bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIF-1α Contributes to the Progression of Chronic Obstructive Pulmonary Disease
Authors: Zhang Kedong , Zhou Feng , Zhu Caixia , Yuan Liang , Li Defu , Wang Jian , Lu Wenju 
Published: January 2022

AbstractBackgroundHypoxia-inducible factor-1α (HIF-1α) plays an important regulatory role in inflammatory and hypoxic diseases. Higher HIF-1α level was found in lungs of chronic obstructive pulmonary disease (COPD) patients, however, its role in cigarette smoke (CS)-induced COPD has not been fully studied. Digoxin has been showed to inhibit HIF-1α translation and block HIF-1α activity and thus is often used as the HIF-1α inhibitor. Therefore, in the present study, we chose digoxin as the inhibitor to investigate whether HIF-1α contributes to the progression of COPD and possible mechanism.MethodsCS-exposed mice were intragastrically treated with different doses of digoxin, and COPD-associated phenotypes such as pathological changes in lungs, inflammation, lung function and mucus secretion in airways were evaluated. Meanwhile, CSE-treated A549 cells were administrated with digoxin or S7959. Moreover, EMT-associated markers together with HIF-1α\TGF-β1\Smad3 signaling pathway were detected both in vivo and in vitro.ResultsThe level of HIF-1α was significantly increased in lungs of COPD mice and CSE-exposed A549 cells, which was markedly suppressed by digoxin. Moreover, digoxin inhibited CS-induced inflammatory responses, lung function decline, and mucus hyper-secretion in COPD mouse model. In in vitro studies, digoxin decreased CSE-induced pro-inflammatory cytokine release. Importantly, CS-induced or CSE-induced EMT and up-regulation of HIF-1α/TGF-β1/Smad pathway was inhibited by digoxin. Additionally, S7959 mitigated CSE-induced EMT in A549 cells.ConclusionsDigoxin can protect CS-induced COPD and prevent CS-induced EMT possibly through HIF-1α/TGF-β1/Smad3 signaling pathway. This study suggests HIF1-α could be a potential intervention target for COPD prevention and treatment, especially for EMT in CS-induced COPD.
Quantitative Assessment of 3D Printed Blood Vessels Produced with J750™ Digital Anatomy™ for Suture Simulation
Authors: Marconi Stefania , Mauri Valeria , Negrello Erika , Pugliese Luigi , Pietrabissa Andrea , Auricchio Ferdinando 
Published: January 2022

AbstractBlood vessels anastomosis is one of the most challenging and delicate tasks to learn in many surgical specialties, especially for vascular and abdominal surgeons. Such a critical skill implies a learning curve that goes beyond technical execution. The surgeon needs to gain proficiency in adapting gestures and the amount of force expressed according to the type of tissue he/she is dealing with. In this context, surgical simulation is gaining a pivotal role in the training of surgeons, but currently available simulators can provide only standard or simplified anatomies, without the chance of presenting specific pathological conditions and rare cases.3D printing technology, allowing the manufacturing of extremely complex geometries, find a perfect application in the production of realistic replica of patient-specific anatomies. According to available technologies and materials, morphological aspects can be easily handled, while the reproduction of tissues mechanical properties still poses major problems, especially when dealing with soft tissues.The present work focuses on blood vessels, with the aim of identifying – by means of both qualitative and quantitative tests - materials combinations able to best mimic the behavior of the biological tissue during anastomoses, by means of J750™ Digital Anatomy™ technology and commercial photopolymers from Stratasys. Puncture tests and stitch traction tests are used to quantify the performance of the various formulations. Surgical simulations involving anastomoses are performed on selected clinical cases by surgeons to validate the results.A total of 37 experimental materials were tested and 2 formulations were identified as the most promising solutions to be used for anastomoses simulation. Clinical applicative tests, specifically selected to challenge the new materials, raised additional issues on the performance of the materials to be considered for future developments.
Examining historical rates of leafcutting bee cell pathogens to establish baseline infectivity rates for alfalfa seed growers
Authors: Clements Justin , Haylett Maggie , Nelson Brenda , Walsh Doug 
Published: January 2022

