bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of SeptiCyte RAPID to discriminate sepsis from non-infectious systemic inflammation
Authors: Balk Robert , Esper Annette M. , Martin Greg S. , Miller Russell R. , Lopansri Bert K. , Burke John P. , Levy Mitchell , Opal Steven , Rothman Richard E. , D’Alessio Franco R. , Sidhaye Venkataramana K. , Aggarwal Neil R. , Greenberg Jared A. , Yoder Mark , Patel Gourang , Gilbert Emily , Parada Jorge P. , Afshar Majid , Kempker Jordan A. , van der Poll Tom , Schultz Marcus J. , Scicluna Brendon P. , Klein Klouwenberg Peter M.C. , Liebler Janice , Blodget Emily , Kumar Santhi , Navalkar Krupa , Yager Thomas D. , Sampson Dayle , Kirk James T. , Cermelli Silvia , Davis Roy F. , Brandon Richard B. 
Published: July 2022

Abstract(1) BackgroundSeptiCyte RAPID is a molecular test for discriminating sepsis from non-infectious systemic inflammation, and for estimating sepsis probabilities. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospective banked and prospectively collected patient samples.(2) MethodsThe cartridge-based SeptiCyte RAPID test accepts a PAXgene blood RNA sample and provides sample-to-answer processing in ∼1 hour. The test output (SeptiScore, range 0-15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (N=356) and prospective (N=63) samples were tested from adult patients in ICU either having the systemic inflammatory response syndrome (SIRS), or suspected of / diagnosed with sepsis. Patients were clinically evaluated by a panel of three expert physicians blinded to the SeptiCyte test results. Results were interpreted under either the Sepsis-2 or Sepsis-3 framework.(3) ResultsUnder the Sepsis-2 framework, SeptiCyte RAPID performance for the combined retrospective and prospective cohorts had Area Under the ROC Curve (AUC) ranging from 0.82 to 0.85, negative predictive value 0.91 (sensitivity 0.94) for SeptiScore Band 1 (score range 0.1-5.0; lowest risk of sepsis), and positive predictive value 0.81 (specificity 0.90) for SeptiScore Band 4 (score range 7.4-15; highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86-0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in Bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. Comparable performance was obtained for the majority of patients reanalyzed under the Sepsis-3 definition, although a subgroup of 16 patients was identified that was called septic under Sepsis-2 but not under Sepsis-3.(4) ConclusionsThis study validates SeptiCyte RAPID for estimating sepsis probability, under both the Sepsis-2 and Sepsis-3 frameworks, for hospitalized patients on their first day of ICU admission.
Lung cancer in the French West Indies: role of sugarcane work and other occupational exposures
Authors: Cabréra Léïla , Auguste Aviane , Michineau Léah , Joachim Clarisse , Deloumeaux Jacqueline , Luce Danièle 
Published: July 2022

AbstractObjectiveTo study the role of occupational exposures in lung cancer risk in the French West Indies, with special attention to some specific activities, such as sugarcane work, that can only be studied in a limited number of populations.MethodsWe used data from a population-based case-control study that included 147 incident lung cancer cases and 405 controls. Smoking history and a detailed occupational history with a description of tasks and substances were collected by questionnaire during face-to-face interviews. Odds ratios (OR) adjusted for sex, age, region, smoking status and cigarette pack-years and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression.ResultsSignificantly increased risks of lung cancer were found in sugarcane farm workers (OR=2.7; 95% CI 1.1-6.6) and more generally in the sugarcane growing sector (OR=2.5; 95% CI 1.0-6.3) and to a lesser extent in rum production. Elevated risks of lung cancer were also observed among other agricultural workers, painters, warehouse porters, labourers, maintenance and motor vehicle repair workers. Exposure to herbicides in sugarcane cultivation was associated with an increased risk of lung cancer (OR=2.6; 95% CI 0.9-7.6).ConclusionThese results showed that occupational exposures contributed to lung cancer risk in the French West Indies, and highlighted the role of exposures related to sugarcane work.
Performance evaluation of the LumiraDx SARS-CoV-2 & Flu A/B Test in diagnosing COVID-19 and influenza in patients with respiratory symptoms
Authors: Ellis Jayne , Guest Poppy , Lawson Vicki , Loecherbach Julia , Lindner Nigel , McCulloch Andrew 
Published: July 2022

