bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative effectiveness and safety of homologous two-dose ChAdOx1 versus heterologous vaccination with ChAdOx1 and BNT162b2
Authors: Hermosilla Eduardo , Coma Ermengol , Xie Junqing , Feng Shuo , Cabezas Carmen , Méndez-Boo Leonardo , Fina Francesc , Ballo Elisabet , Martínez Montserrat , Medina-Peralta Manuel , Argimon Josep Maria , Prieto-Alhambra Daniel
Published: March 2022

Small trials have suggested that heterologous vaccination with first-dose ChAdOx1 and second-dose BNT162b2 may generate a better immune response than homologous vaccination with two doses of ChAdOx1. In this cohort analysis, we use linked data from Catalonia (Spain), where those aged <60 who received a first dose of ChAdOx1 could choose between ChAdOx1 and BNT162b2 for their second dose. Comparable cohorts were obtained after exact-matching 14,325/17,849 (80.3%) people receiving heterologous vaccination to 14,325/149,386 (9.6%) receiving homologous vaccination by age, sex, region, and date of second dose. Of these, 464 (3.2%) in the heterologous and 694 (4.8%) in the homologous groups developed COVID-19 between 1st June 2021 and 5th December 2021. The resulting hazard ratio (95% confidence interval) is 0.66 [0.59–0.74], favouring heterologous vaccination. The two groups had similar testing rates and safety outcomes. Sensitivity and negative control outcome analyses confirm these findings. In conclusion, we demonstrate that a heterologous vaccination schedule with ChAdOx1 followed by BNT162b2 was more efficacious than and similarly safe to homologous vaccination with two doses of ChAdOx1. Most of the infections in our study occurred when Delta was the predominant SARS-CoV-2 variant in Spain. These data agree with previous phase 2 randomised trials.
UACA locus is associated with breast cancer chemoresistance and survival
Authors: Zhu Qianqian , Schultz Emily , Long Jirong , Roh Janise M. , Valice Emily , Laurent Cecile A. , Radimer Kelly H. , Yan Li , Ergas Isaac J. , Davis Warren , Ranatunga Dilrini , Gandhi Shipra , Kwan Marilyn L. , Bao Ping-Ping , Zheng Wei , Shu Xiao-Ou , Ambrosone Christine , Yao Song , Kushi Lawrence H.
Published: March 2022

Few germline genetic variants have been robustly linked with breast cancer outcomes. We conducted trans-ethnic meta genome-wide association study (GWAS) of overall survival (OS) in 3973 breast cancer patients from the Pathways Study, one of the largest prospective breast cancer survivor cohorts. A locus spanning the UACA gene, a key regulator of tumor suppressor Par-4, was associated with OS in patients taking Par-4 dependent chemotherapies, including anthracyclines and anti-HER2 therapy, at a genome-wide significance level ($$P = 1.27 \times 10^{ - 9}$$

P
=
1.27
×
1

0

−
9

). This association was confirmed in meta-analysis across four independent prospective breast cancer cohorts (combined hazard ratio = 1.84, $$P = 1.28 \times 10^{ - 11}$$

P
=
1.28
×
1

0

−
11

). Transcriptome-wide association study revealed higher UACA gene expression was significantly associated with worse OS ($$P = 4.68 \times 10^{ - 7}$$

P
=
4.68
×
1

0

−
7

). Our study identified the UACA locus as a genetic predictor of patient outcome following treatment with anthracyclines and/or anti-HER2 therapy, which may have clinical utility in formulating appropriate treatment strategies for breast cancer patients based on their genetic makeup.
Quantum coherence bounds the distributed discords
Authors: Jin Zhi-Xiang , Li-Jost Xianqing , Fei Shao-Ming , Qiao Cong-Feng
Published: March 2022

Establishing quantum correlations between two remote parties by sending an information carrier is an essential step of many protocols in quantum information processing. We obtain trade-off relations between discords and coherence within a bipartite system. Then we study the distribution of coherence in a bipartite quantum state by using the relations of relative entropy and mutual information. We show that the increase of the relative entropy of discord between two remote parties is bounded by the nonclassical correlations quantified by the relative entropy of coherence between the carrier and two remote parties, providing an optimal protocol for discord distribution and showing that quantum correlations are the essential resource for such tasks.
Inhibition of calcium-triggered secretion by hydrocarbon-stapled peptides
Authors: Lai Ying , Fois Giorgio , Flores Jose R. , Tuvim Michael J. , Zhou Qiangjun , Yang Kailu , Leitz Jeremy , Peters John , Zhang Yunxiang , Pfuetzner Richard A. , Esquivies Luis , Jones Philip , Frick Manfred , Dickey Burton F. , Brunger Axel T.
Published: March 2022

