bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary metabolite profiling identifies biomarkers for risk of progression of diabetic nephropathy in 2,670 individuals with type 1 diabetes
Authors: Mutter Stefan , Valo Erkka , Aittomäki Viljami , Nybo Kristian , Raivonen Lassi , Thorn Lena M , Forsblom Carol , Sandholm Niina , Würtz Peter , Groop Per-Henrik 
Published: October 2020

AbstractAimsThis study examines associations between 51 urinary metabolites and risk of progression of diabetic nephropathy in individuals with type 1 diabetes by employing an automated nuclear magnetic resonance (NMR) metabolomics technique suitable for large-scale urine sample collections.MethodsFor 2,670 individuals with type 1 diabetes from the FinnDiane Study, we collected 24-hour urine samples and measured metabolite concentrations by NMR. Individuals were followed for 9.0 ± 5.0 years until their first sign of progression of diabetic nephropathy, end-stage kidney disease or study end. Cox regression analyses were performed on the entire study population (overall progression), on 1,999 individuals with normoalbuminuria and 347 individuals with macroalbuminuria at baseline.ResultsSeven urinary metabolites were associated with overall progression after adjustment for baseline albuminuria and chronic kidney disease stage (p < 8 × 10-4): Leucine (hazard ratio 1.47, 95% confidence interval [1.30, 1.66] per 1-SD creatinine-scaled metabolite concentration), valine (1.38 [1.22, 1.56]), isoleucine (1.33 [1.18, 1.50]), pseudouridine (1.25 [1.11, 1.42]), threonine (1.27 [1.11, 1.46]) and citrate (0.84 [0.75, 0.93]). 2-hydroxyisobutyrate was associated with overall (1.30 [1.16, 1.45]) and also progression from normoalbuminuria (1.56 [1.25, 1.95]). Six amino acids and pyroglutamate were associated with progression from macroalbuminuria.ConclusionsBranched-amino acids and other urinary metabolites were associated with the progression of diabetic nephropathy on top of baseline albuminuria and chronic kidney disease. We found differences in associations for overall progression and progression from normo- and macroalbuminuria. These novel biomarker discoveries illustrate the utility of analysing urinary metabolites in entire population cohorts.Significance StatementIndividuals with type 1 diabetes are vulnerable to diabetic nephropathy and would benefit from earlier detection of disease progression. Urinary metabolites as a direct read-out of kidney function are potential progression markers. However, analytical tools to quantify a broad panel of urinary metabolites at large scale and low cost are lacking. Recent developments in nuclear magnetic resonance address this need. This study in 2,670 individuals with type 1 diabetes identified ten urinary metabolites associated with progression of diabetic nephropathy. Importantly, different albuminuria categories had different urinary profiles: 2-hydroxyisobutyrate was associated with progression from normoalbuminuria and branched-chain amino acids with progression from macroalbuminuria. These results provide new potential biomarkers and highlight the potential of analysing urinary metabolites on a larger scale.
Clinico-laboratory profile, intensive care needs, treatment details, and outcome of Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): A systematic review and Meta-analysis
Authors: Williams Vijai , Dash Nabaneeta , Suthar Renu , Mohandoss Vichithra , Jaiswal Nishant , Kavitha TK , Nallasamy Karthi , Angurana Suresh Kumar 
Published: October 2020

