bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss-of-function variants inMYCBP2cause neurobehavioural phenotypes and corpus callosum defects
Authors: AlAbdi Lama , Desbois Muriel , Rusnac Domniţa-Valeria , Sulaiman Raashda A , Rosenfeld Jill A , Lalani Seema , Murdock David R , Burrage Lindsay C ,   Undiagnosed Diseases Network, Billie Au Ping Yee , Towner Shelley , Wilson William G , Wong Lawrence , Brunet Theresa , Strobl-Wildemann Gertrud , Burton Jennifer E , Hoganson George , McWalter Kirsty , Begtrup Amber , Zarate Yuri A , Christensen Elyse L , Opperman Karla J , Giles Andrew C , Helaby Rana , Kania Artur , Zheng Ning , Grill Brock , Alkuraya Fowzan S
Published: October 2022

The corpus callosum is a bundle of axon fibres that connects the two hemispheres of the brain. Neurodevelopmental disorders that feature dysgenesis of the corpus callosum as a core phenotype offer a valuable window into pathology derived from abnormal axon development. Here, we describe a cohort of eight patients with a neurodevelopmental disorder characterized by a range of deficits including corpus callosum abnormalities, developmental delay, intellectual disability, epilepsy and autistic features. Each patient harboured a distinct de novo variant in MYCBP2, a gene encoding an atypical really interesting new gene (RING) ubiquitin ligase and signalling hub with evolutionarily conserved functions in axon development. We used CRISPR/Cas9 gene editing to introduce disease-associated variants into conserved residues in the Caenorhabditis elegans MYCBP2 orthologue, RPM-1, and evaluated functional outcomes in vivo. Consistent with variable phenotypes in patients with MYCBP2 variants, C. elegans carrying the corresponding human mutations in rpm-1 displayed axonal and behavioural abnormalities including altered habituation. Furthermore, abnormal axonal accumulation of the autophagy marker LGG-1/LC3 occurred in variants that affect RPM-1 ubiquitin ligase activity. Functional genetic outcomes from anatomical, cell biological and behavioural readouts indicate that MYCBP2 variants are likely to result in loss of function. Collectively, our results from multiple human patients and CRISPR gene editing with an in vivo animal model support a direct link between MYCBP2 and a human neurodevelopmental spectrum disorder that we term, MYCBP2-related developmental delay with corpus callosum defects (MDCD).
The new 2022 ESC Guidelines on Cardio-oncology and their impact on the Acute Cardiovascular Care Society
Authors: von Kemp Berlinde , Halvorsen Sigrun , Nohria Anju
Published: October 2022

Structured summary

In this perspective piece on the recently published ESC Guidelines on Cardio-oncology and the Consensus Statements from the Acute Cardiovascular Care Association, we summarize key learning points regarding the management of acute cardiovascular disease in patients with cancer. This document outlines where other pre-existing ESC Guidelines can be applied to the management of acute cardiovascular disease in patients with cancer while simultaneously highlighting important gaps in knowledge that require further research.

Cancer and cardiovascular disease share common risk factors and often co-exist, especially in older patients. In addition, patients with cancer undergoing active treatment are exposed to multiple, potentially cardiotoxic drugs, which may manifest as a variety of cardiovascular events, including left-ventricular systolic dysfunction and heart failure, arrhythmias, hypertension, or acute venous and arterial vascular events.

Knowledge about potential causative cancer therapeutics is necessary for rapid recognition and management to improve cardiovascular outcomes and guide ongoing cancer treatment. Specifically, the importance of rapidly interrupting culprit cancer drugs is highlighted, as well as instituting standard guideline-based therapies for conditions such as acute heart failure and acute coronary syndromes [ST-elevation myocardial infarction and high-risk non-ST-elevation acute coronary syndrome (ACS)]. Given the high prevalence of thrombocytopenia and increased bleeding risk in patients with cancer, we are provided with platelet cut-offs for the use of different antiplatelet agents and anticoagulants for patients with ACS and atrial arrhythmias. In contrast, given the hypercoagulable milieu of cancer, we are provided information regarding types of anticoagulants, drug–drug interactions, and duration of anticoagulation in patients with acute venous thromboembolism, as well as for atrial fibrillation. They also discuss the diagnostic and treatment strategies for the unique cardiotoxicities seen with novel cancer therapeutics such as immune checkpoint inhibitors and chimeric receptor antigen T-cell therapy. Last, but not least, the authors emphasize that the care of these patients requires close collaboration between cardiology and oncology to maximize both cardiovascular and cancer outcomes.
Noncommunicating acute type A aortic dissection in elderly patients: Surgery versus medical management
Authors: Nakamae Kosuke , Oshitomi Takashi , Uesugi Hideyuki , Ideta Ichiro , Takaji Kentaro , Sassa Toshiharu , Murata Hidetaka , Hirota Masataka
Published: October 2022

OBJECTIVES

Our goal was to evaluate the surgical and conservative outcomes of acute type A aortic dissection with a thrombosed false lumen of the ascending aorta in elderly patients.

METHODS

Patients older than 75 years with acute type A aortic dissection admitted to our hospital from October 2011 to December 2020 were reviewed retrospectively, including those with the noncommunicating type without malperfusion and low physical capacity prehospitalization.

