bluuebunny/crossref_metadata_2025_split huggingface dataset:
A SARS-CoV-2 Reference Standard Quantified by Multi-digital PCR Platforms for Quality Assessment of Molecular Tests
Authors: Zhou Haiwei , Liu Donglai , Ma Liang , Ma Tingting , Xu Tingying , Ren Lili , Li Liang , Xu Sihong 
Published: September 2020

AbstractSARS-CoV-2 is the seventh coronavirus known to infect humans and has caused an emerging and rapidly evolving global pandemic (COVID-19) with significant morbidity and mortality. To meet the urgent and massive demand for the screening and diagnosis of infected individuals, many in vitro diagnostic assays using nucleic acid tests (NATs) have been urgently authorized by regulators worldwide. The limit of detection (LoD) is a crucial feature for a diagnostic assay to detect SARS-CoV-2 in clinical samples, and a reference standard with a well-characterized concentration or titer is of the utmost importance for LoD studies. Although several reference standards of plasmids or synthetic RNA carrying specific genomic regions of SARS-CoV-2 have already been announced, a reference standard for inactivated virus particles with accurate concentration is still needed to evaluate the complete procedure including nucleic acid extraction and to accommodate customized primer-probe sets targeting different genome sequences. Here, we performed a collaborative study to estimate the NAT-detectable units as viral genomic equivalent quantity (GEQ) of an inactivated whole-virus SARS-CoV-2 reference standard candidate using digital PCR (dPCR) on multiple commercialized platforms. The median of the quantification results (4.6×105 ± 6.5×104 GEQ/mL) was treated as the consensus true value of GEQ of virus particles in the reference standard. This reference standard was then used to challenge the LoDs of six officially approved diagnostic assays. Our study demonstrates that an inactivated whole virus quantified by dPCR can serve as a reference standard and provides a unified solution for assay development, quality control, and regulatory surveillance.
Pentoxifylline and Covid-19: A Systematic Review
Authors: Ramonfaur Diego , González-Assad Carlos A. , Paredes-Vázquez José G. 
Published: September 2020

ABSTRACTAt more than 10 months after the first case of COVID-19 was documented, the understanding of the pathogenesis of this viral illness is growing on a daily basis. A massive pro-inflammatory response on infected individuals involving several cytokines seems to play a key role on disease. As a result, therapeutic efforts have focused on anti-inflammatory strategies to ameliorate the disease, in sight of a lack of a truly effective anti-viral agent. Pentoxifylline (PTX) has been proposed by multiple authors as a potential therapeutic ally, targeting a variety of mechanisms as it has been shown to have antiviral, anti-inflammatory and hemodynamic effects. Importantly, anti-inflammatory effects center on down-regulation of cytokines such as interleukins and tumor necrosis factor. In pre-pandemic studies, PTX has demonstrated to change the clinical course of inflammatory diseases such as acute respiratory distress syndrome, which is a hallmark of severe COVID-19. Researchers agree it is pertinent to experimentally evaluate the effect this drug has on COVID-19 patients. The objective of this review is to summarize all the proposed mechanisms by which PTX may aid in the treatment of COVID-19, as well as prevent its deadly complications. Our interpretation of the literature is that the benefits PTX may bring to a patient with COVID-19 outweigh the risks this drug might pose on them. As a result, there is consensus regarding the evaluation of PTX in further experimental studies to better characterize its effects on COVID-19 patients.
Non-stationary Spatio-Temporal Modeling of COVID-19 Progression in The U.S.
Authors: Bai Yue , Safikhani Abolfazl , Michailidis George 
Published: September 2020

