bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genitourinary syndrome of menopause
Authors: Phillips Nancy A. , Bachmann Gloria A. 
Published: February 2021

Abstract
Genitourinary syndrome of menopause (GSM) refers to a collection of symptoms resulting from diminished hormonal, primarily estrogenic stimulation to the vulvovaginal or lower urinary tract and may affect up to 50% of postmenopausal women. Symptoms, which are typically progressive and unlikely to resolve spontaneously, may include, but are not limited to, vulvovaginal dryness, burning or irritation, dyspareunia, or urinary symptoms of urgency, dysuria or recurrent urinary tract infection. These symptoms are typically progressive and unlikely to resolve spontaneously. Diagnosis is clinical. Telemedicine may play a role in diagnosis, initiation of treatment, and follow-up of women with GSM. Effective treatments include moisturizers and lubricants, local hormonal therapy with estrogen or dehydroepiandrosterone, and oral selective estrogen receptor agonists. Laser or radiofrequency procedures, although currently utilized, are being studied to comprehensively understand their overall effectiveness and safety. Additionally, the influence and effect of the vaginal microbiome, as well as potential of treatment via its manipulation, is being studied. We performed a literature search of PubMed, Google Scholar, and Ovid with search terms of vulvovaginal atrophy and GSM and reviewed major US Society Guidelines to create this narrative review of this topic. The literature suggests that healthcare providers can make a significant impact of the health and quality of life of women by being proactive about discussing and providing interventions for GSM. A systematic approach with consideration of current guidelines and attention to developing protocols for interventions should be employed.

Video Summary:

http://links.lww.com/MENO/A702.
GUNC: Detection of Chimerism and Contamination in Prokaryotic Genomes
Authors: Orakov Askarbek , Fullam Anthony , Coelho Luis Pedro , Khedkar Supriya , Szklarczyk Damian , Mende Daniel R , Schmidt Thomas SB , Bork Peer 
Published: February 2021

AbstractGenomes are critical units in microbiology, yet ascertaining quality in prokaryotic genomes remains a formidable challenge. We present GUNC (the Genome UNClutterer), a tool that accurately detects and quantifies genome chimerism based on the lineage homogeneity of individual contigs using a genome’s full complement of genes. GUNC complements existing approaches by targeting previously underdetected types of contamination: we conservatively estimate that 5.7% of genomes in GenBank, 5.2% in RefSeq, and 15-30% of pre-filtered ‘high quality’ metagenome-assembled genomes in recent studies are undetected chimeras. GUNC provides a fast and robust tool to substantially improve prokaryotic genome quality. Source code (GPLv3+):https://github.com/grp-bork/gunc
RISK FACTORS FOR INFECTION AND HEALTH IMPACTS OF THE COVID-19 PANDEMIC IN PEOPLE WITH AUTOIMMUNE DISEASES
Authors: Fitzgerald Kathryn C. , Mecoli Christopher A. , Douglas Morgan , Harris Samantha , Aravidis Berna , Albayda Jemima , Sotirchos Elias S. , Hoke Ahmet , Orbai Ana-Maria , Petri Michelle , Christopher-Stine Lisa , Baer Alan N. , Paik Julie J. , Adler Brittany L. , Tiniakou Eleni , Timlin Homa , Bhargava Pavan , Newsome Scott D. , Venkatesan Arun , Chaudhry Vinay , Lloyd Thomas E. , Pardo Carlos A. , Stern Barney J. , Lazarev Mark , Truta Brindusa , Saidha Shiv , Chen Edward S. , Sharp Michelle , Gilotra Nisha , Kasper Edward K. , Gelber Allan C. , Bingham Clifton O. , Shah Ami A. , Mowry Ellen M. 
Published: February 2021