Membrane fusion triggered by Ca2+ is orchestrated by a conserved set of proteins to mediate synaptic neurotransmitter release, mucin secretion and other regulated exocytic processes1–4. For neurotransmitter release, the Ca2+ sensitivity is introduced by interactions between the Ca2+ sensor synaptotagmin and the SNARE complex5, and sequence conservation and functional studies suggest that this mechanism is also conserved for mucin secretion6. Disruption of Ca2+-triggered membrane fusion by a pharmacological agent would have therapeutic value for mucus hypersecretion as it is the major cause of airway obstruction in the pathophysiology of respiratory viral infection, asthma, chronic obstructive pulmonary disease and cystic fibrosis7–11. Here we designed a hydrocarbon-stapled peptide that specifically disrupts Ca2+-triggered membrane fusion by interfering with the so-called primary interface between the neuronal SNARE complex and the Ca2+-binding C2B domain of synaptotagmin-1. In reconstituted systems with these neuronal synaptic proteins or with their airway homologues syntaxin-3, SNAP-23, VAMP8, synaptotagmin-2, along with Munc13-2 and Munc18-2, the stapled peptide strongly suppressed Ca2+-triggered fusion at physiological Ca2+ concentrations. Conjugation of cell-penetrating peptides to the stapled peptide resulted in efficient delivery into cultured human airway epithelial cells and mouse airway epithelium, where it markedly and specifically reduced stimulated mucin secretion in both systems, and substantially attenuated mucus occlusion of mouse airways. Taken together, peptides that disrupt Ca2+-triggered membrane fusion may enable the therapeutic modulation of mucin secretory pathways.
Autonomic aging – A dataset to quantify changes of cardiovascular autonomic function during healthy aging
Authors: Schumann Andy , Bär Karl-Jürgen
Published: March 2022

Autonomic regulation of blood pressure and cardiac rhythm progressively declines with increasing age. Impaired cardiovascular control promotes a variety of age-related cardio-vascular conditions. This study aims to provide a database of high-resolution biological signals to describe the effect of healthy aging on cardiovascular regulation. Electrocardiogram and continuous non-invasive blood pressure signals were recorded simultaneously at rest in 1,121 healthy volunteers. With this database, we provide raw signals as well as basic demographic information such as gender and body mass index. To demonstrate validity of the acquired data, we present the well-known decline of heart rate variability with increasing age in this database.
Multi-scanner and multi-modal lumbar vertebral body and intervertebral disc segmentation database
Authors: Khalil Yasmina Al , Becherucci Edoardo A. , Kirschke Jan S. , Karampinos Dimitrios C. , Breeuwer Marcel , Baum Thomas , Sollmann Nico
Published: March 2022

Magnetic resonance imaging (MRI) is widely utilized for diagnosing and monitoring of spinal disorders. For a number of applications, particularly those related to quantitative MRI, an essential step towards achieving reliable and objective measurements is the segmentation of the examined structures. Performed manually, such process is time-consuming and prone to errors, posing a bottleneck to its clinical applicability. A more efficient analysis would be achieved by automating a segmentation process. However, routine spine MRI acquisitions pose several challenges for achieving robust and accurate segmentations, due to varying MRI acquisition characteristics occurring in data acquired from different sites. Moreover, heterogeneous annotated datasets, collected from multiple scanners with different pulse sequence protocols, are limited. Thus, we present a manually segmented lumbar spine MRI database containing a wide range of data obtained from multiple scanners and pulse sequences, with segmentations of lumbar vertebral bodies and intervertebral discs. The database is intended for the use in developing and testing of automated lumbar spine segmentation algorithms in multi-domain scenarios.
R code and downstream analysis objects for the scRNA-seq atlas of normal and tumorigenic human breast tissue
Authors: Chen Yunshun , Pal Bhupinder , Lindeman Geoffrey J. , Visvader Jane E. , Smyth Gordon K.
Published: March 2022

Breast cancer is a common and highly heterogeneous disease. Understanding cellular diversity in the mammary gland and its surrounding micro-environment across different states can provide insight into cancer development in the human breast. Recently, we published a large-scale single-cell RNA expression atlas of the human breast spanning normal, preneoplastic and tumorigenic states. Single-cell expression profiles of nearly 430,000 cells were obtained from 69 distinct surgical tissue specimens from 55 patients. This article extends the study by providing quality filtering thresholds, downstream processed R data objects, complete cell annotation and R code to reproduce all the analyses. Data quality assessment measures are presented and details are provided for all the bioinformatic analyses that produced results described in the study.
Genome-wide identification, phylogenetic and expression pattern analysis of MADS-box family genes in foxtail millet (Setaria italica)
Authors: Lai Dili , Yan Jun , He Ailing , Xue Guoxing , Yang Hao , Feng Liang , Wei Xiaobao , Li Long , Xiang Dabing , Ruan Jingjun , Fan Yu , Cheng Jianping
Published: March 2022

Foxtail millet (Setaria italica) is rich in nutrients and extremely beneficial to human health. We identified and comprehensively analyzed 89 MADS-box genes in the foxtail millet genome. According to the classification of MADS-box genes in Arabidopsis thaliana and rice, the SiMADS-box genes were divided into M-type (37) and MIKC-type (52). During evolution, the differentiation of MIKC-type MADS-box genes occurred before that of monocotyledons and dicotyledons. The SiMADS-box gene structure has undergone much differentiation, and the number of introns in the MIKC-type subfamily is much greater than that in the M-type subfamily. Analysis of gene duplication events revealed that MIKC-type MADS-box gene segmental duplication accounted for the vast majority of gene duplication events, and MIKC-type MADS-box genes played a major role in the amplification of SiMADS-box genes. Collinearity analysis showed highest collinearity between foxtail millet and maize MADS-box genes. Analysis of tissue-specific expression showed that SiMADS-box genes are highly expressed throughout the grain-filling process. Expression analysis of SiMADS-box genes under eight different abiotic stresses revealed many stress-tolerant genes, with induced expression of SiMADS33 and SiMADS78 under various stresses warranting further attention. Further, some SiMADS-box proteins may interact under external stress. This study provides insights for MADS-box gene mining and molecular breeding of foxtail millet in the future.
New age constraints on the Lower Jurassic Pliensbachian–Toarcian Boundary at Chacay Melehue (Neuquén Basin, Argentina)
Authors: Al-Suwaidi Aisha H. , Ruhl Micha , Jenkyns Hugh C. , Damborenea Susana E. , Manceñido Miguel O. , Condon Daniel J. , Angelozzi Gladys N. , Kamo Sandra L. , Storm Marisa , Riccardi Alberto C. , Hesselbo Stephen P.
Published: March 2022

