bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discharge Directly Home From the PICU: A Retrospective Cohort Study
Authors: Roumeliotis Nadia , Hassine Chatila Hadj , Ducruet Thierry , Lacroix Jacques 
Published: September 2022

OBJECTIVE:
Healthcare constraints with decreasing bed availability cause strain in acute care units, and patients are more frequently being discharged directly home. Our objective was to describe the population, predictors, and explore PICU readmission rates of patients discharged directly home from PICU, compared with those discharge to the hospital ward, then home.

DESIGN:
An observational cohort study.

SETTING:
Children admitted to the PICU of CHU Sainte-Justine, between January 2014 and 2020.

PATIENTS:
Patients less than 18 years old, who survived their PICU stay, and were discharged directly home or to an inpatient ward. Patients discharged directly home were compared with patients discharged to the ward using descriptive statistics. Logistic regression was used to identify factors associated with home discharge. Propensity scores were used to compare PICU readmission rates in patients discharged directly home to those discharged to the ward.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Among the 5,531 admissions included, 594 (10.7%) were discharged directly home from the PICU. Patients who were more severe ill (odds ratio [OR], 0.93; 95% CI, 0.90–0.97), had invasive ventilation (OR, 0.70; 95% CI, 0.53–0.92), or had vasoactive agents (OR, 0.70; 95% CI, 0.53–0.92) were less likely to be discharged directly home. Diagnoses associated with discharge directly home were acute intoxication, postoperative ear-nose-throat care, and shock states. There was no difference in the rate of readmission to PICU at 2 (relative risk [RR], 0.20 [95% CI, 0.02–1.71]) and 28 days (RR, 1.20 [95% CI, 0.61–3.36]) between propensity matched patients discharged to the ward for 2 or less days, compared with those discharged directly home.

CONCLUSION:
Discharge directly home from the PICU is increasing locally. The population includes less severely ill patients with rapidly resolving diagnoses. Rates of PICU readmission between patients discharged directly home from the PICU versus to ward are similar, but safety of the practice requires ongoing evaluation.
Articular Findings on Chest Computed Tomography: An Algorithmic Approach for Radiologists
Authors: Mansoori Bahar , Kosaraju Vijaya , Yoon James , Chalian Hamid , Shomal Zadeh Firoozeh , Vo Kiet V. , Shafiei Mehrzad , Prabhakar Rajiah , Chalian Majid 
Published: September 2022

Abstract
Chest computed tomography (CT) is one of the most frequently performed imaging studies. Incidental osseous and articular findings are commonly encountered in chest CTs in daily practice. The spectrum of findings is broad, varying from benign to malignant, and interpretation of these incidental musculoskeletal findings could be challenging for radiologists. In this review, we provide a systematic algorithmic approach for the diagnosis of common articular findings seen on chest CT with recommendations for appropriate follow-up evaluation.
Combining phenotypic and genomic data to improve prediction of binary traits
Authors: Jarquin Diego , Roy Arkaprava , Clarke Bertrand , Ghosal Subhashis 
Published: September 2022

AbstractPlant breeders want to develop cultivars that outperform existing genotypes. Some characteristics (here ‘main traits’) of these cultivars are categorical and difficult to measure directly. It is important to predict the main trait of newly developed genotypes accurately. In addition to marker data, breeding programs often have information on secondary traits (or ‘phenotypes’) that are easy to measure. Our goal is to improve prediction of main traits with interpretable relations by combining the two data types using variable selection techniques. However, the genomic characteristics can overwhelm the set of secondary traits, so a standard technique may fail to select any phenotypic variables. We develop a new statistical technique that ensures appropriate representation from both the secondary traits and the phenotypic variables for optimal prediction. When two data types (markers and secondary traits) are available, we achieve improved prediction of a binary trait by two steps that are designed to ensure that a significant intrinsic effect of a phenotype is incorporated in the relation before accounting for extra effects of genotypes. First, we sparsely regress the secondary traits on the markers and replace the secondary traits by their residuals to obtain the effects of phenotypic variables as adjusted by the genotypic variables. Then, we develop a sparse logistic classifier using the markers and residuals so that the adjusted phenotypes may be selected first to avoid being overwhelmed by the genotypes due to their numerical advantage. This classifier uses forward selection aided by a penalty term and can be computed effectively by a technique called the one-pass method. It compares favorably with other classifiers on simulated and real data.
Neurogenin 2 and Neuronal Differentiation 1 control proper development of the chick trigeminal ganglion and its nerve branches
Authors: Bina Parinaz , Taneyhill Lisa A. 
Published: September 2022