ABSTRACTBackgroundPeople with autoimmune or inflammatory conditions who take immunomodulatory/suppressive medications may have a higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences.ObjectiveAssess whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterize pandemic-associated changes to care.DesignLongitudinal registry studyParticipants4666 individuals with autoimmune or inflammatory conditions followed by specialists in neurology, rheumatology, cardiology, pulmonology or gastroenterology at Johns HopkinsMeasurementsPeriodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcareResultsA total of 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medication exposure) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in multivariable models incorporating behavior and other potential confounders (OR: 1.43; 95%CI: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95%CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95%CI: 1.24, 2.28), and chronic kidney disease (OR: 1.76; 95%CI: 1.04, 2.97) were each associated with higher odds of COVID-19. Pandemic-related disruption to care was common. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions. Individuals experiencing changes to employment or income were at highest odds of care disruption.LimitationsResults may not be generalizable to all patients with autoimmune or inflammatory conditions. Information was self-reported.ConclusionsExposure to glucocorticoids may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.
Capacity of countries to reduce biological invasions
Authors: Latombe Guillaume , Seebens Hanno , Lenzner Bernd , Courchamp Franck , Dullinger Stefan , Golivets Marina , Kühn Ingolf , Leung Brian , Roura-Pascual Núria , Cebrian Emma , Dawson Wayne , Diagne Christophe , Jeschke Jonathan M. , Perez-Granados Cristian , Liu Chunlong , Moser Dietmar , Turbelin Anna , Visconti Piero , Essl Franz 
Published: February 2021

AbstractThe extent and impacts of biological invasions on biodiversity are largely shaped by an array of socio-ecological predictors, which exhibit high variation among countries. Yet a global synthetic perspective of how these factors vary across countries is currently lacking. Here, we investigate how a set of five socio-ecological predictors (Governance, Trade, Environmental Performance, Lifestyle and Education, Innovation) explain i) country-level established alien species (EAS) richness of eight taxonomic groups, and ii) country capacity to prevent and manage biological invasions and their impacts. Trade and Governance together best predicted the average EAS richness, increasing variance explained by up to 54% compared to models based on climatic and spatial variables only. Country-level EAS richness increased strongly with Trade, whereas high level of Governance resulted in lower EAS richness. Historical (1996) levels of Governance and Trade better explained response variables than current (2015) levels. Thus, our results reveal a historical legacy of these two predictors with profound implications for the future of biological invasions. We therefore used Governance and Trade to define a two-dimensional socio-economic space in which the position of a country captures its capacity to address issues of biological invasions. Our results provide novel insights into the complex relationship between socio-ecological predictors and biological invasions. Further, we highlight the need for designing better policies and management measures for alien species, and for integrating biological invasions in global environmental scenarios.
The Case for Retaining Natural Language Descriptions of Phenotypes in Plant Databases and a Web Application as Proof of Concept
Authors: Braun Ian R. , Yanarella Colleen F. , Durairaj Rajeswari Jyothi Prasanth , Bassham Diane C. , Lawrence-Dill Carolyn J. 
Published: February 2021

ABSTRACTSimilarities in phenotypic descriptions can be indicative of shared genetics, metabolism, and stress responses, to name a few. Finding and measuring similarity across descriptions of phenotype is not straightforward, with previous successes in computation requiring a great deal of expert data curation. Natural language processing of free text descriptions of phenotype is often less resource intensive than applying expert curation. It is therefore critical to understand the performance of natural language processing techniques for organizing and analyzing biological datasets and for enabling biological discovery. For predicting similar phenotypes, a wide variety of approaches from the natural language processing domain perform as well as curation-based methods. These computational approaches also show promise both for helping curators organize and work with large datasets and for enabling researchers to explore relationships among available phenotype descriptions. Here we generate networks of phenotype similarity and share a web application for querying a dataset of associated plant genes using these text mining approaches. Example situations and species for which application of these techniques is most useful are discussed.Database URLsThe database and analytical tool called QuOATS are available athttps://quoats.dill-picl.org/. Code for the web application is available athttps://git.io/Jtv9J. Datasets are available for direct access viahttps://zenodo.org/record/7947342#.ZGwAKOzMK3I. The code for the analyses performed for the publication is available athttps://github.com/Dill-PICL/Plant-dataandhttps://github.com/Dill-PICL/NLP-Plant-Phenotypes.
Heterogeneous nuclear ribonucleoprotein K is overexpressed in acute myeloid leukemia and causes myeloproliferative disease in mice via altered Runx1 splicing
Authors: Aitken Marisa J. L. , Malaney Prerna , Zhang Xiaorui , Herbrich Shelley M. , Chan Lauren , Ma Huaxian , Jacamo Rodrigo , Duan Ruizhi , Link Todd M. , Kornblau Steven M. , Kanagal-Shamanna Rashmi , Bueso-Ramos Carlos E. , Post Sean M. 
Published: February 2021