AbstractThe fast transmission rate of COVID-19 worldwide has made this virus the most important challenge of year 2020. Many mitigation policies have been imposed by the governments at different regional levels (country, state, county, and city) to stop the spread of this virus. Quantifying the effect of such mitigation strategies on the transmission and recovery rates, and predicting the rate of new daily cases are two crucial tasks. In this paper, we propose a modeling framework which not only accounts for such policies but also utilizes the spatial and temporal information to characterize the pattern of COVID-19 progression. Specifically, a piecewise susceptible-infected-recovered (SIR) model is developed while the dates at which the transmission/recover rates change significantly are defined as “break points” in this model. A novel and data-driven algorithm is designed to locate the break points using ideas from fused lasso and thresholding. In order to enhance the forecasting power and to describe additional temporal dependence among the daily number of cases, this model is further coupled with spatial smoothing covariates and vector auto-regressive (VAR) model. The proposed model is applied to several U.S. states and counties, and the results confirm the effect of “stay-at-home orders” and some states’ early “re-openings” by detecting break points close to such events. Further, the model performed satisfactorily short-term forecasts of the number of new daily cases at regional levels by utilizing the estimated spatio-temporal covariance structures. Finally, some theoretical results and empirical performance of the proposed methodology on synthetic data are reported which justify the good performance of the proposed method.
Communicating the health risks of wildfire smoke exposure: Health literacy considerations of public health campaigns
Authors: Cook Lily A. 
Published: September 2020

AbstractEffective communication about the health effects of wildfire smoke is important to protect the public, especially those most vulnerable to the effects of exposure: people with chronic respiratory conditions, children, and older adults. The objective of this paper is to examine the clarity and accessibility of materials intended to provide education about the health effects of wildfire. The Centers for Disease Control’s Clear Communications Index (CCI) is used to evaluate whether materials adhere to the main principles of health literacy: clarity and accessibility. This analysis found that only 32% of the materials received a passing score on the Clear Communications Index. Most materials were successful at clearly presenting specific behavioral recommendations, particularly that people should avoid exposure to air polluted by wildfire smoke by staying indoors, reducing activity levels, and using air purifiers or approved dust masks. However, materials often failed to acknowledge any uncertainty around these recommendations. Creators of these materials may want to incorporate more relevant illustrations to support the main message, and consider how information about the risks and benefits of the recommended behaviors can most clearly be presented.
A Prospective Study of Outcomes After Tubularized Incised Plate (TIP) Urethroplasty: a Multivariable Analysis of Prognostic Factors in Children 1-3 Years Old
Authors: Roshandel M. Reza , Rashed Fahimeh Kazemi , Badr Tannaz Aghaei , Salomon Samantha , Ferrer Fernando A. 
Published: September 2020

SummaryBackgroundTubularized incised plate (TIP) urethroplasty as the most common hypospadias repair method, aims to achieve normal functioning of the penis along with cosmetic reconstruction. However, there are remaining questions toward anatomical prognostic factors affecting the results of surgery. Lack of age-matched controls or controlling for meatal location, employment of several surgical techniques or multiple surgeons, or age heterogeneity of the study population are the problems affected the results of the current body of literature.ObjectiveThis prospective study aimed to evaluate the preoperative factors to predict future complications associated with hypospadias repair outcomes in males aged between 1-3 years and performed by a single surgeon with employing multivariable analysis.Patients and methodsA prospective cohort of 101 males aging from 1 to 3 years with distal to mid-shaft hypospadias were consecutively selected for TIP repair. The urethral plate dimensions in erect and flaccid states, penile length, glans diameter, and chordee were evaluated individually before reconstruction. After surgery and during follow-up visits, the subsequent transient and persistent complications were recorded.ResultsPostoperatively, the acute transient events were observed in 42 cases (41.6%) and the persistent complications in 16 cases (15.8%). The uncomplicated group had a higher percentage of patients with distal meatal location than the complicated group (P = 0.01%). Furthermore, fistula formation was notably higher in the group with acute surgical site infection (P< 0.001). The analysis also showed the width of the urethral plate to be associated with the development of complications (P = 0.03).ConclusionBy performing TIP by a single surgeon on a homogenous study population and eliminating the impact of severe chordee as a potential cofounding variable, this study prospectively found that out of the anatomical specifications, pre- and postoperative factors, the urethral meatus location was the only significant and independent predictor of the development of complications in young children with midshaft to distal hypospadias. Moreover we found that in young children the wider the plate was, the more complications happened. Consequently, we hypostatized that in young children who their anatomical dimensions are almost in same range of values, a combination of urethral width and depth should be considered in the investigation of prognostic factors for hypospadias repair outcomes. (figure 1)Figure 1.The inverse relationship between width and depth in hypospadias anomalies
Validated ICP-MS method for measurement of plasma and intracellular antimony concentrations applied to pharmacokinetics of meglumine antimoniate
Authors: Garay-Baquero Diana J. , Rebellon-Sánchez David E. , Prieto Miguel D. , Giraldo-Parra Lina , Navas Adriana , Atkinson Sheryl , McDougall Stuart , Gómez Maria Adelaida 
Published: September 2020