RESULTS

Sixty-six patients were enrolled consecutively in the medical (M, n = 30) and surgical (S, n = 36) groups. The ascending aorta was the most replaced section in the S group (78%). Groups did not differ significantly in hospital deaths and in intensive care unit and hospital stays. Two patients (7%) underwent surgery and 3 (10%) underwent redissection in the M group. No significant difference existed between the groups in the decline of physical performance during hospitalization. Seven patients in the M group (24%) had aorta-related events in the late period as opposed to none in the S group (P=0.003). Survival rates after 4 years were 78.3% and 71.4% in the S and M groups, respectively (P=0.154). The cumulative incidence of overall reintervention due to an aortic event was significantly higher in the M group; however, the 2 groups did not differ significantly in overall aorta-related deaths.

CONCLUSIONS

Surgical outcomes of noncommunicating acute type A aortic dissection in elderly patients were favorable. There was no significant difference in maintaining physical function at discharge, and the medical group had a significantly higher overall aortic event rate than the surgical group.
CODE-EHR best practice framework for the use of structured electronic healthcare records in clinical research
Authors: Kotecha Dipak , Asselbergs Folkert W , Achenbach Stephan , Anker Stefan D , Atar Dan , Baigent Colin , Banerjee Amitava , Beger Birgit , Brobert Gunnar , Casadei Barbara , Ceccarelli Cinzia , Cowie Martin R , Crea Filippo , Cronin Maureen , Denaxas Spiros , Derix Andrea , Fitzsimons Donna , Fredriksson Martin , Gale Chris P , Gkoutos Georgios V , Goettsch Wim , Hemingway Harry , Ingvar Martin , Jonas Adrian , Kazmierski Robert , Løgstrup Susanne , Thomas Lumbers R , Lüscher Thomas F , McGreavy Paul , Piña Ileana L , Roessig Lothar , Steinbeisser Carl , Sundgren Mats , Tyl Benoît , van Thiel Ghislaine , van Bochove Kees , Vardas Panos E , Villanueva Tiago , Vrana Marilena , Weber Wim , Weidinger Franz , Windecker Stephan , Wood Angela , Grobbee Diederick E ,   the Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, CODE-EHR international consensus group, Kurz Xavier , Concato John , Kazmierski Robert , Morales Jose Pablo , Piña Ileana , Goettsch Wim , Jonas Adrian , Hedberg Niklas , Crea Filippo , Lüscher Thomas F , Weber Wim , Villanueva Tiago , Spencer Stuart , Sarkar Rupa , Fredriksson Martin , Sundgren Mats , Derix Andrea , Brobert Gunnar , Roessig Lothar , Tyl Benoit , van Bochove Kees , Cronin Maureen , Carroll Colm , Thompson Ceri , Beger Birgit , Løgstrup Susanne , Vrana Marilena , McGreavy Paul , Casadei Barbara , Achenbach Stephan , Tursini Valentina , Vardas Panos E , Atar Dan , Baigent Colin , Gale Chris P , Fitzsimons Donna , Windecker Stephan , Anker Stefan D , Cowie Martin , Banerjee Amitava , Hemingway Harry , Lumbers R Tom , Denaxas Spiros , Asselbergs Folkert W , Grobbee Rick , Van Thiel Ghislaine , Kotecha Dipak , Gkoutos George V , Wood Angela , Ingvar Martin , Steinbeisser Carl , Petrova Ana , Ceccarelli Cinzia , Baljevic Katija , Vairami Polyxeni , Taylor Jennifer
Published: October 2022

Big data is central to new developments in global clinical science aiming to improve the lives of patients. Technological advances have led to the routine use of structured electronic healthcare records with the potential to address key gaps in clinical evidence. The covid-19 pandemic has demonstrated the potential of big data and related analytics, but also important pitfalls. Verification, validation, and data privacy, as well as the social mandate to undertake research are key challenges. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including patient representatives, clinicians, scientists, regulators, journal editors and industry. We propose the CODE-EHR Minimum Standards Framework as a means to improve the design of studies, enhance transparency and develop a roadmap towards more robust and effective utilisation of healthcare data for research purposes.
Transcriptome analysis of FOXO-dependent hypoxia gene expression identifies Hipk as a regulator of low oxygen tolerance in Drosophila
Authors: Ding Kate , Barretto Elizabeth C , Johnston Michael , Lee Byoungchun , Gallo Marco , Grewal Savraj S
Published: October 2022

When exposed to low oxygen or hypoxia, animals must alter their metabolism and physiology to ensure proper cell-, tissue-, and whole-body level adaptations to their hypoxic environment. These alterations often involve changes in gene expression. While extensive work has emphasized the importance of the HIF-1 alpha transcription factor on controlling hypoxia gene expression, less is known about other transcriptional mechanisms. We previously identified the transcription factor FOXO as a regulator of hypoxia tolerance in Drosophila larvae and adults. Here, we use an RNA-sequencing approach to identify FOXO-dependent changes in gene expression that are associated with these tolerance effects. We found that hypoxia altered the expression of over 2,000 genes and that ∼40% of these gene expression changes required FOXO. We discovered that hypoxia exposure led to a FOXO-dependent increase in genes involved in cell signaling, such as kinases, GTPase regulators, and regulators of the Hippo/Yorkie pathway. Among these, we identified homeodomain-interacting protein kinase as being required for hypoxia survival. We also found that hypoxia suppresses the expression of genes involved in ribosome synthesis and egg production, and we showed that hypoxia suppresses tRNA synthesis and mRNA translation and reduces female fecundity. Among the downregulated genes, we discovered that FOXO was required for the suppression of many ribosomal protein genes and genes involved in oxidative phosphorylation, pointing to a role for FOXO in limiting energetically costly processes such as protein synthesis and mitochondrial activity upon hypoxic stress. This work uncovers a widespread role for FOXO in mediating hypoxia changes in gene expression.
The Vinca minor genome highlights conserved evolutionary traits in monoterpene indole alkaloid synthesis
Authors: Stander Emily Amor , Cuello Clément , Birer-Williams Caroline , Kulagina Natalja , Jansen Hans J , Carqueijeiro Ines , Méteignier Louis-Valentin , Vergès Valentin , Oudin Audrey , Papon Nicolas , Dirks Ron P , Jensen Michael Krogh , O’Connor Sarah Ellen , Dugé de Bernonville Thomas , Besseau Sébastien , Courdavault Vincent
Published: October 2022

