 from MON 52276 ingestion. Glyphosate decreased miR-30, whereas miR-10 levels were increased. DNA methylation profiling of liver revealed 5727 and 4496 differentially methylated CpG sites between the control and glyphosate and MON 52276 exposed animals, respectively. Apurinic/apyrimidinic DNA damage formation in liver was increased with glyphosate exposure. Altogether, our results show that Roundup formulations cause more biological changes linked with carcinogenesis than glyphosate.
A Forward Genetic Screen in Sclerotinia sclerotiorum Revealed the Transcriptional Regulation of Its Sclerotial Melanization Pathway
Authors: Xu Yan , Ao Kevin , Tian Lei , Qiu Yilan , Huang Xingchuan , Liu Xueru , Hoy Ryan , Zhang Yishan , Rashid Khalid Youssef , Xia Shitou , Li Xin
Published: November 2021

Most plant fungal pathogens that cause worldwide crop losses are understudied, due to various technical challenges. With the increasing availability of sequenced whole genomes of these non-model fungi, effective genetic analysis methods are highly desirable. Here, we describe a newly developed pipeline, which combines forward genetic screening with high-throughput next-generation sequencing to enable quick gene discovery. We applied this pipeline in the notorious soilborne phytopathogen Sclerotinia sclerotiorum and identified 32 mutants with various developmental and growth deficiencies. Detailed molecular studies of three melanization-deficient mutants provide a proof of concept for the effectiveness of our method. A master transcription factor was found to regulate melanization of sclerotia through the DHN (1,8-dihydroxynaphthalene) melanin biosynthesis pathway. In addition, these mutants revealed that sclerotial melanization is important for sclerotia survival under abiotic stresses, sclerotial surface structure, and sexual reproduction. Foreseeably, this pipeline can be applied to facilitate efficient in-depth studies of other non-model fungal species in the future.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Is gabapentin a safe and effective treatment for nonneuropathic pain?
Authors: Migeon Meghan
Published: November 2021

A review of the recent literature found that compared with placebo or other pain medications, gabapentin did not significantly reduce nonneuropathic pain. The drug also is associated with an increased risk of adverse reactions, including somnolence, dizziness, and nausea. Given the lack of efficacy and risk of adverse reactions, gabapentin should not be used for nonneuropathic pain.
Metabolic acidosis in a lactating woman induced by a deliberate ketogenic diet
Authors: Hong Michelle J. , Schwartz Lauren E. , Ward Hillary H. , Morgan Jason C. , Jacoby Jeanne L.
Published: November 2021

This article describes a rare case of lactation ketoacidosis in a patient who started a ketogenic diet while nursing an infant and toddler. The patient presented to the ED with a history of nausea, vomiting, and postural dizziness, and was found to have a significant metabolic acidosis and elevated lipase level. The metabolic changes induced in this patient could occur in anyone with high metabolic demands who also is on a strict ketogenic diet. The case highlights the importance of a dietary history in patients with unexplained metabolic derangements.
Decisional Regret Among Older Adults Undergoing Corrective Surgery for Adult Spinal Deformity: A Single Institutional Study
Authors: Adogwa Owoicho , Caruso James P. , Eldridge Cody M. , Singh Ravinderjit , Chilakapati Sai , Deme Palvasha , Stutzman Sonja , Aoun Salah G. , Naik Aanand D. , Bagley Carlos A. , Makris Una
Published: November 2021

Study Design.

Retrospective.

Objective.

To investigate the prevalence of decisional regret among older adults undergoing surgery for adult spinal deformity (ASD).

Summary of Background Data.

Among older adults (≥65 years old), ASD is a leading cause of disability, with a population prevalence of 60% to 70%. While surgery is beneficial and results in functional improvement, in over 20% of older adults outcomes from surgery are less desirable.

Methods.

Older adults with ASD who underwent spinal surgery at a quaternary medical center from January 1, 2016 to March 1, 2019, were enrolled in this study. Patients were categorized into medium/high or low-decisional regret cohorts based on their responses to the Ottawa decision regret questionnaire. Decisional regret assessments were completed 24 months after surgery. The primary outcome measure was prevalence of decisional regret after surgery. Factors associated with high decisional regret were analyzed by multivariate logistic regression.

