bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 specific memory T lymphocytes from COVID-19 convalescent donors: identification, biobanking and large-scale production for Adoptive Cell Therapy
Authors: Ferreras C , Pascual-Miguel B , Mestre-Durán C , Navarro-Zapata A , Clares-Villa L , Martín-Cortázar C , De Paz R , Marcos A , Vicario JL , Balas A , García-Sánchez F , Eguizabal C , Solano C , Mora-Rillo M , Soria B , Pérez-Martínez A 
Published: October 2020

ABSTRACTSARS-CoV-2 is causing a second outbreak so the hope for its complete eradication is far from happening. In the absence of effective vaccines, it is mandatory to find effective treatments with low adverse effects able to treat hospitalized patients with COVID-19 disease. In this work, we determined the existence of SARS-CoV-2 specific T cells within the CD45RA−T memory cells from the blood of convalescent donors. Memory T cells can respond quickly to the infection and provide long-term immune protection to reduce the severity of the COVID-19 symptoms. Also, CD45RA−memory T cells confer protection from other pathogens the donors encountered in their life. This is vital to clear other secondary infections usually developed in hospitalized COVID-19 patients. SARS-CoV-2 specific memory T cells were found within all the CD45RA−subsets CD3+, CD4+, CD8+, and in the central memory and effector memory subpopulations. The procedure to obtain the cells is feasible, easy to implement for small scale manufacture, quick and cost-effective involving minimal manipulation, and without GMP condition requirements. This biobank of specific SARS-CoV-2 memory T cells would be immediately available ‘off-the-shelf’ to treat moderate/severe cases of COVID-19 increasing the therapeutic options available for these patients.
MEGA: Machine Learning-Enhanced Graph Analytics for Infodemic Risk Management
Authors: Hang Ching Nam , Yu Pei-Duo , Chen Siya , Tan Chee Wei , Chen Guanrong 
Published: October 2020

AbstractThe COVID-19 pandemic brought not only global devastation but also an unprecedented infodemic of false or misleading information that spread rapidly through online social networks. Network analysis plays a crucial role in the science of fact-checking by modeling and learning the risk of infodemics through statistical processes and computation on mega-sized graphs. This paper proposes MEGA,Machine Learning-EnhancedGraphAnalytics, a framework that combines feature engineering and graph neural networks to enhance the efficiency of learning performance involving massive graphs. Infodemic risk analysis is a unique application of the MEGA framework, which involves detecting spambots by counting triangle motifs and identifying influential spreaders by computing the distance centrality. The MEGA framework is evaluated using the COVID-19 pandemic Twitter dataset, demonstrating superior computational efficiency and classification accuracy.
Profiling of circulating chromosome 21-encoded microRNAs, miR-155 and Let-7c, in Down Syndrome People
Authors: Pérez-Villareal Jesús Manuel , Aviña-Padilla Katia , López Evangelina Beltrán , Guadrón-Llanos Alma Marlene , López-Bayghen Esther , Magaña-Gómez Javier , Meraz-Ríos Marco Antonio , Varela-Echavarría Alfredo , Angulo-Rojo Carla 
Published: October 2020

AbstractDown syndrome (DS), or Trisomy 21 (Ts21), is the most common chromosomal survival aneuploidy. Nevertheless, people with DS have compromised health, and the increase in their life expectancy further heightens the risk of developing chronic degenerative diseases such as obesity, dyslipidemias and diabetes mellitus associated with higher morbidity, and mortality for cardiovascular disease from an early age. DS is also accompanied by a higher risk of neurodegeneration. The extra genetic material that characterizes DS causes an imbalance in the genetic dosage, including overexpression of miR-155 and Let-7c miRNAs, both associated with cognitive impairment and dementia in adults. The dynamics of expression of their putative target genes in the early stages of the development of DS and their clinical associations, however, remain to be ascertained. This study aimed to evaluate the relative expression of miR-155 and Let-7c in young and adult individuals with DS and its possible association with biochemical indicators of lipid metabolism. The anthropometric, clinical, biochemical, and gene expression features of miR-155 and Let-7c were analyzed in a population of 52 control and 50 DS subjects divided into groups of 20 years of age or younger and 21 years or older. Expression changes for miR-155 were not significant. Nevertheless, a negative correlation for HDL-Cholesterol concentrations and miR-155 expression was identified. Notably, Let-7c was overexpressed in DS from young and old ages. Overall, our results suggest that Let-7c is related from early stages to cognitive impairment in DS, while a similar role of miR-155 in late stages could be mediated by alterations in lipid metabolism. Further studies with both miRNAs will shed light on their potential as therapeutic targets to prevent or delay cognitive impairment in DS.
An Inexpensive Smartphone-Based Device and Predictive Models for Rapid, Non-Invasive, and Point-of-Care Monitoring of Ocular and Cardiovascular Complications Related to Diabetes
Authors: Chakravadhanula Kasyap 
Published: October 2020