The Pliensbachian–Toarcian boundary interval is characterized by a ~ 3‰ negative carbon-isotope excursion (CIE) in organic and inorganic marine and terrestrial archives from sections in Europe, such as Peniche (Portugal) and Hawsker Bottoms, Yorkshire (UK). A new high-resolution organic-carbon isotope record, illustrating the same chemostratigraphic feature, is presented from the Southern Hemisphere Arroyo Chacay Melehue section, Chos Malal, Argentina, corroborating the global significance of this disturbance to the carbon cycle. The negative carbon-isotope excursion, mercury and organic-matter enrichment are accompanied by high-resolution ammonite and nannofossil biostratigraphy together with U–Pb CA-ID-TIMS geochronology derived from intercalated volcanic ash beds. A new age of ~ 183.73 + 0.35/− 0.50 Ma for the Pliensbachian–Toarcian boundary, and 182.77 + 0.11/− 0.15 for the tenuicostatum–serpentinum zonal boundary, is assigned based on high-precision U–Pb zircon geochronology and a Bayesian Markov chain Monte Carlo (MCMC) stratigraphic age model.
First evidence of ranunculids in Early Cretaceous tropics
Authors: Gobo William Vieira , Kunzmann Lutz , Iannuzzi Roberto , Bachelier Julien B. , Coiffard Clément
Published: March 2022

Early Cretaceous floras containing angiosperms were described from several geographic areas, nearly from the Arctic to the Antarctic, and are crucial to understand their evolution and radiation. However, most of these records come from northern mid-latitudes whereas those of lower paleolatitude areas, such as the Crato Fossil Lagerstätte in NE Brazil, are less studied. Here, we describe from this region of northern Gondwanan origin, two fossil-species of eudicots belonging to a new extinct genus Santaniella gen. nov. Together with several vegetative axes and leaves, anatomically well-preserved fruits with seeds and persistent perianth-like organs allowed us to reconstruct its potential affinities with ranunculids, and presumably Ranunculaceae. Previous records putatively assigned to Ranunculales are all from mid-latitudes, and their first unequivocal occurrence in a low-latitude area supports further the hypothesis of a widespread radiation of the earliest diverging eudicot lineage by this early age.
Automated quality assessment of large digitised histology cohorts by artificial intelligence
Authors: Haghighat Maryam , Browning Lisa , Sirinukunwattana Korsuk , Malacrino Stefano , Khalid Alham Nasullah , Colling Richard , Cui Ying , Rakha Emad , Hamdy Freddie C. , Verrill Clare , Rittscher Jens
Published: March 2022

Research using whole slide images (WSIs) of histopathology slides has increased exponentially over recent years. Glass slides from retrospective cohorts, some with patient follow-up data are digitised for the development and validation of artificial intelligence (AI) tools. Such resources, therefore, become very important, with the need to ensure that their quality is of the standard necessary for downstream AI development. However, manual quality control of large cohorts of WSIs by visual assessment is unfeasible, and whilst quality control AI algorithms exist, these focus on bespoke aspects of image quality, e.g. focus, or use traditional machine-learning methods, which are unable to classify the range of potential image artefacts that should be considered. In this study, we have trained and validated a multi-task deep neural network to automate the process of quality control of a large retrospective cohort of prostate cases from which glass slides have been scanned several years after production, to determine both the usability of the images at the diagnostic level (considered in this study to be the minimal standard for research) and the common image artefacts present. Using a two-layer approach, quality overlays of WSIs were generated from a quality assessment (QA) undertaken at patch-level at $$5\times$$

5
×

magnification. From these quality overlays the slide-level quality scores were predicted and then compared to those generated by three specialist urological pathologists, with a Pearson correlation of 0.89 for overall ‘usability’ (at a diagnostic level), and 0.87 and 0.82 for focus and H&E staining quality scores respectively. To demonstrate its wider potential utility, we subsequently applied our QA pipeline to the TCGA prostate cancer cohort and to a colorectal cancer cohort, for comparison. Our model, designated as PathProfiler, indicates comparable predicted usability of images from the cohorts assessed (86–90% of WSIs predicted to be usable), and perhaps more significantly is able to predict WSIs that could benefit from an intervention such as re-scanning or re-staining for quality improvement. We have shown in this study that AI can be used to automate the process of quality control of large retrospective WSI cohorts to maximise their utility for research.
Effect of chronic and acute enterotoxigenic E. coli challenge on growth performance, intestinal inflammation, microbiome, and metabolome of weaned piglets
Authors: Boeckman Justin X. , Sprayberry Sarah , Korn Abby M. , Suchodolski Jan S. , Paulk Chad , Genovese Kenneth , Rech Raquel R. , Giaretta Paula R. , Blick Anna K. , Callaway Todd , Gill Jason J.
Published: March 2022

