bluuebunny/crossref_metadata_2025_split huggingface dataset:
Agreement of Corneal Endothelial Cell Analysis Between Konan-Noncon Robo SP-6000 and Tomey EM-3000 Specular Microscopes in Healthy Subjects
Authors: Jbara Doha , Achiron Asaf , Antman Gal , Buhbut Ortal , Hecht Idan , Tuuminen Raimo , Bahar Irit , Elbaz Uri 
Published: May 2020

Purpose:
To compare corneal endothelium parameters taken by two common noncontact specular microscopes in healthy subjects.

Methods:
Healthy participants visiting the outpatient eye clinic at the Rabin Medical Center, Petah Tikva, Israel, were recruited prospectively. All participants underwent three consecutive corneal endothelial cell photographs with both the Konan-Noncon Robo SP-6000 and the Tomey EM-3000 specular microscopes. Endothelial cell density (ECD) was evaluated using the manual center technique in both machines. Bland–Altman graphs were used to assess the agreement between the devices, and intraclass correlation coefficient (ICC) served to assess intraobserver variability for each device.

Results:
Recruited were 49 healthy subjects with a mean age of 48.9±15.6 years, 49 right eyes were included. The mean ECD was comparable between the Tomey EM-3000 and the Konan-Noncon Robo SP-6000 (2,713.2±242.4 vs. 2,700.8±300.5 cells/mm2, respectively, P=0.47) with a mean difference of 12.4 cells/mm2 (0.67%), a mean ECD absolute difference of 93.3 cells/mm2, and low 95% limits of agreement of −222.0 to +246.9 cells/mm2. A folded empirical distribution function curve showed that all differences fell within 525.4 cells/mm2, centered around a median of 13.3 cells/mm2. Intraclass correlation coefficient was high for both the Konan-Noncon Robo SP-6000 (0.93, 95% confidence interval [CI]: 0.89–0.95) and the Tomey EM-3000 (0.88, 95% CI: 0.82–0.93).

Conclusions:
The difference in endothelial cell measurements between the Konan SP-6000 and the Tomey EM-3000 specular microscopes through the center and the L-count analyzing techniques, respectively, is clinically small and not statistically significant. Nevertheless, caution should be taken when used interchangeably because ECD difference between the two machines can be as high as 525.4 cells/mm2.
Adolescent Trichomonas vaginalis in a High-burdened Region of the Southern United States
Authors: Nolan Melissa S. , Lynn Mary K. , Lacroix Robin , Brownlee Josh , Kelly Desmond 
Published: May 2020

Background
We evaluated the clinical management and risk factors for Trichomonas vaginalis–positive adolescents in upstate South Carolina.

Methods
An Epic electronic medical record report was generated to identify any physician-ordered T. vaginalis test from February 2016 to December 2017 for patients aged 12 to 18 years within the Prisma Health Upstate system. Utilizing a case-control study design of patients with a documented T. vaginalis diagnostic result, we reviewed records of patients with physician-ordered T. vaginalis tests for demographics, clinical disease course, sexually transmitted infection test results, treatment order and dosage, infection risk factors, comorbidities, pregnancy term, and neonatal birth outcomes.

Results
Of 789 male and female adolescents with physician-ordered T. vaginalis tests, 44% had a documented result. Of those with a document test result, 13% were T. vaginalis positive. Cases (n = 45) and randomly selected negative controls (n = 45) were all girls. Cases were more likely to be African American, symptomatic, and present with vaginal discharge, pain, and vulvar itch. T. vaginalis patients were more likely to have documented histories of chlamydia (P < 0.0001) and gonorrhea (P = 0.0191), with 18% having concurrent triple infections (T. vaginalis, chlamydia, and gonorrhea). All 26 pregnant girls with T. vaginalis delivered full-term, healthy infants.

Conclusions
We identified a disproportionally high burden of T. vaginalis infection, with an alarmingly high rate of triple infections, among a population of suspected high-risk adolescents. Our results indicate the need to clarify infection prevalence, develop pediatrician-focused education campaigns, and elucidate potentially modifiable risk factors for these high-risk patients.
Determining standardized causes of death of infants, children, and adolescents living with HIV in Asia
Authors: Sohn Annette H. , Lumbiganon Pagakrong , Kurniati Nia , Lapphra Keswadee , Law Matthew , Do Viet C. , Van Nguyen Lam , Truong Khanh H. , Wati Dewi K. , Ounchanum Pradthana , Puthanakit Thanyawee , Sudjaritruk Tavitiya , Ly Penh S. , Yusoff Nik K.N. , Fong Sieu M. , Mohamed Thahira J. , Nallusamy Revathy , Kumarasamy Nagalingaswaran , Kariminia Azar 
Published: May 2020

Objective:
To implement a standardized cause of death reporting and review process to systematically disaggregate causes of HIV-related deaths in a cohort of Asian children and adolescents.