AbstractThe alfalfa leafcutting bee (Megachile rotundata) is one of the primary pollinators for the alfalfa seed industry. The alfalfa leafcutting bee is a solitary cavity nesting bee. Female Megachile rotundata bees will construct and provision individual brood cells lined with cut leaves (cocoon) and will gather nectar and pollen to place within the constructed cocoon. The female bee will lay a single egg within the constructed cocoon and leave the egg to undergo larval stage development and pupation into the adult stage. During this time multiple pathogens and parasitoids can prey on the developing larvae, resulting in the loss of the future adult bee. A major concern for commercial alfalfa seed growers is the presence of invertebrate pests and fugal pathogens. In the present study, we used historical data from the Parma Cocoon Diagnostic Laboratory to determine baseline rates of pathogen and parasite infection of Megachile rotundata cells and used this analysis to determine historical infection rates and cutoffs for management practices. Additionally, using a Faxitron (X-ray) analysis for Megachile rotundata cell obtained in 2020, we compared the presence of chalkbrood, pathogens, and parasitoids in samples collected from both growers’ stocks and newly purchased Canada bees. The results of the investigation demonstrate historical averages of the presence of chalkbrood, pathogens, and parasitoids. We also show a significant increase in chalkbrood and predators in 2007-2011 and a significant difference in chalkbrood and predators between bee samples obtained from Canada and grower stocks.
Multiplex PCR reveals unique trends in pathogen and parasitoid infestations of alfalfa leafcutting brood cells
Authors: Clements Justin , Haylett Maggie , Nelson Brenda , Shumate Silas , Young Nicole , Bradford Benjamin , Walsh Doug , Lamour Kurt 
Published: January 2022

AbstractThe alfalfa leafcutting bee Megachile rotundata Fabricius (HYMENOPTERA: Megachilidae) is an important pollinator for multiple agricultural seed commodities in the United States. Megachile rotundata is a solitary bee that forms brood cocoons where its larvae can develop. During the developmental stages of growth, broods can be preyed upon by multiple different fungal and bacterial pathogens and insect predators and parasitoids, resulting in the loss of the developing larvae. Larval loss is a major concern for alfalfa (Medicago sativa L.) seed producers because they rely on pollinator services provided by Megachile rotundata and reduced pollination rates result in lower yields and increased production costs. In the present study, we examined the taxonomic composition of organisms found within M. rotundata brood cells using a multiplex PCR assay which was developed for the detection of the most common bacterial, fungal, and invertebrate pests and pathogens of M. rotundata larvae. Known pests of M. rotundata were detected, including members of the fungal genus Ascosphaera, the causative agent of chalkbrood. Co-infection of single brood cells by multiple Ascosphaera species was confirmed, with potential implications for chalkbrood disease management. The multiplex assay also identified DNA from more than 2,400 total species including multiple new predators and pathogenetic species not previously documented in associated with M. rotundata brood cells.
Increased resolution in the face of conflict: phylogenomics of the Neotropical bellflowers (Campanulaceae: Lobelioideae), a rapid plant radiation
Authors: Lagomarsino Laura P. , Frankel Lauren , Uribe-Convers Simon , Antonelli Alexandre , Muchhala Nathan 
Published: January 2022