Post-weaning enteropathies in swine caused by pathogenic E. coli, such as post-weaning diarrhea (PWD) or edema disease (ED), remain a significant problem for the swine industry. Reduction in the use of antibiotics over concerns of antibiotic resistance and public health concerns, necessitate the evaluation of effective antibiotic alternatives to prevent significant loss of livestock and/or reductions in swine growth performance. For this purpose, an appropriate piglet model of pathogenic E. coli enteropathy is required. In this study, we attempted to induce clinical signs of post-weaning disease in a piglet model using a one-time acute or lower daily chronic dose of a pathogenic E. coli strain containing genes for both heat stable and labile toxins, as well as Shiga toxin. The induced disease state was monitored by determining fecal shedding and colonization of the challenge strain, animal growth performance, cytokine levels, fecal calprotectin, histology, fecal metabolomics, and fecal microbiome shifts. The most informative analyses were colonization and shedding of the pathogen, serum cytokines, metabolomics, and targeted metagenomics to determine dysbiosis. Histopathological changes of the gastrointestinal (GI) tract and tight junction leakage as measured by fecal calprotectin concentrations were not observed. Chronic dosing was similar to the acute regimen suggesting that a high dose of pathogen, as used in many studies, may not be necessary. The piglet disease model presented here can be used to evaluate alternative PWD treatment options.
Implementation of single-qubit measurement-based t-designs using IBM processors
Authors: Strydom Conrad , Tame Mark
Published: March 2022

Random unitary matrices sampled from the uniform Haar ensemble have a number of important applications both in cryptography and in the simulation of a variety of fundamental physical systems. Since the Haar ensemble is very expensive to sample, pseudorandom ensembles in the form of t-designs are frequently used as an efficient substitute, and are sufficient for most applications. We investigate t-designs generated using a measurement-based approach on superconducting quantum computers. In particular, we implemented an exact single-qubit 3-design on IBM quantum processors by performing measurements on a 6-qubit graph state. By analysing channel tomography results, we were able to show that the ensemble of unitaries realised was a 1-design, but not a 2-design or a 3-design under the test conditions set, which we show to be a result of depolarising noise during the measurement-based process. We obtained improved results for the 2-design test by implementing an approximate 2-design, in which measurements were performed on a smaller 5-qubit graph state, but the test still did not pass for all states. This suggests that the practical realisation of measurement-based t-designs on superconducting quantum computers will require further work on the reduction of depolarising noise in these devices.
How Spanish speakers express norms using generic person markers
Authors: Salvador Cristina E. , Orvell Ariana , Kross Ethan , Gelman Susan A.
Published: March 2022

Language is one powerful vehicle for transmitting norms—a universal feature of society. In English, people use “you” generically (e.g., “You win some you lose some”) to express and interpret norms. Here, we examine how norms are conveyed and interpreted in Spanish, a language that—unlike English—has two forms of you (i.e., formal, informal), distinct generic person markers, and pro-drop, allowing for an examination of underlying conceptual tendencies in how the structure of language facilitates the transmission of norms. In Study 1a-b (N = 838) Spanish speakers used informal generic-you and the generic person marker “se” (but not formal-you) to express norms (vs. preferences). In Study 2 (N = 300), formal you, informal you, and impersonal “se” had persuasive force over personal endorsements (e.g., “I”), informing Spanish speaker’s interpretation of unfamiliar norms. Our findings add to a growing literature on how subtle linguistic shifts reflect and influence cognitive processes.
Atomistic mechanisms of human TRPA1 activation by electrophile irritants through molecular dynamics simulation and mutual information analysis
Authors: Habgood Matthew , Seiferth David , Zaki Afroditi-Maria , Alibay Irfan , Biggin Philip C.
Published: March 2022

The ion channel TRPA1 is a promiscuous chemosensor, with reported response to a wide spectrum of noxious electrophilic irritants, as well as cold, heat, and mechanosensation. It is also implicated in the inception of itch and pain and has hence been investigated as a drug target for novel analgesics. The mechanism of electrophilic activation for TRPA1 is therefore of broad interest. TRPA1 structures with the pore in both open and closed states have recently been published as well as covalent binding modes for electrophile agonists. However, the detailed mechanism of coupling between electrophile binding sites and the pore remains speculative. In addition, while two different cysteine residues (C621 and C665) have been identified as critical for electrophile bonding and activation, the bound geometry has only been resolved at C621. Here, we use molecular dynamics simulations of TRPA1 in both pore-open and pore-closed states to explore the allosteric link between the electrophile binding sites and pore stability. Our simulations reveal that an open pore is structurally stable in the presence of open ‘pockets’ in the C621/C665 region, but rapidly collapses and closes when these pockets are shut. Binding of electrophiles at either C621 or C665 provides stabilisation of the pore-open state, but molecules bound at C665 are shown to be able to rotate in and out of the pocket, allowing for immediate stabilisation of transient open states. Finally, mutual information analysis of trajectories reveals an informational path linking the electrophile binding site pocket to the pore via the voltage-sensing-like domain, giving a detailed insight into the how the pore is stabilized in the open state.
Interaction between a robot and Bunimovich stadium billiards
Authors: Vasconcelos J. V. A. , Miranda-Filho L. H. , de Souza A. J. F. , de C. Romaguera A. R. , Barbosa A. L. R.
Published: March 2022

The robot–environment–task triad provides many opportunities to revisit physical problems with fresh eyes. Hence, we develop a simple experiment to observe chaos in classical billiards with a macroscopic 3.38-m long setup. Using a digital video camera, one records the dynamic time evolution of the interaction between a robot and Bunimovich stadium billiards with specular reflection. From the experimental time series, we calculate the Lyapunov exponent $$\lambda$$
λ
as a function of a geometric parameter. The results are in concordance with theoretical predictions. In addition, we determine the Poincaré surface of section from the experimental data and check its sensitivity to the initial conditions as a function of time.
Differential volume reductions in the subcortical, limbic, and brainstem structures associated with behavior in Prader–Willi syndrome
Authors: Yamada Kenichi , Watanabe Masaki , Suzuki Kiyotaka
Published: March 2022