Design:
Death-related data were retrospectively and prospectively assessed in a longitudinal regional cohort study.

Methods:
Children under routine HIV care at sites in Cambodia, India, Indonesia, Malaysia, Thailand, and Vietnam between 2008 and 2017 were followed. Causes of death were reported and then independently and centrally reviewed. Predictors were compared using competing risks survival regression analyses.

Results:
Among 5918 children, 5523 (93%; 52% male) had ever been on combination antiretroviral therapy. Of 371 (6.3%) deaths, 312 (84%) occurred in those with a history of combination antiretroviral therapy (crude all-cause mortality 9.6 per 1000 person-years; total follow-up time 32 361 person-years). In this group, median age at death was 7.0 (2.9–13) years; median CD4+ cell count was 73 (16–325) cells/μl. The most common underlying causes of death were pneumonia due to unspecified pathogens (17%), tuberculosis (16%), sepsis (8.0%), and AIDS (6.7%); 12% of causes were unknown. These clinical diagnoses were further grouped into AIDS-related infections (22%) and noninfections (5.8%), and non-AIDS-related infections (47%) and noninfections (11%); with 12% unknown, 2.2% not reviewed. Higher CD4+ cell count and better weight-for-age z-score were protective against death.

Conclusion:
Our standardized cause of death assessment provides robust data to inform regional resource allocation for pediatric diagnostic evaluations and prioritization of clinical interventions, and highlight the continued importance of opportunistic and nonopportunistic infections as causes of death in our cohort.
COVID 19: Real-time Forecasts of confirmed cases, active cases, and health infrastructure requirements for India and its states using the ARIMA model
Authors: Tyagi Rishabh , Bramhankar Mahadev , Pandey Mohit , Kishore M 
Published: May 2020

AbstractBackgroundCOVID-19 is an emerging infectious disease which has been declared a Pandemic by the World Health Organization (WHO) on 11th March 2020. The Indian public health care system is already overstretched, and this pandemic is making things even worse. That is why forecasting cases for India is necessary to meet the future demands of the health infrastructure caused due to COVID-19.ObjectiveOur study forecasts the confirmed and active cases for COVID-19 until July mid, using time series Autoregressive Integrated Moving Average (ARIMA) model. Additionally, we estimated the number of isolation beds, Intensive Care Unit (ICU) beds and ventilators required for the growing number of COVID-19 patients.MethodsWe used ARIMA model for forecasting confirmed and active cases till the 15th July. We used time-series data of COVID-19 cases in India from 14th March to 22nd May. We estimated the requirements for ICU beds as 10%, ventilators as 5% and isolation beds as 85% of the active cases forecasted using the ARIMA model.ResultsOur forecasts indicate that India will have an estimated 7,47,772 confirmed cases (95% CI: 493943, 1001601) and 296,472 active cases (95% CI:196820, 396125) by 15th July. While Maharashtra will be the most affected state, having the highest number of active and confirmed cases, Punjab is expected to have an estimated 115 active cases by 15th July. India needs to prepare 2,52,001 isolation beds (95% CI: 167297, 336706), 29,647 ICU beds (95% CI: 19682, 39612), and 14,824 ventilator beds (95% CI: 9841, 19806).ConclusionOur forecasts show an alarming situation for India, and Maharashtra in particular. The actual numbers can go higher than our estimated numbers as India has a limited testing facility and coverage.
Diagnostic power of chest CT for COVID-19: to screen or not to screen
Authors: De Smet K. , De Smet D. , Demedts I. , Bouckaert B. , Ryckaert T. , Laridon E. , Heremans B. , Vandenbulcke R. , Gryspeerdt S. , Martens G.A. 
Published: May 2020

