bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of MLL3/4 decouples enhancer H3K4 monomethylation, H3K27 acetylation, and gene activation during ESC differentiation
Authors: Boileau Ryan M. , Chen Kevin X. , Blelloch Robert 
Published: October 2022

AbstractEnhancers are essential in defining cell fates through the control of cell type specific gene expression. Enhancer activation is a multi-step process involving chromatin remodelers and histone modifiers including the monomethylation of H3K4 (H3K4me1) by MLL3 (KMT2C) and MLL4 (KMT2D). MLL3/4 are thought to be critical for enhancer activation and cognate gene expression including through the recruitment of acetyltransferases for H3K27. Here we test this model by evaluating the impact of MLL3/4 loss on chromatin and transcription during early embryonic stem cell differentiation. We find that MLL3/4 activity is required at most if not all sites that gain or lose H3K4me1 but is largely dispensable at sites that remain stably methylated during this transition. This requirement extends to H3K27 acetylation (H3K27ac) at most transitional sites. However, many sites gain H3K27ac independent of MLL3/4 or H3K4me1 including enhancers regulating key factors in early differentiation. Furthermore, despite the failure to gain active histone marks at thousands of enhancers, transcriptional activation of nearby genes is largely unaffected, thus uncoupling the regulation of these chromatin events from transcriptional changes during this transition. These data challenge current models of enhancer activation and imply distinct mechanisms between stable and dynamically changing enhancers. Collectively, our study highlights gaps in knowledge about the steps and epistatic relationships of enzymes necessary for enhancer activation and cognate gene transcription.
Serum Amyloid A proteins reduce bone mass during mycobacterial infections
Authors: Gomes Ana Cordeiro , Sousa Daniela Monteiro , Oliveira Tiago Carvalho , Fonseca Óscar , Pinto Ricardo J. , Silvério Diogo , Fernandes Ana Isabel , Moreira Ana C. , Silva Tânia , Teles Maria José , Pereira Luísa , Saraiva Margarida , Lamghari Meriem , Gomes Maria Salomé 
Published: October 2022

AbstractOsteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required. Using genetically engineered mice and morphometric, transcriptomic and functional analyses, we found that infection withMycobacterium aviumimpacts bone turnover by decreasing bone formation and increasing bone resorption, in a IFNg- and TNFa-dependent manner. IFNg produced during infection enhanced macrophage TNFa secretion, which in turn increased the production of serum amyloid A (SAA) 3.Saa3expression was upregulated in the bone of bothM. avium- andMycobacterium tuberculosis-infectedmice and SAA proteins were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine network operating in macrophages and bone homeostasis and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.
Understanding the chronic kidney disease landscape using patient representation learning from electronic health records
Authors: Kapur Karen , Freidank Moritz , Rebhan Michael 
Published: October 2022

AbstractUnderstanding various subpopulations in chronic kidney disease can improve patient care and aid in developing treatments targeted to patients’ needs. Due to the general slow disease progression, electronic health records, which comprise a rich source of longitudinal real-world patient-level information, offer an approach for generating insights into disease. Here we apply the open-source ConvAE framework to train an unsupervised deep learning network using a real-world kidney disease cohort consisting of 2.2 million US patients from the OPTUM® EHR database. Numerical patient representations derived from ConvAE are used to derive disease subtypes, inform comorbidities and understand rare disease populations. To identify patients at high risk to develop end-stage kidney disease, we extend a validated algorithm classifying disease severity to hypothesize subpopulations of rapid chronic kidney disease progressors. We demonstrate that using a combination of data-driven methods offers a powerful exploratory approach to understand disease heterogeneity and identify high-risk patients who could be targeted for early therapeutic intervention to prevent end-stage kidney disease.
Covid-19 pandemic has polarized the society toward negative and positive traits depending on a person’s resilience and certain predispositions
Authors: Attary Taraneh , Noorbala Leila , Ghazizadeh Ali 
Published: October 2022