ABSTRACTAimA high-throughput method using inductively coupled plasma mass spectrometry (ICP-MS) was developed and validated for the quantitative analysis of antimony in human plasma and peripheral blood mononuclear cells (PBMCs) from patients with cutaneous leishmaniasis undergoing treatment with meglumine antimoniate.MethodsFor this study, antimony was digested in clinical samples with 1% TMAH / 1% EDTA and indium was used as internal standard. Calibration curves for antimony, over the range of 25 to 10000 ng/mL were fitted to a linear model using a weighting of 1/concentration2. Accuracy, precision and stability were evaluated.ResultsTaking the lower limit of quantitation (LLOQ) to be the lowest validation concentration with precision and accuracy within 20% (25% at the LLOQ), the current assay was successfully validated from 25 to 10000 ng/mL for antimony in human plasma and PBMCs. Dilution studies demonstrated that concentrations up to 100000 ng/mL of antimony in plasma were reliably analyzed when diluted into the calibration range.ConclusionThis protocol will serve as a baseline for future analytical designs, aiming to provide a reference method to allow inter-study comparisons.What is already known about this subjectAntimonial drugs are the mainstay treatment for cutaneous leishmaniasis of which systemically administered pentavalent antimonials (SbV) are widely used, however the pharmacokinetics (PK) of these drugs at the site of action is unknown.A wide range of analytical strategies have been used to quantify antimony in biological samples and atomic absorption spectroscopy is the most employed technique, however, no standardized methods for determination of intracellular concentrations of antimony were available.Relationships between plasma and intracellular drug concentrations remain unknown for most antiparasitic drugs, and PK studies rely on plasma drug concentrations assuming these act as surrogates of intracellular concentrations.What this study addsWe have developed and validated a reproducible and accurate ICP-MS method for the quantification of total antimony in human plasma and peripheral blood mononuclear cells (PBMCs) in accordance with the European Bioanalysis Forum (EBF) recommendations.This method was successfully used to compare pharmacokinetic curves of antimony in plasma and intracellular compartments, in samples collected from patients undergoing treatment for cutaneous leishmaniasis with meglumine antimoniate.
Clinical Thrombosis Rate was not Increased in a Cohort of Cancer Patients with COVID-19
Authors: Zavras Phaedon D. , Kabarriti Rafi , Mehta Vikas , Goel Sanjay , Billett Henny H. 
Published: September 2020

Increased rates of thromboembolic events (TE) have been reported in patients with coronavirus disease (COVID-19), even without prior predisposition to thrombosis. D-dimer levels have been shown to positively correlate with disease severity and mortality, leading to adoption of new empiric anticoagulation protocols by many centers.We aimed to assess whether COVID-19 further increased the risk of TE events in a cancer population who tested positive for COVID-19 at Montefiore Medical Center, Bronx, NY.The electronic medical records of 218 cancer patients were retrospectively reviewed up to April 10th, 2020. Work-up of thrombosis was done by the primary team upon clinical or laboratory suspicion. All imaging studies’ reports, within 20 days of COVID-19 positive test, were reviewed for presence of new arterial or venous thrombosis. Mortality was assessed up to one month since positive COVID-19 test result.Twelve patients (5.5%) were found to have new arterial (N=6, 50%) or venous (N=6, 50%) thrombosis. Five patients (41.7%) had history of prior TE events. Incidence of deep venous thrombosis and pulmonary embolism was 1.8% and 0.5%, respectively. Arterial events occurred in the brain (66.7%), aorta (16.7%) and coronary arteries (16.7%). Median time from COVID test was 8 days (IQR, 1.5 - 11.3). Five patients (41.7%) had received either prophylactic or therapeutic anticoagulation for a median 2 days (IQR, 1 - 5). Median peak D-dimer within 36 hours of the TE event was 9.8 mcg/mL (N=4 patients, IQR, 1.7 - 18.3). Mortality did not differ significantly between the patients with new TE events vs those without; mortality 41.7% vs 37.4%, respectively, p=0.77. Empiric anticoagulation did not improve mortality.Fifty percent of all TE events were arterial. The overall TE rate of 5.5% in the cancer population was not higher than the risk of general population. Our findings support the need for larger studies in the COVID-19+ cancer population.
Extreme Fuzzy Association of an Intrinsically Disordered Protein with Acidic Membranes
Authors: Hicks Alan , Escobar Cristian A. , Cross Timothy A. , Zhou Huan-Xiang 
Published: September 2020