Structured abstractBackgroundchest CT is increasingly used for COVID-19 screening in healthcare systems with limited SARS-CoV-2 PCR capacity. Its diagnostic value was supported by studies with methodological concerns and its use is controversial. Here we investigated its potential to diagnose COVID-19 in symptomatic patients and to screen asymptomatic patients in a prospective study with minimal selection bias.MethodsFrom March 19, 2020 to April 20, 2020 we performed parallel SARS-CoV-2 PCR and CT with categorization of COVID-19 suspicion by CO-RADS, in 859 patients with COVID-19 symptoms and 1138 controls admitted to the hospital for COVID-19 unrelated medical urgencies. CT-CORADS was categorized on a 5-point scale from 1 (very low suspicion) to 5 (very high suspicion). AUC under ROC curve were calculated in symptomatic versus asymptomatic patients to predict positive SARS-CoV-2 positive PCR and likelihood ratios for each CO-RADS score were used for rational selection of diagnostic thresholds.FindingsCT-CORADS had significant (P<0.0001) diagnostic power in both symptomatic (AUC=0.891) and asymptomatic (AUC=0.700) patients hospitalized during SARS-CoV-2 peak prevalence. In symptomatic patients (41.7% PCR+), CO-RADS ≥ 3 detected positive PCR with high sensitivity (89.1%) and 72.5% specificity. In asymptomatic patients (5.3% PCR+), a CO-RADS score ≥ 3 detected SARS-CoV-2 infection with low sensitivity (45.0%) but high specificity (88.8%).InterpretationCT-CORADS has meaningful diagnostic power in symptomatic patients, supporting its application for time-sensitive triage. Sensitivity in asymptomatic patients is insufficient to justify its use as screening approach. Incidental detection of CO-RADS ≥ 3 in asymptomatic patients should trigger reflex testing for respiratory pathogens.
Plasma concentration and safety of lopinavir/ritonavir in patients with Covid-19: a short communication
Authors: Chouchana Laurent , Boujaafar Sana , Gana Ines , Laure-Hélène  , Regard Lucile , Legendre Paul , Azoulay Celia , Canouï Etienne , Zerbit Jeremie , Carlier Nicolas , Terrier Benjamin , Kernéis Solen , Batista Rui , Treluyer Jean-Marc , Zheng Yi , Benaboud Sihem 
Published: May 2020

ABSTRACTBackgroundLopinavir/ritonavir has been proposed as off-label treatment for Covid-19, although efficacy have not been proven. It has previously been shown that lopinavir plasma concentration is dramatically increased in inflammatory settings. As Covid-19 may be associated with major inflammation, assessing lopinavir plasma concentration and its safety in Covid-19 patients is essential.MethodsReal-world Covid-19 experience based on a retrospective study.ResultsOf 31 patients treated by lopinavir/ritonavir for Covid-19, we observed very high lopinavir plasma concentrations, increased of 4.6-fold (IQR, 3.6-6.2) with regards to average plasma concentrations in HIV. All except one patient were above the upper limit of the concentration ranges of HIV treatment. About one over four to five patients prematurely stopped treatment mainly secondary an adverse drug reaction related to hepatic or gastrointestinal disorders.ConclusionLopinavir plasma concentrations in patients with moderate to severe Covid-19 were higher than expected, associated with the occurrence of hepatic or gastrointestinal adverse drug reactions. However, owing that high plasma concentration may be required for in vivo antiviral activity against SARS-CoV-2 as suggested by previous studies, it appears that, in the absence of adverse drug reaction, lopinavir dosage should not be reduced. Cautious is necessary as off-label use can be associated with a new drug safety profile.
Deep learning the collisional cross sections of the peptide universe from a million training samples
Authors: Meier Florian , Köhler Niklas D. , Brunner Andreas-David , Wanka Jean-Marc H. , Voytik Eugenia , Strauss Maximilian T. , Theis Fabian J. , Mann Matthias 
Published: May 2020

ABSTRACTThe size and shape of peptide ions in the gas phase are an under-explored dimension for mass spectrometry-based proteomics. To explore the nature and utility of the entire peptide collisional cross section (CCS) space, we measure more than a million data points from whole-proteome digests of five organisms with trapped ion mobility spectrometry (TIMS) and parallel accumulation – serial fragmentation (PASEF). The scale and precision (CV <1%) of our data is sufficient to train a deep recurrent neural network that accurately predicts CCS values solely based on the peptide sequence. Cross section predictions for the synthetic ProteomeTools library validate the model within a 1.3% median relative error (R > 0.99). Hydrophobicity, position of prolines and histidines are main determinants of the cross sections in addition to sequence-specific interactions. CCS values can now be predicted for any peptide and organism, forming a basis for advanced proteomics workflows that make full use of the additional information.
The choices we make and the impacts they have: Machine learning and species delimitation in North American box turtles (Terrapenespp.)
Authors: Martin Bradley T. , Chafin Tyler K. , Douglas Marlis R. , Placyk John S. , Birkhead Roger D. , Phillips Chris A. , Douglas Michael E. 
Published: May 2020