AbstractObjectivesTo synthesize the current data on clinico-laboratory features, intensive care needs, treatment, and outcome of Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C).Data SourcesArticles published in PubMed, Web of Science, Scopus, Google Scholar, and WHO COVID-19 research database, CDC database, and Cochrane COVID-19 study register between 1stDecember 2019 to 10thJuly 2020.Study SelectionObservational studies involving patients ≤21 years with PIMS-TS or MIS-C, that reported the clinico-laboratory features, intensive care needs, treatment, and outcome.Data ExtractionThe search identified 422 citations and finally 18 studies with 833 participants were included and pooled estimate was calculated for parameters of interest utilising random effect model.Data SynthesisThe median age was 9 (8-11) years. Fever, gastrointestinal symptoms, rash, conjunctival injection, and respiratory symptoms were common clinical features. Majority had positive SARS-CoV-2 antibody test and only 1/3rdhad RT-PCR positive. The commonest laboratory abnormalities were elevated CRP, D-dimer, procalcitonin, BNP, fibrinogen, ferritin, troponin, and IL-6; and lymphopenia, hypoalbuminemia, and thrombocytopenia. The cardiovascular complications included shock (65%), myocardial dysfunction (61%), myocarditis (65%), and coronary artery abnormalities (39%). Three-fourth children required admission in PICU for mechanical ventilation (25%) and vasoactive drugs (61%). The common treatment provided was IVIG (82%), steroids (54%), antiplatelet drugs (64%), and anticoagulation (51%). The mortality was low (n=13).ConclusionFever, gastrointestinal and mucocutaneous symptoms, cardiac dysfunction, shock, and hyperinflammation are common manifestations of PIMS-TS or MIS-C. The short-term outcome is good with supportive intensive care and immunomodulatory treatment.
Epidemiological, clinical, and laboratory findings for patients of different age groups with confirmed coronavirus disease 2019 (COVID-19) in a hospital in Saudi Arabia
Authors: Ibrahim Mutasim E. , AL-Aklobi Obaid S. , Abomughaid Mosleh M. , Al-Ghamdi Mushabab A. 
Published: October 2020

AbstractBackgroundAlthough the coronavirus disease 2019 (COVID-19) pandemic continues to rage worldwide, clinical and laboratory studies of this disease have been limited in many countries. We investigated the epidemiologic, clinical, and laboratory findings of COVID-19 infected patients to identify the effective indicators correlated with the disease.MethodsA retrospective study was conducted at King Abdullah Hospital in Bisha Province, Saudi Arabia, from March 20 to June 30, 2020. Patients of different age groups were confirmed as having COVID-19 infection using a real-time polymerase chain reaction. The demographic, clinical, and laboratory data of the patients were statistically analyzed.ResultsOf the 137 patients, 88 were male and 49 were female, with a mean age of 49.3 years (SD±18.4). The patients were elderly (n=29), adults (n=103), and children (n=5). Of these, 54 (39.4%) had comorbidities, 24% were admitted to the intensive care unit (ICU), and 12 (8.8%) died. On admission, the main clinical manifestations were fever (82.5%), cough (63.5%), shortness of breath (24.8%), chest pain (19.7%), and fatigue (18.2%).In all patients, increased neutrophils and decreased lymphocytes were observed. Patients’ lactate dehydrogenase (LDH) was elevated. C-reactive protein (CRP) was elevated in 46.7%, D-dimer in 41.6%, and the erythrocyte sedimentation rate (ESR) in 39.4% of patients. The elderly showed higher neutrophil (p=0.003) and lower lymphocyte (p=0.001) counts than adults and children. Glucose, creatine kinase-MB, LDH, bilirubin, D-dimer, and ESR were significantly higher in the elderly than in the adults. The COVID-19 death group had a higher leucocyte count (p = 0.043), and higher urea (p=0.025) and potassium (p=0.026) than the recovered group but had a lower hemoglobin concentration (p=0.018). A significant association was determined between COVID-19 death (χ2(1)=17.751, p<0.001), and the presence of cardiovascular disease (χ2(1)=17.049, p<0.001), hypertension (χ2(1)=7.659, p=0.006), renal failure (χ2(1)=4.172, p<0.04), old age (t(135) = 4.747, p <0.001), and ICU admission (χ2(1) = 17.751 (1), p<0.001).ConclusionsThe common symptoms found in this study could be useful for identifying potential COVID-19 patients. Investigating some of the laboratory and clinical parameters could help assess the disease progression, risk of mortality, and follow up patients who could progress to a fatal condition.
Spatial autocorrelation and the dynamics of the mean center of COVID-19 infections in Lebanon
Authors: El Deeb Omar 
Published: October 2020