AbstractMany physiological and pathophysiological processes, including Mycobacterium tuberculosis (Mtb) cell division, may involve fuzzy membrane association by proteins via intrinsically disordered regions. The fuzziness is extreme when the conformation and pose of the bound protein and the composition of the proximal lipids are all highly dynamic. Here we tackled the challenge in characterizing the extreme fuzzy membrane association of the disordered, cytoplasmic N-terminal region (NT) of ChiZ, an Mtb divisome protein, by combining solution and solid-state NMR spectroscopy and molecular dynamics simulations. In a typical pose, NT is anchored to acidic membranes by Arg residues in the midsection. Competition for Arg interactions between lipids and acidic residues, all in the first half of NT, makes the second half more prominent in membrane association. This asymmetry is accentuated by membrane tethering of the downstream transmembrane helix. These insights into sequence-interaction relations may serve as a paradigm for understanding fuzzy membrane association.
Topographic Guidance in Melt-Electrowritten Tubular Scaffolds Enhances Engineered Kidney Tubule Performance
Authors: van Genderen Anne Metje , Jansen Katja , Kristen Marleen , van Duijn Joost , Li Yang , Schuurmans Carl C.L. , Malda Jos , Vermonden Tina , Jansen Jitske , Masereeuw Rosalinde , Castilho Miguel 
Published: September 2020

AbstractTo advance the engineering of kidney tubules for future implantation, constructs should be both self-supportive and yet small-sized and highly porous. Here, we hypothesize that the fabrication of small-sized porous tubular scaffolds with a highly organized fibrous microstructure by means of melt-electrowriting (MEW) allows the development of self-supported kidney proximal tubules with enhanced properties. A custom-built MEW device was used to fabricate tubular fibrous scaffolds with small diameter sizes (Ø = 0.5, 1, 3 mm) and well-defined, porous microarchitectures (rhombus, square, and random). Human umbilical vein endothelial cells (HUVEC) and human conditionally immortalized proximal tubular epithelial cells (ciPTEC) were seeded into the scaffolds and tested for monolayer formation, integrity, and organization, as well as for extracellular matrix (ECM) production and renal transport functionality. Tubular scaffolds were successfully manufactured by fine control of MEW instrument parameters. A minimum inner diameter of 0.5 mm and pore sizes of 0.2 mm were achieved. CiPTEC formed tight monolayers in all scaffold microarchitectures tested, but well-defined rhombus-shaped pores outperformed and facilitated unidirectional cell orientation, increased collagen type IV deposition, and expression of the renal transporters and differentiation markers organic cation transporter 2 (OCT2) and P-glycoprotein (P-gp). To conclude, we present smaller diameter engineered kidney tubules with microgeometry-directed cell functionality. Due to the well-organized tubular fiber scaffold microstructure, the tubes are mechanically self-supported, and the self-produced ECM constitutes the only barrier between the inner and outer compartment, facilitating rapid and active solute transport.
Optimal carbon partitioning reconciles the apparent divergence between optimal and observed canopy profiles of photosynthetic capacity
Authors: Buckley Thomas N. 
Published: September 2020