Results.

A total of 155 patients (mean age, 69.5 yrs) met the study inclusion criteria. Overall, 80% agreed that having surgery was the right decision for them, and 77% would make the same choice in future. A total of 21% regretted the choice that they made, and 21% responded that surgery caused them harm. Comparing patient cohorts reporting medium/high- versus low-decisional regret, there were no differences in baseline demographics, comorbidities, invasiveness of surgery, length of stay, discharge disposition, or extent of functional improvement 12-months after surgery. After adjusting for sex, American Society of Anesthesiologists score, invasiveness of surgery, and presence of a postoperative complication, older adults with preoperative depression had a 4.0 fold increased odds of high-decisional regret (P 
= 0.04). Change in health related quality of life measures were similar between all groups at 12-months after surgery.

Conclusion.

While the majority of older adults were appropriately counseled and satisfied with their decision, one-in-five older adults regret their decision to undergo surgery. Preoperative depression was associated with medium/high decisional regret on multivariate analysis.

Level of Evidence: 4
Calculating Ex-ante Utilities From the Modified Japanese Orthopedic Association Score
Authors: Jiang Eric X. , Fisk Felicity E. , Taliaferro Kevin , Pahuta Markian A.
Published: November 2021

Study Design.

General population utility valuation study.

Objective.

The aim of this study was to develop a technique for calculating utilities from the modified Japanese Orthopedic Association (mJOA) Score.

Summary of Background Data.

The ability to calculate quality-adjusted life-years (QALYs) for degenerative cervical myelopathy (DCM) would enhance treatment decision making and facilitate economic analysis. QALYs are calculated using utilities.

Methods.

We recruited a sample of 760 adults from a market research panel. Using an online discrete choice experiment, participants rated eight choice sets based on mJOA health states. A multiattribute utility function was estimated using a mixed multinomial-logit regression model. The sample was partitioned into a training set used for model fitting and validation set used for model evaluation.

Results.

The regression model demonstrated good predictive performance on the validation set with an area under the curve of 0.81 (95% confidence interval: 0.80–0.82)). The regression model was used to develop a utility scoring rubric for the mJOA. Regression results revealed that participants did not regard all mJOA domains as equally important. The rank order of importance was (in decreasing order): lower extremity motor function, upper extremity motor function, sphincter dysfunction, upper extremity sensation.

Conclusion.

This study provides a simple technique for converting the mJOA score to utilities and quantify the importance of mJOA domains. The ability to evaluate QALYs for DCM will facilitate economic analysis and patient counseling. Clinicians should heed these findings and offer treatments that maximize function in the attributes viewed most important by patients.

Level of Evidence: 3
COVID-19, the Pandemic of the Century and Its Impact on Cardiovascular Diseases
Authors: Zhang Yuanyuan , Wang Mingjie , Zhang Xian , Liu Tianxiao , Libby Peter , Shi Guo-Ping
Published: November 2021

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely ranks among the deadliest diseases in human history. As with other coronaviruses, SARS-CoV-2 infection damages not only the lungs but also the heart and many other organs that express angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2. COVID-19 has upended lives worldwide. Dietary behaviors have been altered such that they favor metabolic and cardiovascular complications, while patients have avoided hospital visits because of limited resources and the fear of infection, thereby increasing out-hospital mortality due to delayed diagnosis and treatment. Clinical observations show that sex, age, and race all influence the risk for SARS-CoV-2 infection, as do hypertension, obesity, and pre-existing cardiovascular conditions. Many hospitalized COVID-19 patients suffer cardiac injury, acute coronary syndromes, or cardiac arrhythmia. SARS-CoV-2 infection may lead to cardiomyocyte apoptosis and necrosis, endothelial cell damage and dysfunction, oxidative stress and reactive oxygen species production, vasoconstriction, fibrotic and thrombotic protein expression, vascular permeability and microvascular dysfunction, heart inflammatory cell accumulation and activation, and a cytokine storm. Current data indicate that COVID-19 patients with cardiovascular diseases should not discontinue many existing cardiovascular therapies such as ACE inhibitors, angiotensin receptor blockers, steroids, aspirin, statins, and PCSK9 inhibitors. This review aims to furnish a framework relating to COVID-19 and cardiovascular pathophysiology.
Improving Nursing Students' COVID-19 Knowledge Using a Serious Game
Authors: Hu Hai , Lai Xiaoqin , Yan Longping
Published: November 2021

