bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noise-robust, physical microscopic deconvolution algorithm enabled by multi-resolution analysis regularization
Authors: Hou Yiwei , Wang Wenyi , Fu Yunzhe , Ge Xichuan , Li Meiqi , Xi Peng 
Published: March 2023

AbstractDespite the grand advances in fluorescence microscopy, the photon budget of fluorescent molecules remains the fundamental limiting factor for major imaging parameters, such as temporal resolution, duration, contrast, and even spatial resolution. Computational methods can strategically utilize the fluorescence photons against the imaging noise, to break the abovementioned limits. Here, we propose a multi-resolution analysis (MRA) approach to recharacterize and extract the two main characteristics of fluorescence images: (1) high contrast across the edge, and (2) high continuity along the edge. By regularizing the solution using framelet and curvelet domain sparsity, we develop MRA deconvolution algorithm for fluorescence image, which allows fine detail recovery even with negative signal-to-noise-ratio (SNR), and can provide more than 2-fold physical resolution enhancement with conspicuously fewer artifacts than maximum likelihood estimation (MLE) methods. Furthermore, we develop DeepMRA deconvolution algorithm that can provide computational background inhibition through a bias thresholding mechanism while deconvolving a fluorescence image. Compared with conventional background mitigation schemes, this novel deconvolution canonical form can deal with severer background and better preserve the high-frequency and low-intensity details, which are commonly disrupted by other algorithms. We demonstrate that the MRA and DeepMRA deconvolution algorithms can improve the SNR and resolution of biological images in various microscopies, such as wide-field, confocal, spinning-disk confocal (SD-confocal), light-sheet, structured illumination microscopy (SIM), and stimulated excitation depletion (STED) microscopy.
Dynamic Bayesian modeling of the social behavior ofDrosophila melanogaster
Authors: Kalaria Kirtan , Mayekar Harshad , Patel Dhaval , Rajpurohit Subhash 
Published: March 2023

AbstractOrganismal behavior has always been a challenge to understand. Insects are one of the amenable systems used to understand behavior. A striking variety of insect behaviors gain support from genetic and physiological studies.Drosophila, a widely studied model organism due to its known molecular pathways, has also been popular in behavioral studies. Several behavioral traits inDrosophilaincluding mating, locomotion, and oviposition choice have been traced to the neuronal level. Yet, the results of behavioral analyses are equivocal since they often overlook the external milieu, such as social context, which evidentially influences behavior. There have been many attempts to modelDrosophilabehavior, however, all have some fundamental issues like lack of complexity, limitation to isolated organisms, and lack of explainability. Here, we model the behavior of a pair ofDrosophila melanogasterflies using a novel Dynamic Bayesian Network based approach to better understand behavior in a social context. Two models are proposed, each of which is further used as a predictor for predicting the behavior of both the flies in the pair. They are evaluated on an existing dataset and achieve a remarkable performance: 98.22% and 98.32% accuracy on the two models. Our modeling approach could be applied in predicting animal behaviors in a wide variety of contexts to support existing behavioral studies.
Genetic Inactivation of β-Catenin Attenuates and Its Activation Aggravates Desmoplakin Cardiomyopathy
Authors: Olcum Melis , Fan Siyang , Rouhi Leila , Cheedipudi Sirisha , Cathcart Benjamin , Jeong Hyun-Hwan , Zhao Zhongming , Gurha Priyatansh , Marian Ali J. 
Published: March 2023