SummaryAcute myeloid leukemia (AML) is driven by numerous molecular events that contribute to disease progression. Herein, we identified hnRNP K overexpression as a recurrent abnormality in AML that is associated with inferior patient outcomes. In murine hematopoietic stem and progenitor cells, hnRNP K overexpression altered self-renewal and differentiation potential. Furthermore, murine transplantation models revealed that hnRNP K overexpression resulted in fatal myeloproliferative phenotypes. Using unbiased approaches, we discovered a direct relationship between hnRNP K and RUNX1—a master transcriptional regulator of hematopoiesis often dysregulated in leukemia. Molecular analyses revealed hnRNP K-dependent alternative splicing of RUNX1, resulting in the generation of a functionally distinct isoform. Taken together, we have established hnRNP K as an oncogene in myeloid leukemia that binds RUNX1 RNA, altering its splicing and subsequent transcriptional activity. These findings shed new light on a mechanism of myeloid leukemogenesis, paving the way for new drug discovery efforts.HighlightshnRNP K, an RNA binding protein, is overexpressed in AML and correlates with poor clinical outcomeshnRNP K overexpression in murine HSPCs drives fatal myeloproliferative phenotypes in micehnRNP K’s oncogenicity can be attributed, at least in part, to its ability to bind and influence the splicing of the RUNX1 transcript
Characterization of a novel Fgf10CreERT2 knock-in mouse line targeting postnatal lung Fgf10 lineages
Authors: Chu Xuran , Taghizadeh Sara , Vasquez-Armendariz Ana Ivonne , Herold Susanne , Chong Lei , Chen Chengshui , Zhang Jin-San , Agha Elie El , Bellusci Saverio 
Published: February 2021

AbstractFgf10 is a key gene during development, homeostasis and repair after injury. We previously reported a Fgf10CreERT2 line (with the CreERT2 cassette inserted in frame with the start codon of exon 1), called thereafter Fgf10Ki-v1, to target Fgf10Pos cells. While this line allowed fairly efficient and specific labeling of Fgf10Pos cells during the embryonic stage, it failed to target these cells after birth, particularly in the postnatal lung, which has been the focus on our research. We report here the generation and validation of a new Fgf10CreERT2 (called thereafter Fgf10Ki-v2) with the insertion of the expression cassette in frame with the stop codon of exon 3. This new Fgf10Ki-v2 line exhibited comparable Fgf10 expression level to their wild type counterpart. However, a disconnection between the Fgf10 and the Cre expression was observed in Fgf10Ki-v2/+ lungs. In addition, lung and limb agenesis were observed in homozygous embryos suggesting a loss of Fgf10 functional allele in Fgf10Ki-v2 mice. Bio-informatics analysis shows that the 3’UTR, where the CreERT2 cassette is inserted, contains numerous putative transcription factor binding sites. By crossing this line with tdTomato reporter line, we demonstrated that tdTomato expression faithfully recapitulated Fgf10 expression during development. Significantly, Fgf10Ki-v2 mouse is capable of significantly targeting Fgf10Pos cells in the adult lung. Therefore, despite the aforementioned limitations, this new Fgf10Ki-v2 line opens the way for future mechanistic experiments involving the postnatal lung.
In vivo magnetic resonance spectroscopy of hyperpolarized [1-13C] pyruvate in a male guinea pig model of life-long Western diet consumption and non-alcoholic fatty liver disease development
Authors: Smith Lauren M. , Pitts Conrad B. , Friesen-Waldner Lanette J. , Prabhu Neetin H. , Mathers Katherine E. , Sinclair Kevin J. , Wade Trevor P. , Regnault Timothy R.H. , McKenzie Charles A. 
Published: February 2021