Vinca minor, also known as the lesser periwinkle, is a well-known species from the Apocynaceae, native to central and southern Europe. This plant synthesizes monoterpene indole alkaloids, which are a class of specialized metabolites displaying a wide range of bioactive- and pharmacologically important properties. Within the almost 50 monoterpene indole alkaloids it produces, V. minor mainly accumulates vincamine, which is commercially used as a nootropic. Using a combination of Oxford Nanopore Technologies long read- and Illumina short-read sequencing, a 679,098 Mb V. minor genome was assembled into 296 scaffolds with an N50 scaffold length of 6 Mb, and encoding 29,624 genes. These genes were functionally annotated and used in a comparative genomic analysis to establish gene families and to investigate gene family expansion and contraction across the phylogenetic tree. Furthermore, homology-based monoterpene indole alkaloid gene predictions together with a metabolic analysis across 4 different V. minor tissue types guided the identification of candidate monoterpene indole alkaloid genes. These candidates were finally used to identify monoterpene indole alkaloid gene clusters, which combined with synteny analysis allowed for the discovery of a functionally validated vincadifformine-16-hydroxylase, reinforcing the potential of this dataset for monoterpene indole alkaloids gene discovery. It is expected that access to these resources will facilitate the elucidation of unknown monoterpene indole alkaloid biosynthetic routes with the potential of transferring these pathways to heterologous expression systems for large-scale monoterpene indole alkaloid production.
Clonality, inbreeding, and hybridization in two extremotolerant black yeasts
Authors: Gostinčar Cene , Sun Xiaohuan , Černoša Anja , Fang Chao , Gunde-Cimerman Nina , Song Zewei
Published: October 2022

Background

The great diversity of lifestyles and survival strategies observed in fungi is reflected in the many ways in which they reproduce and recombine. Although a complete absence of recombination is rare, it has been reported for some species, among them 2 extremotolerant black yeasts from Dothideomycetes: Hortaea werneckii and Aureobasidium melanogenum. Therefore, the presence of diploid strains in these species cannot be explained as the product of conventional sexual reproduction.

Results

Genome sequencing revealed that the ratio of diploid to haploid strains in both H. werneckii and A. melanogenum is about 2:1. Linkage disequilibrium between pairs of polymorphic loci and a high degree of concordance between the phylogenies of different genomic regions confirmed that both species are clonal. Heterozygosity of diploid strains is high, with several hybridizing genome pairs reaching the intergenomic distances typically seen between different fungal species. The origin of diploid strains collected worldwide can be traced to a handful of hybridization events that produced diploids, which were stable over long periods of time and distributed over large geographic areas.

Conclusions

Our results, based on the genomes of over 100 strains of 2 black yeasts, show that although they are clonal, they occasionally form stable and highly heterozygous diploid intraspecific hybrids. The mechanism of these apparently rare hybridization events, which are not followed by meiosis or haploidization, remains unknown. Both extremotolerant yeasts, H. werneckii and even more so A. melanogenum, a close relative of the intensely recombining and biotechnologically relevant Aureobasidium pullulans, provide an attractive model for studying the role of clonality and ploidy in extremotolerant fungi.
Towards fast machine-learning-assisted Bayesian posterior inference of microseismic event location and source mechanism
Authors: Piras D , Spurio Mancini A , Ferreira A M G , Joachimi B , Hobson M P
Published: October 2022

Bayesian inference applied to microseismic activity monitoring allows the accurate location of microseismic events from recorded seismograms and the estimation of the associated uncertainties. However, the forward modelling of these microseismic events, which is necessary to perform Bayesian source inversion, can be prohibitively expensive in terms of computational resources. A viable solution is to train a surrogate model based on machine learning techniques to emulate the forward model and thus accelerate Bayesian inference. In this paper, we substantially enhance previous work, which considered only sources with isotropic moment tensors. We train a machine learning algorithm on the power spectrum of the recorded pressure wave and show that the trained emulator allows complete and fast event locations for any source mechanism. Moreover, we show that our approach is computationally inexpensive, as it can be run in less than 1 hr on a commercial laptop, while yielding accurate results using less than 104 training seismograms. We additionally demonstrate how the trained emulators can be used to identify the source mechanism through the estimation of the Bayesian evidence. Finally, we demonstrate that our approach is robust to real noise as measured in field data. This work lays the foundations for efficient, accurate future joint determinations of event location and moment tensor, and associated uncertainties, which are ultimately key for accurately characterizing human-induced and natural earthquakes, and for enhanced quantitative seismic hazard assessments.
Large-scale earthquake sequence simulations on 3-D non-planar faults using the boundary element method accelerated by lattice H-matrices
Authors: Ozawa So , Ida Akihiro , Hoshino Tetsuya , Ando Ryosuke
Published: October 2022

