Refine Search

New Search

Results in Journal PLOS ONE: 247,482

(searched for: journal_id:(242073))
Page of 4,950
Articles per Page
by
Show export options
  Select all
, , , Gideon M. Wolfaardt
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247910

Abstract:
Fundamental ecological principles of ecosystem-level respiration are extensively applied in greenhouse gas and elemental cycle studies. A laboratory system termed CEMS (Carbon Dioxide Evolution Measurement System), developed to explore microbial biofilm growth and metabolic responses, was evaluated as an early-warning system for microbial disturbances in industrial settings: in (a) potable water system contamination, and (b) bioreactor inhibition. Respiration was detected as CO2 production, rather than O2 consumption, including aerobic and anaerobic metabolism. Design, thresholds, and benefits of the remote CO2 monitoring technology were described. Headspace CO2 correlated with contamination levels, as well as chemical (R2 > 0.83–0.96) and microbiological water quality indicators (R2 > 0.78–0.88). Detection thresholds were limiting factors in monitoring drinking water to national and international standards (0 CFU/100 mL fecal coliforms) in both open- (>1500 CFU/mL) and closed-loop CO2 measuring regimes (>100 CFU/100 mL). However, closed-loop detection thresholds allow for the detection of significant contamination events, and monitoring less stringent systems such as irrigation water (2 fluctuations from chemical CO2 dynamics, to optimize this real-time, sustainable, low-waste technology, facilitating timeous responses to biological disturbances in bioreactors.
Gilson A. Rivas, Oscar M. Lasso-Alcalá, Douglas Rodríguez-Olarte, Mayke De Freitas, John C. Murphy, Cristian Pizzigalli, John C. Weber, Laurent de Verteuil,
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0246829

Abstract:
We examine, for the first time, biogeographic patterns in a series of tropical montane coastal systems in northern South America. We use amphibians and reptiles, which constitute the most critical communities based upon the prevalence of endemic taxa, to assess the region’s biodiversity. The montane coastal system spans an east-west distance of 925 km. It includes peaks ranging from 549 m to 2765 m above sea level and encompasses the montane complexes of northern Venezuela (including Isla de Margarita), an outlier at Santa Marta (Colombia), and ranges on the islands Trinidad and Tobago. The area supports 14 family level amphibian clades and 23 family level reptile clades. Fieldwork, museum specimen surveys, and a literature review suggest that biodiversity decreases at higher elevations. Here we examine the biogeographic patterns in the region to assess the role of the montane systems as possible refugia. We also look at the possible island and sky island effects using data from altitudes >200 m. At lower elevations, we tabulated 294 species, comprising 112 amphibians and 182 reptiles. About 45% of these taxa are endemic or exclusive to different sub-regions. At mid-elevation montane cloud forests, we find a much-reduced biodiversity with a total of 125 species (66 amphibians and 59 reptiles) exclusive or restricted to the region, and few species shared between systems. We find that biogeographical patterns follow a natural topographic disposition above 200 m in elevations. At the lower elevation cut off, there are 118 species (26 amphibians and 92 reptiles) shared among two or more of the studied mountain systems, suggesting a common origin and dispersal events, despite what seem to be topographic barriers. Biogeographical relationships support a topographic disposition of the region with close associations between the islands of Trinidad and Tobago, the Paria Range and the Turimiquire Massif, and close associations between the Sierra Nevada de Santa Marta and the Sierra de San Luis. Overall, the biogeographic relationships between amphibians and reptiles are similar. Species diversity in the eastern Caribbean region is less rich than in the west. This study includes the first herpetological surveys at the two easternmost mountains (Cerro La Cerbatana and Campeare) belonging to the Paria Range biogeographic unit, and aims to contribute to a better understanding of the rich biodiversity of the region.
, Juliana Villanueva Congote, Silvana Zapata Bedoya, Zulma M. Cucunuba
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0246987

Abstract:
Background Contact tracing is a crucial part of the public health surveillance toolkit. However, it is labor-intensive and costly to carry it out. Some countries have faced challenges implementing contact tracing, and no impact evaluations using empirical data have assessed its impact on COVID-19 mortality. This study assesses the impact of contact tracing in a middle-income country, providing data to support the expansion and optimization of contact tracing strategies to improve infection control. Methods We obtained publicly available data on all confirmed COVID-19 cases in Colombia between March 2 and June 16, 2020. (N = 54,931 cases over 135 days of observation). As suggested by WHO guidelines, we proxied contact tracing performance as the proportion of cases identified through contact tracing out of all cases identified. We calculated the daily proportion of cases identified through contact tracing across 37 geographical units (32 departments and five districts). Further, we used a sequential log-log fixed-effects model to estimate the 21-days, 28-days, 42-days, and 56-days lagged impact of the proportion of cases identified through contact tracing on daily COVID-19 mortality. Both the proportion of cases identified through contact tracing and the daily number of COVID-19 deaths are smoothed using 7-day moving averages. Models control for the prevalence of active cases, second-degree polynomials, and mobility indices. Robustness checks to include supply-side variables were performed. Results We found that a 10 percent increase in the proportion of cases identified through contact tracing is related to COVID-19 mortality reductions between 0.8% and 3.4%. Our models explain between 47%-70% of the variance in mortality. Results are robust to changes of specification and inclusion of supply-side variables. Conclusion Contact tracing is instrumental in containing infectious diseases. Its prioritization as a surveillance strategy will substantially impact reducing deaths while minimizing the impact on the fragile economic systems of lower and middle-income countries. This study provides lessons for other LMIC.
, Rachel McCrea
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0229965

Abstract:
Removal models were proposed over 80 years ago as a tool to estimate unknown population size. More recently, they are used as an effective tool for management actions for the control of non desirable species, or for the evaluation of translocation management actions. Although the models have evolved over time, in essence, the protocol for data collection has remained similar: at each sampling occasion attempts are made to capture and remove individuals from the study area. Within this paper we review the literature of removal modelling and highlight the methodological developments for the analysis of removal data, in order to provide a unified resource for ecologists wishing to implement these approaches. Models for removal data have developed to better accommodate important features of the data and we discuss the shift in the required assumptions for the implementation of the models. The relative simplicity of this type of data and associated models mean that the method remains attractive and we discuss the potential future role of this technique.
, , Abdel Majid A. Adam, Hosam A. Saad, Adil A. Gobouri, Fatimah S. Al-Harbi, Fawziah A. Al-Salmi, Tariq Altalhi, Samy M. El-Megharbel
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0246265

Abstract:
Medicinal uses and applications of metals and their complexes are of increasing clinical and commercial importance. The ligation behavior of quercetin (Q), which is a flavonoid, and its Zn (II) (Q/Zn) complex were studied and characterized based on elemental analysis, molar conductance, Fourier-transform infrared (FTIR) spectra, electronic spectra, proton nuclear magnetic resonance (1H-NMR), thermogravimetric analysis, and transmission electron microscopy (TEM). FTIR spectral data revealed that Q acts as a bidentate ligand (chelating ligand) through carbonyl C(4) = O oxygen and phenolic C(3)–OH oxygen in conjugation with Zn. Electronic, FTIR, and 1H-NMR spectral data revealed that the Q/Zn complex has a distorted octahedral geometry, with the following chemical formula: [Zn(Q)(NO3)(H2O)2].5H2O. Diabetes was induced by streptozotocin (STZ) injection. A total of 70 male albino rats were divided into seven groups: control, diabetic untreated group and diabetic groups treated with either MSCs and/or Q and/or Q/Zn or their combination. Serum insulin, glucose, C-peptide, glycosylated hemoglobin, lipid profile, and enzymatic and non-enzymatic antioxidant levels were determined. Pancreatic and lung histology and TEM for pancreatic tissues in addition to gene expression of both SOD and CAT in pulmonary tissues were evaluated. MSCs in combination with Q/Zn therapy exhibited potent protective effects against STZ induced hyperglycemia and suppressed oxidative stress, genotoxicity, glycometabolic disturbances, and structural alterations. Engrafted MSCs were found inside pancreatic tissue at the end of the experiment. In conclusion, Q/Zn with MSC therapy produced a synergistic effect against oxidative stress and genotoxicity and can be considered potential ameliorative therapy against diabetes with pulmonary dysfunction, which may benefit against COVID-19.
, Danilo S. Olivier, Carolina C. Pacca, Clarita M. S. Avilla, Mauricio L. Nogueira, , Dieter Willbold, Raghuvir K. Arni,
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0246319