AbstractModel-based approaches that attempt to delimit species are hampered by computational limitations as well as the unfortunate tendency by users to disregard algorithmic assumptions. Alternatives are clearly needed, and machine-learning (M-L) is attractive in this regard as it functions without the need to explicitly define a species concept. Unfortunately, its performance will vary according to which (of several) bioinformatic parameters are invoked. Herein, we gauge the effectiveness of M-L-based species-delimitation algorithms by parsing 64 variably-filtered versions of a ddRAD-derived SNP dataset collected from North American box turtles (Terrapenespp.). Our filtering strategies included: (A) minor allele frequencies (MAF) of 5%, 3%, 1%, and 0% (=none), and (B) maximum missing data per-individual/per-population at 25%, 50%, 75%, and 100% (=no filtering). We found that species-delimitation via unsupervised M-L impacted the signal-to-noise ratio in our data, as well as the discordance among resolved clades. The latter may also reflect biogeographic history, gene flow, incomplete lineage sorting, or combinations thereof (as corroborated from previously observed patterns of differential introgression). Our results substantiate M-L as a viable species-delimitation method, but also demonstrate how commonly observed patterns of phylogenetic discordance can seriously impact M-L-classification.
Individual differences in spatial learning are correlated across cognitive tasks but not associated with stress response behaviour in the Trinidadian guppy
Authors: Prentice Pamela M. , Mnatzaganian Chloe , Houslay Thomas M. , Thornton Alex , Wilson Alastair J. 
Published: May 2020

AbstractCognition is vital for carrying out behaviours required for survival and reproduction. In animals, we now know that cognitive performance varies not just among species, but also among individuals within populations. While this variation is a prerequisite for contemporary natural selection, it is also true that selection does not act on traits in isolation. The extent to which cognitive traits covary with other aspects of phenotype (e.g. personality traits) is therefore expected to be an important factor in shaping evolutionary dynamics. Here we adopt a multivariate approach to test for spatial learning ability in a captive population of male Trinidadian guppies (Poecilia reticulata), and ask whether differences in cognitive performance are associated with (repeatable) differences in stress response behaviour. We focus on stress response for two reasons. First, functional links between cognitive traits and ‘stress coping style’ have been hypothesised. Second, individual-level studies of cognitive performance typically rely on multiple testing paradigms that may themselves be a stressor. Thus, there is a risk that variation in stress responsiveness is itself a cause of apparent, but artefactual variance in cognitive ability. Using a set of fish exposed repeatedly to two distinct spatial learning tasks (maze layouts), and an acute stress response test (open field trial), we find differences among-individuals in task performance that are repeatable within- and across maze layouts. On average performance improves with experience in the first maze, consistent with spatial learning, but not in the second. In both mazes, there is among-individual variation in the trajectory of mean performance with trial number suggesting individuals differ in ‘learning rate’. Acute stress response behaviour is repeatable but predicts neither average time to solve the maze nor learning rate. We thus find no support for among-individual correlation between acute stress response and cognitive performance. However, we highlight the possibility that cumulative, chronic stress effects may nonetheless cause observed declines in performance across repeats for some individuals (leading to lack of improvement in mean time to solve the second maze). If so, this may represent a pervasive but difficult challenge for our ability to robustly estimate learning rates in studies of animal cognition.
Divergent CPEB prion-like domains reveal different assembly mechanisms for a generic amyloid-like fold
Authors: Hervás Rubén , Fernández-Ramírez María del Carmen , Galera-Prat Albert , Suzuki Mari , Nagai Yoshitaka , Bruix Marta , Menéndez Margarita , Laurents Douglas V. , Carrión-Vázquez Mariano 
Published: May 2020