Large-scale earthquake sequence simulations using the boundary element method (BEM) incur extreme computational costs through multiplying a dense matrix with a slip rate vector. Hierarchical matrices (H-matrices) have often been used to accelerate this multiplication. However, the complexity of the structures of the H-matrices and the communication costs between processors limit their scalability, and they therefore cannot be used efficiently in distributed memory computer systems. Lattice H-matrices have recently been proposed as a tool to improve the parallel scalability of H-matrices. In this study, we developed a method for earthquake sequence simulations applicable to 3-D non-planar faults with lattice H-matrices. We present a simulation example and verify the mesh convergence of our method for a 3-D non-planar thrust fault using rectangular and triangular discretizations. We also performed performance and scalability analyses of our code. Our simulations, using over ${10}^5$ degrees of freedom, demonstrated a parallel acceleration beyond ${10}^4$ MPI processors and a > 10-fold acceleration over the best performance when the normal H-matrices are used. Using this code, we can perform unprecedented large-scale earthquake sequence simulations on geometrically complex faults with supercomputers. The software is made an open-source and freely available.
Imaging with seismic noise: improving extraction of body wave phases from the deep Earth through selective stacking based on H/V ratios
Authors: Pedersen Helle A , Mattern Flavien , Poli Piero , Stehly Laurent
Published: October 2022

Generating high-resolution images of the deep Earth remains a challenge. Body waves extracted from noise correlations hold high promise to complement earthquake-based studies, but data processing and interpretation are still under development. We develop a methodology to improve signal-to-noise ratio (SNR) of P410P and P660P, waves reflected at the top and bottom of the mantle transition zone, using data from the greater Alpine area and focussing on the second microseismic peak (2.5–10 s period). Rather than stacking all available data, we only stack correlations for days with a low ratio of amplitudes between the horizontal plane and vertical direction (H/V). Due to an improved SNR we can stack over fewer correlation pairs, with the result that horizontal resolution is significantly improved. We propose a systematic approach to determine at each study point the optimal combination of station pairs and the H/V threshold. We observe that the optimal choice of parameters is location dependent and that it is generally different for P410P and P660P. Additionally, we show that in our study area the maximum interstation distance needs to be reduced to ∼150 km for P410P to avoid that this arrival is contaminated by surface waves. Applied to the greater Alpine area we demonstrate a significant improvement of signal extraction: while P410P and P660P were only sporadically identified in standard stacks, with the new processing scheme these arrivals are clearly identified with coherent phases across large distances. We also show that amplitudes of P660P decrease drastically around longitude ∼11°E to ∼12°E, indicating that the lower discontinuity of the transition zone in that area is too broad to have a significant reflexion coefficient for P waves in the second microseismic peak.
Vanishing Treaty Claims: Investors Trapped in a Temporal Twilight Zone
Authors: Ren Raphael
Published: October 2022

The recent surge of arbitral awards forging new paths in the less-explored frontier of jurisdiction ratione temporis is laudable. Yet, if left unchecked, the trajectory of jurisdictional barriers expanding in depth and difficulty threatens to shrink the road of arbitration to the eye of a needle. Two emerging rules are especially worrisome: first, the right to claim under BITs vests exclusively with the investor holding the investment at the date of breach; second, the right is extinguished upon disposal of the investment. Concomitantly, once a pre-existing foreign investment is impaired by State measures, a temporal twilight zone is formed between the date of breach and date of institution of arbitration. The right to claim risks vanishing into a legal black hole along with the investment. Impecunious investors are left with a binary choice: litigate or mitigate. Ultimately, the broader lesson is for investment tribunals to avoid two common missteps when examining temporal objections: overreach of jurisdiction ratione temporis into areas more appropriately covered by the other jurisdictional dimensions (ratione materiae and ratione personae) and doctrine of abuse of process; and overreliance on principles transposed from private commercial arbitration (succession and separability).
Limited Humoral and Specific T-Cell Responses After SARS-CoV-2 Vaccination in PWH With Poor Immune Reconstitution
Authors: Benet Susana , Blanch-Lombarte Oscar , Ainsua-Enrich Erola , Pedreño-Lopez Núria , Muñoz-Basagoiti Jordana , Raïch-Regué Dàlia , Perez-Zsolt Daniel , Peña Ruth , Jiménez Esther , de la Concepción María Luisa Rodríguez , Ávila Carlos , Cedeño Samandhy , Escribà Tuixent , Romero-Martín Luis , Alarcón-Soto Yovaninna , Rodriguez-Lozano Gabriel Felipe , Miranda Cristina , González Sandra , Bailón Lucía , Blanco Julià , Massanella Marta , Brander Christian , Clotet Bonaventura , Paredes Roger , Esteve María , Izquierdo-Useros Nuria , Carrillo Jorge , Prado Julia G , Moltó José , Mothe Beatriz
Published: October 2022

Background

We analyzed humoral and cellular immune responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in people with human immunodeficiency virus (HIV; PWH) who had CD4+ T-cell counts <200/µL (HIV<200 group).

Methods

This prospective cohort study included 58 PWH in the HIV<200 group, 36 with CD4+ T-cell counts >500/µL (HIV>500 group), and 33 HIV-1–negative controls (control group). Antibodies against the SARS-CoV-2 spike protein (anti-S immunoglobulin [Ig] G) and the receptor-binding domain (anti-RBD IgG) were quantified before and 4 weeks after the first and the second doses of BNT162b2 or mRNA-1273 (at week 8). Viral neutralization activity and T-cell responses were also determined.