AbstractBackground and AimsThe centropogonid clade (Lobelioideae: Campanulaceae) is an Andean-centered rapid radiation characterized by repeated convergent evolution of morphological traits, including fruit type and pollination syndromes. While previous studies have resolved relationships of lineages with fleshy fruits into subclades, relationships among capsular species remain unresolved, particularly along the phylogenetic backbone. This lack of resolution has impeded reclassification of non-monophyletic genera, whose current taxonomy relies heavily on traits that have evolved multiple times within the clade.MethodsTargeted sequence capture using a probeset recently developed for the centropogonid clade was used to obtain phylogenomic data from DNA extracted from both silica-dried and herbarium leaf tissue. These data were used to infer relationships among species using concatenated and partitioned species tree methods, as well as to quantify gene tree discordance.Key ResultsWhile silica-dried leaf tissue resulted in generally more and longer sequence data, the inclusion of herbarium samples improved phylogenetic reconstruction. Relationships among baccate lineages are similar to those inferred by previous studies, though they differ within and among capsular lineages. We improve resolution of Siphocampylus, which forms ten groups of closely related species to which we provide informal names that largely do not correspond to current infrageneric taxonomy. Two subclades of Siphocampylus and two individual species are rogue taxa whose placement differs widely across analyses. Gene tree discordance is high.ConclusionsThe first phylogenomic study of the centropogonid clade considerably improves our understanding of relationships in this rapid radiation. Differences across analyses and the possibility of additional lineage discoveries still hamper a solid and stable reclassification. Rapid morphological innovation corresponds with a high degree of phylogenomic complexity, including cytonuclear discordance, nuclear gene tree conflict, and well-supported differences between analyses based on different nuclear loci. Taken together, these results point to a potential role of hemiplasy underlying repeated convergent evolution. This hallmark of rapid radiations is likely present in many other species-rich Andean plant radiations.
ATm4sf1-Marked Subpopulation of Endothelial Stem/Progenitor Cells Identified by Lung Single-Cell Omics of Pulmonary Arterial Hypertension
Authors: Hong Jason , Wong Brenda , Huynh Caroline , Tang Brian , Umar Soban , Yang Xia , Eghbali Mansoureh 
Published: January 2022

AbstractRationaleThe identification and role of endothelial progenitor cells (EPCs) in pulmonary arterial hypertension (PAH) remains controversial. Single-cell omics analysis can shed light on EPCs and their potential contribution to PAH pathobiology.ObjectivesWe aim to identify EPCs in rat lungs and assess their relevance to preclinical and human PAH.MethodsDifferential expression, gene set enrichment, cell-cell communication, and trajectory reconstruction analyses were performed on lung endothelial cells from single-cell RNA-seq of Sugen-hypoxia, monocrotaline, and control rats. Relevance to human PAH was assessed in multiple independent blood and lung transcriptomic datasets.Measurements and Main ResultsA subpopulation of endothelial cells (EA2) marked byTm4sf1, a gene strongly implicated in cancer, harbored a distinct transcriptomic signature includingBmpr2downregulation that was enriched for pathways such as inflammation and angiogenesis. Cell-to-cell communication networks specific to EA2 were activated in PAH such as CXCL12 signaling. Trajectory analysis demonstrated EA2 has a stem/progenitor cell phenotype. Analysis of independent datasets revealedTm4sf1is a marker for hematopoietic stem cells and is upregulated in PAH peripheral blood, particularly in patients with worse WHO functional class. EA2 signature genes includingProcrandSulf1were found to be differentially regulated in the lungs of PAH patients and in PAH modelsin vitro, such as BMPR2 knockdown.ConclusionsOur study uncovered a novelTm4sf1-marked stem/progenitor subpopulation of rat lung endothelial cells and demonstrated its relevance to preclinical and human PAH. Future experimental studies are warranted to further elucidate the pathogenic role and therapeutic potential of targeting EA2 andTm4sf1in PAH.
Frequent co-regulation of splicing and polyadenylation by RNA-binding proteins inferred with MAPP
Authors: Bak Maciej , van Nimwegen Erik , Schmidt Ralf , Zavolan Mihaela , Gruber Andreas J. 
Published: January 2022