Abstract:
The potential outcome of flavivirus and alphavirus co-infections is worrisome due to the development of severe diseases. Hundreds of millions of people worldwide live under the risk of infections caused by viruses like chikungunya virus (CHIKV, genus Alphavirus), dengue virus (DENV, genus Flavivirus), and zika virus (ZIKV, genus Flavivirus). So far, neither any drug exists against the infection by a single virus, nor against co-infection. The results described in our study demonstrate the inhibitory potential of two flavonoids derived from citrus plants: Hesperetin (HST) against NS2B/NS3pro of ZIKV and nsP2pro of CHIKV and, Hesperidin (HSD) against nsP2pro of CHIKV. The flavonoids are noncompetitive inhibitors and the determined IC50 values are in low µM range for HST against ZIKV NS2B/NS3pro (12.6 ± 1.3 µM) and against CHIKV nsP2pro (2.5 ± 0.4 µM). The IC50 for HSD against CHIKV nsP2pro was 7.1 ± 1.1 µM. The calculated ligand efficiencies for HST were > 0.3, which reflect its potential to be used as a lead compound. Docking and molecular dynamics simulations display the effect of HST and HSD on the protease 3D models of CHIKV and ZIKV. Conformational changes after ligand binding and their effect on the substrate-binding pocket of the proteases were investigated. Additionally, MTT assays demonstrated a very low cytotoxicity of both the molecules. Based on our results, we assume that HST comprise a chemical structure that serves as a starting point molecule to develop a potent inhibitor to combat CHIKV and ZIKV co-infections by inhibiting the virus proteases.
Tingfu Li, Hongbo Zhao, Hua Zhou, Tingting Geng
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247817

Abstract:
Background Pancreatic adenocarcinoma (PAAD) is a pancreatic disease with a high mortality rate in the world. This present research intends to identify the function of lncRNA LINC00857/miR-340-5p/Transforming growth factor alpha (TGFA) in the progression of PAAD. Methods Bioinformatics analysis was used to explore the differentially expressed lncRNA/miRNA/mRNA and analyze the relationship between lncRNA/miRNA/mRNA expression and prognosis of PAAD by enquiring TCGA, GEO and GTEX. KEGG pathway analysis and GO enrichment analysis were implemented to annotate the crucial genes regulated by LINC00857. The biological behaviors of PAAD cells were detected by CCK-8, colony formation and transwell assays. Interactive associations between LINC00857 and miR-340-5p, as well as miR-340-5p and TGFA were analyzed by dual luciferase assay. Results By enquiring TCGA database, we got that LINC00857 was highly expressed in patients with PAAD and positively associated with worse prognosis in PAAD patients. Moreover, LINC00857 upregulation promoted the proliferation and clone formation abilities of PAAD cells. Afterwards, the downstream miRNA and mRNA targets of LINC00857 were picked up to construct a ceRNA network. Further study revealed that TGFA expression was positively regulated by LINC00857 and negatively regulated by miR-340-5p. Besides that, the inhibitory effect of miR-340-5p on PAAD cells growth and movement can be blocked by LINC00857 upregulation. While, the malignant behavior of PAAD cells induced by TGFA overexpression can be eliminated by LINC00857 knockdown. Conclusions Upregulation of LINC00857 improved growth, invasion and migration abilities of PAAD cells by modulation of miR-340-5p/TGFA, affording potential targets and biomarkers for the clinical diagnosis and treatment.
, Juan J. Llibre-Rodriguez, Daisy Acosta, William H. Dow
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247831

Abstract:
Background Cuba’s life expectancy at 79 is third highest in Latin America. Many attribute this to social investments in health and education, but comparative research is sparse, thus we compare Cuba with neighboring Dominican Republic, Costa Rica due to its strong social protections, and the U.S. Given high cardiovascular mortality, we focus on cardiovascular risk factor levels. To assess the role of health care, we distinguish medically amenable biomarkers from behavioral risk factors. To assess the role of Cuba’s focus on equity, we compare education gradients in risk factors. Methods We analyze Cuban data from the 10/66 Dementia Research Group baseline survey of urban adults ages 65 plus. Comparison samples are drawn from the Dominican Republic 10/66 survey, the Costa Rican CRELES, and U.S. NHANES. We analyze cross-country levels and education gradients of medically amenable (hypertension, diabetes, hypercholesterolemia, access to health care) and behavioral (smoking, obesity) risk factors,–using sex-stratified weighted means comparisons and age-adjusted logistic regression. Results Neither medically amenable nor behavioral risk factors are uniformly better in Cuba than comparison countries. Obesity is lower in Cuba, but male smoking is higher. Hypertension, diabetes, and hypercholesterolemia levels are high in all countries, though Cuba’s are lower than Costa Rica. Hypertension awareness in Cuba is similar to Costa Rica. Cuba has a higher proportion of hypertensives on treatment than Costa Rica, though lower than the U.S. Comparative gradients by education are similarly mixed. For behavioral factors, Cuba shows the strongest gradients (primarily for men) among the countries compared: smoking improves, but obesity worsens with education. Hypertension awareness also improves with education in Cuba, but Cuba shows no significant differences by education in hypertension treatment. Conclusion Smoking is comparatively high in Cuba, but obesity is low, and the resulting biomarkers show comparatively mixed patterns. Cuba’s social protections have not eliminated strong educational gradients in behavioral risk factors, but the healthcare system appears to have eliminated disparities such as in hypertension treatment.
Honggang Zhao, , Dongming Zhang, Chao Liu
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0246815

Abstract:
Two kinds of common tunnel shapes, i.e. elliptical opening and square opening were selected for biaxial compression tests, and the influences of two kinds of opening shapes on the mechanical properties, failure characteristics and failure modes of sandstone were compared and analyzed. The complex variable theory and mapping functions were used to obtain the analytical stress solution around elliptical and square openings. The results show that the stability of the specimen containing an elliptical opening was better than that of the specimen containing a square opening under the same lateral stress. Compared with the elliptical opening, the local damage was formed earlier in the square opening which might be caused by a higher stress concentration around the square opening. The stress distributions around openings were influenced by the opening shape and lateral stress coefficient. The top and bottom of square opening were more prone to tensile fracture, and the distribution range of tensile was larger than that of elliptical opening. When the opening failed, the intensity of square opening failure was weaker than that of elliptical opening. On the basis of the average frequency value and the rise angle value, the failure mode of specimen containing elliptical or square opening was distinguished. It was found that the mixed tension and shear failure dominated the failure of specimens with different opening shapes, and the number of shear cracks in the specimen containing a square opening was greater than that in the specimen containing an elliptical opening. The above method of judging failure mode by acoustic emission signals was well verified by the CT images of damaged specimens.
, Zawiyah Mohammad Yusof, Hazura Mohamed
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0243355

Abstract:
CRM adoption can provide innumerable benefits to the SMEs performance, including solving customer problems in a timely manner, enhancing customer satisfaction by appointing an expert to solve issues and queries, and the like. This study aims to examine the moderating effects of the firm size in the adoption of CRM in the Palestinian SMEs. A quantitative approach was used to investigate the relationships between the variables, which are compatibility, IT infrastructure, complexity, relative advantage, security, top management support, customer pressure, and competitive pressure. A questionnaire was designed to collect data from 420 SMEs in Palestine. A total of 331 respondents completed and returned the survey. The Partial Least Square-Structural Equation Model (PLS-SEM) approach was used to assess both the measurement and structural models. The Diffusion of Innovation Theory (DOI) and Technology, Organization, and Environment Framework (TOE) framework were employed to identify the determinant factors from the technological, organizational, and environmental perspectives. The findings and conclusions of this study provide show that the moderating effect of firm size has significant effect compatibility, top management support, customer pressure, and IT infrastructure factors.
Bruce A. Berkowitz, Robert H. Podolsky, Karen Lins Childers, Aicha Saadane, Timothy S. Kern, Robin Roberts, Hailey Olds, Joydip Joy, Collin Richards, Tilman Rosales, et al.
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245161

Abstract:
Purpose The phosphodiesterase inhibitor sildenafil is a promising treatment for neurodegenerative disease, but it can cause oxidative stress in photoreceptors ex vivo and degrade visual performance in humans. Here, we test the hypotheses that in wildtype mice sildenafil causes i) wide-spread photoreceptor oxidative stress in vivo that is linked with ii) impaired vision. Methods In dark or light-adapted C57BL/6 mice ± sildenafil treatment, the presence of oxidative stress was evaluated in retina laminae in vivo by QUEnch-assiSTed (QUEST) magnetic resonance imaging, in the subretinal space in vivo by QUEST optical coherence tomography, and in freshly excised retina by a dichlorofluorescein assay. Visual performance indices were also evaluated by QUEST optokinetic tracking. Results In light-adapted mice, 1 hr post-sildenafil administration, oxidative stress was most evident in the superior peripheral outer retina on both in vivo and ex vivo examinations; little evidence was noted for central retina oxidative stress in vivo and ex vivo. In dark-adapted mice 1 hr after sildenafil, no evidence for outer retina oxidative stress was found in vivo. Evidence for sildenafil-induced central retina rod cGMP accumulation was suggested as a panretinally thinner, dark-like subretinal space thickness in light-adapted mice at 1 hr but not 5 hr post-sildenafil. Cone-based visual performance was impaired by 5 hr post-sildenafil and not corrected with anti-oxidants; vision was normal at 1 hr and 24 hr post-sildenafil. Conclusions The sildenafil-induced spatiotemporal pattern of oxidative stress in photoreceptors dominated by rods was unrelated to impairment of cone-based visual performance in wildtype mice.
, Nobuhiro Nishii, Takayoshi Shinya, Akihito Miyoshi, Yoshimasa Morimoto, Masakazu Miyamoto, Koji Nakagawa, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245502