ABSTRACTAimMutations in theDSPgene encoding desmoplakin, a constituent of the desmosomes at the intercalated discs (IDs), cause a phenotype that spans arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy (DCM). It is typically characterized by biventricular enlargement and dysfunction, severe myocardial fibrosis, cell death, and arrhythmias.The canonical WNT (cWNT)/β-catenin signaling pathway is implicated in the pathogenesis of ACM. Given that β-catenin, an indispensable co-transcriptional regulator of the cWNT pathway, is also a member of the IDs, we genetically inactivated or activated β-catenin to determine its role in the pathogenesis of the desmoplakin cardiomyopathy.Methods and ResultsTheDspgene was conditionally deleted in cardiac myocytes concomitant with the genetic inactivation or activation of β-catenin using the tamoxifen-inducible MerCreMer mice. Inactivation and activation of β-catenin were achieved upon deletion of its transcriptional domain and degrons, respectively. Analysis of cardiac myocytes transcripts and proteins showed marked dysregulation of the cWNT/β-catenin pathway in the DSP-deficient mouse cardiac myocytes (Myh6-McmTam:DspF/F), as indicated by increased expression of cWNT/β-catenin targets along with its inhibitors and isoforms of its key co-effectors. Genetic inactivation of β-catenin in theMyh6-McmTam:DspF/Fmice prolonged survival, improved cardiac function, reduced cardiac arrhythmias, and attenuated myocardial fibrosis, and cell death caused by apoptosis, necroptosis, pyroptosis, i.e., PANoptosis, whereas its activation had the opposite effects. Inactivation of β-catenin was associated with partial restoration of the suppressed genes involved in OXPHOS, whereas its activation has the opposite effect. The beneficial effects were independent of the changes in the transcript levels of the cWNT target genes.ConclusionThe cWNT/β-catenin was markedly dysregulated in the cardiac myocytes from a mouse model of DC. Inactivation of β-catenin attenuated the phenotype partly through the recovery of OXPHOS genes whereas its activation had deleterious effects. The findings suggest suppression of β-catenin might be beneficial in desmoplakin-cardiomyopathy.SummaryGenetic inactivation of β-catenin improved desmoplakin cardiomyopathy, in part through the restoration of expression of genes involved in oxidative phosphorylation, whereas its activation was deleterious.
Type I interferon dynamics determines memory B cell epigenetic identity in chronic viral infection
Authors: Cooper Lucy , Xu Hui , Polmear Jack , Szeto Christopher , Pang Ee Shan , Gupta Mansi , Taylor Justin J , Jackson Katherine J L , Nguyen Angela , Gruta Nicole La , Martelotto Luciano , Parish Ian A , O’Keeffe Meredith , Scharer Christopher D , Gras Stephanie , Good-Jacobson Kim L 
Published: March 2023

SUMMARYMemory B cells are key providers of long-lived immunity against infectious disease, yet in chronic viral infection they do not produce effective protection. How chronic viral infection disrupts memory B cell development, and whether such changes are reversible, remains unknown. Here, we uncover type-I interferon (IFN-I) dynamics as a key determinant in shaping chronic memory B cell development. Through single-cell (sc)ATAC-sequencing and scRNA-sequencing, we identified a unique memory subset enriched for IFN-stimulated genes (ISGs) during chronic lymphocytic choriomeningitis virus infection. Blockade of IFNAR-1 early in infection transformed the chromatin landscape of chronic memory B cells, decreasing accessibility at ISG-inducing transcription factor binding motifs and inducing a phenotypic change in the dominating memory B cell subset. However, timing was critical, with memory B cells resistant to intervention after 4 weeks post-infection. Together, our research identifies a key mechanism to instruct memory B cell identity during viral infection.One Sentence Summary:IFN dynamics in chronic versus acute viral infection determines memory B cell development.
Neuronal wiring receptors Dprs and DIPs are GPI anchored and this modification contributes to their cell surface organization
Authors: Lobb-Rabe Meike , Nawrocka Wioletta I. , Carrillo Robert A. , Özkan Engin 
Published: March 2023

ABSTRACTTheDrosophilaDpr and DIP proteins belong to the immunoglobulin superfamily of cell surface proteins (CSPs). Their hetero- and homophilic interactions have been implicated in a variety of neuronal functions, including synaptic connectivity, cell survival, and axon fasciculation. However, the signaling pathways underlying these diverse functions are unknown. To gain insight into Dpr–DIP signaling, we sought to examine how these CSPs are associated with the membrane. Specifically, we asked whether Dprs and DIPs are integral membrane proteins or membrane anchored through the addition of glycosylphosphatidylinositol (GPI) linkage. We demonstrate that Dprs and DIPs are GPI anchored to the membrane of insect cells and validate these findings for some family members in vivo usingDrosophilalarvae, where GPI anchor cleavage results in loss of surface labeling. Additionally, we show that GPI cleavage abrogates aggregation of insect cells expressing cognate Dpr–DIP partners. To test if the GPI anchor affects Dpr–DIP localization, we replaced it with a transmembrane domain and observed perturbation of sub-cellular localization on motor neurons and muscles. These data suggest that membrane anchoring of Dprs and DIPs through GPI linkage is required for localization and that Dpr–DIP intracellular signaling likely requires transmembrane co-receptors.
Transcript Isoform Diversity of Ampliconic Genes on the Y Chromosome of Great Apes
Authors: Tomaszkiewicz Marta , Sahlin Kristoffer , Medvedev Paul , Makova Kateryna D. 
Published: March 2023