AbstractDiabetes is a massive global problem, with growth especially rapid in developing regions, which can lead to several damaging complications. Among the most impactful of these are diabetic retinopathy, the leading cause of blindness among working class adults, and cardiovascular disease, the leading cause of death worldwide. However, diagnosis is often too late to prevent irreversible damage caused by these linked conditions. This study describes the development of an integrated test, automated and not requiring laboratory blood analysis, for screening of these conditions. First, a random forest model was developed by retrospectively analyzing the influence of various risk factors (obtained quickly and non-invasively) on cardiovascular risk. Next, a deep-learning model was developed for prediction of diabetic retinopathy from retinal fundus images by a modified and re-trained InceptionV3 image classification model. The input was simplified by automatically segmenting the blood vessels in the retinal image. The technique of transfer learning enables the model to capitalize on existing infrastructure on the target device, meaning more versatile deployment, especially helpful in low-resource settings. The models were integrated into a smartphone-based device, combined with an inexpensive 3D-printed retinal imaging attachment. Accuracy scores, as well as the receiver operating characteristic curve, the learning curve, and other gauges, were promising. This test is much cheaper and faster, enabling continuous monitoring for two damaging complications of diabetes. It has the potential to replace the manual methods of diagnosing both diabetic retinopathy and cardiovascular risk, which are time consuming and costly processes only done by medical professionals away from the point of care, and to prevent irreversible blindness and heart-related complications through faster, cheaper, and safer monitoring of diabetic complications. As well, tracking of cardiovascular and ocular complications of diabetes can enable improved detection of other diabetic complications, leading to earlier and more efficient treatment on a global scale.
Clinical evaluation of a fully automated, lab developed multiplex RT-PCR assay integrating dual-target SARS-CoV-2 and Influenza–A/B detection on a high-throughput platform
Authors: Nörz Dominik , Hoffmann Armin , Aepfelbacher Martin , Pfefferle Susanne , Lütgehetmann Marc 
Published: October 2020

1AbstractBackgroundLaboratories worldwide face high demands for molecular testing during the SARS-CoV-2 pandemic that might be further aggravated with the upcoming influenza season in the northern hemisphere. Considering that symptoms of influenza are largely undistinguishable from COVID-19, both SARS-CoV-2 and the Influenza viruses require concurrent testing by RT-PCR in patients presenting with symptoms of respiratory tract infection. In this study, we adapted and evaluated a laboratory developed multiplex RT-PCR assay for simultaneous detection of SARS-CoV-2 (dual-target), Influenza-A and Influenza-B (SC2/InflA/InflB-UCT) on a fully automated high-throughput system (cobas6800).MethodsAnalytical performance was assessed by serial dilution of quantified reference material and cell culture stocks in transport medium, including pre-treatment for chemical inactivation. For clinical evaluation, residual portions of 164 predetermined patient samples containing SARS-CoV-2 (n=52), Influenza-A (n=43) or Influenza-B (n=19), as well as a set of negative samples was subjected to the novel multiplex assay.ResultsThe assay demonstrated analytical performance comparable to currently available commercial tests, with limits of detection of 94.9 cp/ml for SARS-CoV-2, 14.6 cp/ml for Influenza-A and 422.3 cp/ml for Influenza-B. Clinical evaluation showed excellent agreement with the comparator assays (sensitivity 98.1%, 97.7% and 100% for Sars-CoV-2, Influenza-A and -B respectively).ConclusionThe SC2/InflA/InflB-UCT allows for efficient high-throughput testing for all three pathogens and thus provides streamlined diagnostics while conserving resources during the Influenza-season.HighlightsSimultaneous detection of highly pathogenic respiratory viruses Influenza-A/B and SARS-CoV-2Including a dual-target assay for SARS-CoV-2 detectionFull automation on the cobas6800 high-throughput platform
Estimating the Case Fatality Ratio for COVID-19 using a Time-Shifted Distribution Analysis
Authors: Thomas B. S. , Marks N. A. 
Published: October 2020