Abstract:
Purpose High-risk patients can be identified by preprocedural computed tomography (CT) before lead extraction. However, CT evaluation may be difficult especially for lead tip identification due to artifacts in the leads. Selective right ventriculography (RVG) may enable preprocedural evaluation of lead perforation. We investigated the efficacy of RVG for identifying right ventricular (RV) lead perforation compared with CT in patients who underwent lead extraction. Methods Ninety-five consecutive patients who were examined by thin-section non-ECG-gated multidetector CT and RVG before lead extraction were investigated retrospectively. Newly recognized pericardial effusion after lead extraction was used as a reference standard for lead perforation. We analyzed the prevalence of RV lead perforation diagnosed by each method. The difference in the detection rates of lead perforation by RVG and CT was evaluated. Results Of the 115 RV leads in the 95 patients, lead perforation was diagnosed for 35 leads using CT, but the leads for 29 (83%) of those 35 leads diagnosed as lead perforation by CT were shown to be within the right ventricle by RVG. Three patients with 5 leads could not be evaluated by CT due to motion artifacts. The diagnostic accuracies of RVG and CT were significantly different (p < 0.001). There was no complication of pericardial effusion caused by RV lead extraction. Conclusion RVG for identification of RV lead perforation leads to fewer false-positives compared to non-ECG-gated CT. However, even in cases in which lead perforation is diagnosed, most leads may be safely extracted by transvenous lead extraction.
Nicole M. Davis Armstrong, Kelsey J. Spragley, Wei-Min Chen, Fang-Chi Hsu, Michael S. Brewer, Patrick J. Horn, Stephen R. Williams, Michèle M. Sale, Bradford B. Worrall,
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247257

Abstract:
African Americans endure a nearly two-fold greater risk of suffering a stroke and are 2–3 times more likely to die from stroke compared to those of European ancestry. African Americans also have a greater risk of recurrent stroke and vascular events, which are deadlier and more disabling than incident stroke. Stroke is a multifactorial disease with both heritable and environmental risk factors. We conducted an integrative, multi-omic study on 922 plasma metabolites, 473,864 DNA methylation loci, and 556 variants from 50 African American participants of the Vitamin Intervention for Stroke Prevention clinical trial to help elucidate biomarkers contributing to recurrent stroke rates in this high risk population. Sixteen metabolites, including cotinine, N-delta-acetylornithine, and sphingomyelin (d17:1/24:1) were identified in t-tests of recurrent stroke outcome or baseline smoking status. Serum tricosanoyl sphingomyelin (d18:1/23:0) levels were significantly associated with recurrent stroke after adjusting for covariates in Cox Proportional Hazards models. Weighted Gene Co-expression Network Analysis identified moderate correlations between sphingolipid markers and clinical traits including days to recurrent stroke. Integrative analyses between genetic variants in sphingolipid pathway genes identified 29 nominal associations with metabolite levels in a one-way analysis of variance, while epigenomic analyses identified xenobiotics, predominately smoking-associated metabolites and pharmaceutical drugs, associated with methylation profiles. Taken together, our results suggest that metabolites, specifically those associated with sphingolipid metabolism, are potential plasma biomarkers for stroke recurrence in African Americans. Furthermore, genetic variation and DNA methylation may play a role in the regulation of these metabolites.
, Ling Guo, Jing Huo, Guoliang Zhou
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247333

Abstract:
Objectives To review cross-sectional studies on the prevalence of sleep disturbance in Chinese adolescents and use a meta-analysis to explore the factors that may explain the heterogeneity between estimates of the prevalence. Methods We followed the Preferred Reporting Items for Systematic Review and Meta-analysis and searched the PubMed, Embase, Cochrane Library, PsycINFO, Scopus, Web of Science, SinoMed, Chinese National Knowledge Infrastructure (CNKI), WanFang, and VIP Database for Chinese Technical Periodicals databases from their inception through June 30, 2020. Analysis of the abstract, full-text, and data were conducted independently with uniform standards. Sub-group analyses and meta-regression analyses were performed to explore the associations between prevalence and gender, sex ratio, mean age, area, studying stage, sample size, survey time, response rate, assessment tools, PSQI cut-off, and quality score of the study. Results A total of 63 studies (64 groups of outcomes) were included in our analysis, covering 430,422 adolescents across China, of which 104,802 adolescents had sleep disturbances. The overall pooled prevalence was 26% (95% CI: 24–27%). Adolescents in senior high school (28%, 95% CI: 24–31%, ppp Conclusion This systematic review and meta-analysis revealed that sleep disturbances are common in Chinese adolescents, and effective psychological and behavior intervention may be needed to help adolescents solve their sleep problems.
Ming-En Hsu, Yu-Ting Cheng, Chih-Hsiang Chang, Yi‐Hsin Chan, Victor Chien-Chia Wu, Kuo-Chun Hung, Chia-Pin Lin, Kuo-Sheng Liu, , Shao-Wei Chen
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247340

Abstract:
Objective Several serum biomarkers have been investigated for their potential as diagnostic tools in aortic disease; however, no study has investigated the association between serum biomarkers and outcomes after aortic surgery. This study explored the predictive ability of serum soluble lumican in postoperative outcomes after aortic surgery. Methods In total, 58 patients receiving aortic surgery for aortic dissection or aneurysm at Linkou Chang Gung Memorial Hospital in Taiwan in December 2011–September 2018 were enrolled. Blood samples were collected immediately upon patients’ arrival in the intensive care unit after aortic surgery. The diagnostic properties of soluble lumican levels were assessed by performing receiver operating characteristic (ROC) curve analysis. The confidence interval (CI) of the area under the ROC curve (AUC) was measured using DeLong’s nonparametric method and the optimal cutoff was determined using the Youden index. Results The serum soluble lumican level distinguished prolonged ventilation (AUC, 73.5%; 95% CI, 57.7%–89.3%) and hospital stay for >30 days (AUC, 78.2%; 95% CI, 61.6%–94.7%). The optimal cutoffs of prolonged ventilation and hospital stay for >30 days were 1.547 and 5.992 ng/mL, respectively. The sensitivity and specificity were respectively 100% (95% CI, 71.5%–100%) and 40.4% (95% CI, 26.4%–55.7%) for prolonged ventilation and 58% (95% 27.7%–84.8%) and 91.3% (95% CI, 79.2%–97.6%) for hospital stay for >30 days. Conclusions The serum soluble lumican level can be a potential prognostic factor for predicting poor postoperative outcomes after aortic surgery. However, more studies are warranted in the future.
, Shohreh Raeisi, Jingyun Yang, Sue Leurgans, Christopher B. Forsyth, , David A. Bennett, Ali Keshavarzian
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0240342

Abstract:
The inflammatory hypothesis posits that sustained neuroinflammation is sufficient to induce neurodegeneration and the development of Alzheimer’s disease (AD) and Alzheimer’s dementia. One potential source of inflammation is the intestine which harbors pro-inflammatory microorganisms capable of promoting neuroinflammation. Systemic inflammation is robustly associated with neuroinflammation as well as low levels of brain derived neurotrophic factor (BDNF) in the systemic circulation and brain. Thus, in this pilot study, we tested the hypothesis that intestinal barrier dysfunction precedes risk of death, incident AD dementia and MCI, cognitive impairment and neuropathology. Serum BDNF was associated with changes in global cognition, working memory, and perceptual speed but not risk of death, incident AD dementia, incident MCI, or neuropathology. Neither of the markers of intestinal barrier integrity examined, including lipopolysaccharide binding protein (LBP) nor intestinal fatty acid binding protein (IFABP), were associated with risk of death, incident AD dementia, incident mild cognitive impairment (MCI), change in cognition (global or domains), or neuropathology. Taken together, the data in this pilot study suggest that intestinal barrier dysfunction does not precede diagnosis of AD or MCI, changes in cognition, or brain pathology. However, since MCI and AD are related to global cognition, the findings with BDNF and the contiguous cognitive measures suggest low power with the trichotomous cognitive status measures. Future studies with larger sample sizes are necessary to further investigate the results from this pilot study.
Changwei Yuan, Yaxin Duan, Xinhua Mao, Ningyuan Ma, Jiannan Zhao
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247431

Abstract:
As an important service industry in cities, taxis provide people with an all-weather travel mode. And its demand is greatly affected by the internal functions of the city. It is very important to understand the relationship between the mixed degree of urban internal functions and the residents’ taxi travel demand to alleviate traffic congestion and formulate corresponding urban traffic strategies. This paper combined two heterogeneous data in the main urban area of Xi’an, urban points of interest (POIs) and taxi GPS. Firstly, a spatial information entropy model was constructed to quantitatively evaluate the mixed degree of functions in different spaces within the city. Secondly, the kernel density estimation method was used to analyze the spatial distribution evolution characteristics of residents’ taxi travel demand. A geographically weighted regression (GWR) model was further used to study the spatial and temporal influences of the mixed degree of urban internal functions on taxi travel demand. Results indicate that there is an obvious spatiotemporal pattern in the impact of the mixed degree of urban functions on taxi travel demand. And the GWR model is used to study the impact is superior to the ordinary least squares (OLS). In more developed areas, improving the mixed degree of urban functions will be more attractive than backward areas. It is also found that although the single function of the city has an impact on the taxi travel demand, the result of the single function is not ideal. This study can provide a reference for the optimal combination of basic units of urban space in urban planning, promote the balance of supply and demand of urban taxis, rationalize urban taxis’ operation and allocation, and solve the problems of urban transportation systems.
Adam Booth, Angus Bruno Reed, Sonia Ponzo, Arrash Yassaee, Mert Aral, , Alain Labrique, Diwakar Mohan
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247461