ABSTRACTY-chromosomal Ampliconic Genes (YAGs) are important for male fertility, as they encode proteins functioning in spermatogenesis. The variation in copy number and expression levels of these multicopy gene families has been recently studied in great apes, however, the diversity of splicing variants remains unexplored. Here we deciphered the sequences of polyadenylated transcripts of all nine YAG families (BPY2,CDY,DAZ,HSFY,PRY,RBMY,TSPY,VCY, andXKRY) from testis samples of six great ape species (human, chimpanzee, bonobo, gorilla, Bornean orangutan, and Sumatran orangutan). To achieve this, we enriched YAG transcripts with capture-probe hybridization and sequenced them with long (Pacific Biosciences) reads. Our analysis of this dataset resulted in several findings. First, we uncovered a high diversity of YAG transcripts across great apes. Second, we observed evolutionarily conserved alternative splicing patterns for most YAG families except forBPY2andPRY. Our results suggest thatBPY2transcripts and predicted proteins in several great ape species (bonobo and the two orangutans) have independent evolutionary origins and are not homologous to human reference transcripts and proteins. In contrast, our results suggest that thePRYgene family, having the highest representation of transcripts without open reading frames, has been undergoing pseudogenization. Third, even though we have identified many species-specific protein-coding YAG transcripts, we have not detected any signatures of positive selection. Overall, our work illuminates the YAG isoform landscape and its evolutionary history, and provides a genomic resource for future functional studies focusing on infertility phenotypes in humans and critically endangered great apes.
Non-contrast-Enhanced Functional Lung MRI to evaluate treatment response of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis: a pilot study
Authors: Benlala Ilyes , Klaar Rabea , Gaass Thomas , Macey Julie , Bui Stéphanie , Berger Patrick , Laurent François , Dournes Gael , Dinkel Julien 
Published: March 2023

AbstractBackgroundAllergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients is associated with severe lung damage and requires specific therapeutic management. Repeated imaging is recommended to both diagnose and follow-up the response to treatment of ABPA in CF.PurposeTo evaluate whether Fourier decomposition (FD) functional lung MRI can detect the response to treatment of ABPA in CF patients.Study typeRetrospective longitudinal.PopulationA total of 12 CF patients.Field strength/sequence2D balanced steady-state free precession (bSSFP) sequence with Fourier decomposition (FD) at 1.5T scanner.AssessmentVentilation weighted (V) and perfusion weighted (Q) maps were obtained after FD processing of the 2D coronal bSSFP time resolved images before and after treatment of ABPA. Defects extent was assessed on the functional maps using a visual semi quantitative score. Mean and coefficient of variation (cv) of the ventilation signal intensity (VSI) and the perfusion signal intensity (QSI) were calculated. Measurements were performed independently by two readers and averaged. The reproducibility of the measurements was also assessed. Pulmonary function tests (PFTs) were performed as markers of the airflow limitation severity.Statistical testsComparisons of medians were assessed using paired Wilcoxon test. Reproducibility was assessed using the intraclass correlation coefficient (ICC). Correlations were assessed using Spearman test. A p value <0.05 was considered as significant.ResultsDefects extent on both V and Q maps showed a significant reduction after ABPA treatment (p<0.01). VSI_mean was significantly increased after treatment (p<0.01). Visual analyses reproducibility showed an ICC >0.93. ICC of the quantitative measurements was almost perfect (>0.99). VSI_cv and QSI_cv variations correlated inversely with the variation of obstructive parameters of PFTs (rho = -0.68, p=0.01).Data conclusionNon-contrast enhanced FD lung MRI appears to be able to reproducibly assess response to treatment of ABPA in CF patients and correlates with PFTs’ obstructive parameters.
Somatic mutations in chronic lung disease are associated with reduced lung function
Authors: Yun Jeong H. , Khan M.A. Wasay , Ghosh Auyon , Hobbs Brian D. , Castaldi Peter J. , Hersh Craig P. , Miller Peter G. , Cool Carlyne D. , Sciurba Frank , Barwick Lucas , Limper Andrew H. , Flaherty Kevin , Criner Gerard J. , Brown Kevin , Wise Robert , Martinez Fernando , Silverman Edwin K. , Demeo Dawn , Cho Michael H. , Bick Alexander G. 
Published: March 2023