AbstractEstimating the case fatality ratio (CFR) for COVID-19 is an important aspect of public health. However, calculating CFR accurately is problematic early in a novel disease outbreak, due to uncertainties regarding the time course of disease and difficulties in diagnosis and reporting of cases. In this work, we present a simple method for calculating the case fatality ratio using only public case and death data over time by exploiting the correspondence between the time distributions of cases and deaths. The time-shifted distribution (TSD) analysis generates two parameters of interest: the delay time between reporting of cases and deaths and the case fatality ratio. These parameters converge reliably over time once the exponential growth phase has finished. Analysis is performed for early COVID-19 outbreaks in many countries, and we discuss corrections to CFR values using excess-death and seroprevalence data to estimate the infection fatality ratio (IFR). While CFR values range from 0.2-20% in different countries, estimates for IFR are mostly around 0.5-0.8% for countries that experienced moderate outbreaks and 1-3% for severe outbreaks. The simplicity and transparency of TSD analysis enhance its usefulness in characterizing a new disease as well as the state of the health and reporting systems.
Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time
Authors: Walker A. Sarah , Pritchard Emma , House Thomas , Robotham Julie V , Birrell Paul J , Bell Iain , Bell John I , Newton John N , Farrar Jeremy , Diamond Ian , Studley Ruth , Hay Jodie , Vihta Karina-Doris , Peto Tim , Stoesser Nicole , Matthews Philippa C. , Eyre David W. , Pouwels Koen B. ,   the COVID-19 Infection Survey team
Published: October 2020

ABSTRACTInformation on SARS-CoV-2 in representative community surveillance is limited, particularly cycle threshold (Ct) values (a proxy for viral load). Of 3,312,159 nose and throat swabs taken 26-April-2020 to 13-March-2021 in the UK’s national COVID-19 Infection Survey, 27,902(0.83%) were RT-PCR-positive, 10,317(37%), 11,012(40%) and 6,550(23%) for 3, 2 or 1 of the N, S and ORF1ab genes respectively, with median Ct=29.2 (∼215 copies/ml; IQR Ct=21.9-32.8, 14-56,400 copies/ml). Independent predictors of lower Cts (i.e. higher viral load) included self-reported symptoms and more genes detected, with at most small effects of sex, ethnicity and age. Single-gene positives almost invariably had Ct>30, but Cts varied widely in triple-gene positives, including without symptoms. Population-level Cts changed over time, with declining Ct preceding increasing SARS-CoV-2 positivity. Of 6,189 participants with IgG S-antibody tests post-first RT-PCR-positive, 4,808(78%) were ever antibody-positive; Cts were significantly higher in those remaining antibody-negative. Community SARS-CoV-2 Ct values could be a useful epidemiological early-warning indicator.IMPACT STATEMENTCt values from SARS-CoV-2 RT-PCR tests vary widely and over calendar time. They have the potential to be used more broadly in public testing programmes as an “early-warning” system for shifts in infectious load and hence transmission.
Saliva is a promising alternative specimen for the detection of SARS-CoV-2 in children and adults
Authors: Yee Rebecca , Truong Thao , Pannaraj Pia S. , Eubanks Natalie , Gai Emily , Jumarang Jaycee , Turner Lauren , Peralta Ariana , Lee Yesun , Bard Jennifer Dien 
Published: October 2020