Abstract:
Aim COVID-19 clinical presentation is heterogeneous, ranging from asymptomatic to severe cases. While there are a number of early publications relating to risk factors for COVID-19 infection, low sample size and heterogeneity in study design impacted consolidation of early findings. There is a pressing need to identify the factors which predispose patients to severe cases of COVID-19. For rapid and widespread risk stratification, these factors should be easily obtainable, inexpensive, and avoid invasive clinical procedures. The aim of our study is to fill this knowledge gap by systematically mapping all the available evidence on the association of various clinical, demographic, and lifestyle variables with the risk of specific adverse outcomes in patients with COVID-19. Methods The systematic review was conducted using standardized methodology, searching two electronic databases (PubMed and SCOPUS) for relevant literature published between 1st January 2020 and 9th July 2020. Included studies reported characteristics of patients with COVID-19 while reporting outcomes relating to disease severity. In the case of sufficient comparable data, meta-analyses were conducted to estimate risk of each variable. Results Seventy-six studies were identified, with a total of 17,860,001 patients across 14 countries. The studies were highly heterogeneous in terms of the sample under study, outcomes, and risk measures reported. A large number of risk factors were presented for COVID-19. Commonly reported variables for adverse outcome from COVID-19 comprised patient characteristics, including age >75 (OR: 2.65, 95% CI: 1.81–3.90), male sex (OR: 2.05, 95% CI: 1.39–3.04) and severe obesity (OR: 2.57, 95% CI: 1.31–5.05). Active cancer (OR: 1.46, 95% CI: 1.04–2.04) was associated with increased risk of severe outcome. A number of common symptoms and vital measures (respiratory rate and SpO2) also suggested elevated risk profiles. Conclusions Based on the findings of this study, a range of easily assessed parameters are valuable to predict elevated risk of severe illness and mortality as a result of COVID-19, including patient characteristics and detailed comorbidities, alongside the novel inclusion of real-time symptoms and vital measurements.
, Mark C. Wheldon, , Philipp Ueffing, Helena Cruz Castanheira
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247479

Abstract:
Expanding access to contraception and ensuring that need for family planning is satisfied are essential for achieving universal access to reproductive healthcare services, as called for in the 2030 Agenda for Sustainable Development. To quantify the gaps that remain in meeting needs among adolescents, this study provides a harmonised data set and global estimates and projections of family planning indicators for adolescents aged 15–19 years. We compiled a comprehensive dataset of family-planning indicators among women aged 15–19 from 754 nationally representative surveys. We used a Bayesian hierarchical model with country-specific annual trends to estimate contraceptive prevalence and unmet need for family planning, with 95% uncertainty intervals (UIs), for 185 countries, taking into account changes in proportions married or in a union and differences in sexual activity among unmarried women across countries. Among 300 million women aged 15–19 years in 2019, 29.8 million (95% UI 24.6–41.7) use any contraception, and 15.0 million (95% UI 12.1–29.2) have unmet need for family planning. Population growth and the postponement of marriage influence trends in the absolute number of adolescents using contraception or experiencing unmet need. Large gaps remain in meeting family-planning needs among adolescents. The proportion of the need satisfied by modern methods, Sustainable Development Goals (SDG) indicator 3.7.1, was 59.2% (95% UI 44.8–67.2) globally among adolescents, lower compared to 75.7% (95% UI 73.2%–78.0%) among all women age 15–49 years. It was less than one half of adolescents in need in Western Asia and Northern Africa (38.7%, 95%UI = 20.9–56.5), Central and Southern Asia (43.5%, 95%UI = 36.6–52.3), and sub-Saharan Africa (45.6%, 95%UI = 42.2–49.0). The main limitations of the study are: (i) the uncertainty surrounding estimates for countries with limited or biased data is large; and (ii) underreporting of contraceptive use and needs is likely, especially among unmarried adolescents.
Yujie Du, Junli Du, Xi Liu, Zhifa Yuan
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247722

Abstract:
One-to-multiple path analysis model describes the regulation mechanism of multiple independent variables to one dependent variable by dividing the correlation coefficient and the determination coefficient. How to analyse more complex regulation mechanisms of multiple independent variables to multiple dependent variables? Similarly, according to multiple-to-multiple linear regression analysis, multiple-to-multiple path analysis model was proposed in this paper and it demonstrated more complex regulation mechanisms among multiple independent variables and multiple dependent variables by dividing the generalized determination coefficient. Differently, three other types of paths were generated in multiple-to-multiple path analysis model in that the correlation among multiple dependent variables was considered. Then, the decision coefficient of each independent variable was constructed for dependent variables system, and its hypothesis testing statistics were given. Finally, the research example of the wheat breeding rules in arid area demonstrated that the multiple-to-multiple path analysis considering more correlation information can get better results.
Romina Marcoccia, , , Giulia Ballotta, Cristina Algieri, Alessandra Pagliarani, Eleonora Iacono
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247567

Abstract:
Despite the increasing demand of cellular therapies for dogs, little is known on the differences between adult and fetal adnexa canine mesenchymal stem cells (MSCs), and data on their metabolic features are lacking. The present study aimed at comparing the characteristics of canine adipose tissue (AT) and umbilical cord matrix (UC) MSCs. Moreover, for the first time in the dog, the cellular bioenergetics were investigated by evaluating the two main metabolic pathways (oxidative phosphorylation and glycolysis) of ATP production. Frozen-thawed samples were used for this study. No differences in mean cell proliferation were found (P>0.05). However, while AT-MSCs showed a progressive increase in doubling time over passages, UC-MSCs showed an initial post freezing-thawing latency. No differences in migration, spheroid formation ability, and differentiation potential were found (P>0.05). RT-PCR analysis confirmed the expression of CD90 and CD44, the lack of CD14 and weak expression of CD34, mostly by AT-MSCs. DLA-DRA1 and DLA-DQA1 were weakly expressed only at passage 0 by UC-MSCs, while they were expressed at different passages for AT-MSCs. There was no difference (P>0.05) in total ATP production between cell cultures, but the ratio between the “mitochondrial ATP Production Rate” and the “glycolytic ATP Production Rate” was higher (P
, Adina Draghici, Jason W. Hamner, Rich Goldstein, J. Andrew Taylor
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247576

Abstract:
Blood pressure regulation following spinal cord injury (SCI) is often compromised due to impaired vascular sympathetic control, leading to increased reliance on cardiovagal baroreflex sensitivity to maintain pressure. Whole-body exercise improves cardiovagal baroreflex sensitivity in uninjured individuals, though has not been explored in those with SCI. Our objective was to determine changes in cardiovagal baroreflex sensitivity following 6 months of high-intensity, whole-body exercise in individuals with SCI compared to lower-intensity, arms only exercise, or waitlist. This randomized controlled trial recruited individuals with SCI aged 18–40 years old. Sixty-one individuals were randomized, with 38 completing at least one cardiovagal baroreflex sensitivity assessment. Whole-body exercise was performed with hybrid functional electrical stimulation rowing prescribed as two to three times per week, for 30–60 minutes with a target heart rate of >75% of maximum. The arms only exercise group performed upper body rowing exercise with the same prescription as whole-body exercise. Waitlist controls were not enrolled in any explicit training regimen. After 6 months, those in arms only exercise or waitlist crossed over to whole-body exercise. Cardiovagal baroreflex sensitivity was assessed via the neck suction technique at baseline and at three-month intervals thereafter. Intention to treat analysis with a structured equation model demonstrated no significant effect of waitlist control or arms only exercise on cardiovagal baroreflex sensitivity. Whole-body exercise significantly improved cardiovagal baroreflex sensitivity at 6 months for those initially randomized (p = 0.03), as well as those who crossed over from arms only exercise or waitlist control (p = 0.03 for each). However, amount of exercise performed and aerobic gains (VO2max) each poorly correlated with increases in cardiovagal baroreflex sensitivity (R2
, Kaif Rashid Khan, , Umme Kulsum Rowzatur Romman, Ershad Halim
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247619

Abstract:
Thiazolidinediones are very important and used as a drug for the treatment of type 2 diabetes. Here, we report a convenient approach to synthesis 3-m-tolyl-5-arylidene-2,4-thiazolidinediones (TZDs) derivatives 7a-e in two steps with moderate to good yield using morpholine as a catalyst. All the structures were confirmed by their spectral IR, 1H NMR and 13C NMR data. The anti-diabatic activity of all synthesized molecules is evaluated by docking with peroxisome proliferator-activated receptor-γ (PPARγ). Preliminary flexible docking studies reveals that our compounds 7a, 7d and 7e showed better binding affinity with the protein and could be a potential candidate for the treatment of type 2 diabetes in near future.
, Stephen A. Rawlings, , Florence Y. Lee, Clarence W. Chan, Bethany Barrick, Zoe C. Burger, Kiang-Teck J. Yeo, Dena Marrinucci
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247797

