bluuebunny/crossref_metadata_2025_split huggingface dataset:
A machine learning approach identifies unresolving secondary pneumonia as a contributor to mortality in patients with severe pneumonia, including COVID-19
Authors: Gao Catherine A. , Markov Nikolay S. , Stoeger Thomas , Pawlowski Anna , Kang Mengjia , Nannapaneni Prasanth , Grant Rogan A. , Pickens Chiagozie , Walter James M. , Kruser Jacqueline M. , Rasmussen Luke , Schneider Dan , Starren Justin , Donnelly Helen K. , Donayre Alvaro , Luo Yuan , Scott Budinger GR , Wunderink Richard G. , Misharin Alexander V. , Singer Benjamin D. ,   The NU SCRIPT Study Investigators
Published: September 2022

AbstractBackgroundPatients with severe SARS-CoV-2 pneumonia experience longer durations of critical illness yet similar mortality rates compared to patients with severe pneumonia secondary to other etiologies. As secondary bacterial infection is common in SARS-CoV-2 pneumonia, we hypothesized that unresolving ventilator-associated pneumonia (VAP) drives the apparent disconnect between length-of-stay and mortality rate among these patients.MethodsWe analyzed VAP in a prospective single-center observational study of 585 mechanically ventilated patients with suspected pneumonia, including 190 patients with severe SARS-CoV-2 pneumonia. We developed CarpeDiem, a novel machine learning approach based on the practice of daily ICU team rounds to identify clinical states for each of the 12,495 ICU patient-days in the cohort. We used the CarpeDiem approach to evaluate the effect of VAP and its resolution on clinical trajectories.FindingsPatients underwent a median [IQR] of 4 [2,7] transitions between 14 clinical states during their ICU stays. Clinical states were associated with differential hospital mortality. The long length-of-stay among patients with severe SARS-CoV-2 pneumonia was associated with prolonged stays in clinical states defined by severe respiratory failure and with a lower frequency of transitions between clinical states. In all patients, including those with COVID-19, unresolving VAP episodes were associated with transitions to unfavorable states and hospital mortality.InterpretationCarpeDiem offers a machine learning approach to examine the effect of VAP on clinical outcomes. Our findings suggest an underappreciated contribution of unresolving secondary bacterial pneumonia to outcomes in mechanically ventilated patients with pneumonia, including due to SARS-CoV-2.Abstract FigureGraphical abstractDisentangling the contributions of ICU complications and interventions to ICU outcomes. (A) Traditional approaches evaluate the ICU stay as a black box with severity of illness measured on presentation and dichotomized survival at an arbitrary time point (e.g., day 28) or on ICU or hospital discharge. Hence, the effect of intercurrent complications and interventions cannot be easily measured, a problem that is compounded when ICU stays are long or significantly differ between groups. (B) Defining the ICU course by clinical features during each day in the ICU permits the association of a complication or intervention with transitions toward clinical states associated with favorable or unfavorable outcomes.
Knowledge of behavioural risk factors for types 2 diabetes mellitus and its associated factors among reproductive-age women in Arba Minch town, Gamo zone, 2022
Authors: Seyoum Tinsae , Tesfaye Selamnesh , Shiferaw Yohannes , Hailu Rahel , Tefera Dagim , Gebru zeleke 
Published: September 2022

AbstractBackgroundType 2 diabetes accounts for over 90% of all types of diabetes. It is caused by a combination of behavioral risk factors. Currently, it is a serious health problem, especially in reproductive-age women associated with reproductive disorders. To prevent it, knowledge is vital, but there is a scarcity of data on behavioral risk factors in Ethiopia.ObjectiveTo assess knowledge of the behavioral risks of Type 2 diabetes mellitus and its associated factors among reproductive-age women in Gamo zone, Arba Minch town, 2022.Materials and MethodsA community-based cross-sectional study was employed, and all women in the town were considered as the source population. A multistage sampling procedure with simple random sampling was adopted for the recruitment of kebeles. A systematic random selection procedure was also applied to the household with a 13th interval. A total of 623 samples were completed with an interview questionnaire. A bivariate logistic model was used to calculate the crude odds ratio, and multivariate analysis to control for confounding and identify the association for model fitting variables with AOR.ResultThe level of BRF knowledge among reproductive women is 47.0% [95% CI, 43.5-50.9], with the following factors having significant associations: average family income 3000–5000 Eth. Birr 1.81 [95% CI, 1.03-3.18], >= 5001 Eth. Birr 1.93 [95% CI, 1.02-3.68], DM in the friend or relatives 4.03[95% CI,1.56-10.46], Family history of DM 9.47 [95% CI, 4.74–18.90], source of information: health workers 1.87 [95% CI, 1.04-3.34] and friend or relatives 1.65 [95%CI,1.04-2.62].ConclusionThe knowledge of behavioral risk factors for type 2 diabetes was poor among study participants. Family income, DM in the friend or relatives, family history of DM, and source of information were the associated factors with good knowledge. Health education about behavioral risk factors should be given emphasis broadly for women.
Water exchange rates measure active transport and homeostasis in neural tissue
Authors: Williamson Nathan H. , Ravin Rea , Cai Teddy X. , Falgairolle Melanie , O’Donovan Michael J. , Basser Peter J. 
Published: September 2022