AbstractMaturation of eukaryotic pre-mRNAs via splicing, 3’ end cleavage and polyadenylation is modulated across cell types and conditions by a variety of RNA-binding proteins (RBPs). Although over 1’500 proteins are associated with RNAs in human cells, their binding motifs, targets and functions still remain to be elucidated, especially in the complex environment of human tissues and in the context of diseases. To overcome the lack of methods for systematic and automated detection of sequence motif-guided changes in pre-mRNA processing based on RNA sequencing (RNA-seq) data we have developed MAPP (Motif Activity on Pre-mRNA Processing). We demonstrate MAPP’s functionality by applying it to RNA-seq data from 284 RBP knock-down experiments in the ENCODE project, from which MAPP not only infers position-dependent impact profiles of known regulators, but also reveals RBPs that modulate both the inclusion of cassette exons and the poly(A) site choice. Among these, the Polypyrimidine Tract Binding Protein 1 (PTBP1) has a similar activity in glioblastoma samples. This highlights the ability of MAPP to unveil global regulators of mRNA processing under physiological and pathological conditions.
Patterns of Structural Variation Define Prostate Cancer Across Disease States
Authors: Zhou Meng , Ko Minjeong , Hoge Anna C. , Luu Kelsey , Liu Yuzhen , Russell Magdalena L. , Hannon William W. , Zhang Zhenwei , Carrot-Zhang Jian , Beroukhim Rameen , Van Allen Eliezer M. , Choudhury Atish D. , Nelson Peter S. , Freedman Matthew L. , Taplin Mary-Ellen , Meyerson Matthew , Viswanathan Srinivas R. , Ha Gavin 
Published: January 2022

ABSTRACTThe complex genomic landscape of prostate cancer evolves across disease states under therapeutic pressure directed toward inhibiting androgen receptor (AR) signaling. While significantly altered genes in prostate cancer have been extensively defined, there have been fewer systematic analyses of how structural variation shapes the genomic landscape of this disease across disease states. We uniformly characterized structural alterations across 278 localized and 143 metastatic prostate cancers profiled by whole genome and transcriptome sequencing. We observed distinct significantly recurrent breakpoints in localized and metastatic castration-resistant prostate cancers (mCRPC), with pervasive alterations in noncoding regions flanking the AR, MYC, FOXA1, and LSAMP genes enriched in mCRPC and TMPRSS2-ERG rearrangements enriched in localized prostate cancer. We defined nine subclasses of mCRPC based on signatures of structural variation, each associated with distinct genetic features and clinical outcomes. Our results comprehensively define patterns of structural variation in prostate cancer and identify clinically actionable subgroups based on whole genome profiling.
SARS-CoV-2 risk taxation model and validation based on large scale Dutch test-events
Authors: Kolen Bas , Znidarsic Laurens , Voss Andreas , Donders Simon , Kamphorst Iris , van Rijn Maarten , Bonthuis Dimitri , Cloquet Merit , Schram Maarten , Scharloo Rutger , Boersma Tim , Stobernack Tim , van Gelder Pieter 
Published: January 2022

AbstractIn response to the outbreak of SARS-CoV-2 many governments decided in 2020 to impose lockdowns on societies. Although the package of measures which constitute such lockdowns differs between countries, it is a general rule that contacts between people, and especially in large groups of people, are avoided or prohibited. The main reasoning behind these measures is preventing that healthcare systems become overloaded. As of 2021 vaccines against SARS-CoV-are available, but these do not guarantee 100% risk reduction and it will take a while for the world to reach a sufficient immune status. This raises the question whether and under which conditions events like theater shows, conferences, professional sports events, concerts and festivals can be organized. The current paper presents a COVID-19 Risk taxation method for (large scale) events. This method can be applied to events to define an alternative package of measures replacing generic social distancing.
Machine Learning Prediction of Progression in FEV1in the COPDGene Study
Authors: Boueiz Adel , Xu Zhonghui , Chang Yale , Masoomi Aria , Gregory Andrew , Lutz Sharon M. , Qiao Dandi , Crapo James D. , Dy Jennifer G. , Silverman Edwin K. , Castaldi Peter J. ,   for the COPDGene investigators
Published: January 2022