Results

At week 8, anti-S/anti-RBD IgG responses increased in all groups (P < .001). Median (interquartile range) anti-S and anti-RBD IgG levels at week 8 were 153.6 (26.4–654.9) and 171.9 (61.8–425.8) binding antibody units (BAU)/mL, respectively, in the HIV<200 group, compared with 245.6 (145–824) and 555.8 (166.4–1751) BAU/mL in the HIV>500 group and 274.7 (193.7–680.4) and 281.6 (181–831.8) BAU/mL in controls (P < .05). Neutralizing capacity and specific T-cell immune responses were absent or reduced in 33% of those in the HIV<200 group, compared with 3.7% in the HIV>500 group (P < .01).

Conclusions

One-third of PWH with CD4+ T-cell counts <200/µL show low anti-S/anti-RBD IgG levels, reduced in vitro neutralization activity against SARS-CoV-2, and no vaccine-induced T cells after receiving coronavirus disease 2019 mRNA vaccines.
Residual Humoral Immunity Sustained Over Decades in a Cohort of Vaccinia-Vaccinated Individuals
Authors: Chan Conrad E Z , Wong Steven K K , Yazid Nurhidayah Binte M , Ng Oon Tek , Marimuthu Kalisvar , Chan Monica , Howe Hwee Siew , Leo Yee-Sin , Leung Bernard P , Vasoo Shawn S , Young Barnaby E
Published: October 2022

Serological testing of Singaporeans who received childhood smallpox vaccination found anti-vaccinia IgG binding and neutralizing activity indicating long-term humoral immunity. There was correlation between IgG and neutralizing titers indicating IgG could be used as a surrogate marker for humoral immunity.

In 2019, Singapore experienced a case of imported monkeypox. As with smallpox, disease can be prevented through vaccination, which was mandatory for Singaporean infants until 1981. However, the degree of residual immunity in older vaccinated Singaporeans remains unknown. Sera from individuals born 1946–1984 were therefore tested and those born prior to 1981 were found to have higher anti-vaccinia IgG and neutralizing activity titers. This suggests that protective humoral immunity remains, which could reduce disease severity in an orthopoxvirus outbreak. Correlation between IgG and neutralizing titers was observed indicating that serology could be used as a surrogate marker for immunity.
Metabolism of crown tissue is crucial for drought tolerance and recovery after stress cessation inLolium/Festucaforage grasses
Authors: Perlikowski Dawid , Skirycz Aleksandra , Marczak Łukasz , Lechowicz Katarzyna , Augustyniak Adam , Michaelis Änna , Kosmala Arkadiusz
Published: October 2022

A process of plant recovery after drought cessation is a complex trait which has not been fully recognized. The most important organ associated with this phenomenon in monocots, including forage grasses, is the crown tissue located between shoots and roots. The crown tissue is a meristematic crossroads for metabolites and other compounds between these two plant organs. Here, for the first time, we present a metabolomic and lipidomic study focused on the crown tissue under drought and recovery in forage grasses, important for agriculture in European temperate regions. The plant materials involve high (HDT) and low drought-tolerant (LDT) genotypes of Festuca arundinacea, and Lolium multiflorum/F. arundinacea introgression forms. The obtained results clearly demonstrated that remodeling patterns of the primary metabolome and lipidome in the crown under drought and recovery were different between HDT and LDT plants. Furthermore, HDT plants accumulated higher contents of primary metabolites under drought in the crown tissue, especially carbohydrates which could function as osmoprotectants and storage materials. On the other hand, LDT plants characterized by higher membranes damage under drought, simultaneously accumulated membrane phospholipids in the crown and possessed the capacity to recover their metabolic functions after stress cessation to the levels observed in HDT plants.
Candida auris and some Candida parapsilosis strains exhibit similar characteristics on CHROMagarTMCandida Plus
Authors: Sasoni Natalia , Maidana Melani , Latorre-Rapela María Gabriela , Morales-Lopez Soraya , Berrio Indira , Gamarra Soledad , Garcia-Effron Guillermo
Published: October 2022

Candida auris is considered a public health problem because of its resistance and its tendency to cause nosocomial outbreaks. CHROMagarTMCandida Plus has recently been marketed as capable of presumptively identifying C. auris. The objective of this work was to analyze the ability of this new chromogenic medium to differentiate C. auris from other members of the C. haemulonii complex and from other yeasts commonly isolated in clinical practice. A collection of 220 strains including species of the C. haemulonii (n = 83) and C. parapsilosis (n = 80) complexes was studied. The strains were identified by molecular methods and cultured as individual or as mixed aqueous inoculum on CHROMagarTMCandida Plus plates. Colony morphotypes were evaluated at five time points. CHROMagarTMCandida Plus was a helpful tool for presumptive identification for C. auris. Better reading results were obtained after 48 h of incubation at 35°C. It is able to easily differentiate C. auris from other closely related species of the C. haemulonii complex and other yeasts. This chromogenic medium would be also useful as screening and surveillance tool for C. auris colonization. However, we demonstrated that it would be a possible misidentification of C. parapsilosis as C. auris (44.3% showed similar morphotypes). To reduce false positives when it is used in a context of a C. auris outbreak, we propose to supplement the chromogenic medium with 8 μg/ml fluconazole. This modified medium was tested, and it clearly differentiate C. parapsilosis from C. auris.
Detection of 2460 double-lined spectroscopic binary candidates in the LAMOST-MRS using projected rotational velocities and a binary spectral model
Authors: Kovalev Mikhail , Chen Xuefei , Han Zhanwen
Published: October 2022