Abstract:
Since the initial identification of the novel coronavirus SARS-CoV-2 in December of 2019, researchers have raced to understand its pathogenesis and begun devising vaccine and treatment strategies. An accurate understanding of the body’s temporal immune response against SARS-CoV-2 is paramount to successful vaccine development and disease progression monitoring. To provide insight into the antibody response against SARS-CoV-2, plasma samples from 181 PCR-confirmed COVID-19 patients collected at various timepoints post-symptom onset (PSO) were tested for the presence of anti-SARS-CoV-2 IgM and IgG antibodies via lateral flow. Additionally, 21 donors were tracked over time to elucidate patient-specific immune responses. We found sustained levels of anti-SARS-CoV-2 antibodies past 130 days PSO, with 99% positivity observed at 31–60 days PSO. By 61–90 days PSO, the percentage of IgM-/IgG+ results were nearly equal to that of IgM+/IgG+ results, demonstrating a shift in the immune response with a decrease in IgM antibody levels. Results from this study not only provide evidence that the antibody response to COVID-19 can persist for over 4 months, but also demonstrates the ability of Easy Check™ to monitor seroconversion and antibody response of patients. Easy Check was sufficiently sensitive to detect antibodies in patient samples as early as 1–4 days PSO with 86% positivity observed at 5–7 days PSO. Further studies are required to determine the longevity and efficacy of anti-SARS-CoV-2 antibodies, and whether they are protective against re-infection.
, Anne Elise Eggen, Terje Steigen, Tom Wilsgaard, Andreas Kristensen, Anne Skogsholm, Elizabeth Holme, Christian Van Den Heuvel, Jan Erik Nordrehaug, Bjørn Bendz, et al.
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247358

Abstract:
Introduction Bleeding is a concern after percutaneous coronary intervention (PCI) and subsequent dual antiplatelet therapy (DAPT). We herein report the incidence and risk factors for major bleeding in the Norwegian Coronary Stent Trial (NORSTENT). Materials and methods NORSTENT was a randomized, double blind, pragmatic trial among patients with acute coronary syndrome or stable coronary disease undergoing PCI during 2008–11. The patients (N = 9,013) were randomized to receive either a drug-eluting stent or a bare-metal stent, and were treated with at least nine months of DAPT. The patients were followed for a median of five years, with Bleeding Academic Research Consortium (BARC) 3–5 major bleeding as one of the safety endpoints. We estimated cumulative incidence of major bleeding by a competing risks model and risk factors through cause-specific Cox models. Results The 12-month cumulative incidence of major bleeding was 2.3%. Independent risk factors for major bleeding were chronic kidney disease, low bodyweight (< 60 kilograms), diabetes mellitus, and advanced age (> 80 years). A myocardial infarction (MI) or PCI during follow-up increased the risk of major bleeding (HR = 1.67, 95% CI 1-29-2.15). Conclusions The 12-month cumulative incidence of major bleeding in NORSTENT was higher than reported in previous, explanatory trials. This analysis strengthens the role of chronic kidney disease, advanced age, and low bodyweight as risk factors for major bleeding among patients receiving DAPT after PCI. The presence of diabetes mellitus or recurrent MI among patients is furthermore a signal of increased bleeding risk. Clinical trial registration Unique identifier NCT00811772; http://www.clinicaltrial.gov.
, Aaron M. Olsen, Ryan Caillouet, Matthew D. Campbell, William F. Patterson Iii
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247985

Abstract:
We tested the efficacy of a stereo camera (SC) system adapted for use with a remotely operated vehicle (ROV) to estimate fish length distributions at reef sites in the northern Gulf of Mexico. A pool experiment was conducted to test the effect of distance (1, 2, 3 or 5 m), angle of incidence (AOI; 0° to 40° at 5° increments), and SC baseline distance (BD; BD1 = 406, BD2 = 610, and BD3 = 762 mm camera separation) on the accuracy and precision of fish model length (288, 552, or 890 mm fork length) estimates compared to a red laser scaler (RLS). A field experiment was then conducted at 20 reef sites with SCs positioned at BD1 to compare fish length distribution estimates between the SC and RLS systems under in situ conditions. In the pool experiment, mean percent errors were consistently within the a priori selected threshold of ±5% at AOIs ≤10° at all distances with all four systems. However, SCs produced accurate estimates at AOIs up to 30° at all distances tested; 2–3 m was optimal. During reef site surveys, SCs collected 10.4 times as many length estimates from 4.3 times as many species compared to the RLS. Study results demonstrate that, compared to laser scalers, ROV-based SC systems can substantially increase the number of available fish length estimates by producing accurate length estimates at a wider range of target orientations while also enabling measurements from a greater portion of the cameras’ field of view.
, Rajiv Tripathi, Bo-Sen Wu, Sarah MacPherson, Jaswinder Singh,
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247380

Abstract:
The impacts of wavelengths in 500–600 nm on plant response and their underlying mechanisms remain elusive and required further investigation. Here, we investigated the effect of light quality on leaf area growth, biomass, pigments content, and net photosynthetic rate (Pn) across three Arabidopsis thaliana accessions, along with changes in transcription, photosynthates content, and antioxidative enzyme activity. Eleven-leaves plants were treated with BL; 450 nm, AL; 595 nm, RL; 650 nm, and FL; 400–700 nm as control. RL significantly increased leaf area growth, biomass, and promoted Pn. BL increased leaf area growth, carotenoid and anthocyanin content. AL significantly reduced leaf area growth and biomass, while Pn remained unaffected. Petiole elongation was further observed across accessions under AL. To explore the underlying mechanisms under AL, expression of key marker genes involved in light-responsive photosynthetic reaction, enzymatic activity of antioxidants, and content of photosynthates were monitored in Col-0 under AL, RL (as contrast), and FL (as control). AL induced transcription of GSH2 and PSBA, while downregulated NPQ1 and FNR2. Photosynthates, including proteins and starches, showed lower content under AL. SOD and APX showed enhanced enzymatic activity under AL. These results provide insight into physiological and photosynthetic responses to light quality, in addition to identifying putative protective-mechanisms that may be induced to cope with lighting-stress in order to enhance plant stress tolerance.
, Oishee Mazumder, Aniruddha Sinha, Sundeep Khandelwal
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247921

Abstract:
Valvular heart diseases are a prevalent cause of cardiovascular morbidity and mortality worldwide, affecting a wide spectrum of the population. In-silico modeling of the cardiovascular system has recently gained recognition as a useful tool in cardiovascular research and clinical applications. Here, we present an in-silico cardiac computational model to analyze the effect and severity of valvular disease on general hemodynamic parameters. We propose a multimodal and multiscale cardiovascular model to simulate and understand the progression of valvular disease associated with the mitral valve. The developed model integrates cardiac electrophysiology with hemodynamic modeling, thus giving a broader and holistic understanding of the effect of disease progression on various parameters like ejection fraction, cardiac output, blood pressure, etc., to assess the severity of mitral valve disorders, naming Mitral Stenosis and Mitral Regurgitation. The model mimics an adult cardiovascular system, comprising a four-chambered heart with systemic, pulmonic circulation. The simulation of the model output comprises regulated pressure, volume, and flow for each heart chamber, valve dynamics, and Photoplethysmogram signal for normal physiological as well as pathological conditions due to mitral valve disorders. The generated physiological parameters are in agreement with published data. Additionally, we have related the simulated left atrium and ventricle dimensions, with the enlargement and hypertrophy in the cardiac chambers of patients with mitral valve disorders, using their Electrocardiogram available in Physionet PTBI dataset. The model also helps to create ‘what if’ scenarios and relevant analysis to study the effect in different hemodynamic parameters for stress or exercise like conditions.
Manna Zhang, Lin Li, Ma Luo,
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247799

Abstract:
COVID-19 has greatly affected public health and world economy. In this study, we analyzed 129 full-length genomes of SARS-CoV-2 viruses of a Canadian population during early phase of the pandemic. Phylogenetic analysis revealed three major paths of transmission of SARS-CoV-2 viruses into Canada. Twenty-one substitutions that have frequencies greater than 3% of viral population were identified. Analysis of these substitutions indicated that P1427I (ORF1b), Y1464C (ORF1b), and Q57H (ORF3a) might affect functions of the corresponding SARS-CoV-2 encoded proteins. Additionally, we found the evidence of positive selection on the ORF3a and codon 614 of Spike protein, suggesting the viral components responsible for host entry and activation of inflammation response were targeted by host immune responses. The study showed genomic variation and evolution of SARS-CoV-2 in a Canadian population. These information may help develop preventive strategies and be used for further study of SARS-CoV-2 pathogenesis and therapeutics development.
Jesús Gómez, , Piotr Minias
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0248021