ABSTRACTBackgroundThe heterogeneous nature of COPD complicates the identification of the predictors of disease progression and consequently the development of effective therapies. We aimed to improve the prediction of disease progression in COPD by using machine learning and incorporating a rich dataset of phenotypic features.MethodsWe included 4,496 smokers with available data from their enrollment and 5-year follow-up visits in the Genetic Epidemiology of COPD (COPDGene) study. We constructed supervised random forest models to predict 5-year progression in FEV1from 46 baseline demographic, clinical, physiologic, and imaging features. Using cross-validation, we randomly partitioned participants into training and testing samples. We also validated the results in the COPDGene 10-year follow-up visit.ResultsPredicting the change in FEV1over time is more challenging than simply predicting the future absolute FEV1level. Nevertheless, the area under the ROC curves for the prediction of subjects in the top quartile of observed disease progression was 0.70 in the 10-year follow-up data. The model performance accuracy was best for GOLD1-2 subjects and it was harder to achieve accurate prediction in advanced stages of the disease. Predictive variables differed in their relative importance as well as for the predictions by GOLD grade.ConclusionThis state-of-the art approach along with deep phenotyping predicts FEV1progression with reasonable accuracy. There is significant room for improvement in future models. This prediction model facilitates the identification of smokers at increased risk for rapid disease progression. Such findings may be useful in the selection of patient populations for targeted clinical trials.
Factors influencing the motivation of maternal health workers in conflict setting of Mogadishu, Somalia
Authors: Sheikh Naima Said , Gele Abdi 
Published: January 2022

AbstractBackgroundMotivated health workers play an important role in delivering high-quality maternal health services, especially in low-income countries where maternal mortality rates are high, and shortages of human resource for health is prevalent. The aim of this study is to investigate maternal health workers’ motivation in three tertiary hospitals in Mogadishu Somalia.MethodTo investigate health worker motivation in Somalia, we used a semi-structured questionnaire that was validated and widely used in Sub-Saharan Africa. Data were collected from 220 health workers across three tertiary hospitals in Mogadishu between February and April 2020. Health worker motivation was measured using seven constructs: general motivation, burnout, job satisfaction, intrinsic job satisfaction, organizational commitment, conscientiousness, timeliness and attendance. A multivariate regression analysis was performed to determine the predictors of health worker motivation.ResultsThe study found that male health workers have a higher work motivation, with a mean score of 92.75 (SD 21.31) versus 90.43 (SD 21.61) in women. A significant correlation was found between health workers’ motivation and being an assistant, nurse, physician, pediatric-assistant, midwife, supervisor and pharmacist. Unexpectedly, the gynecologists and midwives were the least motivated groups among the different professions, with mean scores of 83.63, (SD: 27.41) and 86.95 (SD: 21.08), respectively. Of the aforementioned seven motivation constructs, the highest mean motivation scores (from 1-5) were observed in conscientiousness and intrinsic job satisfaction.ConclusionThe results highlight the importance of targeted interventions that increase female health workers’ motivation, particularly gynecologists and midwives in Somalia. This can be done by providing non-financial incentives, in addition to encouraging their participation in the decision-making process. Further research is needed to investigate the effect of a lack of motivation among gynecologists and midwives on maternal health in Somalia.
Development of tool for assessment of performance motivation and job satisfaction among the Community Health Workers of Central India
Authors: Revadi G , Joshi Ankur , Pakhare Abhijit P 
Published: January 2022

AbstractIntroductionAmong the various factors influencing the performance of Community health workers, motivation and job satisfaction serves as a potential drive to perform better. Hence, this study aimed at constructing a motivation and job satisfaction tool in a systematic method that would serve as a potential tool for further research considering the heterogeneity in the study population.ObjectiveTo develop a tool to measure how well the CHWs are motivated and satisfied pertaining to individual, community and health system determinants.MethodsThis cross-sectional study from rural block of Madhya Pradesh in Central India included relatively high performing and low performing CHWs based on their annual performance-based incentives for the year (April 2017-March 2018). The CHWs were administered a self-reported questionnaire that contained a 5-point Likert scale with individual, health system and community determinants of motivation and job satisfaction.ResultsThe performance motivation scale with 18 items and job satisfaction scale with 15 items were administered to the 92 CHWs. Their item content validity index was 0.66 and 0.83 respectively. The finalized tool consisted of 11 items in motivation scale and all the 15 items in job satisfaction scale following the Explanatory factor analysis. All the individual constructs in both the scales showed good internal consistency with Cronbachs alpha ranging from 0.62-0.88. The overall median (IQR) score of both RLP and RHP CHWs were 4(4–5) in both the questionnaires.ConclusionThe CHWs in our study were intrinsically motivated and were satisfied with their performance as voluntary village health workers. Further research would be planned to validate the constructs using confirmatory factor analysis.