Improving nursing students' understanding of the novel COVID-19 is an essential component of their education. We designed and developed a serious game-based computer learning application that requires nursing students to solve problems through simulated cases. This study aimed to compare knowledge mastery among nursing students who used this teaching method versus those who received online lectures. A retrospective observational study was conducted using preclass, postclass, and final test scores of 130 students retrieved from the university's database of test scores. Both teaching methods produced significant increases in short-term knowledge of COVID-19. There was no statistical difference between the two methods in pre- and postclass scores; however, the serious game group scored higher than the online lecture group in knowledge retention. In summary, the serious game application is a potentially effective method for COVID-19 education among nursing students, particularly in terms of its capacity for improved knowledge retention.
Association of SGLT2 Inhibitors With Risk of Atrial Fibrillation and Stroke in Patients With and Without Type 2 Diabetes: A Systemic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Zheng Ru-Jie , Wang Yue , Tang Jun-Nan , Duan Jie-Ying , Yuan Ming-Yue , Zhang Jin-Ying
Published: November 2021

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have well-documented effects on reducing hospitalization for heart failure and cardiovascular mortality, although the effect on atrial fibrillation (AF) has not been comprehensively investigated. Therefore, we performed a meta-analysis to assess the association between SGLT2 inhibitors and AF risk by systematically searching PubMed, Embase, and ClinicalTrials.gov. Two investigators independently identified randomized controlled trials, which compared SGLT2 inhibitors with control in patients with type 2 diabetes, heart failure, or chronic kidney disease. Primary outcomes were incident AF and stroke. We included 20 randomized trials involving 63,604 patients. The SGLT2 inhibitors used were dapagliflozin (7 studies, 28,834 patients), canagliflozin (7 studies, 17,440 patients), empagliflozin (5 studies, 9082 patients), and ertugliflozin (1 study, 8246 patients). Follow-up ranged from 24 weeks to 202 weeks. SGLT2 inhibitors treatment was associated with a significant attenuation in the risk of incident AF (odds ratio = 0.82; 95% confidence interval, 0.72–0.93; P = 0.002) compared with control. No significant difference in stroke between SGLT2 inhibitors and control groups was found (odds ratio = 0.99; 95% confidence interval, 0.85–1.15; P = 0.908). This present meta-analysis indicates that SGLT2 inhibitors are associated with a lower risk of incident AF and do not significantly affect stroke risk for patients with and without type 2 diabetes.
Renal denervation alters ambulatory blood pressure-derived salt sensitivity index in patients with uncontrolled hypertension
Authors: Carnagarin Revathy , Nolde Janis M. , Lee Rebecca , Lugo-Gavidia Leslie Marisol , Ward Natalie C. , Lambert Gavin W. , Lambert Elisabeth A. , Esler Murray D. , Walton Antony , Kiuchi Márcio Galindo , Schlaich Markus P.
Published: November 2021

Background:

Renal denervation (RDN) has been proven in multiple sham-controlled trials to lower blood pressure (BP) in various forms of hypertension. RDN-mediated interruption of sympathetic signaling through its effects on renal blood flow, salt retention, and renin release are likely contributors to the BP-lowering effects. However, the impact of RDN on salt sensitivity in humans has not yet been explored.