We present a new method for the detection of double-lined spectroscopic binaries (SB2s) using Vsin i values from spectral fits. The method is tested on synthetic and real spectra from the Large Sky Area Multi-Object fiber Spectroscopic Telescope Medium Resolution Survey. It can reliably detect SB2 candidates for double-lined binaries with $V \sin {i}_1+V \sin {i}_2\lt 300\, {\rm km}\, {\rm s}^{-1}$ if the radial velocity separation is large enough. Using this method, we detected 2460 SB2 candidates, 1410 of which are new discoveries. We confirmed the correlation between the radial velocity separation estimated by the binary model and Vsin i0 estimated by the single-star model using the selected sample. Additionally, our method found one new SB2 candidate in open cluster M11.
Spectroscopic study of solar transition region oscillations in the quiet-Sun observed by IRIS using the Si iv spectral line
Authors: Sangal Kartika , Srivastava A K , Kayshap P , Wang T J , González-Avilés J J , Prasad Abhinav
Published: October 2022

In this paper, we use the Si iv 1393.755 Å spectral line observed by the Interface Region Imaging Spectrograph (IRIS) in the quiet-Sun (QS) to determine the physical nature of the solar transition region (TR) oscillations. We analyse the properties of these oscillations using wavelet tools (e.g. power, cross-power, coherence, and phase difference) along with the stringent noise model (i.e. power law + constant). We estimate the period of the intensity and Doppler velocity oscillations at each chosen location in the QS and quantify the distribution of the statistically significant power and associated periods in one bright region and two dark regions. In the bright TR region, the mean periods in intensity and velocity are 7 min and 8 min, respectively. In the dark regions, the mean periods in intensity and velocity are 7 min and 5.4 min, respectively. We also estimate the phase difference between the intensity and Doppler velocity oscillations at each location. The statistical distribution of the phase difference is estimated, which peaks at −119° ± 13°, 33° ± 10°, 102° ± 10° in the bright region and at −153° ± 13°, 6° ± 20°, 151° ± 10° in the dark regions. The statistical distribution reveals that the oscillations are caused by propagating slow magneto-acoustic waves encountered with the TR. Some of these locations may also be associated with standing slow waves. Moreover, in the given time domain, several locations exhibit the presence of both propagating and standing oscillations at different frequencies.
Self-regulated AGN feedback of light jets in cool-core galaxy clusters
Authors: Ehlert K , Weinberger R , Pfrommer C , Pakmor R , Springel V
Published: October 2022

Heating from active galactic nuclei (AGNs) is thought to stabilize cool-core clusters, limiting star formation and cooling flows. We employ radiative magnetohydrodynamic (MHD) simulations to model light AGN jet feedback with different accretion modes (Bondi–Hoyle–Lyttleton and cold accretion) in an idealized Perseus-like cluster. Independent of the probed accretion model, accretion efficiency, jet density and resolution, the cluster self-regulates with central entropies and cooling times consistent with observed cool-core clusters in this non-cosmological setting. We find that increased jet efficiencies lead to more intermittent jet powers and enhanced star formation rates. Our fiducial low-density jets can easily be deflected by orbiting cold gaseous filaments, which redistributes angular momentum and leads to more extended cold gas distributions and isotropic bubble distributions. In comparison to our fiducial low momentum-density jets, high momentum-density jets heat less efficiently and enable the formation of a persistent cold gas disc perpendicular to the jets that is centrally confined. Cavity luminosities measured from our simulations generally reflect the cooling luminosities of the intracluster medium and correspond to averaged jet powers that are relatively insensitive to short periods of low-luminosity jet injection. Cold gas structures in our MHD simulations with low momentum-density jets generally show a variety of morphologies ranging from discy to very extended filamentary structures. In particular, magnetic fields are crucial to inhibit the formation of unrealistically massive cold gas discs by redistributing angular momentum between the hot and cold phases and by fostering the formation of elongated cold filaments that are supported by magnetic pressure.
SODA: a TypeScript/JavaScript library for visualizing biological sequence annotation
Authors: Roddy Jack W , Lesica George T , Wheeler Travis J
Published: October 2022

We present SODA, a lightweight and open-source visualization library for biological sequence annotations that enables straightforward development of flexible, dynamic and interactive web graphics. SODA is implemented in TypeScript and can be used as a library within TypeScript and JavaScript.
Real-world Clinical Outcomes of Bebtelovimab and Sotrovimab Treatment of High-risk Persons With Coronavirus Disease 2019 During the Omicron Epoch
Authors: Razonable Raymund R , Tulledge-Scheitel Sidna M , Hanson Sara N , Arndt Richard F , Speicher Leigh L , Seville Teresa A , Larsen Jennifer J , Ganesh Ravindra , O’Horo John C
Published: October 2022

Background

Antispike monoclonal antibodies are recommended for early treatment of high-risk persons with mild to moderate coronavirus disease 2019 (COVID-19). However, clinical outcomes of their use during the severe acute respiratory syndrome coronavirus 2 Omicron wave are limited.

Methods

This is a descriptive retrospective study of high-risk adult patients who received treatment with sotrovimab (January 1–March 20, 2022) or bebtelovimab (March 21–April 30, 2022). The primary outcome was the proportion of patients who progressed to severe outcome within 30 days after receiving antispike-neutralizing monoclonal antibody infusion.