Abstract:
Brood parasitized and/or colonial birds use egg features as visual identity signals, which allow parents to recognize their own eggs and avoid paying fitness costs of misdirecting their care to others’ offspring. However, the mechanisms of egg recognition and discrimination are poorly understood. Most studies have put their focus on individual abilities to carry out these behavioural tasks, while less attention has been paid to the egg and how its signals may evolve to enhance its identification. We used 92 clutches (460 eggs) of the Eurasian coot Fulica atra to test whether eggs could be correctly classified into their corresponding clutches based only on their external appearance. Using SpotEgg, we characterized the eggs in 27 variables of colour, spottiness, shape and size from calibrated digital images. Then, we used these variables in a supervised machine learning algorithm for multi-class egg classification, where each egg was classified to the best matched clutch out of 92 studied clutches. The best model with all 27 explanatory variables assigned correctly 53.3% (CI = 42.6–63.7%) of eggs of the test-set, greatly exceeding the probability to classify the eggs by chance (1/92, 1.1%). This finding supports the hypothesis that eggs have visual identity signals in their phenotypes. Simplified models with fewer explanatory variables (10 or 15) showed lesser classification ability than full models, suggesting that birds may use multiple traits for egg recognition. Therefore, egg phenotypes should be assessed in their full complexity, including colour, patterning, shape and size. Most important variables for classification were those with the highest intraclutch correlation, demonstrating that individual recognition traits are repeatable. Algorithm classification performance improved by each extra training egg added to the model. Thus, repetition of egg design within a clutch would reinforce signals and would help females to create an internal template for true recognition of their own eggs. In conclusion, our novel approach based on machine learning provided important insights on how signallers broadcast their specific signature cues to enhance their recognisability.
Carlos Berlanga-Macías, Mairena Sánchez-López, , Ana Díez-Fernández, Inmaculada Ballesteros-Yáñez, Carlos A. Castillo-Sarmiento, Isabel A. Martínez-Ortega,
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0248023

Abstract:
Objective A positive relationship between breastfeeding and brain-derived neurotrophic factor (BDNF) in infants has been suggested due to the presence of BDNF in human milk. This study aimed to determine the relationship between exclusive breastfeeding and BDNF serum levels in Spanish schoolchildren. Methods A cross-sectional analysis including 202 schoolchildren, aged eight to 11 years, from Cuenca, Spain, was conducted. Information on sociodemographic and anthropometric variables, sexual maturation, birth weight and exclusive breastfeeding (‘no exclusive breastfeeding’, and exclusive breastfeeding for ≤6 and >6 months), and BDNF serum levels using an ELISA method were obtained. Covariance analyses (ANCOVA) were conducted to examine the relationship between serological BDNF and exclusive breastfeeding after controlling for potential confounders. Results ANCOVA models showed no significant differences in BDNF levels between children who were exclusively breastfed for more than six months versus those who were not (p > 0.05). No significant differences were observed by age group (eight to nine years versus 10 to 11 years; p > 0.05). Additionally, no clear negative trend in BDNF serum levels according to sexual maturation categories was found (p > 0.05). Conclusion These findings suggest that exclusive breastfeeding does not have a significant positive association on BDNF from eight to 11 years, since children who were exclusively breastfed did not have significantly higher BDNF levels than those who were not exclusively breastfed. Likewise, BDNF levels were not found to be negatively affected by hormonal development. Future research should examine the influence of exclusive breastfeeding on BDNF over the different developmental stages.
Martina Aida Angeles, Carlos Martínez-Gómez, Mathilde Del, Federico Migliorelli, Manon Daix, Anaïs Provendier, Muriel Picard, Jean Ruiz, Elodie Chantalat, Hélène Leray, et al.
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0248205

Abstract:
Background Gastric perforation after cytoreductive surgery (CRS) is an infrequent complication. There is lack of evidence regarding the risk factors for this postoperative complication. The aim of this study was to assess the prevalence of postoperative gastric perforation in patients undergoing CRS for peritoneal carcinomatosis (PC) and to evaluate risk factors predisposing to this complication. Methods We designed a unicentric retrospective study to identify all patients who underwent an open upfront or interval CRS after a primary diagnosis of PC of different origins between March 2007 and December 2018 at a French Comprehensive Cancer Center. The main outcome was the occurrence of postoperative gastric perforation. Results Five hundred thirty-three patients underwent a CRS for PC during the study period and 13 (2.4%) presented a postoperative gastric perforation with a mortality rate of 23% (3/13). Neoadjuvant chemotherapy was administered in 283 (53.1%) patients and 99 (18.6%) received hyperthermic intraperitoneal chemotherapy (HIPEC). In the univariate analysis, body mass index (BMI), peritoneal cancer index, splenectomy, distal pancreatectomy, and histology were significantly associated with postoperative gastric perforation. After multivariate analysis, BMI (OR [95%CI] = 1.13 [1.05–1.22], p = 0.002) and splenectomy (OR [95%CI] = 26.65 [1.39–509.67], p = 0.029) remained significantly related to the primary outcome. Conclusions Gastric perforation after CRS is a rare event with a high rate of mortality. While splenectomy and increased BMI are risk factors associated with this complication, HIPEC does not seem to be related. Gastric perforation is probably an ischemic complication due to a multifactorial process. Preventive measures such as preservation of the gastroepiploic arcade and prophylactic suture of the greater gastric curvature require further assessment.
Correction
Rani Cathrine Chellappa, Bincy Lukose, P. Rani
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0248252

Correction
Rodrigo A. Brandão Neto, Julio F. Marchini, Lucas O. Marino, Julio C. G. Alencar, Felippe Lazar Neto, Sabrina Ribeiro, Fernando S. Valente, Hassan Rahhal, Luz Marina Gomez Gomez, Caue G. Bueno, et al.
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0248327

Correction
The Plos One Staff
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0248443

Ron Baik, Stacia K. Wyman, ,
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247858

Abstract:
Myeloproliferative neoplasms (MPNs) cause the over-production of blood cells such as erythrocytes (polycythemia vera) or platelets (essential thrombocytosis). JAK2 V617F is the most prevalent somatic mutation in many MPNs, but previous modeling of this mutation in mice relied on transgenic overexpression and resulted in diverse phenotypes that were in some cases attributed to expression level. CRISPR-Cas9 engineering offers new possibilities to model and potentially cure genetically encoded disorders via precise modification of the endogenous locus in primary cells. Here we develop “scarless” Cas9-based reagents to create and reverse the JAK2 V617F mutation in an immortalized human erythroid progenitor cell line (HUDEP-2), CD34+ adult human hematopoietic stem and progenitor cells (HSPCs), and immunophenotypic long-term hematopoietic stem cells (LT-HSCs). We find no overt in vitro increase in proliferation associated with an endogenous JAK2 V617F allele, but co-culture with wild type cells unmasks a competitive growth advantage provided by the mutation. Acquisition of the V617F allele also promotes terminal differentiation of erythroid progenitors, even in the absence of hematopoietic cytokine signaling. Taken together, these data are consistent with the gradually progressive manifestation of MPNs and reveals that endogenously acquired JAK2 V617F mutations may yield more subtle phenotypes as compared to transgenic overexpression models.
, Pascal J. Kieslich, Andrea M. Wycoff, Katja Bertsch, Christian Schmahl, Inga Niedtfeld
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247955

Abstract:
Individuals with Borderline Personality Disorder (BPD) or Social Anxiety Disorder (SAD) suffer from substantial interpersonal dysfunction and have difficulties establishing social bonds. A tendency to form negative first impressions of others could contribute to this by way of reducing approach behavior. We tested whether women with BPD or SAD would show negative impression formation compared to healthy women (HCs). We employed the Thin Slices paradigm and showed videos of 52 authentic target participants to 32 women with BPD, 29 women with SAD, and 37 HCs. We asked participants to evaluate whether different positive or negative adjectives described targets and expected BPD raters to provide the most negative ratings, followed by SAD and HC. BPD and SAD raters both agreed with negative adjectives more often than HCs (e.g., ‘Yes, the person is greedy’), and BPD raters rejected positive adjectives more often (e.g., ‘No, the person is not humble.’). However, BPD and SAD raters did not differ significantly from each other. Additionally, we used the novel process tracing method mouse-tracking to assess the cognitive conflict (via trajectory deviations) raters experienced during decision-making. We hypothesized that HCs would experience more conflict when making unfavorable (versus favorable) evaluations and that this pattern would flip in BPD and SAD. We quantified cognitive conflict via maximum absolute deviations (MADs) of the mouse-trajectories. As hypothesized, HCs showed more conflict when rejecting versus agreeing with positive adjectives. The pattern did not flip in BPD and SAD but was substantially reduced, such that BPD and SAD showed similar levels of conflict when rejecting and agreeing with positive adjectives. Contrary to the hypothesis for BPD and SAD, all three groups experienced substantial conflict when agreeing with negative adjectives. We discuss therapeutic implications of the combined choice and mouse-tracking results.
, Catalina Tolsada-Velasco, Sergio Roig-Casasús, Elena Costa-Moreno, Irene Borja-De-Fuentes, José-María Blasco
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247885