AbstractIntroductionCoronavirus disease 2019 (COVID-19) and influenza share similar symptoms, which hampers diagnosis. Given that they require different containment and treatment strategies, fast and accurate distinction between the two infections is needed. This study evaluates the sensitivity and specificity of the LumiraDx SARS-CoV-2 & Flu A/B Test for simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A/B from a single nasal swab.MethodsNasal samples were collected from patients as part of the ASPIRE (NCT04557046) and INSPIRE (NCT04288921) studies at point-of-care testing sites in the USA. ASPIRE study participants were included after developing COVID-19 symptoms in the last 14 days or following a positive SARS-CoV-2 test in the last 48 hours. INSPIRE study participants were included after developing influenza symptoms in the last 4 days. Samples were extracted into proprietary buffer and analysed using the LumiraDx SARS-CoV-2 & Flu A/B Test. A reference sample was taken from each subject, placed into universal transport medium and tested using reference SARS-CoV-2 and influenza reverse transcription polymerase chain reaction (RT-PCR) tests. The test and reference samples were compared using the positive percent agreement (PPA) and negative percent agreement (NPA), together with their 95% confidence intervals (CI).ResultsAnalysis of the data from the ASPIRE (N=124) and INSPIRE (N=159) studies revealed high levels of agreement between the LumiraDx SARS-CoV-2 & Flu A/B Test and the reference tests in detecting SARS-CoV-2 (PPA=95.5% [95% CI: 84.9%, 98.7%]; NPA=96.0% [95% CI: 90.9%, 98.3%]), influenza A (PPA=83.3% [95% CI: 66.4%, 92.7%]; NPA=97.7% [95% CI: 93.4%, 99.2%]) and influenza B (PPA=80.0% [95% CI: 62.7%, 90.5%]; NPA=95.3% [95% CI: 90.2%, 97.9%]).ConclusionsThe LumiraDx SARS-CoV-2 & Flu A/B Test shows a high agreement with the reference RT-PCR tests while simultaneously detecting and differentiating between SARS-CoV-2 and influenza A/B.Trial registration, ClinicalTrials.gov identifier: NCT04557046 and NCT04288921
Integrating pharmacogenomics data-driven prediction with bulk and single-cell RNAseq to demonstrate the efficacy of an NAMPT inhibitor against aggressive, taxane-resistant, and stem-like cells in lethal prostate cancer
Authors: Mazumder Suman , Ghosh Taraswi Mitra , Mukherjee Ujjal K. , Chakravarti Sayak , Amiri Farshad , Hemmati Farnaz , Mistriotis Panagiotis , Elhussin Isra , Salam Ahmad-bin , Dean-Colomb Windy , Li Feng , Yates Clayton , Arnold Robert D. , Mitra Amit K. 
Published: July 2022