AbstractThe trigeminal ganglion contains the cell bodies of sensory neurons comprising cranial nerve V, which relays information related to pain, touch, and temperature from the face and head to the brain. Like other cranial ganglia, the trigeminal ganglion is composed of neuronal derivatives of two critical embryonic cell types, neural crest and placode cells. Neurogenesis within the cranial ganglia is promoted by Neurogenin 2 (Neurog2), which is expressed in trigeminal placode cells and their neuronal derivatives and transcriptionally activates neuronal differentiation genes like Neuronal Differentiation 1 (NeuroD1). Little is known, however, about the role of Neurog2 and NeuroD1 during chick trigeminal gangliogenesis. To address this, we depleted Neurog2 and NeuroD1 from trigeminal placode cells with morpholinos and demonstrated that Neurog2 and NeuroD1 influence trigeminal ganglion development. While knockdown of both Neurog2 and NeuroD1 affected innervation of the eye, Neurog2 and NeuroD1 had opposite effects on ophthalmic nerve branch organization. Taken together, our results highlight, for the first time, functional roles for Neurog2 and NeuroD1 during chick trigeminal gangliogenesis. These studies shed new light on the molecular mechanisms underlying trigeminal ganglion formation and may also provide insight into general cranial gangliogenesis and diseases of the peripheral nervous system.
TMAO and its precursors in relation to host genetics, gut microbial composition, diet, and clinical outcomes: Meta-analysis of 5 prospective population-based cohorts
Authors: Andreu-Sánchez Sergio , Ahmad Shahzad , Kurilshikov Alexander , Beekman Marian , Ghanbari Mohsen , van Faassen Martijn , van den Munckhof Inge C.L. , Steur Marinka , Harms Amy , Hankemeier Thomas , Ikram M. Arfan , Kavousi Maryam , Voortman Trudy , Kraaij Robert , Netea Mihai G. , Rutten Joost H.W. , Riksen Niels P. , Zhernakova Alexandra , Kuipers Folkert , Slagboom P. Eline , van Duijn Cornelia M. , Fu Jingyuan , Vojinovic Dina 
Published: September 2022

ABSTRACTTrimethylamine N-oxide (TMAO) is a circulating microbiome-derived metabolite implicated in the development of atherosclerosis and cardiovascular disease (CVD). We investigated whether plasma levels of TMAO, its precursors (betaine, carnitine, deoxycarnitine, choline) and TMAO-to-precursor ratios associate with clinical outcomes, including CVD and mortality. This was followed by an in-depth analysis of their genetic, gut microbial and dietary determinants. The analyses were conducted in five Dutch prospective cohort studies including 7,834 individuals. To further investigate association results, Mendelian Randomization (MR) was also explored. We found only plasma choline levels (hazard ratio (HR) 1.17, (95% CI 1.07; 1.28)) and not TMAO to be associated with CVD risk. Our association analyses uncovered 10 genome-wide significant loci, including novel genomic regions for betaine (6p21.1, 6q25.3), choline (2q34, 5q31.1) and deoxycarnitine (10q21.2, 11p14.2) comprising several metabolic gene associations, e.g.,CPS1orPEMT. Furthermore, our analyses uncovered 68 gut microbiota associations, mainly related to TMAO-to-precursors ratios and theOscillospiraceaefamily and 16 associations of food groups and metabolites including fish-TMAO, meat-carnitine and plant-based food-betaine associations. No significant association was identified by MR approach. Our analyses provide novel insights into the TMAO pathway, its determinants and pathophysiological impact in the general population.
N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity
Authors: Varland Sylvia , Silva Rui Duarte , Kjosås Ine , Faustino Alexandra , Bogaert Annelies , Billmann Maximilian , Boukhatmi Hadi , Kellen Barbara , Costanzo Michael , Drazic Adrian , Osberg Camilla , Chan Katherine , Zhang Xiang , Tong Amy Hin Yan , Andreazza Simonetta , Lee Juliette J. , Nedyalkova Lyudmila , Ušaj Matej , Whitworth Alexander J. , Andrews Brenda J. , Moffat Jason , Myers Chad L. , Gevaert Kris , Boone Charles , Martinho Rui Gonçalo , Arnesen Thomas 
Published: September 2022