AbstractThe Covid-19 pandemic has caused a major disruption affecting almost all aspects of health, social and economic dimensions of our lives on an almost unprecedented global scale. While Covid-19 itself is, first and foremost, a pernicious physical illness, its highly contagious nature has caused significant psychological stress with occasional dire mental health consequences which are still not fully understood. To address this issue, we have conducted a longitudinal study by administering standard self-reporting questionnaires covering five major personalities and six mental traits of subjects before and a few months after the outbreak. Results revealed the distribution of population scores to become more extreme in either positive or negative trait directions despite the stability of average trait scores across the population. Higher resilience was found to be positively correlated with improved trait scores post-pandemic. Further investigations showed that certain predispositions could have an effect on trait score change post-Covid depending on the subject’s pre-Covid scores. In particular, in the subjects with moderate scores, there was a significant negative correlation between the positive trait scores and the post minus pre-positive trait scores. By examining various traits and personalities, these findings depict a more thorough picture of the pandemic’s impact on society’s psychological well-being and reveal certain predispositions and vulnerabilities that shape the mental health landscape in the post-Covid period with implications for mental health policies in dealing with Covid-19.
Non-invasive three-dimensional 1H-MR Spectroscopic Imaging of human brain glucose and neurotransmitter metabolism using deuterium labeling at 3T
Authors: Niess Fabian , Hingerl Lukas , Strasser Bernhard , Bednarik Petr , Goranovic Dario , Niess Eva , Hangel Gilbert , Krššák Martin , Spurny-Dworak Benjamin , Scherer Thomas , Lanzenberger Rupert , Bogner Wolfgang 
Published: October 2022

AbstractObjectivesNon-invasive, affordable, and reliable mapping of brain glucose metabolism is of critical interest for clinical research and routine application as metabolic impairment is linked to numerous pathologies e.g., cancer, dementia and depression. A novel approach to map glucose metabolism non-invasively in the human brain and separate normal oxidative from pathologic anaerobic pathways has been presented recently on experimental MR scanners using direct or indirect detection of deuterium-labeled glucose and downstream metabolites such as glutamate, glutamine and lactate.The aim of this study was to demonstrate the feasibility to non-invasively detect deuterium labeled downstream glucose metabolites indirectly in the human brain via 3D proton (1H) MR spectroscopic imaging on a clinical 3T MR scanner without additional hardware.Materials and MethodsThis prospective, institutional review board approved study was performed in seven healthy volunteers (mean age, 31±4 years, 5 m/ 2 f) following written informed consent. After overnight fasting and oral deuterium-labeled glucose administration 3D metabolic maps were acquired every ∼4 min with ∼0.24 ml isotropic spatial resolution using real-time motion-, shim- and frequency-corrected echo-less 3D1H-MR Spectroscopic Imaging. Time courses were analyzed using linear regression and non-parametric statistical tests. Deuterium labeled glucose and downstream metabolites were detected indirectly via their respective signal decrease in dynamic1H MR spectra due to deuterium to proton exchange in the molecules.ResultsSixty-five minutes after deuterium-labeled glucose administration, glutamate+glutamine (Glx) signal intensities decreased in gray/white matter (GM,WM) by -15±2%,(p=0.02)/-14±3%,(p=0.02), respectively. Strong negative correlation between Glx and time was observed in GM/WM (r=-0.71p<0.001)/(r=-0.67,p<0.001) with 38±18% (p=0.02) steeper slopes, indicating faster metabolic activity in GM compared to WM. Other non-labeled metabolites showed no significant changes.ConclusionOur approach translates deuterium metabolic imaging to widely available clinical routine MR scanners without specialized hardware offering a safe, affordable, and versatile (other substances than glucose can be labeled) approach for non-invasive imaging of glucose and neurotransmitter metabolism in the human brain.
Cardiovascular magnetic resonance imaging after normal echocardiography in myocardial infarction with nonobstructed coronary arteries
Authors: Sundqvist Martin G. , Sörensson Peder , Ekenbäck Christina , Lundin Magnus , Agewall Stefan , Bacsovics Brolin Elin , Cederlund Kerstin , Collste Olov , Daniel Maria , Jensen Jens , Y-Hassan Shams , Henareh Loghman , Hofman-Bang Claes , Lyngå Patrik , Maret Eva , Sarkar Nondita , Spaak Jonas , Winnberg Oscar , Caidahl Kenneth , Ugander Martin , Tornvall Per 
Published: October 2022