ABSTRACTMetastatic prostate cancer is the second leading cause of cancer deaths in US men. Resistance to standard medical castration and secondary taxane-based chemotherapy is nearly universal. Further, presence of cancer stem-like cells (EMT/epithelial to mesenchymal transdifferentiation) and neuroendocrine PCa (NEPC) subtypes significantly contribute to aggressive/advanced/lethal variants of PCa (AVPC).In this study, first we used single-cell RNA sequencing (scRNAseq) analysis to demonstrate that ARlow PCa cells in metastatic prostate cancer, including castration-sensitive tumors, harbored signatures of EMT, and ‘cancer stemness’. Next, we introduced a novel pharmacogenomics data-driven computational approach and identified several potential agents that can be re-purposed as novel secondary drugs (“secDrugs”) to treat advance variants of Prostate cancer. Using scRNAseq as a biomarker-based drug screen, we demonstrated that a majority of the single-cell subclones in mCRPC and mCSPC cell lines also showed significantly high expression of the NAMPT pathway genes, indicating that the secDrug FK866, which targets NAMPT, is potentially effective against drug-resistant and stem-cell-like subpopulation cluster. Next, we showed significant in vitro cytotoxicity of FK866 as single-agent and in combination with the taxanes or Enzalutamide against models of clinically-advanced PCa. We performed bulk- and single-cell RNAseq to identify several pathways underlining FK866 mechanism of action and found that in addition to NAMPT inhibition, FK866 regulates tumor metastasis, cell migration, invasion, DNA repair machinery, redox homeostasis, autophagy, as well as cancer stemness–related genes HES1 and CD44. Further, we performed a microfluidic chip-based cell migration assay that demonstrated that FK866 reduces cancer cell invasion and motility, indicating abrogation of metastasis. Finally, using multiple PCa patient datasets, we showed that FK866 is potentially capable of reversing expression of several genes associated with biochemical recurrence and inter-ethnic differences, including IFITM3 and LTB4R.Thus, using FK866 as a proof-of-concept drug, we introduced a novel, universally applicable preclinical drug development pipeline to circumvent subclonal aggressiveness, drug resistance, and stemness in lethal PCa.
Cleavage of protein kinase c δ by caspase-3 mediates pro-inflammatory cytokine-induced apoptosis in pancreatic islets
Authors: Collins Jillian , Piscopio Robert A. , Reyland Mary E. , Johansen Chelsea G. , Benninger Richard K. P. , Farnsworth Nikki L. 
Published: July 2022

AbstractIn type 1 diabetes (T1D), autoreactive immune cells infiltrate the pancreas and secrete pro-inflammatory cytokines that initiate cell death in insulin producing islet β-cells. Protein kinase C δ (PKCδ) plays a role in mediating cytokine-induced β-cell death; however, the exact mechanisms are not well understood. To address this, we utilized an inducible β-cell specific PKCδ KO mouse as well as a small peptide specific inhibitor of PKCδ. We identified a role for PKCδ in mediating cytokine-induced β-cell death and have shown that inhibiting PKCδ protects pancreatic β-cells from cytokine-induced apoptosis in both mouse and human islets. We determined that cytokines induced nuclear translocation and activity of PKCδ and that caspase-3 cleavage of PKCδ may be required for cytokine-mediated islet apoptosis. Further, cytokine-activated PKCδ increases activity both of pro-apoptotic Bax with acute treatment and JNK with prolonged treatment. Overall, our results suggest that PKCδ mediates cytokine-induced apoptosis via nuclear translocation, cleavage by caspase-3, and upregulation of pro-apoptotic signaling in pancreatic β-cells. Combined with the protective effects of PKCδ inhibition with δV1-1, the results of this study will aid in the development of novel therapies to prevent or delay β-cell death and preserve β-cell function in T1D.
A de novo transcriptome assembly of the annelid worm Hediste diversicolor
Authors: Samico Rodrigo , Machado André M. , Domingues Marcos , Hagemann Andreas , Valente Luísa , Malzahn Arne , Gomes-dos-Santos André , Ruivo Raquel , Monroig Óscar , Castro L. Filipe C. 
Published: July 2022

AbstractThe development of Next-Generation Sequencing (NGS) technologies has revolutionized multiple fields of Biology. The ability to sequence DNA and RNA in an automated, parallel and low-cost approach, was key to boost the applicability and acquisition efficiency of omics resources. In this context, the availability of these tools has become indispensable towards our understanding of biodiversity, deepening our knowledge on the distinct complexity levels, from cells to ecosystems.In this study we comprehensively characterised and annotated a whole-body transcriptome of Hediste diversicolor. This annelid worm species belongs to the family Nereididae and inhabits estuarine and lagoon areas on the Atlantic coasts of Europe and North America. Ecologically, this species plays an important role in benthic food webs. The ability of rework sediments through bioturbation activity makes this species essential to the estuarine mechanisms.Here, we used Illumina next-generation sequencing technology, to sequence a total 105 million (M) paired-end (PE) raw reads and produce the first multi-tissue transcriptome assembly of an adult of H. diversicolor. This transcriptome contains 69,335 transcripts with a N50 transcript length of 2,313 bp and a BUSCO gene completeness of 97.7% and 96% (S: 88.2%; D: 7.8%) in Eukaryota and Metazoa lineage-specific profile libraries. Our findings offer a valuable resource for multiple biological studies using this species.
Tardigrade small heat shock proteins can limit desiccation-induced protein aggregation
Authors: Hibshman Jonathan D. , Carra Serena , Goldstein Bob 
Published: July 2022