AbstractTesting efforts for SARS-CoV-2 have been burdened by the scarcity of testing materials and personal protective equipment for healthcare workers. The simple and painless process of saliva collection allows for widespread testing, but enthusiasm is hampered by variable performance compared to nasopharyngeal swab (NPS) samples. We prospectively collected paired NPS and saliva samples from a total of 300 unique adult and pediatric patients. SARS-CoV-2 RNA was detected in 32.2% (97/300) of the individuals using the TaqPath COVID-19 Combo Kit (Thermo Fisher). Performance of saliva and NPS were compared against the total number of positives regardless of specimen type. The overall concordance for saliva and NPS was 91.0% (273/300) and 94.7% (284/300), respectively. The positive percent agreement (PPA) for saliva and NPS was 81.4% (79/97) and 89.7% (87/97), respectively. Saliva detected 10 positive cases that were negative by NPS. In symptomatic and asymptomatic pediatric patients not previously diagnosed with COVID-19, the performances of saliva and NPS were comparable (PPA: 82.4% vs 85.3%). The overall PPA for adults were 83.3% and 90.7% for saliva and NPS, respectively, with saliva detecting 4 cases less than NPS. However, saliva performance in symptomatic adults was identical to NPS (PPA of 93.8%). With lower cost and self-collection capabilities, saliva can be an appropriate alternative sample choice to NPS for detection of SARS-CoV-2 in children and adults.SummarySaliva is an acceptable alternative specimen compared to nasopharyngeal swabs for detection of SARS-CoV-2. Specifically, saliva demonstrated comparable performance to nasopharyngeal swabs in symptomatic and asymptomatic pediatric patients and in symptomatic adults.
Stay-at-home and face mask policies intentions inconsistent with incidence and fatality during US COVID-19 pandemic
Authors: Wu Samuel X. , Wu Xin 
Published: October 2020

AbstractIn addition to the United States CDC recommendations, many states imposed stay-at-home (SAH) and mandatory face mask (MFM) orders during COVID-19 pandemic. The purpose of this study was to characterize the relationship between SAH and MFM approaches with the incidence and fatality during the pandemic period until the 2020-08-23 (about 171 days). States with SAH orders showed potential decreases of infection and fatality during SAH period (about 45 days). However, many results in this study were inconsistent with the intent of public health strategies of SAH and MFM. There were similar incidence rates among SAH + MFM, SAH + no-MFM and no-SAH + no-MFM states. After normalized to population density, there were no significant differences in total positive cases, average daily new cases and average daily fatality among the 3 groups during the pandemic period. This study suggested that SAH and MFM orders in the general public alone, probably have limited effects in lowering transmission and fatality. From the policy-making level, if we cannot strictly isolate contagious patients with effective contact tracing, we presume that following the CDC recommendations could be appropriate in helping mitigate the COVID-19 disaster and limiting collateral social-economic damage with close monitoring of healthcare capacity.
Incidence and risk factors of pulmonary hypertension after venous thromboembolism: An analysis of a large healthcare database
Authors: Lutsey Pamela L. , Prins Kurt W. , Evensen Line H. , Walker Rob F. , Farley Joel F. , MacLehose Richard F. , Alonso Alvaro , Zakai Neil A. , Thenappan Thenappan 
Published: October 2020

AbstractBackgroundPulmonary hypertension (PH) is a devastating potential complication of pulmonary embolism (PE), a manifestation of venous thromboembolism (VTE). The incidence of and risk factors for PH in those with prior VTE is poorly characterized.MethodsICD codes from inpatient and outpatient medical claims from MarketScan administrative databases for years 2011-2018 were used were used to identify cases of VTE, comorbidities prior to the VTE event, and PH occurring subsequent to the VTE event. Cumulative incidence and hazard ratios (HR), and their 95% confidence intervals (CI), were calculated.ResultsThe 170,021 VTE cases included in the analysis were on average (± SD) 57.5 ± 15.8 years old and 50.5% were female. A total of 5,946 PH cases accrued over an average follow-up of 1.94 years. Two years after incident VTE the cumulative incidence (95% CI) of PH was 3.5% (3.4%, 3.7%) overall. It was higher among women [3.9% (3.8%-4.1%)] than men [3.2% (3.0%-3.3%)], and among patients presenting with PE [6.2% (6.0%-6.5%)] than those presenting with deep vein thrombosis-only [1.1% (1.0%-1.2%)]. Adjusting for age and sex, risk of PH was higher among VTE patients with underlying comorbidities. The strongest associations were observed with concomitant heart failure [HR: 2.17 (1.04-2.31)], chronic pulmonary disease [2.01 (1.90-2.14)], and myocardial infarction [1.53 (1.40-1.67)].ConclusionsIn this large real-world population of insured people with VTE, 3.5% developed PH in the 2 years following their initial VTE event. Risk was higher among women, with increasing age, and in those with additional comorbidities at the time of the VTE event. These data provide insights into the burden of PH and risk factors for PH among VTE patients.
Efficacy of Convalescent Plasma Therapy compared to Fresh Frozen Plasma in Severely ill COVID-19 Patients: A Pilot Randomized Controlled Trial
Authors: Bajpai Meenu , Kumar Suresh , Maheshwari Ashish , Chhabra Karan , kale Pratibha , Gupta Amita , Narayanan Ashad , Gupta Ekta , Trehanpati Nirupama , Bihari Chhagan , Agarwal Reshu , Gupta Kamini , Gupta Upendra kumar , Bhardwaj Ankit , Kumar Guresh , Islam Mojahidul , Singh Ravinder , Yadav Pushpa , Maiwall Rakhi , Sarin Shiv Kumar 
Published: October 2020