For its size, the brain is the most metabolically active organ in the body. Most of its energy demand is used to maintain stable homeostatic physiological conditions. Altered homeostasis and active states are hallmarks of many diseases and disorders. Yet there is currently no reliable method to assess homeostasis and absolute basal activity or activity-dependent changes non-invasively. We propose a novel, high temporal resolution low-field, high-gradient diffusion exchange NMR method capable of directly measuring cellular metabolic activity via the rate constant for water exchange across cell membranes. Using viable ex vivo neonatal mouse spinal cords, we measure a component of the water exchange rate which is active, i.e., coupled to metabolic activity. We show that this water exchange rate is sensitive primarily to tissue homeostasis and viability and provides distinct functional information in contrast to the Apparent Diffusion Coefficient (ADC), which is sensitive primarily to tissue microstructure but not activity.SIGNIFICANCE STATEMENTDespite what physiology text-books may report, water transport across membranes is not only a passive process. However, current understanding is limited because standard techniques can only measure net flux (the difference between water moving in and water moving out). Even so, water is constantly exchanging between the inside and outside of cells and organelles without net flux during homeostasis. We developed a Magnetic Resonance method able to “see” water molecules exchanging on shorter timescales than could be observed before. In neural tissue we find most water exchange is active, that is, linked to ATP-driven processes. This method may one day be translated to clinical MRI applications for measuring cellular function and activity in the human brain and body.
High-resolution profiling of neoantigen-specific T cell receptor activation signatures links moderate stimulation patterns to resilience and sustained tumor control
Authors: Füchsl Franziska , Untch Johannes , Kavaka Vladyslav , Jarosch Sebastian , Vogelsang Carolin , Krätzig Niklas de Andrade , Gosmann Dario , Rad Roland , Busch Dirk , Beltrán Eduardo , Bräunlein Eva , Krackhardt Angela M. 
Published: September 2022

AbstractNeoantigen-specific T cell receptors (neoTCRs) promise a safe, highly personalized therapeutic approach in anti-tumor immunotherapy. Substantial progress has been made regarding their identification whereas detailed functional assessment of single TCR characteristics impacting therapeutic efficacy is lacking.We previously identified and functionally characterized neoTCRs specific for neoepitopes derived from KIF2C and SYTL4 demonstrating differences in functional avidity in a patient with metastatic melanoma. In this work, we now combined single-cell TCR- and RNA-sequencing using stimulated peripheral blood derived CD8+T cells of this patient and thereby identified two new neoTCRs recognizing the previously identified mutated epitope KIF2CP13L. Analyzing patient-derived neoTCR expressing T cells, we detected distinct activation patterns as a measure for substantial heterogeneity within oligoclonal T cell responses towards neoantigens upon specific ex vivo-restimulation. Moreover, neoTCR-transgenic T cells from healthy donors were employed for detailed in vitro and in vivo fine-characterization focusing on TCR-intrinsic functional patterns. Most importantly, in a xenogeneic mouse model experimentally simulating rechallenge of tumor infiltrating lymphocytes (TILs) after adoptive T cell transfer, we found that T cells expressing neoTCRs with a moderate activation profile provide a stable and more sustained anti-tumor response upon repeated in vivo tumor challenge as compared to neoTCRs with a stronger, burst-like reactivity. These insights have significant implications for engineering TCR-transgenic T cells for therapeutic purposes.One Sentence SummaryCombining TCR specificity linked single-cell transcriptomics with in vitro and in vivo characterization of transgenic T cells helps to decipher functional potential and persistence of neoantigen-specific T cell receptors (TCRs) for TCR-transgenic T cell-based adoptive cellular anti-tumor immunotherapy.
The giant diploid faba genome unlocks variation in a global protein crop
Authors: Jayakodi Murukarthick , Golicz Agnieszka A. , Kreplak Jonathan , Fechete Lavinia I. , Angra Deepti , Bednář Petr , Bornhofen Elesandro , Zhang Hailin , Boussageon Raphaël , Kaur Sukhjiwan , Cheung Kwok , Čížková Jana , Gundlach Heidrun , Hallab Asis , Imbert Baptiste , Keeble-Gagnère Gabriel , Koblížková Andrea , Kobrlová Lucie , Krejčí Petra , Mouritzen Troels W. , Neumann Pavel , Nadzieja Marcin , Nielsen Linda Kærgaard , Novák Petr , Orabi Jihad , Padmarasu Sudharsan , Robertson-Shersby-Harvie Tom , Robledillo Laura Ávila , Schiemann Andrea , Tanskanen Jaakko , Törönen Petri , Warsame Ahmed O. , Wittenberg Alexander H.J. , Himmelbach Axel , Aubert Grégoire , Courty Pierre-Emmanuel , Doležel Jaroslav , Holm Liisa U. , Janss Luc L. , Khazaei Hamid , Macas Jiří , Mascher Martin , Smýkal Petr , Snowdon Rod J. , Stein Nils , Stoddard Frederick L. , Tayeh Nadim , Torres Ana M. , Usadel Björn , Schubert Ingo , O’Sullivan Donal Martin , Schulman Alan H. , Andersen Stig Uggerhøj 
Published: September 2022

