bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunogenicity and protective efficacy of a highly thermotolerant, trimeric SARS-CoV-2 receptor binding domain derivative
Authors: Malladi Sameer Kumar , Patel Unnatiben Rajeshbhai , Rajmani Raju S , Singh Randhir , Pandey Suman , Kumar Sahil , Khaleeq Sara , van Vuren Petrus Jansen , Riddell Shane , Goldie Sarah , Gayathri Savitha , Chakraborty Debajyoti , Kalita Parismita , Pramanick Ishika , Agarwal Nupur , Reddy Poorvi , Girish Nidhi , Upadhyaya Aditya , Khan Mohammad Suhail , Kanjo Kawkab , Bhat Madhuraj , Mani Shailendra , Bhattacharyya Sankar , Siddiqui Samreen , Tyagi Akansha , Jha Sujeet , Pandey Rajesh , Tripathi Shashank , Dutta Somnath , McAuley Alexander J. , Singanallur Nagendrakumar Balasubramanian , Vasan Seshadri S. , Ringe Rajesh P. , Varadarajan Raghavan 
Published: January 2021

AbstractThe Receptor Binding Domain (RBD) of SARS-CoV-2 is the primary target of neutralizing antibodies. We designed a trimeric, highly thermotolerant glycan engineered RBD by fusion to a heterologous, poorly immunogenic disulfide linked trimerization domain derived from cartilage matrix protein. The protein expressed at a yield of ∼80-100 mg/liter in transiently transfected Expi293 cells, as well as CHO and HEK293 stable cell lines and formed homogeneous disulfide-linked trimers. When lyophilized, these possessed remarkable functional stability to transient thermal stress of upto 100 °C and were stable to long term storage of over 4 weeks at 37 °C unlike an alternative RBD-trimer with a different trimerization domain. Two intramuscular immunizations with a human-compatible SWE adjuvanted formulation, elicited antibodies with pseudoviral neutralizing titers in guinea pigs and mice that were 25-250 fold higher than corresponding values in human convalescent sera. Against the beta (B.1.351) variant of concern (VOC), pseudoviral neutralization titers for RBD trimer were ∼ three-fold lower than against wildtype B.1 virus. RBD was also displayed on a designed ferritin-like Msdps2 nanoparticle. This showed decreased yield and immunogenicity relative to trimeric RBD. Replicative virus neutralization assays using mouse sera demonstrated that antibodies induced by the trimers neutralized all four VOC to date, namely B.1.1.7, B.1.351, P.1 and B.1.617.2 without significant differences. Trimeric RBD immunized hamsters were protected from viral challenge. The excellent immunogenicity, thermotolerance, and high yield of these immunogens suggest that they are a promising modality to combat COVID-19, including all SARS-CoV-2 VOC to date.
Epidemiological Investigation of New SARS-CoV-2 Variant of Concern 202012/01 in England
Authors: Gravagnuolo Alfredo Maria , Faqih Layla , Cronshaw Cara , Wynn Jackie , Burglin Lewis , Klapper Paul , Wigglesworth Mark 
Published: January 2021

AbstractLighthouse Labs network tests for the presence of RNA of SARS-CoV-2, the causative agent of COVID-19. The Thermofisher TaqPath assay targets three regions of SARS-CoV-2; ORF1ab, N and S-genes. The assay identified a drop in S-gene target detection among positive samples due to the circulation of a new SARS-CoV-2 Variant of Concern (VOC) designated as 202012/01. By end of December 2020, 60% of daily positive test results at Alderley Park Lighthouse Labs, were linked to the new Variant of Concern. This timeline view identifies the rapid spread of the variant across the country.
Comparison and analysis of various complementary diagnosis methods for the current situation and problems of COVID-19 diagnosis
Authors: Huh Hee Jin , Chae Seok Lae , Kim Dong-Min 
Published: January 2021