AbstractBackgroundThe role of convalescent plasma (COPLA) for the treatment of severely ill Corona Virus Disease-2019 is under investigation. We compared the efficacy and safety of convalescent plasma with fresh frozen plasma (FFP) in severe COVID-19 patients.Methods and findingsThis was an open-label, single-centre phase II RCT on 29 patients with severe COVID-19 from India. One group received COPLA with standard medical care (SMC) (n=14), and another group received FFP with SMC (n=15). A total of 29 patients were randomized in the two treatment groups. Eleven out of 14 (78.5%) patients remained free of ventilation at day seven in the intervention arm while the proportion was 14 out of 15 (93.3 %) in the control arm (p= 0.258). The median reductions in RR per min at 48-hours in COPLA-group and FFP group were -6.5 and -3 respectively [p=0.004] and at day seven were -14.5 and -10 respectively (p=0.008). The median improvements in percentage O2 saturation at 48-hours were 6.5 and 2 respectively [p=0.001] and at day seven were 10 and 7.5 respectively (p=0.026). In the COPLA-group, the median improvement in PaO2/FiO2 was significantly superior to FFP at 48-hours [41.94 and 231.15, p=0.009], and also at day-7 [5.55 and 77.01 p<0.001]. We did not find significant differences in hospitalization duration between the groups (0.08).ConclusionCOPLA therapy resulted in rapid improvement in respiratory parameters and shortened time to clinical recovery, although no significant reduction in mortality was observed in this pilot trial. We need larger trials to draw conclusive evidence on the use of Convalescent plasma in COVID-19. This trial is registered with ClinicalTrial.gov (identifier: NCT04346446).
The Genetics and Evolution of Eye Color in Domestic Pigeons (Columba livia)
Authors: Si Si , Xu Xiao , Zhuang Yan , Gao Xiaodong , Zhang Honghai , Zou Zhengting , Luo Shu-Jin 
Published: October 2020

AbstractThe avian eye color, generally referred to the color of the iris, results from both pigments and structural coloration. Avian iris colors exhibit striking interspecific and, in some domestic species, intraspecific variations, suggesting unique evolutionary and ecological histories. Here we tackled the genetic basis of the pearl (white) iris color in domestic pigeons (Columba livia), to elucidate the largely unknown genetic mechanism underlying the evolution of avian iris coloration. Using a genome-wide association study (GWAS) in 92 pigeons, we mapped the pearl iris trait to a 9 kb region and a facilitative glucose transporter geneSLC2A11B. A nonsense mutation W49X leading to a premature stop codon in SLC2A11B was identified as the causal variant. Transcriptome analysis suggested that SLC2A11B loss-of-function may downregulate the xanthophore-differentiation geneCSF1R, and a key geneGCH1involved in biosynthesis of pteridine, whose absence results in pearl iris. Coalescence and phylogenetic analyses indicated the mutation originated about 5,400 years ago coinciding with the onset of pigeon domestication, while positive selection was detected likely associated with artificial breeding. Within Aves, potentially impaired SLC2A11B was found in 10 species from six distinct lineages correlated to their signature brown or blue eyes. Analysis of vertebrate SLC2A11B orthologs revealed relaxed selection in the avian clade, consistent with the scenario that, during and after avian divergence from reptile ancestor, the SLC2A11B-involved development of dermal chromatophores likely degenerated due to feather coverage. Our findings provide new insight into the mechanism of avian iris color variations and the evolution of pigmentation in vertebrates.