AbstractIncreasing the proportion of locally produced plant protein in currently meat-rich diets could substantially reduce greenhouse gas emission and loss of biodiversity. However, plant protein production is hampered by the lack of a cool-season legume equivalent to soybean in agronomic value. Faba bean (Vicia faba L.) has a high yield potential and is well-suited for cultivation in temperate regions, but genomic resources are scarce. Here, we report a high-quality chromosome-scale assembly of the faba bean genome and show that it has grown to a massive 13 Gb in size through an imbalance between the rates of amplification and elimination of retrotransposons and satellite repeats. Genes and recombination events are evenly dispersed across chromosomes and the gene space is remarkably compact considering the genome size, though with significant copy number variation driven by tandem duplication. Demonstrating practical application of the genome sequence, we develop a targeted genotyping assay and use high-resolution genome-wide association (GWA) analysis to dissect the genetic basis of hilum colour. The resources presented constitute a genomics-based breeding platform for faba bean, enabling breeders and geneticists to accelerate improvement of sustainable protein production across Mediterranean, subtropical, and northern temperate agro-ecological zones.
In host evolution of Exophiala dermatitidis in cystic fibrosis lung micro-environment
Authors: Kurbessoian Tania , Murante Daniel , Crocker Alex , Hogan Deborah A. , Stajich Jason E. 
Published: September 2022

AbstractIndividuals with cystic fibrosis (CF) are susceptible to chronic lung infections that lead to inflammation and irreversible lung damage. While most respiratory infections that occur in CF are caused by bacteria, some are dominated by fungi such as the slow-growing black yeast Exophiala dermatitidis. Here, we analyze isolates of E. dermatitidis cultured from two samples, collected from a single subject two years apart. One isolate genome was sequenced using long-read Nanopore technology as an in-population reference to use in comparative single nucleotide polymorphism (SNP) and insertion-deletion (INDEL) variant analyses of twenty-three isolates. We then used population genomics and phylo-genomics to compare the isolates to each other as well as the type strain E. dermatitidis NIH/UT8656. Within the CF lung population, three E. dermatitidis clades were detected, each with varying mutation rates. Overall, the isolates were highly similar suggesting that they were recently diverged. All isolates were MAT 1-1, which was consistent with their high relatedness and the absence of evidence for mating or recombination between isolates. Phylogenetic analysis grouped sets of isolates into clades that contained isolates from both early and late time points indicating there are multiple persistent lineages. Functional assessment of variants unique to each clade identified alleles in genes that encode transporters, cytochrome P450 oxidoreductases, iron acquisition and DNA repair processes. Consistent with the genomic heterogeneity, isolates showed some stable phenotype heterogeneity in melanin production, subtle differences in antifungal minimum inhibitory concentrations, growth on different substrates. The persistent population heterogeneity identified in lung-derived isolates is an important factor to consider in the study of chronic fungal infections, and the analysis of changes in fungal pathogens over time may provide important insights into the physiology of black yeasts and other slow-growing fungi in vivo.
CURLYLEAF is a key modulator of apoplast water status in Arabidopsis leaf
Authors: Wu Jingni , Zhang Jinyu , Mei Xiao , Ye Luhuan , Chen Tao , Wang Yiping , Liu Menghui , Zhang Yijing , Xin Xiu-Fang 
Published: September 2022