Abstract:
Background and purpose Ankle function declines with age. The objective of this study was to investigate the association between ankle function and balance in older adults, with a focus on range of motion (ROM) and strength. Methods This was a cross-sectional study that included 88 healthy community-dwelling older adults. Ankle mobility was measured while bearing weight (lunge test) and not bearing weight. The plantar-flexor muscle strength was assessed using a hand-held dynamometer. Balance was measured in terms of dynamic balance and mobility (timed up and go test), monopodal and bipodal static balance with open and closed eyes (single-leg stand test and platform measures), and margins of stability (functional reach test). Linear correlation and multiple regression analyses were conducted with a 95% CI. Results and discussion Most participants had limited ankle mobility (n = 75, 86%). Weight-bearing ankle dorsiflexion ROM was the strongest predictor of dynamic balance and included general mobility and stability ( R a d j 2 = [0.34]; β = [-0.50]). In contrast, plantar-flexor muscle strength was a significant predictor of static standing balance with open eyes ( R a d j 2 = [0.16–0.2]; β = [0.29–0.34]). Overall, weight-bearing ankle dorsiflexion ROM was a more representative measure of balance and functional performance; however, a non-weight-bearing mobility assessment provides complementary information. Therefore, both measures can be used in clinical practice. Conclusion This study supports the concept that ankle mobility contributes to the performance of dynamic tasks, while the plantar-flexor muscle strength helps to develop a standing static balance. Identification of alterations in ankle function is warranted and may assist in the design of tailored interventions. These interventions can be used in isolation or to augment conventional balance training in order to improve balance performance in community-dwelling older adults.
, Anne McMunn
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247959

Abstract:
Objective To describe how men and women divided childcare and housework demands during the height of the first Covid-19 lockdown in the UK, and whether these divisions were associated with worsening mental health during the pandemic. Background School closures and homeworking during the Covid-19 crisis have resulted in an immediate increase in unpaid care work, which draws new attention to gender inequality in divisions of unpaid care work. Methods Data come from the wave 9 (2017–19) of Understanding Society and the following April (n = 15,426) and May (n = 14,150) waves of Understanding Society Covid-19 study. Psychological distress was measured using the General Health Questionnaire (GHQ) at both before and during the lockdown, and unpaid care work was measured during the lockdown. Linear regression models were used. Results Women spent much more time on unpaid care work than men during lockdown, and it was more likely to be the mother than the father who reduced working hours or changed employment schedules due to increased time on childcare. Women who spent long hours on housework and childcare were more likely to report increased levels of psychological distress. Working parents who adapted their work patterns increased more psychological distress than those who did not. This association was much stronger if he or she was the only member in the household who adapted their work patterns, or if she was a lone mother. Fathers increased more psychological distress if they reduced work hours but she did not, compared to neither reducing work hours. Conclusion There are continued gender inequalities in divisions of unpaid care work. Juggling home working with homeschooling and childcare as well as extra housework is likely to lead to poor mental health for people with families, particularly for lone mothers.
Alexander A. Cohen, Zhi Yang, Priyanthi N. P. Gnanapragasam, Susan Ou, Kim-Marie A. Dam, Haoqing Wang,
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247963

Abstract:
Current influenza vaccines do not elicit broadly protective immune responses against multiple strains. New strategies to focus the humoral immune response to conserved regions on influenza antigens are therefore required for recognition by broadly neutralizing antibodies. It has been suggested that B-cells with receptors that recognize conserved epitopes would be preferentially stimulated through avidity effects by mosaic particles presenting multiple forms of a variable antigen. We adapted SpyCatcher-based platforms, AP205 virus-like particles (VLPs) and mi3 nanoparticles (NPs), to covalently co-display SpyTagged hemagglutinin (HA) trimers from group 1 and group 2 influenza A strains. Here we show successful homotypic and heterotypic conjugation of up to 8 different HA trimers to both VLPs and NPs. We characterized the HA-VLPs and HA-NPs by cryo-electron tomography to derive the average number of conjugated HAs and their separation distances on particles, and compared immunizations of mosaic and homotypic particles in wild-type mice. Both types of HA particles elicited strong antibody responses, but the mosaic particles did not consistently elicit broader immune responses than mixtures of homotypic particles. We conclude that covalent attachment of HAs from currently-circulating influenza strains represents a viable alternative to current annual influenza vaccine strategies, but in the absence of further modifications, is unlikely to represent a method for making a universal influenza vaccine.
Korie A. Grayson, , Nerymar Ortiz-Otero,
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0246733

Abstract:
Three-dimensional spheroid cultures have been shown to better physiologically mimic the cell-cell and cell-matrix interactions that occur in solid tumors more than traditional 2D cell cultures. One challenge in spheroid production is forming and maintaining spheroids of uniform size. Here, we developed uniform, high-throughput, multicellular spheroids that self-assemble using microwell plates. DU145 and PC3 cells were cultured as 2D monolayers and 3D spheroids to compare sensitization of TRAIL-resistance cancer cells to TRAIL mediated apoptosis via chemotherapy based on dimensionality. Monocultured monolayers and spheroids were treated with soluble TRAIL alone (24 hr), DTX or CBZ alone (24 hr), or a combination of taxane and TRAIL (24 + 24 hr) to determine the effectiveness of taxanes as TRAIL sensitizers. Upon treatment with soluble TRAIL or taxanes solely, monolayer cells and spheroids exhibited no significant reduction in cell viability compared to the control, indicating that both cell lines are resistant to TRAIL and taxane alone in 2D and 3D. Pretreatment with CBZ or DTX followed by TRAIL synergistically amplified apoptosis in 2D and 3D DU145 cell cultures. PC3 spheroids were more resistant to the combination therapy, displaying a more additive effect in the DTX + TRAIL group compared to 2D. There was a downregulation of DR4/5 expression in spheroid form compared to monolayers in each cell line. Additionally, normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) were cocultured with both PCa cell lines as spheroids to determine if CAFs confer additional resistance to chemotherapy. We determined that co-cultured spheroids show similar drug resistance to monocultured spheroids when treated with taxane plus TRAIL treatment. Collectively, these findings suggest how the third dimension and cocultures of different cell types effect the sensitization of androgen-independent prostate cancer cells to TRAIL, suggesting therapeutic targets that could overcome TRAIL-resistance in metastatic castration-resistant prostate cancer (mCRPC).
Marya Bengali, Spencer Goodman, Xiaoying Sun, Magdalene A. Dohil, Ranjan Dohil, Robert Newbury, Tatiana Lobry, Laura Hernandez, Corinne Antignac, Sonia Jain, et al.
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247846

Abstract:
Importance Development of noninvasive methodology to reproducibly measure tissue cystine crystal load to assess disease status and guide clinical care in cystinosis, an inherited lysosomal storage disorder characterized by widespread cystine crystal accumulation. Objective To develop an unbiased and semi-automated imaging methodology to quantify dermal cystine crystal accumulation in patients to correlate with disease status. Design, setting and participants 101 participants, 70 patients and 31 healthy controls, were enrolled at the University of California, San Diego, Cystinosis Clinics, Rady Children’s Hospital, San Diego and at the annual Cystinosis Research Foundation family conference for an ongoing prospective longitudinal cohort study of cystinosis patients with potential yearly follow-up. Exposures Intradermal reflectance confocal microscopy (RCM) imaging, blood collection via standard venipuncture, medical record collection, and occasional skin punch biopsies. Main outcomes and measures The primary outcome was to establish an automated measure of normalized confocal crystal volume (nCCV) for each subject. Secondary analysis examined the association of nCCV with various clinical indicators to assess nCCV’s possible predictive potential. Results Over 2 years, 57 patients diagnosed with cystinosis (median [range] age: 15.1 yrs [0.8, 54]; 41.4% female) were intradermally assessed by RCM to produce 84 image stacks. 27 healthy individuals (38.7 yrs [10, 85]; 53.1% female) were also imaged providing 37 control image stacks. Automated 2D crystal area quantification revealed that patients had significantly elevated crystal accumulation within the superficial dermis. 3D volumetric analysis of this region was significantly higher in patients compared to healthy controls (mean [SD]: 1934.0 μm3 [1169.1] for patients vs. 363.1 μm3 [194.3] for controls, PP = 0.02) and stage of chronic kidney disease (slope estimate = 0.53, 95%CI: [0.05, 1.00], P = 0.03). Conclusions and relevance This study used non-invasive RCM imaging to develop an intradermal cystine crystal quantification method. Results showed that cystinosis patients had increased nCCV compared to healthy controls. Level of patient nCCV correlated with several clinical outcomes suggesting nCCV may be used as a potential new biomarker for cystinosis to monitor long-term disease control and medication compliance.
, Mabel Carabali, Jacqueline K. Lim
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247255

Abstract:
Background The force of infection, or the rate at which susceptible individuals become infected, is an important public health measure for assessing the extent of outbreaks and the impact of control programs. Methods and findings We present Bayesian methods for estimating force of infection using serological surveys of infections which produce a lasting immune response, accounting for imperfections of the test, and uncertainty in such imperfections. In this estimation, the sensitivity and specificity can either be fixed, or belief distributions of their values can be elicited to allow for uncertainty. We analyse data from two published serological studies of dengue, one in Colombo, Sri Lanka, with a single survey and one in Medellin, Colombia, with repeated surveys in the same individuals. For the Colombo study, we illustrate how the inferred force of infection increases as the sensitivity decreases, and the reverse for specificity. When 100% sensitivity and specificity are assumed, the results are very similar to those from a standard analysis with binomial regression. For the Medellin study, the elicited distribution for sensitivity had a lower mean and higher variance than the one for specificity. Consequently, taking uncertainty in sensitivity into account resulted in a wide credible interval for the force of infection. Conclusions These methods can make more realistic estimates of force of infection, and help inform the choice of serological tests for future serosurveys.
Gab-Chol Choi, Sokho Kim, Mahbubur Rahman, Ji Hyun Oh, Yun Seok Cho,
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0235454