SUMMARYMost eukaryotic proteins are N-terminally acetylated, but the functional impact on a global scale has remained obscure. Using genome-wide CRISPR knockout screens in human cells, we reveal a strong genetic dependency between a major N-terminal acetyltransferase and specific ubiquitin ligases. Biochemical analyses uncover that both the ubiquitin ligase complex UBR4-KCMF1 and the acetyltransferase NatC recognize proteins bearing an unacetylated N-terminal methionine followed by a hydrophobic residue. NatC KO-induced protein degradation and phenotypes are reversed by UBR knockdown, demonstrating the central cellular role of this interplay. We reveal that loss of Drosophila NatC is associated with male sterility, reduced longevity, and age-dependent loss of motility due to developmental muscle defects. Remarkably, muscle-specific overexpression of UbcE2M, one of the proteins targeted for NatC KO mediated degradation, suppresses defects of NatC deletion. In conclusion, NatC-mediated N-terminal acetylation acts as a protective mechanism against protein degradation, which is relevant for increased longevity and motility.In BriefVarland, Silva et al. define that a major cellular role of N-terminal acetylation is shielding proteins from proteasomal degradation by specific ubiquitin ligases. The human N-terminal acetyltransferase NatC protects the neddylation regulator UBE2M from degradation, while overexpression of Drosophila UBE2M/UbcE2M rescues the longevity and motility defects of NatC deletion.HighlightsN-terminal acetylation by NatC protects proteins from degradation, including UBE2MUBR4-KCMF1 targets unacetylated N-terminal Met followed by a hydrophobic residueDrosophila NatC is required for adult longevity and motility in elderlyOverexpression of UBE2M/UbcE2M suppresses Drosophila NatC deletion phenotypes
Simultaneous adjunctive treatment of malaria and its co-evolved genetic disorder sickle cell anaemia
Authors: Safeukui Innocent , Ware Russell E. , Mohandas Narla , Haldar Kasturi 
Published: September 2022

AbstractEffective treatments for genetic disorders that co-evolved with pathogens require simultaneous betterment of both conditions. Hydroxyurea (HU) offers safe and efficacious treatment for sickle cell anemia (SCA) by reducing clinical complications, transfusions, and death. Despite concerns that HU-treatment for SCA would increase infection risk by the human malaria Plasmodium falciparum, (the genetic driver of the sickle mutation), HU instead reduced clinical malaria. We show that at physiologically relevant exposures, HU (and other ribonucleotide reductase inhibitors) have significant, intrinsic killing activity in vitro against blood stages of P. falciparum, with low risk of eliciting stably resistant parasites or compromising potency of current antimalarial drugs. Additive activity devoid of antagonism by HU was observed with a wide spectrum of commonly used antimalarial treatments. These data endorse broad, safe, long-term use of HU for SCA in malaria endemic countries and provide a novel biological model for simultaneous, adjunct therapy of a life-threatening infection and concomitant management of a co-evolved genetic disorder.SignificanceGenetic disorders are increasingly being treated in global health settings. Hydroxyurea (HU; a ribonucleotide reductase inhibitor) is safe and efficacious for treating sickle cell anemia (SCA). Since the sickle mutation co-evolved with the human malaria parasite Plasmodium falciparum, HU-treatment may potentially have increased malarial infection in SCA patients. However, HU reduced clinical malaria, but why this occurred was not understood. We discovered that in doses used in patients, HU kills P. falciparum and shows strong potential for safe, adjunctive use with current antimalarial drugs. Our findings endorse, long-term use of HU for SCA in malaria-endemic countries and a novel model for simultaneous, adjunct treatment of a life-threatening infection like malaria with concomitant management of multiple genetic hematological disorders of global proportions.
Machine learning classification by fitting amplicon sequences to existing OTUs
Authors: Armour Courtney R. , Sovacool Kelly L. , Close William L. , Topçuoğlu Begüm D. , Wiens Jenna , Schloss Patrick D. 
Published: September 2022