Individuals with Prader–Willi syndrome (PWS) exhibit complex behavioral characteristics, including hyperphagia, autistic features, and subsequent age-related maladaptive behaviors. While this suggests functional involvements of subcortical, limbic, and brainstem areas, developmental abnormalities in such structures remain to be investigated systematically. Twenty-one Japanese individuals with PWS and 32 healthy controls with typical development were included. T1-weighted three-dimensional structural magnetic resonance images were analyzed for subcortical, limbic, and brainstem structural volumes, with age as a covariate, using a model-based automatic segmentation tool. Correlations were determined between each volume measurement and behavioral characteristics as indexed by questionnaires and block test scores for hyperphagia (HQ), autistic and obsessional traits, non-verbal intelligence (IQ), and maladaptive behavior (VABS_mal). Compared with the control group, the PWS group showed significantly reduced relative volume ratios per total intracranial volume (TIV) in thalamus, amygdala, and brainstem structures, along with TIV and native volumes in all substructures. While the brainstem volume ratio was significantly lower in all age ranges, amygdala volume ratios were significantly lower during early adulthood and negatively correlated to HQ and VABS_mal but positively correlated to Kohs IQ. Thus, limbic and brainstem volume alterations and differential volume trajectories may contribute to the developmental and behavioral pathophysiology of PWS.
Down-regulation of the transcriptional repressor ZNF802 (JAZF1) reactivates fetal hemoglobin in β0-thalassemia/HbE
Authors: Wongborisuth Chokdee , Chumchuen Sukanya , Sripichai Orapan , Anurathaphan Usanarat , Sathirapongsasuti Nuankanya , Songdej Duantida , Tangprasittipap Amornrat , Hongeng Suradej
Published: March 2022

Reactivating of fetal hemoglobin (HbF; α2γ2) can ameliorate the severity of β-thalassemia disease by compensating for adult hemoglobin deficiency in patients. Previously, microarray analysis revealed that zinc finger protein (ZNF)802 (also known as Juxta-posed with another zinc finger gene-1 (JAZF1)) was upregulated in human erythroblasts derived from adult peripheral blood compared with fetal liver-derived cells, implying a potential role as a HbF repressor. However, deficiency in ZNF802 induced by lentiviral shRNA in β0-thalassemia/hemoglobinE erythroblasts had no effect on erythroblast proliferation and differentiation. Remarkably, the induction of HBG expression was observed at the transcriptional and translational levels resulting in an increase of HbF to 35.0 ± 3.5%. Interestingly, the embryonic globin transcripts were also upregulated but the translation of embryonic globin was not detected. These results suggest ZNF802 might be a transcriptional repressor of the γ-globin gene in adult erythroid cells.
Revealing key lncRNAs in cytogenetically normal acute myeloid leukemia by reconstruction of the lncRNA–miRNA–mRNA network
Authors: Sun Tao , Dong Lin , Guo Yan , Zhao Hai , Wang Manzhi
Published: March 2022

Cytogenetically normal acute myeloid leukemia (CN-AML) is a heterogeneous disease with different prognoses. Researches on prognostic biomarkers and therapy targets of CN-AML are still ongoing. Instead of protein-coding genes, more and more researches were focused on the non-coding RNAs especially long non-coding RNAs (lncRNAs) which may play an important role in the development of AML. Although a large number of lncRNAs have been found, our knowledge of their functions and pathological process is still in its infancy. The purpose of this research is to identify the key lncRNAs and explore their functions in CN-AML by reconstructing the lncRNA–miRNA–mRNA network based on the competitive endogenous RNA (ceRNA) theory. We reconstructed a global triple network based on the ceRNA theory using the data from National Center for Biotechnology Information Gene Expression Omnibus and published literature. According to the topological algorithm, we identified the key lncRNAs which had both the higher node degrees and the higher numbers of lncRNA–miRNA pairs and total pairs in the ceRNA network. Meanwhile, Gene Ontology (GO) and pathway analysis were performed using databases such as DAVID, KOBAS and Cytoscape plug-in ClueGO respectively. The lncRNA–miRNA–mRNA network was composed of 90 lncRNAs,33mRNAs,26 miRNAs and 259 edges in the lncRNA upregulated group, and 18 lncRNAs,11 mRNAs,6 miRNAs and 45 edges in the lncRNA downregulated group. The functional assay showed that 53 pathways and 108 GO terms were enriched. Three lncRNAs (XIST, TUG1, GABPB1-AS1) could possibly be selected as key lncRNAs which may play an important role in the development of CN-AML. Particularly, GABPB1-AS1 was highly expressed in CN-AML by both bioinformatic analysis and experimental verification in AML cell line (THP-1) with quantitative real‐time polymerase chain reaction. In addition, GABPB1-AS1 was also negatively correlated with overall survival of AML patients. The lncRNA–miRNA–mRNA network revealed key lncRNAs and their functions in CN-AML. Particularly, lncRNA GABPB1-AS1 was firstly proposed in AML. We believe that GABPB1-AS1 is expected to become a candidate prognostic biomarker or a potential therapeutic target.
NaCl exposure results in increased expression and processing of IL-1β in Meniere’s disease patients
Authors: Pathak Shresh , Vambutas Andrea
Published: March 2022