AbstractThe apoplast of plant leaf, the intercellular space between mesophyll cells, is normally largely filled with air with a minimal amount of water in it, which is essential for key physiological processes such as gas exchange to occur. Interestingly, phytopathogens exploit virulence factors to induce a water-rich environment, known as “water soaking”, in the apoplast of the infected leaf tissue to promote disease. We propose that plants evolved a “water soaking” pathway, which normally keeps a “minimized and balanced” water level in the leaf apoplast for plant growth but is disturbed by microbial pathogens to facilitate infection. Investigation of the “water soaking” pathway and leaf water control mechanisms is a fundamental, yet previously-overlooked, aspect of plant physiology. To identify key components in the “water soaking” pathway, we performed a genetic screen to isolate Arabidopsis severe water soaking (sws) mutants that show leaf water over-accumulation under high air humidity, a condition required for visible water soaking. Here we report the sws1 mutant, which displays rapid water soaking upon high humidity treatment due to a loss-of-function mutation in CURLY LEAF (CLF), encoding a histone methyl-transferase in the POLYCOMB REPRESSIVE COMPLEX 2 (PRC2). We found that the sws1 (clf) mutant exhibits an enhanced abscisic acid (ABA) level and stomatal closure, which are indispensable for its water soaking phenotype and mediated by CLF’s direct regulation of a group of ABA-associated NAC transcription factors, NAC019/055/072. Interestingly, the clf mutant showed a weakened immunity, which likely also contributes to the water soaking phenotype. In addition, the clf plant supports a significantly higher level of Pseudomonas syringae pathogen-induced water soaking and bacterial multiplication, in an ABA pathway and NAC019/055/072-dependent manner. Collectively, our study probes into a fundamental question in plant biology and demonstrates CLF as a key modulator of leaf water status via epigenetic regulation of ABA pathway and stomatal movement.
Cadmium treatment induces endoplasmic reticulum stress and unfolded protein response in Arabidopsis thaliana
Authors: De Benedictis Maria , Gallo Antonia , Migoni Danilo , Papadia Paride , Roversi Pietro , Santino Angelo 
Published: September 2022

AbstractWe report about the response of Arabidopsis thaliana to chronic and temporary Cd2+ stress, and the Cd2+ induced activation of ER stress and unfolded protein response (UPR). Cd2+-induced UPR proceeds mainly through the bZIP60 arm, which in turn activates relevant ER stress marker genes such as BiP3, CNX, PDI5 and ERdj3B in a concentration- (chronic stress) or time- (temporary stress) dependent manner. A more severe Cd-stress triggers programmed cell death (PCD) through the activation of the NAC089 transcription factor. Toxic effects of Cd2+ exposure are reduced in the Atbzip28/bzip60 double mutant in terms of primary root length and fresh shoot weight, likely due to reduced UPR and PCD activation. We also hypothesised that the enhanced Cd2+ resistance of the Atbzip28/bzip60 double mutant is due to an increase in brassinosteroids signaling, since the amount of the brassinosteroid insensitive1 receptor (BRI1) protein decreases under Cd2+ stress only in Wt plants. These data highlight the complexity of the UPR pathway, since the ER stress response is strictly related to the type of the treatment applied and the multifaceted connections of ER signaling. The reduced sensing of Cd2+ stress in plants with UPR defects can be used as a novel strategy for phytoremediation.
Foliar application of preparations as a method of protecting plants from the penetration of lead
Authors: Wierzbicka M. , Bodzon K. , Naziębło A. , Tarnawska Z. , Wróbel M. 
Published: September 2022