AbstractBACKGROUNDAlterations in glycolysis and oxidative pathways are central to the increasing incidence of non-alcoholic fatty liver disease (NAFLD), highlighting a need forin vivo, non-invasive technologies to understand the development of hepatic metabolic aberrations in lean NAFLD.PURPOSE/HYPOTHESISTo use hyperpolarized magnetic resonance spectroscopy (MRS) and proton density fat fraction (PDFF) MRI techniques to investigate effects of a chronic, life-long exposure to the Western Diet (WD) in a model of NAFLD and identify cellular metabolite changes and correlations related to enzyme activity. It is hypothesized that exposure to the WD will result in NAFLD in association with altered pyruvate metabolism.STUDY TYPEProspective POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL: 28 male guinea pigs were weaned onto a control diet or WD.FIELD STRENGTH/SEQUENCE3T; T1, T2, IDEAL, broadband PRESS MRS.ASSESSMENTMedian PDFF was calculated in the liver and hind limbs. [1-13C]pyruvate dynamic MRS in the liver was quantified by the time to peak (TTP), calculated as the time from pyruvate peak to metabolite peak. After a recovery period, animals were euthanized, and tissue was analyzed for lipid and cholesterol concentration and enzyme level and activity.STATISTICAL TESTSUnpaired Student’s t-tests were used to determine differences in measurements between the two diet groups. The Pearson correlation coefficient was calculated to determine correlations between measurements.RESULTSLife-long WD consumption resulted in significantly higher liver PDFF correlated with elevated triglyceride content in the liver. The WD group exhibited a decreased TTP for lactate production, andex vivoanalysis highlighted increased liver lactate dehydrogenase (LDH) activity. DATA CONCLUSION: PDFF MRI results suggest differential fat deposition patterns occurring in animals fed a life-long WD, corresponding with increased liver triglyceride levels characteristic of lean NAFLD. The decreased liver lactate TTP and increasedex vivoLDH activity suggest lipid accumulation occurs in association with a shift from oxidative metabolism to anaerobic glycolytic metabolism in WD livers.
IL-1-driven stromal-neutrophil interaction in deep ulcers defines a pathotype of therapy non-responsive inflammatory bowel disease
Authors: Friedrich Matthias , Pohin Mathilde , Jackson Matthew A. , Korsunsky Ilya , Bullers Samuel , Rue-Albrecht Kevin , Christoforidou Zoe , Sathananthan Dharshan , Ravindran Rahul , Peres Raphael Sanches , Sharpe Hannah , Wei Kevin , Watts Gerald F. M. , Mann Elizabeth H. , Geremia Alessandra , Thomas Tom , Attar Moustafa ,   Oxford IBD Cohort Investigators,   Roche Fibroblast Network Consortium, McCuaig Sarah , Thomas Lloyd , Collantes Elena , Uhlig Holm H. , Sansom Stephen , Easton Alistair , Raychaudhuri Soumya , Travis Simon P. , Powrie Fiona M. 
Published: February 2021

AbstractCurrent inflammatory bowel disease (IBD) therapies are ineffective in a high proportion of patients. Combining bulk and single-cell transcriptomics, quantitative histopathology, and in situ localisation, we describe heterogeneity of the tissular inflammatory response in IBD treatment failure. Among inflammatory pathotypes, we found high neutrophil infiltration, activation of fibroblasts, and vascular remodelling at sites of deep ulceration was a feature of non-response to several anti-inflammatory therapies. Activated fibroblasts in the ulcer bed display neutrophil chemoattractant properties that are IL-1R- but not TNF-dependent. The identification of distinct, localised, tissular pathotypes associated with treatment non-response will aid precision targeting of current therapeutics and provide a biological rationale for IL-1 signalling blockade in ulcerating disease.
Osteomacs support osteoclast-mediated resorption and contribute to bone pathology in a postmenopausal osteoporosis mouse model
Authors: Batoon Lena , Millard Susan M. , Raggatt Liza J. , Wu Andy C. , Kaur Simranpreet , Sun Lucas W.H. , Williams Kyle , Sandrock Cheyenne , Ng Pei Ying , Bartnikowski Michal , Glatt Vaida , Pavlos Nathan J. , Pettit Allison R. 
Published: February 2021