Meniere’s disease (MD) is a chronic disease that causes episodic vertigo, fluctuating hearing loss, and aural fullness, initially managed by dietary salt reduction, and use of diuretics. Our prior research in autoimmune inner ear disease (AIED) demonstrated that in peripheral blood mononuclear cell (PBMC) from corticosteroid-resistant AIED patients, increased production, processing and release of interleukin-1β (IL-1β) is observed and hearing could be improved with use of anakinra, an interleukin-1 receptor antagonist. We have further identified that in these AIED patients, IL-1β is uniquely processed to a 28 kDa pro-inflammatory product by caspase-7. In the present study, we characterize the production, processing and release of the pro-inflammatory cytokines IL-1β and IL-6 from PBMC of MD (n = 14) patients in response to sodium chloride (NaCl), and determined the effect of the diuretic triamterene-hydrocholothiazide (T-HCTZ), or anakinra in these patients. We observed that PBMC cultured with NaCl from MD patients show processing of IL-1β to the 28 kDa product, and that this product is abrogated with T-HCTZ. Our observations are consistent with other autoimmune diseases where high concentrations of NaCl caused release of pro-inflammatory cytokines and may provide further insight as to the mechanism of disease progression in MD patients.
Electrocautery smoke exposure and efficacy of smoke evacuation systems in minimally invasive and open surgery: a prospective randomized study
Authors: Kocher Gregor J. , Koss Abigail R. , Groessl Michael , Schefold Joerg C. , Luedi Markus M. , Quapp Christopher , Dorn Patrick , Lutz Jon , Cappellin Luca , Hutterli Manuel , Lopez-Hilfiker Felipe D. , Al-Hurani Mohammad , Sesia Sergio B.
Published: March 2022

Worldwide, health care professionals working in operating rooms (ORs) are exposed to electrocautery smoke on a daily basis. Aims of this study were to determine composition and concentrations of electrocautery smoke in the OR using mass spectrometry. Prospective observational study at a tertiary care academic center, involving 122 surgical procedures of which 84 were 1:1 computer randomized to smoke evacuation system (SES) versus no SES use. Irritating, toxic, carcinogenic and mutagenic VOCs were observed in OR air, with some exceeding permissible exposure limits (OSHA/NIOSH). Mean total concentration of harmful compounds was 272.69 ppb (± 189 ppb) with a maximum total concentration of harmful substances of 8991 ppb (at surgeon level, no SES). Maximum total VOC concentrations were 1.6 ± 1.2 ppm (minimally-invasive surgery) and 2.1 ± 1.5 ppm (open surgery), and total maximum VOC concentrations were 1.8 ± 1.3 ppm at the OR table ‘at surgeon level’ and 1.4 ± 1.0 ppm ‘in OR room air’ away from the operating table. Neither difference was statistically significant. In open surgery, SES significantly reduced maximum concentrations of specific VOCs at surgeon level, including aromatics and aldehydes. Our data indicate relevant exposure of health care professionals to volatile organic compounds in the OR. Surgical technique and distance to cautery devices did not significantly reduce exposure. SES reduced exposure to specific harmful VOC’s during open surgery.

Trial Registration Number: NCT03924206 (clinicaltrials.gov).
Genetic variation in released gametes produces genetic diversity in the offspring of the broadcast spawning coral Acropora tenuis
Authors: Kitanobo Seiya , Toshino Sho , Morita Masaya
Published: March 2022

All coral species in the genus Acropora are broadcast-spawning hermaphrodites. Fertilization in the ocean requires sufficient numbers of gametes from conspecifics and the contact time for fertilization is thought to be limited by the rapid diffusion of sperm. Many studies have reported a positive correlation between sperm concentration and fertilization success, but it is not clear how gametes diffuse in seawater to produce mixtures of gametes from many colonies, leading to fertilization that improves genetic diversity. To elucidate this, we analyzed the changes in sperm concentration of A.tenuis in situ after spawning and genotyped sperm and fertilized eggs from seawater using seven microsatellite (MS) markers. Results showed that most of the eggs were fertilized at below 106 sperm/mL in situ. MS genotyping showed that the alleles of released sperm were diverse and those alleles also appeared in the fertilized eggs. The MS fragment peak height in released sperm, which presumably reflects the allele frequency of the sperm, was positively correlated with the allele frequencies of the fertilized eggs. Collectively, synchronous spawning populations composed of highly fecund and genetically diverse colonies potentially increases genetic diversity and the number of descendants.
Development and validation of a risk-score model for opioid overdose using a national claims database
Authors: Heo Kyu-Nam , Lee Ju-yeun , Ah Young-Mi
Published: March 2022

Opioid overdose can be serious adverse effects of opioid analgesics. Thus, several strategies to mitigate risk and reduce the harm of opioid overdose have been developed. However, despite a marked increase in opioid analgesic consumption in Korea, there have been no tools predicting the risk of opioid overdose in the Korean population. Using the national claims database of the Korean population, we identified patients who were incidentally prescribed non-injectable opioid analgesic (NIOA) at least once from 2017 to 2018 (N = 1,752,380). Among them, 866 cases of opioid overdose occurred, and per case, four controls were selected. Patients were randomly allocated to the development (80%) and validation (20%) cohort. Thirteen predictive variables were selected via logistic regression modelling, and a risk-score was assigned for each predictor. Our model showed good performance with c-statistics of 0.84 in the validation cohort. The developed risk score model is the first tool to identify high-risk patients for opioid overdose in Korea. It is expected to be applicable in the clinical setting and useful as a national level surveillance tool due to the easily calculable and identifiable predictors available from the claims database.
Evidence of the role of the cerebellum in cognitive theory of mind using voxel-based lesion mapping
Authors: Beuriat Pierre-Aurélien , Cohen-Zimerman Shira , Smith Gretchen N. L. , Krueger Frank , Gordon Barry , Grafman Jordan
Published: March 2022