Results

A total of 3872 high-risk patients (median age, 62.7 years; 41.1% male) with mild to moderate COVID-19 received sotrovimab (n = 2182) or bebtelovimab (n = 1690). Among sotrovimab-treated patients, the most common comorbidities were an immunosuppressed condition (46.7%), hypertension (38.2%), and diabetes (21.2%). The rates of severe outcome, intensive care unit (ICU) admission, and mortality were 2.2%, 1.0%, and 0.4%, respectively, after sotrovimab infusion. Among bebtelovimab-treated patients, the most common comorbidities were hypertension (42.7%), diabetes (17.1%), and an immunosuppressed condition (17.0%). The rates of severe disease, ICU admission, and mortality were 1.3%, 0.5%, and 0.2%, respectively, after bebtelovimab infusion. Older age, immunosuppressed status, and several comorbidities were associated with severe disease progression, while COVID-19 vaccination was associated with lower risk. No anaphylaxis was reported during monoclonal antibody infusion.

Conclusions

This real-world analysis of a large cohort of high-risk patients demonstrates low rates of severe disease after treatment with sotrovimab during the era dominated by Omicron B.1.1.529 and after treatment with bebtelovimab during the era dominated by BA.2 and Omicron subvariants.
Pregnancy-Related Tuberculous Meningitis and Immune Reconstitution Inflammatory Syndrome: A Case Series and Systematic Review
Authors: Pastick Katelyn A , Kagimu Enock , Dobbin Joanna , Ssebambulidde Kenneth , Gakuru Jane , Milln Jack , Nakabuye Betty , Meya David B , Boulware David R , Cresswell Fiona V , Bahr Nathan C
Published: October 2022

Background

Tuberculosis is a leading cause of death among women of reproductive age. However, tuberculous meningitis, the most severe form of extrapulmonary tuberculosis, is rarely discussed in pregnancy despite this being a unique period of immune modulation that may predispose women to active disease.

Methods

We identified and described cases of tuberculous meningitis among pregnant or postpartum women screened during meningitis clinical trials in Uganda from 2018 to 2022. We conducted a systematic literature review via PubMed/Medline and Embase for all English-language publications from 1970 to 10 July 2022, to identify additional cases.

Results

We identified 8 cases of pregnancy-related tuberculous meningitis in Ugandan women living with human immunodeficiency virus (HIV) and 40 additional cases via systematic literature review (none HIV-positive). Of all combined cases, 50% (24/48) were diagnosed postpartum; 50% (24/48) had initial onset during pregnancy, of which 38% (9/24) had worsening of symptoms or disease relapse following pregnancy cessation. Diagnosis was missed or delayed in 33% (16/48) of cases. For those with known outcomes, maternal mortality was 23% (11/48) and fetal/neonatal mortality was 30% (13/44). Of maternal survivors, 30% (11/37) had residual neurologic deficits.

Conclusions

The true incidence of tuberculous meningitis in pregnancy or the postpartum period is unclear but likely underappreciated. To date, nearly all published cases have occurred in HIV-negative or otherwise immunocompetent women. Given the well-described physiological immunosuppression during pregnancy and subsequent reconstitution postpartum, physicians must be aware of tuberculous meningitis and pregnancy-related immune reconstitution inflammatory syndrome, especially in countries with a high burden of tuberculosis and in women living with HIV.
Using a Knowledge-Based Clinical Decision Support System to Reduce the Time to Appropriate Antimicrobial Therapy in Hospitalized Patients With Bloodstream Infections: A Single-Center Observational Study
Authors: Chen Chii-Shiang , Huang Tsi-Shu , Lee Susan Shin-Jung , Chien Fu-Chin , Yang Ching-Hsiang , Li Sin-Sian , Hsu Chia-Jung , Sy Cheng Len , Wu Kuan-Sheng
Published: October 2022

Background

Inappropriate antimicrobial use is a crucial determinant of mortality in hospitalized patients with bloodstream infections. Current literature reporting on the impact of clinical decision support systems on optimizing antimicrobial prescription and reducing the time to appropriate antimicrobial therapy is limited.

Methods

Kaohsiung Veterans General Hospital implemented a hospital-wide, knowledge-based, active-delivery clinical decision support system, named RAPID (Real-time Alert for antimicrobial Prescription from virtual Infectious Diseases experts), to detect whether there was an antimicrobial agent–pathogen mismatch when a blood culture result was positive. Once RAPID determines the current antimicrobials as inappropriate, an alert text message is immediately sent to the clinicians in charge. This study evaluated how RAPID impacted the time to appropriate antimicrobial therapy among patients with bloodstream infections.

Results

During the study period, 633 of 11 297 recorded observations (5.6%) were determined as inappropriate antimicrobial prescriptions. The time to appropriate antimicrobial therapy was significantly shortened after the implementation of RAPID (1.65 vs 2.45 hours, P < .001), especially outside working hours (1.24 vs 6.43 hours, P < .001), in the medical wards (1.40 vs 2.14 hours, P < .001), in participants with candidemia (0.74 vs 5.36 hours, P < .001), and for bacteremia due to non-multidrug-resistant organisms (1.66 vs 2.49 hours, P < .001).

Conclusions

Using a knowledge-based clinical decision support system to reduce the time to appropriate antimicrobial therapy in a real-world scenario is feasible and effective. Our results support the continued use of RAPID.
Added diagnostic yield of temporal artery magnetic resonance angiography in the evaluation of giant cell arteritis
Authors: Junek Mats L , Riaz Shaista , Garner Stephanie , Khalidi Nader , Rebello Ryan
Published: October 2022

Objectives

Temporal artery magnetic resonance angiography (TAMRA) is a useful tool to investigate possible diagnoses of GCA. As acquired images also reveal other local structures, they may assist in finding alternative diagnoses when assessing for possible GCA. We sought to assess the utility of TAMRA in identifying other significant abnormalities either associated with a diagnosis of GCA or potentially mimicking a clinical presentation of GCA.