AbstractOsteal macrophages (osteomacs) support osteoblast function and promote bone anabolism, but their contribution to osteoporosis has not been explored. While mouse ovariectomy models have been repeatedly used, variation in strain, experimental design and assessment modalities, have contributed to no single model being confirmed as comprehensively replicating the full gamut of osteoporosis pathological manifestations. We validated an ovariectomy model in adult C3H/HeJ mice and demonstrated that it presents with human post-menopausal osteoporosis features, including reduced bone volume in axial and appendicular bone and bone loss in both trabecular and cortical bone including increased cortical porosity. Bone loss was associated with increased osteoclasts on trabecular and endocortical bone and decreased osteoblasts on trabecular bone. Importantly, this OVX model was characterised by delayed fracture healing. Using this validated model, we demonstrated that osteomacs are increased post-ovariectomy on both trabecular and endocortical bone. Dual F4/80 (pan-macrophage marker) and TRAP staining revealed osteomacs frequently located near TRAP+osteoclasts and containing TRAP+intracellular vesicles. Using anin vivoinducible macrophage depletion model that does not simultaneously deplete osteoclasts, we observed that osteomac loss was associated with elevated extracellular TRAP in bone marrow interstitium and increased serum TRAP. Usingin vitrohigh-resolution confocal imaging of mixed osteoclast-macrophage cultures on bone substrate, we observed macrophages juxtaposed to osteoclast basolateral functional secretory domains scavenging degraded bone by-products. These data demonstrate a role for osteomacs in supporting osteoclastic bone resorption through phagocytosis and sequestration of resorption by-products. Finally, usingSiglec1knockout mice, we demonstrated that loss of the macrophage-restricted molecule Siglec-1/CD169 is sufficient to cause age-associated low bone mass, emphasizing the macrophages, independent of osteoclasts, contribute to optimal skeletal health. Overall, our data expose a novel role for osteomacs in supporting osteoclast function and provide the first evidence of their involvement in osteoporosis pathogenesis.
Long-term antitumor CD8+T cell immunity induced by endogenously engineered extracellular vesicles
Authors: Ferrantelli Flavia , Manfredi Francesco , Chiozzini Chiara , Olivetta Eleonora , Giovannelli Andrea , Leone Patrizia , Federico Maurizio 
Published: February 2021

AbstractWe developed a novel approach to induce antigen-specific CD8+T cytotoxic lymphocyte (CTL) immunity based onin vivoengineering of extracellular vesicles (EVs). This is an innovative vaccination approach employing a DNA vector expressing a mutated HIV-1 Nef protein (Nefmut) that has lost the anti-cellular effects typical of the wild-type isoform, meanwhile showing an unusual efficiency of incorporation into EVs. This function persists even when foreign antigens are fused to its C-terminus. In this way, Nefmuttraffics large amounts of antigens fused to it into EVs spontaneously released by cells expressing the Nefmut_based DNA vector. We previously provided evidence that the inoculation in mice of a DNA vector expressing the Nefmut/HPV16-E7 fusion protein induced an E7-specific CTL immune response as detected 2 weeks after the second immunization. In an effort to optimize the anti-HPV16 CD8+T cell immune response, we found that the co-injection of DNA vectors expressing Nefmutfused with E6 and E7 generated a stronger anti-HPV16 immune response compared to that we observed in mice injected with the single vectors. When TC-1 cells, i.e., a tumor cell line co-expressing E6 and E7, were implanted before immunization, all mice survived until day 44, whereas no mice injected with either void or Nefmut_expressing vectors survived until day 32 after tumor implantation. A substantial part of mice (7 out of 12) cleared the tumor. When cured mice were re-challenged with a second sub cute implantation of TC-1 cells, and followed for additional 135 days, whereas none of them developed tumors. Both E6- and E7-specific CD8+T immunity was still detectable at the end of the observation time.Hence, the immunity elicited by engineered EVs, besides curing already developed tumors, is strong enough to guarantee the resistance to additional tumor attack. This results is of relevance for therapy against both metastatic and relapsing tumors.