AbstractFunctional amyloids are present in a wide variety of organisms ranging from bacteria to humans. Experience-dependent aggregation of the cytoplasmic polyadenylation element-binding (CPEB) prion-like protein to a translationally active state has emerged as a plausible biochemical substrate of long-lasting memories. CPEB aggregation is driven by prion-like domains (PLD) that are highly divergent in sequence across species. Here, we describe the amyloid-like features of the neuronalAplysiaCPEB (ApCPEB) PLDin vitrousing single-molecule and bulk biophysical methods and compare them with those previously reported for neuronalDrosophilaCPEB, Orb2 PLD. The existence of transient oligomers and mature filaments suggests similarities in the late stages of the assembly pathway for both PLDs. However, while prior to aggregation the Orb2 PLD monomer remains as a random coil in solution,ApCPEB PLD adopts a diversity of conformations comprisingα-helical structures that evolve to coiled-coil species, suggesting structural differences at the beginning of their amyloid assembly pathways. Our results show how divergent PLDs of CPEB proteins from different species retain the ability to form a generic amyloid-like fold through different assembly mechanisms.
Deterministic scRNA-seq of individual intestinal organoids reveals new subtypes and coexisting distinct stem cell pools
Authors: Bues Johannes , Biočanin Marjan , Pezoldt Joern , Dainese Riccardo , Chrisnandy Antonius , Rezakhani Saba , Saelens Wouter , Gardeux Vincent , Gupta Revant , Russeil Julie , Saeys Yvan , Amstad Esther , Claassen Manfred , Lutolf Matthias , Deplancke Bart 
Published: May 2020

AbstractSingle-cell RNA-sequencing (scRNA-seq) has transformed our ability to resolve cellular properties across systems. However, current scRNA-seq platforms are one-size-fits-all approaches that are tailored toward large cell inputs (> 1,000 cells), rendering them inefficient and costly when processing small, individual tissue samples. This important drawback tends to be resolved by loading bulk samples, but this yields confounded mosaic cell population read-outs. To overcome these technological limitations, we developed adeterministic, mRNA-capture bead and cellco-encapsulation dropleting system, DisCo. We demonstrate that DisCo enables precise particle and cell positioning and droplet sorting control through combined machine-vision and multilayer microfluidics. In comparison to other microfluidics systems, the active flow control driving DisCo, enables continuous operation and processing of low-input samples (< 100 cells) at high capture efficiency (> 70%). To underscore the unique capabilities of our approach, we analyzed intestinal organoid development by “DisCo-ing” 31 individual organoids at varying developmental stages. This revealed extensive organoid heterogeneity, identifying distinct subtypes including a regenerative fetal-likeLy6a+stem cell population which persists as symmetrical cysts even under differentiation conditions. Furthermore, we uncovered a so far uncharacterized “gobloid” subtype consisting predominantly of precursor and mature (Muc2+) goblet cells. These findings demonstrate the unique power of DisCo in providing high-resolution snapshots of cellular heterogeneity among small, individual tissues.
Drug Repurposing Through a Bioinformatics Pipeline Applied on Fibrotic Diseases
Authors: Karatzas Evangelos , Kakouri Andrea , Kolios George , Delis Alex , Spyrou George M. 
Published: May 2020

AbstractSubjectFibrotic diseases cover a spectrum of systemic and organ-specific maladies that affect a large portion of the population, currently without cure. The shared characteristic these diseases feature is their uncontrollable fibrogenesis deemed responsible for the accumulated damage in the susceptible tissues.Idiopathic Pulmonary Fibrosis(IPF), an interstitial lung disease, is one of the most common and studied fibrotic diseases and still remains an active research target.ObjectiveWe highlight unique and common (i) genes, (ii) biological pathways and (iii) candidate repurposed drugs among nine fibrotic diseases. We bibliographically explore the resulting candidate substances for potential anti-fibrotic mode of action and focus on diseases that appear to be more similar toIPFso as to jointly examine potential treatments.MethodologyWe identify key genes for the 9 fibrotic diseases by analyzing transcriptomics datasets. We construct gene-to-gene networks for each disease and examine these networks to explore functional communities of biological pathways. We also use the most significant genes as input in Drug Repurposing (DR) tools and re-rank the resulting candidates according to their structural properties and functional relationship to each investigated disease.ResultsWe identify 7 biological pathways involved in all 9 fibrotic diseases as well as pathways unique to some of these diseases. Based on our DR results, we suggest captopril and ibuprofen that both appear to slow the progression of fibrotic diseases according to existing bibliography. We also recommend nafcillin and memantine, which haven’t been studied against fibrosis yet, for further wet-lab experimentation. We also observe a group of cardiomyopathy-related pathways that are exclusively highlighted forOral Submucous Fibrosis(OSF). We suggest digoxin to be tested againstOSF, since we observe cardiomyopathy-related pathways implicated inOSFand there is bibliographic evidence that digoxin may potentially clear myocardial fibrosis. Finally, we establish thatIPFshares several involved genes, biological pathways and candidate inhibiting-drugs withDupuytren’s Disease,IgG4-related Disease,SScandCystic Fibrosis. We propose that treatments for these fibrotic diseases should be jointly pursued.