AbstractBackgroundIn patients with myocardial infarction with nonobstructive coronary arteries (MINOCA), cardiovascular magnetic resonance imaging (CMR) can often establish a causal diagnosis. It is unknown if CMR is warranted in patients with normal echocardiographic findings, or if measurement of high-sensitive troponin T (hs-TnT) and NT-pro-BNP can be of value in selecting patients for further imaging.ObjectivesTo assess the diagnostic accuracy of echocardiography and hs-TnT and NT-pro-BNP for identifying patients receiving any diagnosis using CMR.MethodsWe included patients (n = 123) from the SMINC2 study who underwent same day CMR and echocardiography, at a median of 3 days after hospital admission for MINOCA. Normal echocardiography was defined as left ventricular ejection fraction ≥ 55%, absolute global longitudinal strain ≥ 17%, E/e′ ≤ 14, and no regional wall motion abnormalities. Logistic regression models were fitted to assess the probability of CMR diagnosis at increasing levels of hs-TnT and NT-pro-BNP.ResultsOf patients with a normal echocardiographic examination, 23/33 (70%) received a diagnosis using CMR. Pathological echocardiography identified patients with a diagnosis using CMR with a sensitivity of 77%, specificity 38%, positive predictive value 82%, and negative predictive value 30%, respectively. There was no level of hs-TnT or NT-pro-BNP below which a CMR diagnosis could be reliably excluded.ConclusionsThe majority of patients with MINOCA and a normal echocardiogram will receive a diagnosis by CMR. A CMR diagnosis was common even among patients with low levels of biomarkers. CMR should be recommended regardless of echocardiographic findings and hs-TnT or NT-pro-BNP levels in patients with MINOCA.
Bacterial Etiology of Urinary Tract Infections In patients treated at Kenyan Health Facilities And their resistance towards commonly used antibiotics
Authors: Kiiru Susan , Maina John , Katana Japhet , Mwaniki John , Asiimwe Benon B , Mshana Stephen E , Keenan Katherine , Gillespie Stephen H. , Stelling John , Kiiru John , Holden Matthew T G ,   HATUA Consortium
Published: October 2022

1.0AbstractBackgroundEvidence-based empirical antibiotic prescribing requires knowledge of local antimicrobial resistance patterns. The spectrum of pathogens and their susceptibility strongly influences guidelines for empirical therapies for urinary tract infections (UTI) management.ObjectiveThis study aimed to determine the prevalence of UTI causative bacteria and their corresponding antibiotic resistance profiles in in three counties of Kenya. Such data could be used to determine the optimal empirical therapy.MethodsIn this cross-sectional study, urine samples were collected from patients who presented with symptoms suggestive of UTI in the following healthcare facilities; Kenyatta National Hospital, Kiambu Hospital, Mbagathi, Makueni, Nanyuki, Centre for Microbiology Research, and Mukuru Health Centres. Urine cultures were done on Cystine Lactose Electrolyte Deficient (CLED) to isolate UTI bacterial etiologies, while antibiotic sensitivity testing was done using the Kirby-Bauer disk diffusion using CLSI guidelines and interpretive criteria.ResultsA total of 1,027(54%) uropathogens were isolated from the urine samples of 1898 participants. Staphylococcus spp. and Escherichia coli were the main uropathogens at 37.6% and 30.9 %, respectively. The percentage resistance to commonly used drugs for the treatment of UTI were as follows: trimethoprim (64%), sulfamethoxazole (57%), nalidixic acid(57%), ciprofloxacin (27%), amoxicillin-clavulanic acid (5%), and nitrofurantoin (9%) and cefixime (9%). Resistance rates to broad-spectrum antimicrobials, such as ceftazidime, gentamicin, and ceftriaxone, were 15%, 14%, and 11%, respectively. Additionally, the proportion of Multidrug-resistant (MDR) bacteria was 66%.ConclusionHigh resistance rates toward fluoroquinolones, sulfamethoxazole, and trimethoprim were reported. These antibiotics are commonly used drugs as they are inexpensive and readily available. Based on these findings, more robust standardised surveillance is needed to confirm the patterns observed while recognizing the potential impact of sampling biases on observed resistance rates.
For She had Eyes and Chose Preprints -– Social Media Impact, Citation and Publication rates of Ophthalmology preprints
Authors: Menshawey Rahma , Menshawey Esraa , Massoud Maryam 
Published: October 2022