AbstractDue to the contamination of soil with lead, there is still a danger of lead penetrating into our diet through crops. So far, no method has been developed to reduce the concentration of this toxic element in plants and to prevent it from entering the biological cycle. In this paper, an attempt was made for the first time to reduce lead concentrations in plants by using foliar calcium preparations.This was based on the hypothesis that an increased amount of calcium in the plant would lead to the reduction in the amount of lead as the entry routes of calcium and lead are similar; therefore, an increase in the amount of calcium will result in the saturation of the routes through which lead enters cells (e.g. calcium channels). It should be clarified that the research was experimental. Three crop species (Linum usitatissimumL.,Solanum lycopersicumL.,Cucumis sativusL.) were tested at the organismal level, whereas the epidermis ofAllium cepaL. was used to conduct tests at the cellular level. The InCa calcium transport activator (by Plant Impact) was selected for the test, followed by calcium nitrate. The preparations were administered foliarly. Lead, on the other hand, was applied to roots before adding lead nitrate into the mineral medium. The plants were cultivated hydroponically. The growth and development of seedlings, the concentration of lead in roots and shoots and the microscopic visualisation of lead in plant organisms and cells were studied. Ultimately, the InCa activator administered foliarly was shown to reduce the concentration of lead in plant organs by approximately 44%.Further findings revealed that the mechanism of this process mainly resulted from the supply of calcium nitrate to plant leaves. A commercial calcium foliar fertiliser also showed a similar effect.The potential to reduce the uptake of lead by crops by approximately 44% is a very satisfactory result. In addition, spraying plants with InCA biostimulant and calcium nitrate is environmentally friendly. This is cutting-edge research that was described for the first time in the present paper.
Inhibition of Phosphodiesterase 12 results in Antiviral Activity against several RNA Viruses including SARS-CoV-2
Authors: Thursz Mark , Sadiq Fouzia , Tree Julia A. , Karayiannis Peter , Beasley David W. C. , Dejnirattisai Wanwissa , Mongkolsapaya Juthathip , Screaton Gavin , Wand Matthew , Elmore Michael J. , Carroll Miles W. , Matthews Ian , Thomas Howard 
Published: September 2022

AbstractPhosphodiesterase 12 (PDE12) is a negative regulator of the type 1 interferon (IFN) response and here we show that PDE12 inhibitors (lead compounds 63 and 17) are associated with increased RNAseL activity, are well tolerated at the therapeutic range and inhibit, both in vitro and in vivo, the replication of several RNA viruses including hepatitis C virus (HCV), dengue virus (DENV), West Nile Virus (WNV) and SARS-CoV-2.
Combination Ad26.RSV.preF/RSV preF protein vaccine induces superior humoral, cellular, and protective immunity compared with individual vaccine components in preclinical models
Authors: Saeland Eirikur , van der Fits Leslie , Bolder Renske , Heemskerk-van der Meer Marjolein , Drijver Joke , van Polanen Yolinda , Vaneman Cornelis , Tettero Lisanne , Cox Freek , Serroyen Jan , Jorgenssen Matthew J. , Langedijk Johannes P.M. , Schuitemaker Hanneke , Callendret Benoit , Zahn Roland C. 
Published: September 2022

AbstractRespiratory syncytial virus (RSV) is a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously shown that a prefusion (preF) conformation– stabilized RSV F protein antigen and an adenoviral vector encoding RSV preF protein (Ad26.RSV.preF) are immunogenic and protective in animals when administered as single components. Here, we evaluated a combination of the 2 components. Strong induction of both humoral and cellular responses was shown in RSV-naïve and pre-exposed mice and pre-exposed African green monkeys (AGMs). Both components of the combination vaccine contributed to humoral immune responses, while the Ad26.RSV.preF component was the main contributor to cellular immune responses in both mice and AGMs. Immunization with the combination elicited superior protection against RSV A2 challenge in cotton rats. These results demonstrate the advantage of a combination vaccine and support further clinical development.
Gaze following in Archosauria – Alligators and palaeognath birds suggest dinosaur origin of visual perspective taking
Authors: Zeiträg Claudia , Reber Stephan A. , Osvath Mathias 
Published: September 2022

ABSTRACTVisual perspective taking marks an evolutionary shift in the formation of advanced social cognition. In humans, it is foundational for our communication and understanding of others. Visual perspective taking has also been found in some other primates, a few songbirds, and some canids. Despite its essential role for social cognition, visual perspective taking has only been fragmentedly studied in animals, leaving its evolution and origins uncharted. To begin to narrow this knowledge gap, we investigated extant archosaurs by comparing the neurocognitively least derived extant birds – palaeognaths – with the closest living relatives of birds, the crocodylians. In a gaze following paradigm, we showed that palaeognaths engage in visual perspective taking and grasp the referentiality of gazes, while crocodylians do not This suggests that visual perspective taking originated in early birds or non-avian dinosaurs – likely earlier than in mammals.