AbstractSmall heat shock proteins (sHSPs) are chaperones known for their response to heat stress. While sHSPs have well-characterized roles in heat tolerance, potential roles for sHSPs in desiccation tolerance have not been as thoroughly explored. We identified nine sHSPs from the genome of the tardigrade Hypsibius exemplaris, each containing a conserved alpha-crystallin domain flanked by disordered regions. Many of these sHSPs are highly expressed and in some cases are upregulated during desiccation. We found that tardigrade sHSPs were sufficient to improve desiccation tolerance when expressed in E. coli. Purification and subsequent analysis of two sHSPs, HSP21 and HSP24.6, revealed that these proteins can form large complexes in vitro, similar to oligomeric assemblies documented for other sHSPs. These proteins limited heat-induced aggregation of the model enzyme citrate synthase. Heterologous expression of HSP24.6 improved bacterial heat shock survival, and the protein significantly reduced heat-induced aggregation of soluble bacterial protein. Thus, HSP24.6 likely chaperones against protein aggregation to promote survival of heat stress. Furthermore, HSP21 and HSP24.6 also limited desiccation-induced aggregation and loss of function of citrate synthase. This suggests a mechanism by which tardigrade sHSPs promote desiccation tolerance: by limiting desiccation-induced protein aggregation, thereby maintaining proteostasis and supporting survival. These results suggest that sHSPs, classical chaperones, provide a mechanism of general stress resistance that can also be deployed to support survival during anhydrobiosis.
Prediction error neurons in mouse cortex are molecularly targetable cell types
Authors: O’Toole Sean M. , Oyibo Hassana K. , Keller Georg B. 
Published: July 2022

ABSTRACTPredictive processing postulates the existence of prediction error neurons in cortex. Functionally, both negative and positive prediction error neurons have been identified in layer 2/3 of visual cortex, but whether they correspond to transcriptionally defined subpopulations is unclear. Here we used the activity-dependent, photoconvertible marker CaMPARI2 to tag neurons in layer 2/3 of visual cortex during stimuli and behaviors designed to trigger prediction errors. We performed single-cell RNA-sequencing on these populations and found that previously annotated Adamts2 and Rrad layer 2/3 cell types were enriched when photolabeling for negative or positive prediction error responses respectively. Finally, we validated these results functionally by designing artificial promoters for use in AAV vectors to express genetically encoded calcium indicators. Thus, positive and negative prediction error responses mapped onto transcriptionally distinct cell types in layer 2/3 that can be targeted using AAV vectors.
Optogenetically induced reward and ‘frustration’ memory in larval Drosophila
Authors: Thoener Juliane , Weiglein Aliće , Gerber Bertram , Schleyer Michael 
Published: July 2022

AbstractHumans and animals alike form oppositely valenced memories for stimuli that predict the occurrence versus the termination of a reward: appetitive ‘reward’ memory for stimuli associated with the occurrence of a reward and aversive ‘frustration’ memory for stimuli that are associated with its termination. We characterize these memories in larval Drosophila using a combination of Pavlovian conditioning, optogenetic activation of the dopaminergic central-brain DAN-i1864 neuron, and high-resolution video-tracking. This reveals their dependency on the number of training trials and the duration of DAN-i1864 activation, their temporal stability, and the parameters of locomotion that are modulated during memory expression. Together with previous results on ‘punishment’ versus ‘relief’ learning by DAN-f1 neuron activation, this reveals a 2×2 matrix of timing-dependent memory valence for the occurrence/ termination of reward/ punishment. These findings should aid the understanding and modelling of how brains decipher the predictive, causal structure of events around a target reinforcing occurrence.
Single Photon smFRET. III. Application to Pulsed Illumination
Authors: Safar Matthew , Saurabh Ayush , Sarkar Bidyut , Fazel Mohamadreza , Ishii Kunihiko , Tahara Tahei , Sgouralis Ioannis , Pressé Steve 
Published: July 2022