AbstractBackgroundPreprinting, is the sharing of non-peer reviewed, unpublished scholarly manuscripts. Across many fields of medicine, an exponential rise of manuscripts being posted to preprint servers has been observed. This has exploded during the COVID19 pandemic where early dissemination of information was critical, or where COVID19 priority disrupted the publication dynamics and priorities in other areas. We examined the characteristics of ophthalmology related preprints in this study.MethodsWe searched the bioRxiv and medRxiv servers for preprints relating to field of ophthalmology. Preprints were screened by title and abstract to ensure they were related to the field of ophthalmology. Outcomes included number of tweets, upper bound followers of tweeters, number of citations, news outlets reports and dates posted/published. If a preprint was published the same outcomes were collected for the published version to allow for comparisons, as well as journal publisher and cite score.ResultsAfter screening, a total of 720 preprints met our inclusion criteria. 420 of the preprints went on to be published. The publication rate of the preprints was 58.3%. The median number of tweets received on preprints was 3.5, IQR 5.5. 98.75% of preprints were tweeted about. Citation rate was 40.14%. The average number of days from date posted on server to date published was 180.5±124 days. Regression analysis revealed that tweets as a preprint predicts tweets as a published article, P=0.0135. citations as a preprint predicts citations as a published article, P<0.001. The average cite score was 8.5±6.2 among those preprints that we published in journals. 16.66% of papers were published by Elsevier (n = 70). 3.19% of preprints were COVID19 related, with significant differences found between them and non-COVID19 preprints in terms of number of tweets and number of citations.ConclusionsOphthalmology preprints are increasing across preprint servers. This maybe to bypass publication times and allow early dissemination of work, as well as increase visibility and citations. We identified that preprint citations and tweets predict published version citation and tweets.
Severe COVID-19 is associated with fungal colonization of the nasopharynx and potent induction of IL-17 responses in the nasal epithelium
Authors: Ziegler Carly G. K. , Owings Anna H. , Miao Vincent N. , Navia Andrew W. , Tang Ying , Bromley Joshua D. , Lotfy Peter , Sloan Meredith , Laird Hannah , Williams Haley B. , George Micayla , Drake Riley S. , Pride Yilianys , Abraham George E. , Senitko Michal , Robinson Tanya O. , Lionakis Michail S. , Shalek Alex K. , Ordovas-Montanes Jose , Horwitz Bruce H. , Glover Sarah C. 
Published: October 2022

ABSTRACTRecent case reports and epidemiological data suggest fungal infections represent an under-appreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing (scRNA-seq) dataset characterizing the upper respiratory microenvironment during COVID-19, and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells. Our study, in agreement with findings from related human cohorts, demonstrated that a profound deficiency in host immunity, particularly in type I and type III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. We have now performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent detection ofCandidaspecies-derived transcripts within samples collected from the nasopharynx and trachea. Here, we present the clinical characteristics of these individuals, including confirmatory diagnostic testing demonstrating elevated serum (1, 3)-β-D-glucan and/or confirmed fungal culture of the predicted pathogen. Using matched single-cell transcriptomic profiles of these individuals’ respiratory mucosa, we identify epithelial immune signatures suggestive of IL-17 stimulation and anti-fungal immunity. Further, we observe significant expression of anti-fungal inflammatory cascades in the nasal and tracheal epithelium of all participants who went on to develop severe COVID-19, even among participants without detectable genetic material from fungal pathogens. Together, our data suggests that IL-17 stimulation – in part driven byCandidacolonization – and blunted type I/III interferon signaling represents a common feature of severe COVID-19 infection.
SARS-CoV-2 S1 Subunit Booster Vaccination Elicits Robust Humoral Immune Responses in Aged Mice
Authors: Kim Eun , Khan Muhammad S. , Ferrari Alessandro , Huang Shaohua , Sammartino Josè C. , Percivalle Elena , Kenniston Thomas W. , Cassaniti Irene , Baldanti Fausto , Gambotto Andrea 
Published: October 2022