Theory of Mind (ToM) is a social-cognitive skill that allows the understanding of the intentions, beliefs, and desires of others. There is a distinction between affective and cognitive ToM, with evidence showing that these processes rely on partially distinct neural networks. The role of the cerebellum in social cognition has only been rarely explored. In this study, we tested whether the cerebellum is necessary for cognitive and affective ToM performance. We investigated adults with traumatic brain injury (n = 193) and healthy controls (n = 52) using voxel-based lesion-symptom mapping (VLSM) and by measuring the impact on functional connectivity. First, we observed that damage to the cerebellum affected pure Cognitive ToM processing. Further, we found a lateralization effect for the role of the cerebellum in cognitive ToM with participants with left cerebellar injury performing worse than those with right cerebellar injury. Both VLSM and standard statistical analysis provided evidence that left cerebellar Crus I and lobule VI contributed to ToM processing. Lastly, we found that disconnection of the left thalamic projection and the left fronto-striatal fasciculus was associated with poor cognitive ToM performance. Our study is the first to reveal direct causal neuropsychological evidence for a role of the cerebellum in some but not all types of ToM, processing. It reinforces the idea that social cognition relies on a complex network functionally connected through white matter pathways that include the cerebellum. It supports evidence that the neural networks underpinning the different types of ToM can be differentiated.
The role of lysine palmitoylation/myristoylation in the function of the TEAD transcription factors
Authors: Mesrouze Yannick , Aguilar Gustavo , Meyerhofer Marco , Bokhovchuk Fedir , Zimmermann Catherine , Fontana Patrizia , Vissières Alexandra , Voshol Hans , Erdmann Dirk , Affolter Markus , Chène Patrick
Published: March 2022

The TEAD transcription factors are the most downstream elements of the Hippo pathway. Their transcriptional activity is modulated by different regulator proteins and by the palmitoylation/myristoylation of a specific cysteine residue. In this report, we show that a conserved lysine present in these transcription factors can also be acylated, probably following the intramolecular transfer of the acyl moiety from the cysteine. Using Scalloped (Sd), the Drosophila homolog of human TEAD, as a model, we designed a mutant protein (Glu352GlnSd) that is predominantly acylated on the lysine (Lys350Sd). This protein binds in vitro to the three Sd regulators—Yki, Vg and Tgi—with a similar affinity as the wild type Sd, but it has a significantly higher thermal stability than Sd acylated on the cysteine. This mutant was also introduced in the endogenous locus of the sd gene in Drosophila using CRISPR/Cas9. Homozygous mutants reach adulthood, do not present obvious morphological defects and the mutant protein has both the same level of expression and localization as wild type Sd. This reveals that this mutant protein is both functional and able to control cell growth in a similar fashion as wild type Sd. Therefore, enhancing the lysine acylation of Sd has no detrimental effect on the Hippo pathway. However, we did observe a slight but significant increase of wing size in flies homozygous for the mutant protein suggesting that a higher acylation of the lysine affects the activity of the Hippo pathway. Altogether, our findings indicate that TEAD/Sd can be acylated either on a cysteine or on a lysine, and suggest that these two different forms may have similar properties in cells.
Accelerated remodeling of the mesophyll-bundle sheath interface in the maize C4 cycle mutant leaves
Authors: Gao Peng , Wang Pengfei , Du Baijuan , Li Pinghua , Kang Byung-Ho
Published: March 2022

C4 photosynthesis in the maize leaf involves the exchange of organic acids between mesophyll (M) and the bundle sheath (BS) cells. The transport is mediated by plasmodesmata embedded in the suberized cell wall. We examined the maize Kranz anatomy with a focus on the plasmodesmata and cell wall suberization with microscopy methods. In the young leaf zone where M and BS cells had indistinguishable proplastids, plasmodesmata were simple and no suberin was detected. In leaf zones where dimorphic chloroplasts were evident, the plasmodesma acquired sphincter and cytoplasmic sleeves, and suberin was discerned. These modifications were accompanied by a drop in symplastic dye mobility at the M-BS boundary. We compared the kinetics of chloroplast differentiation and the modifications in M-BS connectivity in ppdk and dct2 mutants where C4 cycle is affected. The rate of chloroplast diversification did not alter, but plasmodesma remodeling, symplastic transport inhibition, and cell wall suberization were observed from younger leaf zone in the mutants than in wild type. Our results indicate that inactivation of the C4 genes accelerated the changes in the M-BS interface, and the reduced permeability suggests that symplastic transport between M and BS could be regulated for normal operation of C4 cycle.
Modal gain characteristics of a two-section InGaAs/GaAs double quantum well passively mode-locked laser with asymmetric waveguide
Authors: Qiao Zhongliang , Li Xiang , Sia Jia Xu Brian , Wang Wanjun , Wang Hong , Li Zaijin , Zhao Zhibin , Li Lin , Gao Xin , Bo Baoxue , Qu Yi , Liu Guojin , Liu Chongyang
Published: March 2022