AbstractAmong human organs, the lung harbors one of the highest rates of somatic mutations. However, the relationship of these mutations to lung disease and function is not known. We analyzed the somatic mutational pattern from 1,251 samples of normal and diseased non-cancerous lung tissue from the Lung Tissue Research Consortium using RNA-seq. In two of the most common diseases represented in our dataset, chronic obstructive pulmonary disease (COPD, 29%) and idiopathic pulmonary fibrosis (IPF, 13%), we found a significantly increased burden of somatic mutations compared to normal. Using deconvoluted cell type proportions, we found that a major predictor of somatic mutations was the airway to alveolar cell proportion and pathogenic cell types. We also found that mutational burden was associated with reduced lung function. This relationship remained even after adjustment for age, sex, smoking, and cell type proportion and in COPD and IPF. Our identification of an increased prevalence of somatic mutation in diseased lung that correlates with cell type proportion and disease severity highlights for the first time the role of somatic mutational processes in lung disease genetics.
Quality of Drug Prescription and Dispensing Practices in a Teaching Hospital in a developing country
Authors: Samuel Owhondah King , Zorte Zite , Samuel Ogaji Daprim 
Published: March 2023

AbstractBackgroundThe World Health Organization recommends rational drug usage to protect patient health and quality of life. Study assessed the quality of drug prescription and dispensing in a tertiary hospital.MethodsCross-sectional study with retrospective and prospective data collection underpinned by the WHO core prescribing indicators. A cluster sample of 10 clinical units and their attached pharmacies in the hospital. Six hundred prescriptions from the pharmacy over six months were randomly selected to evaluate the prescription indicators, 330 patient encounters observed for patient care indicators, and 48 randomly selected doctors to evaluate factors influencing their prescribing practices across the 10 clinics. Descriptive analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 25 and comparison done across all indicators of rational drug use.ResultsAverage drugs per encounter was 3.4 ± 1.9 drugs. Antibiotics and injections were prescribed in 40.2% and 24.8% encounters respectively. Generic names were used in 43.6% and 97.1% of prescription were from the essential medicine list. Average time for consultation was 17.5 ± 8.0 minutes, dispensing time was 7.7 ± 3.8 minutes, 99.8% of medications were properly labelled, and 82% of patients understood the drug doses. The pharmacies stocked 93.3% of key drugs but no consultation room had the essential drug list. Only 43.7% of physicians demonstrated accurate understanding of rational drug use.ConclusionFindings on the WHO core drug indicators showed poor quality of drug prescription. Brand prescription, polypharmacy, and antibiotic overuse observed requires intensifying training and monitoring on rational drug use.
Estimation of Life’s Essential 8 Score with Incomplete Data of Individual Metrics
Authors: Zheng Yi , Huang Tianyi , Guasch-Ferre Marta , Hart Jaime , Laden Francine , Chavarro Jorge , Rimm Eric , Coull Brent , Hu Hui 
Published: March 2023

AbstractBackgroundThe American Heart Association’s Life’s Essential 8 (LE8) is an updated construct of cardiovascular health (CVH), including blood pressure, lipids, glucose, body mass index, nicotine exposure, diet, physical activity, and sleep health. It is challenging to simultaneously measure all eight metrics at multiple time points in most research and clinical settings, hindering the use of LE8 to assess individuals’ overall CVH trajectories over time.Methods and ResultsWe obtained data from 5,588 participants in the Nurses’ Health Studies (NHS, NHSII) and Health Professional’s Follow-up Study (HPFS), and 27,194 participants in the 2005-2016 National Health and Nutrition Examination Survey (NHANES) with all eight metrics available. Individuals’ overall cardiovascular health (CVH) was determined by LE8 score (0-100). CVH-related factors that are routinely collected in many settings (i.e., demographics, BMI, smoking, hypertension, hypercholesterolemia, and diabetes) were included as predictors in the base models of LE8 score, and subsequent models further included less frequently measured factors (i.e., physical activity, diet, blood pressure, and sleep health). Gradient boosting decision trees were trained with hyper-parameters tuned by cross-validations. The base models trained using NHS, NHSII, and HPFS had validated root mean squared errors (RMSEs) of 8.06 (internal) and 16.72 (external). Models with additional predictors further improved performance. Consistent results were observed in models trained using NHANES. The predicted CVH scores can generate consistent effect estimates in associational studies as the observed CVH scores.ConclusionsCVH-related factors routinely measured in many settings can be used to accurately estimate individuals’ overall CVH when LE8 metrics are incomplete.Clinical PerspectiveWhat Is New?Life’s Essential 8 (LE8) has great potential to assess and promote cardiovascular health (CVH) across life course, however, it is challenging to simultaneously collect all eight metrics at multiple time points in most research and clinical settings.We demonstrated that CVH-related factors routinely collected in many research and clinical settings can be used to accurately estimate individuals’ overall CVH across time even when LE8 metrics are incomplete.What Are the Clinical Implications?The approach introduced in this study provides a cost-effective and feasible way to estimate individuals’ overall CVH.It can be used to track individuals’ CVH trajectories in clinical settings.
Possible biological control of ash dieback using the parasitic Hymenoscyphus fraxineus mitovirus 2?
Authors: Shamsi Wajeeha , Mittelstrass Jana , Kondo Hideki , Ulrich Sven , Rigling Daniel , Prospero Simone 
Published: March 2023