AbstractCurrently approved COVID-19 vaccines prevent symptomatic infection, hospitalization, and death of the disease. However, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants raises concerns of reduced vaccine effectiveness and increased risk of infection. Repeated homologous booster in elderly individuals and immunocompromised patients is considered to solve severe form of disease caused by new SARS-CoV-2 variants but cannot protect completely against breakthrough infection. In our previous study we assessed the immunogenicity of an adenovirus-based vaccine expressing SARS-CoV-2-S1 (Ad5.S1) in mice, resulting in that a single immunization with Ad5.S1, via subcutaneously injection or intranasal delivery, induced robust humoral and cellular immune responses [1]. As a follow up study, here we showed that vaccinated mice had high titers of anti-S1 antibodies at one year after vaccination compared to PBS immunized mice. Furthermore, one booster dose of non-adjuvanted recombinant S1Beta (rS1Beta) subunit vaccine was effective in stimulating strong long-lived S1-specific immune responses and inducing significantly high neutralizing antibodies against the Wuhan, Beta, and Delta strain with 3.6- to 19.5-fold change increases. Importantly, the booster dose elicits cross-reactive antibody responses resulting in ACE2 binding inhibition against spike of SARS-CoV-2 variants (Wuhan, Alpha, Beta, Gamma, Delta, Zeta, Kappa, New York, India) as early as two-week post-boost injection, persisting over 28 weeks after a booster vaccination. Interestingly, levels of neutralizing antibodies were correlated with not only level of S1-binding IgG but also level of ACE2 inhibition in the before- and after-booster serum samples. Our findings show that S1 recombinant protein subunit vaccine candidate as a booster has potential to offer cross-neutralization against broad variants, and has important implications for vaccine control of new emerging breakthrough SARS-CoV-2 variants in elderly individuals primed with adenovirus-based vaccine like AZD1222 and Ad26.COV2.S.
Presence and Perceived Body Orientation Affect the Recall of Out-of-Sight Places in an Immersive Sketching Experiment
Authors: Grochulla Banafsheh , Mallot Hanspeter A. 
Published: October 2022

AbstractThe orientation of sketch maps of remote but familiar city squares produced from memory has been shown to depend on the distance and airline direction from the production site to the remembered square (position dependent recall, Röhrich, Hardiess, & Mallot, 2014). Here, we present a virtual reality version of the original experiment and additionaly study the role of body orientation. Three main points can be made: First, “immersive sketching” is a novel and useful paradigm in which subjects sketch maps live on paper while being immersed in virtual reality. Second, the original effect of position dependent recall was confirmed, indicating that the sense of presence generated in a virtual environment suffices to bias the imagery of distant places. Finally, the orientation of the produced sketch maps depended also on the body orientation of the subjects. At each production site, body orientation was controlled by varying the position of the life feed in the virtual environment such that subjects had to turn towards the prescribed direction. Position dependent recall is strongest if subjects are aligned with the airline direction to the target and virtually goes away if they turn in the opposite direction.
iPSC Motor Neurons with Familial ALS Mutations Capture Gene Expression Changes in Postmortem Sporadic ALS Motor Neurons
Authors: Held Aaron , Adler Michelle , Marques Christine , Kavuturu Amey S. , Quadros Ana R.A.A. , Ndayambaje I. Sandra , Lara Erika , Ward Michael , Lagier-Tourenne Clotilde , Wainger Brian J. 
Published: October 2022

AbstractMotor neuron degeneration, the defining feature of ALS, is a primary example of cell-type specificity in neurodegenerative diseases. Using isogenic pairs of iPSCs harboring different familial ALS mutations, we assess the capacity of iPSC-derived spinal motor neurons, sensory neurons, astrocytes, and superficial cortical neurons to capture disease features including transcriptional and splicing dysregulation observed in human post-mortem neurons. At surprisingly early time points, differentially regulated genes in iPSC-derived spinal motor neurons, but not other cell types, overlap with one-third of the differentially regulated genes in laser-dissected motor neurons from postmortem spinal cords. The extent of dysregulation correlates well between iPSC-derived andbona fidespinal motor neurons. In iPSC-derived spinal motor neurons, but not other derived cell types, we detect downregulation of genes affected by TDP-43-dependent aberrant splicing. This reduction takes place exclusively within genotypes known to involve TDP-43 pathology and occurs without evidence of TDP-43 mislocalization or protein level alteration.