AbstractIn this paper we study the spatial spread of the COVID-19 infection in Lebanon. We inspect the spreading of the daily new infections across the 26 administrative districts of the country, and implement Moran’s I statistics in order to analyze the tempo-spatial clustering of the infection in relation to various variables parameterized by adjacency, proximity, population, population density, poverty rate and poverty density, and we find out that except for the poverty rate, the spread of the infection is clustered and associated to those parameters with varying magnitude for the time span between July (geographic adjacency and proximity) or August (population, population density and poverty density) through October. We also determine the temporal dynamics of geographic location of the mean center of new and cumulative infections since late March. The results obtained allow for regionally and locally adjusted health policies and measures that would provide higher levels of public health safety in the country.
In vivoprogressive degeneration of Huntington’s disease patient-derived neurons reveals human-specific pathological phenotypes
Authors: Miguez Andrés , Fernández-García Sara , Monguió-Tortajada Marta , Bombau Georgina , Galofré Mireia , García-Bravo María , Vila Cristina , Sanders Phil , Fernández-Medina Helena , Poquet Blanca , Salado-Manzano Cristina , Roura Santiago , Alberch Jordi , Segovia José Carlos , Allen Nicholas D. , Borràs Francesc E. , Canals Josep M. 
Published: October 2020

AbstractResearch on neurodegenerative disorders has been hampered by the limited access to patients’ brain tissue and the absence of relevant physiological models with human neurons, accounting for the little success of clinical trials. Moreover, post-mortem samples cannot provide a detailed picture of the complex pathological mechanisms taking place throughout the course of the disease. This holds particularly true for Huntington’s disease (HD), an incurable inherited brain disorder marked by a massive striatal degeneration due to abnormal accumulation of misfolded huntingtin protein. To characterize progressive human neurodegenerationin vivo, we transplanted induced pluripotent stem cell-derived human neural progenitor cells (hNPCs) from control (CTR-hNPCs) and HD patients (HD-hNPCs) into the striatum of neonatal wild-type mice. Implanted human cells were examined by immunohistochemistry and electron microscopy, and chimeric mice were subjected to behavioral testing. Most grafted hNPCs differentiated into striatal neurons that sent axonal projections to their natural targets and established synaptic connections within the host basal ganglia circuitry. HD-hNPCs first showed developmental abnormalities characterized by an increased proliferation and accelerated medium spiny neuron (MSN) differentiation, mimicking the initial striatal hypertrophy of child mutant huntingtin (mHTT) carriers. HD human striatal neurons progressively developed mHTT oligomers and aggregates, which primarily targeted mitochondria, endoplasmic reticulum and nuclear membrane to cause structural alterations. Five months after transplantation, selective death of human MSNs and striatal degeneration altered mouse behavior, suggesting disease propagation to non-mutated host cells. Histological analysis and co-culture experiments revealed that HD-hNPCs secreted extracellular vesicles containing soluble mHTT oligomers, which were internalized by mouse striatal neurons triggering cell death. Finally,in vivopharmacological inhibition of the exosomal secretory pathway through sphingosine-1 phosphate receptor functional antagonism, limited the spreading of apoptosis within the host striatum. Our findings cast new light on human neurodegeneration, unveiling cell and non-cell autonomous mechanisms that drive HD progression in patients.
Online information on face masks in Italian and English websites: deficiencies and responsibilities of search engines
Authors: Meta Shaily , Ghezzi Daria , Catalani Alessia , Vanzolini Tania , Ghezzi Pietro 
Published: October 2020

AbstractCountries have major differences in the acceptance of face mask use for the prevention of COVID-19. We analyzed 450 webpages returned by searching the string “are face masks dangerous” in Italy, the UK and the USA using three search engines (Bing, Duckduckgo and Google). The majority (64-79%) were pages from news outlets, with few (2-6%) pages from government and public health agencies. Webpages with a positive stance on masks were more frequent in English (50%) than in Italian (36%), and those with a negative stance were more frequent in Italian (28% vs. 19% in English). Google returned the highest number of mask-positive pages and Duckduckgo the lowest. Google also returned the lowest number of pages mentioning conspiracy theories and Duckduckgo the highest. Webpages in Italian scored lower than those in English in transparency (reporting authors, their credentials and backing the information with references). When issues about the use of face masks were analyzed, mask effectiveness was the most discussed followed by hypercapnia (accumulation of carbon dioxide), contraindication in respiratory disease, and hypoxia, with issues related to their contraindications in mental health conditions and disability mentioned by very few pages. This study suggests that: 1) public health agencies should increase their web presence in providing correct information on face masks; 2) search engines should improve the information quality criteria in their ranking; 3) the public should be more informed on issues related to the use of masks and disabilities, mental health and stigma arising for those people who cannot wear masks.
Neuronal and synaptic plasticity in the visual thalamus in mouse models of glaucoma
Authors: Van Hook Matthew J. , Monaco Corrine , Smith Jennie C. 
Published: October 2020