Monolithic two-section InGaAs/GaAs double quantum well (DQW) passively mode-locked lasers (MLLs) with asymmetric waveguide, consisting of the layers of p-doped AlGaAs waveguide and no-doped InGaAsP waveguide, emitting at ~ 1.06 μm, with a fundamental repetition rate at ~ 19.56 GHz have been demonstrated. Modal gain characteristics, such as a gain bandwidth and a gain peak wavelength of the MLL, as a function of the saturable absorber (SA) bias voltage (Va) as well as the injection current of gain section (Ig), were investigated by the Hakki-Paoli method. With the increase of Va, the lasing wavelength and net modal gain peak of the MLL both exhibited red-shifts to longer wavelength significantly, while the modal gain bandwidth was narrowed. Both the net modal gain bandwidth and gain peak of the MLL followed a polynomial distribution versus the reverse bias at the absorber section. In addition, for the first time, it was found that Va had an obvious effect on the modal gain characteristics of the MLL.
The role of future anthropogenic methane emissions in air quality and climate
Authors: Staniaszek Zosia , Griffiths Paul T. , Folberth Gerd A. , O’Connor Fiona M. , Abraham N. Luke , Archibald Alexander T.
Published: March 2022

Mitigation of greenhouse gas emissions is crucial for achieving the goals of the Paris climate agreement. One key gas is methane, whose representation in most climate models is limited by using prescribed surface concentrations. Here we use a new, methane emissions-driven version of the UK Earth System Model (UKESM1) and simulate a zero anthropogenic methane emissions scenario (ZAME) in order to (i) attribute the role of anthropogenic methane emissions on the Earth system and (ii) bracket the potential for theoretical maximum mitigation. We find profound, rapid and sustained impacts on atmospheric composition and climate, compared to a counterfactual projection (SSP3-7.0, the ’worst case’ scenario for methane). In ZAME, methane declines to below pre-industrial levels within 12 years and global surface ozone decreases to levels seen in the 1970s. By 2050, 690,000 premature deaths per year and 1° of warming can be attributed to anthropogenic methane in SSP3-7.0. This work demonstrates the significant maximum potential of methane emissions reductions, and their air-quality co-benefits, but also reiterates the need for action on carbon dioxide (CO2) emissions. We show that a methane emissions-driven treatment is essential for simulating the full Earth system impacts and feedbacks of methane emissions changes.
Culturally adapting internet- and mobile-based health promotion interventions might not be worth the effort: a systematic review and meta-analysis
Authors: Balci Sumeyye , Spanhel Kerstin , Sander Lasse Bosse , Baumeister Harald
Published: March 2022

Health promotion interventions offer great potential in advocating a healthy lifestyle and the prevention of diseases. Some barriers to communicating health promotion to people of certain cultural groups might be overcome via the internet- and mobile-based interventions (IMI). This systematic review and meta-analysis aims to explore the effectiveness of culturally adapted IMI for health promotion interventions among culturally diverse populations. We systematically searched on Cochrane Central Register of Controlled Trials (CENTRAL), EbscoHost/MEDLINE, Ovid/Embase, EbscoHost/PsychINFO, and Web of Science databases in October 2020. Out of 9438 records, 13 randomized controlled trials (RCT) investigating culturally adapted health promotion IMI addressing healthy eating, physical activity, alcohol consumption, sexual health behavior, and smoking cessation included. From the included studies 10,747 participants were eligible. Culturally adapted IMI proved to be non-superior over active control conditions in short- (g = 0.10, [95% CI −0.19 to 0.40]) and long-term (g = 0.20, [95% CI −0.11 to 0.51]) in promoting health behavior. However, culturally adapted IMI for physical activity (k = 3, N = 296) compared to active controls yielded a beneficial effect in long-term (g = 0.48, [95%CI 0.25 to 0.71]). Adapting health promotion IMI to the cultural context of different cultural populations seems not yet to be recommendable given the substantial adaption efforts necessary and the mostly non-significant findings. However, these findings need to be seen as preliminary given the limited number of included trials with varying methodological rigor and the partly substantial between-trial heterogeneity pointing in the direction of potentially useful culturally adapted IMI which now need to be disentangled from the less promising approaches.

PROSPERO registration number: 42020152939
Cryo-EM structure of transmembrane AAA+ protease FtsH in the ADP state
Authors: Liu Wu , Schoonen Martien , Wang Tong , McSweeney Sean , Liu Qun
Published: March 2022

AAA+ proteases regulate numerous physiological and cellular processes through tightly regulated proteolytic cleavage of protein substrates driven by ATP hydrolysis. FtsH is the only known family of membrane-anchored AAA+ proteases essential for membrane protein quality control. Although a spiral staircase rotation mechanism for substrate translocation across the FtsH pore has been proposed, the detailed conformational changes among various states have not been clear due to absence of FtsH structures in these states. We report here the cryo-EM structure for Thermotoga maritima FtsH (TmFtsH) in a fully ADP-bound symmetric state. Comparisons of the ADP-state structure with its apo-state and a substrate-engaged yeast YME1 structure show conformational changes in the ATPase domains, rather than the protease domains. A reconstruction of the full-length TmFtsH provides structural insights for the dynamic transmembrane and the periplasmic domains. Our structural analyses expand the understanding of conformational switches between different nucleotide states in ATP hydrolysis by FtsH.
(In situ) spectroscopic studies on state-of-the-art Pd(ii) catalysts in solution for the alkoxycarbonylation of alkenes
Authors: Kucmierczyk Peter , Behrens Stephan , Kubis Christoph , Baumann Wolfgang , Wei Zhihong , Jiao Haijun , Dong Kaiwu , Spannenberg Anke , Neumann Helfried , Jackstell Ralf , Börner Armin , Franke Robert , Beller Matthias
Published: March 2022

(In situ) liquid-phase spectroscopic investigations on state-of-the-art Pd catalysts modified with pyridyl-substituted diphosphine ligands for alkene alkoxycarbonylations have been performed for characterizing resting state complexes in solution.