AbstractInvasive fungal diseases represent a major threat to forest ecosystems worldwide. As fungicides are often unfeasible and not a sustainable solution, only a few other control options are available, including biological control. In this context, the use of parasitic mycoviruses as biocontrol agents of fungal pathogens has recently gained particular attention. Since the 1990s, the Asian fungusHymenoscyphus fraxineushas been causing lethal ash dieback across Europe. In the present study, we investigated the biocontrol potential of the mitovirus Hymenoscyphus fraxineus mitovirus 2 (HfMV2) previously identified in Japanese populations of the pathogen. HfMV2 could be successfully introduced via co-culturing into 16 out of 105 virus-free isolates. A virus infection had contrasting effects on fungal growthin vitro, from cryptic to detrimental or beneficial. Virus-infectedH. fraxineusisolates whose growth was reduced by HfMV2 showed a lower virulence on ash (Fraxinus excelsior) saplings compared to their isogenic virus-free isolates. The results suggest that mycoviruses exist in the native populations ofH. fraxineusin Asia that have the potential for biological control of ash dieback in Europe.
Within-host density and duration of colonization of multidrug-resistant Enterobacterales acquired during travel to the tropics
Authors: Cotto Olivier , Armand-Lefèvre Laurence , Matheron Sophie , Ruppé Etienne , Blanquart François 
Published: March 2023

AbstractAlthough it seems obvious that antibiotic use promotes antibiotic resistance, the processes underlying the changes in prevalence of MRE in European communities are still poorly understood. Information on how the within-host bacterial density varies after acquisition of a resistant strain and in the absence of antibiotic selection is key to our ability to further understand, model and manage resistance in the community. Empirical studies on the within-host dynamics following colonization by MRE are very scarce. Here, we study the within-host strain dynamics in healthy travelers colonized with MRE upon their return from tropical regions. Densities of both sensitive and resistant strains are stable for a few months, until resistant strains are abruptly cleared. Multivariate survival analysis further revealed that MRE acquired from Asia and carried at larger densities persist for longer. These dynamics do not support the classically assumed slow competitive exclusion of MRE. Rather, MRE and sensitive strains coexist in apparent equilibrium for months, with MRE representing about 0.1% of total Enterobacterales, before MRE are abruptly cleared. These results inform potential therapeutic strategies to clear MRE and epidemiological models of antibiotic resistance.
Maned wolves (Chrysocyon brachyurus) in the Ecological Station of Itirapina-Brazil: temporal and spatial distribution based on long-distance vocalizations recordings
Authors: da Costa Angélica Felício , Padovese Linilson 
Published: March 2023

ABSTRACTThe maned wolf (Chrysocyon brachyurus; Illiger, 1815) is considered the largest canid in South America, it has crepuscular nocturnal behavior, solitary and skittish habits. Its vocalization has different classifications, one of them called roar-barks, which helps in long-distance communication, being ideal for passive acoustic monitoring. For the study of the vocalizations of C. brachyurus in the Ecological Station of Itirapina in Brazil, were implanted 6 autonomous recorders called EcoPods. The locations of the station with the highest detection of vocalizations, their characteristics, temporal distribution in relation to sunset and moon phases were studied. The point with the highest concentration of roar-barks is the same as the point with the litter’s vocalization, indicating the importance of vocalizations in parental care. Passive acoustic monitoring allows a less invasive study and helps to understand the behavior of the maned wolf for its preservation.