AbstractWe evaluated and compared the diagnostic performance of fluorescence immunoassay (FIA) and two types of serological diagnostic tests: enzyme-linked immunosorbent assay (ELISA) and immunochromatographic assay (ICA) for detection of SARS-CoV-2 antigen and antibody to diagnose COVID-19 infections. This study is aimed to analyze and compare the current status and problems of COVID-19 diagnosis and various alternative diagnostic methods that are viable. The enrolled subjects in our study population were tested with real-time polymerase chain reaction (RT-PCR). ELISA and immunochromatographic diagnostic kit were used to diagnose 362 positive and 3010 negative SARS-CoV-2 specimens, and antigen fluorescence immunoassay kit was used on 62 positive and 70 negative SARS-CoV-2 RT-PCR confirmed samples for diagnosis. As a result, categorizing by the patient symptom onset days, PCL COVID19 Total Ab EIA (ELISA) showed the sensitivity of 93.4% from 15 to 21 days, 94.2% from over 22 days, and the specificity of 99.97%. PCL COVID19 IgG/IgM Rapid Gold (ICA) had a sensitivity of 86.9%, 97.4%, and the specificity of 98.14% respectively. PCL COVID19 Ag Rapid FIA sensitivity was 93.8% from 0 to 7 days, 71.4% from 8 to 12 days and specificity was 98.57%. In conclusion, COVID-19 Ab ELISA and ICA, and COVID-19 Ag FIA are all complementary and applicable diagnostic methods to resolve the current problems of COVID-19 diagnosis.
SARS-CoV-2 infection control implementation based on sources of infection showing directions for three age groups in Japan
Authors: Hata Atsuko , Kurita Junko , Muso Eri , Katayama Toshiro , Hata Takahide , Ohkusa Yasushi 
Published: January 2021

AbstractBackgroundSome aspects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in children and adults remain unclear. This report describes different SARS-CoV-2 transmission patterns by age group in Japan.Methods and findingsThis retrospective observational case series study analyzed transmission patterns of real-time polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections found by local health authorities and commercial laboratories during January 14 through July 31, 2020 in Japan. After ascertaining the infection source for every symptomatic case as clusters at households, daycare facilities, schools, hospitals and workplaces etc., their associated transmission patterns were analyzed. Identified cases were divided into three groups: underage, < 20; adults, 20–59; and elderly people 60 years old and older. The reproductive number (R)s of respective transmission directions found for the respective age groups were compared.Of 26,986 total cases, 23,746 unknown cases were found, leaving 3,240 ascertained sources of infection (12.0%) comprising 125 (3.9%) underage, 2350 (72.5%) adult, and 765 (23.6%) elderly people. The respective Rs of underage infection sources directed to underage, adult, and elderly people were estimated respectively as 0.0415 (95% CI, 0.0138–0.0691), 1.11 (95% CI, 0.9171–1.3226), and 0.2811 (95% CI, 0.2074–0.3687). The respective Rs of adult infection source directed to underage, adult, and elderly people were estimated respectively as 0.0140 (95% CI, 0.0120–0.0162), 0.5392 (95% CI, 0.5236–0.5550), and 0.1135 (95% CI, 0.1074–0.1197). The respective Rs of elderly infection source directed to underage, adult, and elderly people were estimated as 0.065 (95% CI, 0.0039–0.0091), 0.3264 (95% CI, 0.3059–0.3474), and 0.3991 (95% CI, 0.3757–0.4229).ConclusionsThe main sources of SARS-CoV-2 infection were adults and elderly people. The R of underage people directed to adults was greater than 1 because of close familial contact but they were unlikely to become carriers transmitting SARS-CoV-2 because they accounted for a minority for transmissions. Apparently, SARS-CoV-2 was transmitted among adults and elderly people, suggesting that infection control of SARS-CoV-2 should be managed specifically by generation.
Reference values and validation of the 1-min sit-to-stand test in healthy 5- to 16-year-old youth: a cross-sectional study
Authors: Haile Sarah R , Fühner Thea , Granacher Urs , Stocker Julien , Radtke Thomas , Kriemler Susi 
Published: January 2021