Methods

A retrospective cohort study was undertaken at St Joseph’s Healthcare in Hamilton, Ontario, Canada between February 2007 and April 2020 and included patients who underwent TAMRA for a possible diagnosis of GCA. Patient demographics, diagnosis and imaging findings were extracted, and descriptive analysis of findings was performed.

Results

We included 340 individuals who underwent TAMRA for assessment of a potential diagnosis of GCA and had clinical information available; there were 126 (37.1%) diagnoses of GCA. Fourteen (4.1%) patients had findings on TAMRA that demonstrated an alternative diagnosis, findings were predominantly in the temporomandibular joint, orbit and meninges. Eighteen (14.3%) patients with GCA had intracranial vascular changes that were demonstrative of intracranial vasculitis; one stroke was attributed to intracranial GCA.

Conclusions

TAMRA has proven utility in diagnosing GCA, and these data suggest that it also has utility in identifying alternative diagnoses to rule out the disease. Intracranial vasculitis was also seen in 14.3% of patients; the clinical impact of these findings is currently poorly understood and requires further study.
Who are the “Immigrants”?: How Whites’ Diverse Perceptions of Immigrants Shape Their Attitudes
Authors: Flores René D , Azar Ariel
Published: October 2022

Past scholars find that there is a public consensus in the United States on the traits of ideal immigrants. Nevertheless, is there also a consensus on the perceived traits of actual immigrants living in the country? Further, are these perceptions attitudinally consequential? We find no consensus among whites on the composition of the immigrant population in the United States. Further, the immigrant traits they perceive are correlated in specific stereotypical patterns we label “immigrant archetypes.” Using latent class analysis, we find five archetypes. Two of them are extreme—one represents a high-status, documented non-Latino immigrant, which is associated with the most positive immigration attitudes. The other extreme represents a low-status, undocumented Latino man, which is associated with the most restrictionist immigration views. Nevertheless, a second Latino archetype, a better-educated and documented Latina woman working to support her family, is correlated with more positive attitudes than her male counterpart. Archetypes do not seem entirely rooted in objective reality and are stronger predictors of immigration attitudes than most other independent variables. Their existence has significant implications for public opinion dynamics. When researchers, politicians, or journalists reference a single immigrant trait, they may knowingly or unknowingly conjure up entire archetypes in people’s minds.
Gut microbiome changes due to sleep disruption in older and younger individuals: a case for sarcopenia?
Authors: Morwani-Mangnani Jordi , Giannos Panagiotis , Belzer Clara , Beekman Marian , Eline Slagboom P , Prokopidis Konstantinos
Published: October 2022

Major hallmarks of functional loss, loss of metabolic and musculoskeletal health and (multi)morbidity with aging are associated with sleep disturbances. With poor sleep shifts in gut microbial composition commonly manifest, which could mediate the pro-inflammatory state between sleep disturbances and sarcopenia. This systematic review presents the recent evidence on how sleep disturbances throughout the lifespan associate with and contribute to gut microbial composition changes, proposing a mechanism to understand the etiology of sarcopenia through sleep disturbances. The relationship between disturbed sleep and clinically relevant gut microbiota composition on health aspects of aging is discussed. A search was performed in PubMed, Cochrane Library, Scopus, Web of Science using keywords including (microbio* OR microflora) AND (sleep OR sleep disorder). Six cross-sectional population-based studies and five experimental clinical trials investigating healthy individuals with ages ranging from 4 to 71 were included. The cross-sectional studies reported similarities in associations with sleep disturbance and gut microbial diversity. In older adults, shorter sleep duration is associated with an increase in pro-inflammatory bacteria whereas increasing sleep quality is positively associated with an increase of beneficial Verrucomicrobia and Lentisphaerae phyla. In young adults, the effect of sleep disruption on gut microbiome composition, specifically the ratio of beneficial Firmicutes over Bacteroidetes phyla, remains contradictory and unclear. The findings of this review warrant further research in the modulation of the gut microbiome linking poor sleep with muscle-catabolic consequences throughout the lifespan.
Highly-automated, high-throughput replication of yeast-based logic circuit design assessments
Authors: Goldman Robert P , Moseley Robert , Roehner Nicholas , Cummins Breschine , Vrana Justin D , Clowers Katie J , Bryce Daniel , Beal Jacob , DeHaven Matthew , Nowak Joshua , Higa Trissha , Biggers Vanessa , Lee Peter , Hunt Jeremy P , Mosqueda Lorraine , Haase Steven B , Weston Mark , Zheng George , Deckard Anastasia , Gopaulakrishnan Shweta , Stubbs Joseph F , Gaffney Niall I , Vaughn Matthew W , Maheshri Narendra , Mikhalev Ekaterina , Bartley Bryan , Markeloff Richard , Mitchell Tom , Nguyen Tramy , Sumorok Daniel , Walczak Nicholas , Myers Chris , Zundel Zach , Hatch Benjamin , Scholz James , Colonna-Romano John
Published: October 2022

We describe an experimental campaign that replicated the performance assessment of logic gates engineered into cells of Saccharomyces cerevisiae by Gander et al. Our experimental campaign used a novel high-throughput experimentation framework developed under Defense Advanced Research Projects Agency’s Synergistic Discovery and Design program: a remote robotic lab at Strateos executed a parameterized experimental protocol. Using this protocol and robotic execution, we generated two orders of magnitude more flow cytometry data than the original experiments. We discuss our results, which largely, but not completely, agree with the original report and make some remarks about lessons learned.

Graphical Abstract