AbstractHomeostatic plasticity plays important roles in regulating synaptic and intrinsic neuronal function to stabilize output following perturbations to circuit activity. In glaucoma, a neurodegenerative disease of the visual system commonly associated with elevated intraocular pressure (IOP), early disease is associated with altered synaptic inputs to retinal ganglion cells (RGCs), changes in RGC intrinsic excitability, and deficits in optic nerve transport and energy metabolism. These early functional changes can precede RGC degeneration and are likely to alter RGC outputs to their target structures in the brain and thereby trigger homeostatic changes in synaptic and neuronal properties in those brain regions. In this study, we sought to determine whether and how neuronal and synaptic function is altered in the dorsal lateral geniculate nucleus (dLGN), an important RGC projection target in the thalamus, and how functional changes relate to IOP. We accomplished this using patch-clamp recordings from thalamocortical (TC) relay neurons in the dLGN in two established mouse models of glaucoma – the DBA/2J (D2) genetic mouse model and an inducible glaucoma model with intracameral microbead injections to elevate IOP. We found that the intrinsic excitability of TC neurons was enhanced in D2 mice and these functional changes were mirrored in recordings of TC neurons from microbead-injected mice. Notably, many neuronal properties were correlated with IOP in older D2 mice, but not younger D2 mice or microbead-injected mice. The frequency of miniature excitatory synaptic currents (mEPSCs) was reduced in both ages of D2 mice, and vGlut2 staining of RGC synaptic terminals was reduced in an IOP-dependent manner in older D2 mice. Among D2 mice, functional changes observed in younger mice without elevated IOP were distinct from those observed in older mice with elevated IOP and RGC degeneration, suggesting that glaucoma-associated changes to neurons in the dLGN might represent a combination of stabilizing/homeostatic plasticity at earlier stages and pathological dysfunction at later stages.
Geometric and Topological Approaches to Shape Variation inGinkgoLeaves
Authors: Hang Haibin , Bauer Martin , Mio Washington , Mander Luke 
Published: October 2020

AbstractLeaf shape is a key plant trait that varies enormously. The diversity of leaf shape, and the range of applications for data on this trait, requires frequent methodological developments so that researchers have an up-to-date toolkit with which to quantify leaf shape. We generated a dataset of 468 leaves produced byGinkgo biloba, and 24 fossil leaves produced by evolutionary relatives of extantGinkgo. We quantified the shape of each leaf by developing a geometric method based on elastic curves and a topological method based on persistent homology. Our geometric method indicates that shape variation in our modern sample is dominated by leaf size, furrow depth, and the angle of the two lobes at the base of the leaf that is also related to leaf width. Our topological method indicates that shape variation in our modern sample is dominated by leaf size and furrow depth. We have applied both methods to modern and fossil material: the methods are complementary, identifying similar primary patterns of variation, but also revealing some different aspects of morphological variation. Our topological approach distinguishes long-shoot leaves from short-shoot leaves and both methods indicate that leaf shape influences or is at least related to leaf area.
The anti-mycobacterial activity ofArtemisia annuaL is based on deoxyartemisinin and artemisinic acid
Authors: Bhowmick Sumana , Baptista Rafael , Fazakerley David , Whatley Kezia E. , Hoffmann Karl F. , Shen Jianying , Mur Luis A. J. 
Published: October 2020