Abstract:
Background and aims Inflammation and calcification are major factors responsible for degeneration of bioprosthetic valve and other substitute heart valve implantations. The objective of this study was to evaluate the anti-inflammatory and anti-calcification effects of Entelon150® (consisting of grape-seed extract) in a beagle dog model of intravascular bovine pericardium implantation. Methods In total, 8 healthy male beagle dogs were implanted with a bovine pericardium bilaterally in the external jugular veins and divided into two groups. Animals in the Entelon150® group (n = 4) were treated with 150 mg of Entelon150® twice daily for six weeks after surgery. The negative control (NC) group (n = 4) was treated with 5 ml of saline using the same method. After six weeks, we measured the calcium content, performed histological examination, and performed molecular analysis. Results The calcium content of implanted tissue in the Entelon150® group (0.56±0.14 mg/g) was significantly lower than that in the NC group (1.48±0.57 mg/g) (p < 0.05). Histopathological examination showed that infiltration of chronic inflammatory cells, such as fibroblasts and macrophages, occurred around the graft in all groups; however, the inflammation level of the implanted tissue in the Entelon150® group was s lower than that in the NC group. Both immunohistochemical and western blot analyses revealed that bone morphogenetic protein 2 expression was significantly attenuated in the Entelon150® group. Conclusions Our results indicate that Entelon150® significantly attenuates post-implantation inflammation and degenerative calcification of the bovine pericardium in dogs. Therefore, Entelon150® may increase the longevity of the bovine pericardium after intravascular implantation.
, Csaba Jeney, Darius Halm, Günter Finkenzeller, G. Björn Stark, Roland Zengerle, Peter Koltay, Stefan Zimmermann
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0238330

Abstract:
The homogeneity of the genetically modified single-cells is a necessity for many applications such as cell line development, gene therapy, and tissue engineering and in particular for regenerative medical applications. The lack of tools to effectively isolate and characterize CRISPR/Cas9 engineered cells is considered as a significant bottleneck in these applications. Especially the incompatibility of protein detection technologies to confirm protein expression changes without a preconditional large-scale clonal expansion creates a gridlock in many applications. To ameliorate the characterization of engineered cells, we propose an improved workflow, including single-cell printing/isolation technology based on fluorescent properties with high yield, a genomic edit screen (Surveyor assay), mRNA RT-PCR assessing altered gene expression, and a versatile protein detection tool called emulsion-coupling to deliver a high-content, unified single-cell workflow. The workflow was exemplified by engineering and functionally validating RANKL knockout immortalized mesenchymal stem cells showing bone formation capacity of these cells. The resulting workflow is economical, without the requirement of large-scale clonal expansions of the cells with overall cloning efficiency above 30% of CRISPR/Cas9 edited cells. Nevertheless, as the single-cell clones are comprehensively characterized at an early, highly parallel phase of the development of cells including DNA, RNA, and protein levels, the workflow delivers a higher number of successfully edited cells for further characterization, lowering the chance of late failures in the development process.
Michael Hansen, Xiaopin Cai, Sara Bowen, David A. Largaespada,
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247375

Abstract:
Gene editing has become an essential tool for interrogation of gene function in biomedical research and is also a promising approach for gene therapy. Despite recent progresses, the gene-editing procedure is still a tedious process involving manually isolating large number of single cell colonies to screen for desired mutations. For diploid eukaryotic cells, there is the additional challenge to inactivate both alleles for genes-of-interest, i.e., generating double knockouts (DKOs), for the desired phenotypes or therapeutic effects. In this report, we present a novel method based on Fluorescence Assisted Cell Sorting (FACS) to enrich for DKO cells, using a cell surface marker β2-microglobulin (B2M) as a basis for negative selection. This method significantly increased percentage of DKOs in isolated cells after gene editing, and in the meantime, significantly improve the efficiency of workflow by automating colony isolation. It would greatly facilitate future biomedical research including potential gene/cell therapies.
Maryam Honari-Jahromi, Brea Chouinard, Esti Blanco-Elorrieta, Liina Pylkkänen,
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0242754

Abstract:
In language, stored semantic representations of lexical items combine into an infinitude of complex expressions. While the neuroscience of composition has begun to mature, we do not yet understand how the stored representations evolve and morph during composition. New decoding techniques allow us to crack open this very hard question: we can train a model to recognize a representation in one context or time-point and assess its accuracy in another. We combined the decoding approach with magnetoencephalography recorded during a picture naming task to investigate the temporal evolution of noun and adjective representations during speech planning. We tracked semantic representations as they combined into simple two-word phrases, using single words and two-word lists as non-combinatory controls. We found that nouns were generally more decodable than adjectives, suggesting that noun representations were stronger and/or more consistent across trials than those of adjectives. When training and testing across contexts and times, the representations of isolated nouns were recoverable when those nouns were embedded in phrases, but not so if they were embedded in lists. Adjective representations did not show a similar consistency across isolated and phrasal contexts. Noun representations in phrases also sustained over time in a way that was not observed for any other pairing of word class and context. These findings offer a new window into the temporal evolution and context sensitivity of word representations during composition, revealing a clear asymmetry between adjectives and nouns. The impact of phrasal contexts on the decodability of nouns may be due to the nouns’ status as head of phrase—an intriguing hypothesis for future research.
, Anthea Pun, Andrew Scott Baron, Gil Diesendruck
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247710

Abstract:
Recent studies indicate that a preference for people from one’s own race emerges early in development. Arguably, one potential process contributing to such a bias has to do with the increased discriminability of own- vs. other-race faces–a process commonly attributed to perceptual narrowing of unfamiliar groups’ faces, and analogous to the conceptual homogenization of out-groups. The present studies addressed two implications of perceptual narrowing of other-race faces for infants’ social categorization capacity. In Experiment 1, White 11-month-olds’ (N = 81) looking time at a Black vs. White face was measured under three between-subjects conditions: a baseline “preference” (i.e., without familiarization), after familiarization to Black faces, or after familiarization to White faces. Compared to infants’ a priori looking preferences as revealed in the baseline condition, only when familiarized to Black faces did infants look longer at the "not-familiarized-category" face at test. According to the standard categorization paradigm used, such longer looking time at the novel (i.e., "not-familiarized-category") exemplar at test, indicated that categorization of the familiarized faces had ensued. This is consistent with the idea that prior to their first birthday, infants already tend to represent own-race faces as individuals and other-race faces as a category. If this is the case, then infants might also be less likely to form subordinate categories within other-race than own-race categories. In Experiment 2, infants (N = 34) distinguished between an arbitrary (shirt-color) based sub-categories only when shirt-wearers were White, but not when they were Black. These findings confirm that perceptual narrowing of other-race faces blurs distinctions among members of unfamiliar categories. Consequently, infants: a) readily categorize other-race faces as being of the same kind, and b) find it hard to distinguish between their sub-categories.
Rin Yokoyama, , Yoshifumi Morita, Takuya Shimura, Yuki Nakano, Chungen Qian, Fuzhen Xia, Fan He, Yoshiro Kishi, Jun Okada, et al.
Published: 4 March 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0247711

Abstract:
PCR methods are presently the standard for the diagnosis of Coronavirus disease 2019 (COVID-19), but additional methodologies are needed to complement PCR methods, which have some limitations. Here, we validated and investigated the usefulness of measuring serum antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the iFlash3000 CLIA analyzer. We measured IgM and IgG titers against SARS-CoV-2 in sera collected from 26 PCR-positive COVID-19 patients, 53 COVID-19-suspected but PCR-negative patients, and 20 and 100 randomly selected non-COVID-19 patients who visited our hospital in 2020 and 2017, respectively. The repeatability and within-laboratory precision were obviously good in validations, following to the CLSI document EP15-A3. Linearity was also considered good between 0.6 AU/mL and 112.7 AU/mL for SARS-CoV-2 IgM and between 3.2 AU/mL and 55.3 AU/mL for SARS-CoV-2 IgG, while the linearity curves plateaued above the upper measurement range. We also confirmed that the seroconversion and no-antibody titers were over the cutoff values in all 100 serum samples collected in 2017. These results indicate that this measurement system successfully detects SARS-CoV-2 IgM/IgG. We observed four false-positive cases in the IgM assay and no false-positive cases in the IgG assay when 111 serum samples known to contain autoantibodies were evaluated. The concordance rates of the antibody test with the PCR test were 98.1% for SARS-CoV-2 IgM and 100% for IgG among PCR-negative cases and 30.8% for SARS-CoV-2 IgM and 73.1% for SARS-CoV-2 IgG among PCR-positive cases. In conclusion, the performance of this new automated method for detecting antibody against both N and S proteins of SARS-CoV-2 is sufficient for use in laboratory testing.
Page of 4,950
Articles per Page
by
Show export options
  Select all
Back to Top Top