AbstractThe ability to use 16S rRNA gene sequence data to train machine learning classification models offers the opportunity diagnose patients based on the composition of their microbiome. In some applications the taxonomic resolution that provides the best models may require the use ofde novoOTUs whose composition changes when new data are added. We previously developed a new reference-based approach, OptiFit, that fits new sequence data to existingde novoOTUs without changing the composition of the original OTUs. While OptiFit produces OTUs that are as high quality asde novoOTUs, it is unclear whether this method for fitting new sequence data into existing OTUs will impact the performance of classification models relative to models trained and tested only usingde novoOTUs. We used OptiFit to cluster sequences into existing OTUs and evaluated model performance in classifying a dataset containing samples from patients with and without colonic screen relevant neoplasia (SRN). We compared the performance of this model to standard methods includingde novoand database-reference-based clustering. We found that using OptiFit performed as well or better in classifying SRNs. OptiFit can streamline the process of classifying new samples by avoiding the need to retrain models using reclustered sequences.
Key role of auxin cellular accumulation in totipotency and pluripotency acquisition
Authors: Karami Omid , Khadem Azadeh , Rahimi Arezoo , Offringa Remko 
Published: September 2022

SummaryGenome editing and in vitro based-plant propagation require efficient plant regeneration system. Somatic embryogenesis (SE) or de novo shoot regeneration are two major systems that widely used for plant in vitro regeneration. Most SE or shoot regeneration protocols rely on the exogenous application of the synthetic auxin analog 2,4-dichlorophenoxyacetic acid (2,4-D) and naphthylene acetic acid (NAA), whereas the natural auxins indole-3-acetic acid (IAA), 4-chloroindole-3-acetic acid (4-Cl-IAA) or indole-3-butyric acid (IBA) are not or less effective for plant regeneration. Although these synthetic auxins mimics the physiological activity of the main natural auxin IAA in many aspects, there are also clear differences that have been attributed to differences in stability or to different affinities for certain TIR1/AFB-Aux/IAA auxin co-receptor pairs. Here we show that the success of 2,4-D in inducing SE from Arabidopsis is related to ineffectiveness as substrate for auxin efflux, resulting in its intracellular 2,4-D accumulation. Reducing auxin efflux by addition of the auxin transport inhibitor naphthylphthalamic acid (NPA) also allowed natural auxins and other synthetic analogs to induce SE in Arabidopsis with similar efficiencies as 2,4-D. The PIN-FORMED auxin efflux carriers PIN1, PIN2 and the ATP-binding cassette-B auxin transporters ABCB1 and ABCB19 were shown to be partially responsible for the efflux of natural auxins during SE induction. Importantly, all somatic embryos induced in Arabidopsis by IAA in the presence of NPA showed a normal embryo to seedling conversion and subsequent plant development, whereas for the 2,4-D system this was limited to 50-60% of the embryos. We showed that the auxin transport inhibition promotes de novo shoot regeneration capacity from callus induced by 4-Cl-IAA in Brassica napus. In addition, we observed a obvious acceleration in shoot bud emerging from callus induced by 4-Cl-IAA than 2,4-D. Based on our data we conclude, that the efficiency of plant propagation can be significantly improved by applying the natural auxins in the presence of the auxin transport inhibitor NPA.
Population Genetics and Analysis of Molecular Variance (AMOVA) of the Monkeypox virus interferon-alpha-beta receptor gene and its evolutionary relationship with the Orthopoxvirus genus
Authors: Felix Pierre Teodosio , Clara da Silva Santos Ana , Nascimento Iasmin Auta do , Santos da Silva Lidiane 
Published: September 2022

SummaryIn this work are used 59 haplotypes of the gene of the interferon-alpha-beta receptor of Monkeypox virus, Buffalopox virus, Camelpox virus, Cowpox virus, Ectromelia virus, Rabbitpox virus, Vaccinia virus and Variola virus, recuperated from GENBANK/NCBI. All sequences were publicly available on the Platform of the National Center for Biotechnology Information (NCBI) and were analyzed for their Molecular Variance (AMOVA), haplotypic diversity, mismatch, demographic and spatial expansion, molecular diversity and time of evolutionary divergence. The results suggested that there was a high diversity among haplotypes, with high numbers of transitions, transversions and mutations of the indels type for 5 of the 8 groups analyzed and with slight population expansion perceived in the neutrality tests. The estimators used in this study did not support a uniformity among all the results found, which ensures the lack of conservation of the gene, as well as its protein product, a fact that stimulates the use of therapies based on neutralizing antibodies and the development of new drugs that act as adjuvants to the function of the interferon-alpha-beta receptor gene.
Molecular Determinants for Differential Activation of theVibrio parahaemolyticusBile Acid Receptor
Authors: Zou Angela J. , Kinch Lisa , Chimalapati Suneeta , Rodriguez Nalleli Garcia , Tomchick Diana R. , Orth Kim 
Published: September 2022