Methods:

We, therefore, investigated the effect of RDN on ambulatory BP monitoring-derived salt sensitivity in a cohort of patients with uncontrolled hypertension on habitual salt intake. RDN was performed in 153 hypertensive patients, who were categorized into low intermediate and high-salt sensitivity groups, based on the ambulatory BP monitoring-derived salt sensitivity index estimated prior to (baseline) and at 3, 6 and 12 months after the procedure as previously described. Crude and adjusted mixed effects ordinal regression models were fitted to test for changes in the proportions of salt sensitivity risk during follow-up.

Results:

The proportions of individuals in the intermediate and high-salt sensitivity risk group increased after RDN and the odds for being in a higher estimated salt sensitivity risk group at 3, 6 and 12 months follow-up compared with baseline were highly significant during the 12 months follow-up period.

Conclusion:

Increased salt sensitivity after RDN may represent a compensatory mechanism to maintain renal capacity for adequate salt handling. This novel finding may have implications for patient management after RDN, such as prescription of salt moderation to further optimize RDN-induced BP-lowering efficacy.
Baoyuan decoction alleviates myocardial infarction through the regulation of metabolic dysfunction and the mitochondria-dependent caspase-9/3 pathway
Authors: Du Zhiyong , Shu Zeliu , Li Chun , Song Xiaomin , Ma Xiaoli , Liao Lixi , Li Jun , Tu Pengfei , Zeng Kewu , Jiang Yong
Published: November 2021

Objective:

Baoyuan decoction (BYD) is a traditional Chinese formula with myocardial protection efficacy validated by modern pharmacological tests. The present study aimed to investigate the effect and mechanism of BYD on alleviating myocardial infarction (MI).

Methods:

Nuclear magnetic resonance-based serum and urinary metabolomics were employed to explore the metabolic regulation effects of BYD in rats with MI induced by left anterior descending ligation. Oxygen-glucose deprivation/recovery (OGD/R) model in H9c2 cells and multiple molecular biology approaches were used to clarify the underlying action mechanisms of BYD.

Results:

BYD treatment recovered the serum and urinary metabolite profiles of the MI rats toward normal metabolic status and significantly improved mitochondrial energy metabolism and apoptosis pathways perturbed by MI. Analysis of the molecular mechanism of BYD indicated that it suppressed OGD/R-induced H9c2 cell apoptosis in a concentration-dependent manner by inhibiting the mitochondria-dependent caspase-9/3-poly ADP-ribose polymerase pathway.

Conclusions:

Our results demonstrate that BYD protects against myocardial apoptosis via the mitochondrial metabolic and apoptosis pathways. They also provide novel insights into the clinical application of BYD for the treatment of ischemic heart diseases.
Arousal effect and potential mechanism of dopamine-mediated acupuncture on traumatic brain injury
Authors: Zhao Yadan , Fang Yuxin , Zhang Zichen , Liu Jingyi , Qin Siru , Li Wei , Wang Songtao , Guo Yi , Xu Zhifang , Ulloa Luis
Published: November 2021

Traumatic brain injury (TBI) is a brain injury caused by direct external forces, and its prognosis depends on the extent of the damage and the changes in level of consciousness. Timely awakening from a coma is the first thorny problem to be solved in TBI treatment. Therefore, there is a need for the development of safe and effective methods for timely awakening after TBI coma. Dopamine (DA) and its receptors in the nervous system are involved in the regulation of wakefulness. The amount and activity of dopaminergic neurons can affect cellular function and neuroinflammatory response, and are also significant for the awakening process after TBI. The current common awakening therapy for TBI may also be related to the activation of dopaminergic neurons. Acupuncture plays a beneficial role in timely awakening, recovery of conscious level, and functional rehabilitation after TBI. The mechanism may be related to the targeted regulation of DA and its receptors via acupuncture. Among acupuncture first aid therapies, acupuncture at hand 12 Jing-Well points, with its advantages of simple operation and ultra-early intervention, has shown great promise in timely awakening following TBI and triggering a series of subsequent nerve repair effects in the treatment of TBI. We here present a review that provides a new perspective for the timely awakening from TBI-induced coma, with a focus on the role of DA in the regulation of wakefulness and the efficacy and potential mechanism of DA systems in the treatment of TBI by acupuncture.