SummaryResearch conductedPhotosynthetic capacity per unit irradiance is greater, and the marginal carbon revenue of water (∂A/∂E) is smaller, in shaded leaves than sunlit leaves, apparently contradicting optimization theory. I tested the hypothesis that these patterns arise from optimal carbon partitioning subject to biophysical constraints on leaf water potential.MethodsIn a whole plant model with two canopy modules, I adjusted carbon partitioning, nitrogen partitioning and leaf water potential to maximize carbon profit or canopy photosynthesis, and recorded how gas exchange parameters compared between shaded and sunlit modules in the optimum.Key resultsThe model predicted that photosynthetic capacity per unit irradiance should be larger, and ∂A/∂Esmaller, in shaded modules compared to sunlit modules. This was attributable partly to radiation-driven differences in evaporative demand, and partly to differences in hydraulic conductance arising from the need to balance marginal returns on stem carbon investment between modules. The model verified, however, that invariance in the marginal carbon revenue of N (∂A/∂N) is in fact optimal.ConclusionThe Cowan-Farquhar optimality solution (invariance of ∂A/∂E) does not apply to spatial variation within a canopy. The resulting variation in carbon-water economy explains differences in capacity per unit irradiance, reconciling optimization theory with observations.
Single cell RNA sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis
Authors: Bais Abha S. , Cerqueira Débora M. , Clugston Andrew , Ho Jacqueline , Kostka Dennis 
Published: September 2020

ABSTRACTThe kidney is a complex organ composed of more than 30 terminally differentiated cell types that all are required to perform its numerous homeostatic functions. Defects in kidney development are a significant cause of chronic kidney disease in children, which can lead to kidney failure that can only be treated by transplant or dialysis. A better understanding of molecular mechanisms that drive kidney development is important for designing strategies to enhance renal repair and regeneration. In this study, we profiled gene expression in the developing mouse kidney at embryonic day 14.5 at single cell resolution. Consistent with previous studies, clusters with distinct transcriptional signatures clearly identify major compartments and cell types of the developing kidney. Cell cycle activity distinguishes between the “primed” and “self-renewing” sub-populations of nephron progenitors, with increased expression of the cell cycle related genesBirc5, Cdca3, Smc2andSmc4in “primed” nephron progenitors. AugmentedBirc5expression was also detected in immature distal tubules and a sub-set of ureteric bud cells, suggesting thatBirc5might be a novel key molecule required for early events of nephron patterning and tubular fusion between the distal nephron and the collecting duct epithelia.
Short Peptides as Predictors for the Structure of Polyarginine Sequences in Disordered Proteins
Authors: Milorey B. , Schweitzer-Stenner R. , Andrews B. , Schwalbe H. , Urbanc B. 
Published: September 2020

AbstractIntrinsically disordered proteins (IDPs) and regions (IDRs) are frequently enriched in charged amino acids. IDRs are regularly involved in important biological processes, where one or more charged residues is the driving force behind a protein-biomolecule interaction. Several lines of experimental and computational evidence suggest that polypeptides and proteins that carry high net charges have a high preference for extended conformations with average end to end distances exceeding expectations for self-avoiding random coils. Here, we show that charged arginine (R) residues in even short glycine (G) capped model peptides (GRRG and GRRRG) significantly affect the conformational propensities of each other when compared to the intrinsic propensities of a mostly unperturbed arginine in the tripeptide GRG. A conformational analysis based on experimentally determined J-coupling constants from heteronuclear NMR spectroscopy and amide I’ band profiles from polarized Raman spectroscopy reveals that nearest neighbor interactions stabilize extended β-strand conformations at the expense of polyproline II and turn conformations. The results from MD simulations with an CHARMM36m force field and TIP3P water reproduce our results only to a limited extent. The use of the Ramachandran distribution of the central residue of GRRRG in a calculation of end-to-end distances of polyarginines of different length yielded the expected power law behavior. The scaling coefficient of 0.66 suggests that such peptides would be more extended than predicted by a self-avoiding random walk. Our findings thus support in principle theoretical predictions of Mao et al. (Proc. Natl. Acad. Sci. USA, 107, 8183-8188, 2010).SignificanceIntrinsically disordered proteins are rich in charged and deficient in hydrophobic residues. High net charges of disordered protein segments favor statistical coil ensembles which are more extended than a self-avoiding random coil. It is unclear whether the chain extension solely reflects the avoidance of non-local interactions or also local nearest neighbor interactions provide significant contributions. The relevance of nearest neighbor interactions, which are neglected in random coil models, has been emphasized in the literature, but only sporadically considered in molecular modellings of disordered proteins and peptides. We determined the Ramachandran distributions of protonated arginine in GRRG and GRRRG peptides. Our results reveal the contribution of nearest neighbor interactions to the extended conformations reported for a variety of poly-arginine protein segments.