AbstractFörster resonance energy transfer (FRET) using pulsed illumination has been pivotal in leveraging lifetime information in FRET analysis. However, there remain major challenges in quantitative single photon, single molecule FRET (smFRET) data analysis under pulsed illumination including: 1) simultaneously deducing kinetics and number of system states; 2) providing uncertainties over estimates, particularly uncertainty over the number of system states; 3) taking into account detector noise sources such as crosstalk, and the instrument response function contributing to uncertainty; in addition to 4) other experimental noise sources such as background. Here, we implement the Bayesian nonparametric framework described in the first companion manuscript that addresses all aforementioned issues in smFRET data analysis specialized for the case of pulsed illumination. Furthermore, we apply our method to both synthetic as well as experimental data acquired using Holliday junctions.Why It MattersIn the first companion manuscript of this series, we developed new methods to analyze noisy smFRET data. These methods eliminate the requirement ofa priorispecifying the dimensionality of the physical model describing a molecular complex’s kinetics. Here, we apply these methods to experimentally obtained datasets with samples illuminated by laser pulses at regular time intervals. In particular, we study conformational dynamics of Holliday junctions.
Metheor: Ultrafast DNA methylation heterogeneity calculation from bisulfite read alignments
Authors: Lee Dohoon , Koo Bonil , Yang Jeewon , Kim Sun 
Published: July 2022

AbstractMotivationPhased DNA methylation states within bisulfite sequencing reads are valuable source of information that can be used to estimate epigenetic diversity across cells as well as epigenomic instability in individual cells. Various measures capturing the heterogeneity of DNA methylation states have been proposed for a decade. However, in routine analyses on DNA methylation, this heterogeneity is often overlooked by computing average methylation levels at CpG sites. In this study, to facilitate the application of the DNA methylation heterogeneity measures in downstream epigenomic analyses, we present a Rust-based, extremely fast and lightweight bioinformatics toolkit called Metheor.ResultsWe benchmark the performance of Metheor against existing code implementation for DNA methylation heterogeneity measures in three different scenarios of simulated bisulfite sequencing datasets. Metheor was shown to dramatically reduce the execution time up to 300-fold and memory footprint up to 60-fold, while producing the same results with the original implementation.AvailabilitySource code for Metheor is at https://github.com/dohlee/metheor and is freely available for non-commercial users.Contactsunkim.bioinfo@snu.ac.kr
Emergence of Small Colony Variants (SCVs) is an adaptive strategy used byPseudomonas aeruginosato palliate O2limitations
Authors: Besse Alison , Groleau Marie-Christine , Déziel Eric 
Published: July 2022

ABSTRACTThe ability to generate a subpopulation of Small Colony Variants (SCVs) is a conserved feature ofPseudomonas aeruginosaand could represent a key adaptive strategy to colonize and persist in multiple niches. However, very little is known about the role of the SCV phenotype, the conditions that promote its emergence and its possible involvement in an adaptive strategy. In the present work, we investigated thein vitroselective conditions promoting the emergence of SCVs from the prototypical strain PA14, which readily forms SCVs in non-agitated standing cultures. We found that O2limitations, which cause a redox imbalance, is the main factor selecting for the SCV phenotype, which promotes survival of the populationviaformation of a biofilm at the air-liquid interface to access the electron acceptor. When this selective pressure is relieved by aeration or supplementation of an alternative electron acceptor, SCVs are barely detectable. We also observed that SCV emergence contributes to redox rebalancing, suggesting that it is involved in an adaptive strategy. We conclude that selection for the SCV phenotype is an adaptive solution adopted byP. aeruginosato access poorly available O2.IMPORTANCEThe bacteriumP. aeruginosais an opportunistic pathogen that thrives in many environments. It poses a significant health concern, notably because it is a causative agent of nosocomial infections and the most prevalent pathogen found in the lungs of people with cystic fibrosis. In infected hosts, its persistence is often related to the emergence of an alternative phenotype known as Small Colony Variant (SCV). Identification of conditions selecting for the SCV phenotype contributes to knowledge regarding adaptive mechanisms exploited byP. aeruginosato survive in multiple niches and persist during infections. Hindering this adaptation strategy could help controlP. aeruginosapersistent infections.