AbstractBile acids are important for digestion of food and for antimicrobial activity. PathogenicVibrio parahaemolyticussenses bile acids via the co-component signal transduction system receptor VtrA/VtrC, an obligate membrane heterodimer. Intestinal bile acids bind to the periplasmic domain of the VtrA/VtrC complex, activating a DNA-binding domain in VtrA that induces expression of another membrane protein, VtrB. VtrB induces expression of the pathogenic Type III Secretion System 2. The bile acid taurodeoxycholate (TDC) activates VtrA/VtrC-inducedVtrBexpression, while others such as chenodeoxycholate (CDC) do not. This study demonstrates both CDC and TDC bind to the VtrA/VtrC periplasmic heterodimer using isothermal titration calorimetry (ITC). The crystal structure of the VtrA/VtrC heterodimer bound to CDC revealed it binds in the same hydrophobic pocket as TDC, but differently. Mutation of the binding pocket caused a decrease in bile acid binding affinity with exception of the S123A mutant, which bound with a similar affinity as the wild-type protein. The S123A mutant decreased TDC-induced T3SS2 activation, providing a molecular explanation for the selective activation of the T3SS2 by bile acids.
The combination of morphogenic regulators BABY BOOM and GRF-GIF improves maize transformation efficiency
Authors: Chen Zongliang , Debernardi Juan M. , Dubcovsky Jorge , Gallavotti Andrea 
Published: September 2022

ABSTRACTTransformation is an indispensable tool for plant genetics and functional genomic studies. Although stable transformation no longer represents a major technology bottleneck in maize, there is still need for easily accessible and efficient transformation methods in most academic labs. Here we present the GGB transformation system, a rapid and highly efficient transformation system optimized for the immature embryo transformation of two maize genetic backgrounds, including the inbred line B104. The combination of distinct morphogenetic factors, the maize BABY BOOM transcriptional regulator (ZmBBM/EREB53) and the wheat GRF4-GIF1 (GROWTH REGULATING FACTOR4 - GRF-INTERACTING FACTOR1) chimera, together with a modified QuickCorn protocol, regenerated transformed maize seedlings in approximately two months with an efficiency of 26 to 37%; notably, the efficiency was 7-fold higher than with using either component in isolation. Additionally, ectopic expression of both morphogenetic factors did not show obvious effects on B104 development, and in particular fertility was not affected, obviating the need to remove the morphogenetic regulators post Agrobacterium infections. The GGB transformation system is designed for CRISPR-Cas9 editing but can be adapted for other purposes and should be easy to implement in most academic labs with little transformation experience.
Local induction of IAA5 and IAA29 promotes DNA damage-triggered stem cell death in Arabidopsis roots
Authors: Takahashi Naoki , Ogita Nobuo , Koike Toshiya , Nishimura Kohei , Inagaki Soichi , Umeda Masaaki 
Published: September 2022

AbstractPlants generate organs continuously during post-embryonic development, thus how to preserve stem cells in changing environments is crucial for their survival. Genotoxic stress threatens genome stability in all somatic cells, whereas, in the meristem, only stem cells undergo cell death in response to DNA damage, followed by stem cell replenishment. It was previously shown that inhibition of downward auxin flow in roots participates in DNA damage-induced stem cell death; however, how cell death is confined to stem cells in tissues with reduced auxin content remains elusive. Here we show that, in response to DNA double-strand breaks, the Aux/IAA family members IAA5 and IAA29, which encode the negative regulators of auxin signaling, were locally induced in vascular stem cells and their daughters in Arabidopsis roots. This is an active response to DNA damage in which the transcription factor SUPPRESSOR OF GAMMA RESPONSE 1 directly induces their expression. In the iaa5 iaa29 double mutant, DNA damage-induced stem cell death was significantly suppressed, while it was fully restored by the expression of a stable form of IAA5 in vascular stem cells. Our genetic data revealed that both the suppression of auxin signaling and reduced auxin content are prerequisite for cell death induction, suggesting the central role in maintaining genome integrity in stem cells.One-sentence summaryThe induction of IAA5 and IAA29 promotes stem cell death in Arabidopsis roots under DNA stress.