AbstractThe discovery of antimalarial artemisinin fromArtemisia annuaL. is an example of how Traditional Chinese Medicine (TCM) may be exploited to meet a recognized need. In this study, we systemically investigatedA. annuaL. for its antimicrobial activity and assessed it as a source of bioactive natural products for anti-mycobacterial activity.We used a silica gel column to perform antimicrobial activity-guided purification of theA. annualeaf, whose identity was confirmed byrbcLDNA barcoding, and used UHPLC-HRMS and NMR to elucidate the structure of purified active compounds. The antimicrobial activity of crude extracts, isolated compounds and the control artemisinin (Apollo Scientific Ltd) was assessed againstEscherichia coli,Pseudomonas aeruginosa,Staphylococcus aureus, methicillin-resistantStaphylococcus aureus(MRSA),Mycobacterium smegmatisstrains by serial micro dilution method (31.25-1000 μg/mL). The isolated compounds were tested for synergistic effects against mycobacterium.Bioactive compounds were purified and identified as deoxyartemisinin and artemisinic acid. Artemisinic acid (MIC 250 μg/mL) was more effective in comparison to deoxyartemisinin (MIC 500 μg/mL) and artemisinin (MIC 1000 μg/mL) againstM. smegmatis. We used a molecular docking approach to investigate the interactions between selected anti-mycobacterial compounds and proteins involved in vital physiological functions inM. tuberculosis, namelyMtPks13, MtPknB, MtPanK, MtKasA, MtInhA andMtDprE1 and found artemisinic acid showed docking scores superior to the control inhibiters forMtKasA, suggesting it to be a potential nick for furtherin vitrobiological evaluation and anti-TB drug design.
Latent Evolutionary Signatures: A General Framework for Analyzing Music and Cultural Evolution
Authors: Warrell Jonathan , Salichos Leonidas , Gancz Michael , Gerstein Mark B. 
Published: October 2020

AbstractCultural processes of change bear many resemblances to biological evolution. The underlying units of non-biological evolution have, however, remained elusive, especially in the domain of music. Here, we introduce a general framework to jointly identify underlying units and their associated evolutionary processes. We model musical styles and principles of organization in dimensions such as harmony and form as following an evolutionary process. Furthermore, we propose that such processes can be identified by extracting latent evolutionary signatures from musical corpora, analogous to identifying mutational signatures in genomics. These signatures provide a latent embedding for each song or musical piece. We develop a deep generative architecture for our model, which can be viewed as a type of Variational Autoencoder with an evolutionary prior constraining the latent space; specifically, the embeddings for each song are tied together via an energy-based prior, which encourages songs close in evolutionary space to share similar representations. As illustration, we analyze songs from the McGill Billboard dataset. We find frequent chord transitions and formal repetition schemes and identify latent evolutionary signatures related to these features. Finally, we show that the latent evolutionary representations learned by our model outperform non-evolutionary representations in such tasks as period and genre prediction.
Alignment-free methods for polyploid genomes: quick and reliable genetic distance estimation
Authors: VanWallendael Acer , Alvarez Mariano 
Published: October 2020

AbstractPolyploid genomes pose several inherent challenges to population genetic analyses. While alignment-based methods are fundamentally limited in their applicability to polyploids, alignment-free methods bypass most of these limits. We investigated the use ofMash, a k-mer analysis tool that uses the MinHash method to reduce complexity in large genomic datasets, for basic population genetic analyses of polyploid sequences. We measured the degree to whichMashcorrectly estimated pairwise genetic distance in simulated diploid and polyploid short-read sequences with various levels of missing data.Mash-based estimates of genetic distance were comparable to alignment-based estimates, and were less impacted by missing data. We also usedMashto analyze publicly available short-read data for three polyploid and one diploid species, then comparedMashresults to published results. For both simulated and real data,Mashaccurately estimated pairwise genetic differences for polyploids as well as diploids as much as 476 times faster than alignment-based methods, though we found thatMashgenetic distance estimates could be biased by per-sample read depth.Mashmay be a particularly useful addition to the toolkit of polyploid geneticists for rapid confirmation of alignment-based results and for basic population genetics in reference-free systems with poor quality DNA.