AbstractObjectivesIt is essential to have simple, reliable and valid tests to measure children’s functional capacity in schools or medical practice. The 1-min sit-to-stand test (STS) is a quick fitness test requiring little equipment or space that is increasingly used in both healthy populations and those with chronic disease. We aimed to provide age and sex-specific reference values of STS in healthy children and adolescents and to evaluate its short-term reliability and construct validity.Design, setting and participantsCross-sectional random sample from 6 public schools and 1 science fair in central Europe. Overall, 587 healthy participants aged 5-16 years were recruited and divided into age groups of 3 years each.Outcomes1-minute STS. To evaluate short-term reliability, some children performed the STS twice. To evaluate construct validity, some children also performed a standing long jump (SLJ) and a maximal incremental exercise test.ResultsData from 547 5-16 year old youth were finally included in the analyses. The median number of repetitions in 1 minute in males (females) ranged from 55 [95% CI 38 to 72] (53 [35 to 76]) in 14-16 year-olds to 59 [41 to 77] (60 [38 to 77]) in 8-10 year-olds. Children who repeated STS showed a learning effect of on average 4.8 repetitions more than the first test (95% limits of agreement −6.7 to 16.4). Moderate correlations were observed between the STS and the SLJ (r= 0.48) and the maximal exercise test (r= 0.43).ConclusionsThe reported STS reference values can be used to interpret STS test performance in children and adolescents. The STS appears to have good test-retest reliability, but a learning effect of about 10%. The association of STS with other measures of physical fitness should be further explored in a larger study and technical standards for its conduct are needed.Strengths and Limitations of this StudyLarge sample size (N = 547)Reference values according to sex and age group (5-7, 8-10, 11-13 and 14-16)Evaluation of test-retest reliability and construct validityConvenience not population-based sampleNot all outcomes have been measured on each participant
Importance of patient bed pathways and length of stay differences in predicting COVID-19 bed occupancy in England
Authors: Leclerc Quentin J. , Fuller Naomi M. , Keogh Ruth H. , Diaz-Ordaz Karla , Sekula Richard , Semple Malcolm G ,   ISARIC4C Investigators,   CMMID COVID-19 Working Group, Atkins Katherine E. , Procter Simon R. , Knight Gwenan M. 
Published: January 2021

AbstractObjectivesPredicting bed occupancy for hospitalised patients with COVID-19 requires understanding of length of stay (LoS) in particular bed types. LoS can vary depending on the patient’s “bed pathway” - the sequence of transfers between bed types during a hospital stay. In this study, we characterise these pathways, and their impact on predicted hospital bed occupancy.DesignWe obtained data from University College Hospital (UCH) and the ISARIC4C COVID-19 Clinical Information Network (CO-CIN) on hospitalised patients with COVID-19 who required care in general ward or critical care (CC) beds to determine possible bed pathways and LoS. We developed a discrete-time model to examine the implications of using either bed pathways or only average LoS by bed type to forecast bed occupancy. We compared model-predicted bed occupancy to publicly available bed occupancy data on COVID-19 in England between March and August 2020.ResultsIn both the UCH and CO-CIN datasets, 82% of hospitalised patients with COVID-19 only received care in general ward beds. We identified four other bed pathways, present in both datasets: “Ward, CC, Ward”, “Ward, CC”, “CC” and “CC, Ward”. Mean LoS varied by bed type, pathway, and dataset, between 1.78 and 13.53 days.For UCH, we found that using bed pathways improved the accuracy of bed occupancy predictions, while only using an average LoS for each bed type underestimated true bed occupancy. However, using the CO-CIN LoS dataset we were not able to replicate past data on bed occupancy in England, suggesting regional LoS heterogeneities.ConclusionsWe identified five bed pathways, with substantial variation in LoS by bed type, pathway, and geography. This might be caused by local differences in patient characteristics, clinical care strategies, or resource availability, and suggests that national LoS averages may not be appropriate for local forecasts of bed occupancy for COVID-19.
U-shaped effect of blood pressure on structural OCT metrics and retinal blood flow autoregulation in ophthalmologically healthy subjects
Authors: Pappelis Konstantinos , Jansonius Nomdo M. 
Published: January 2021

AbstractObjective1) To investigate the effect of low blood pressure (BP), treated arterial hypertension (AHT), and untreated AHT on the ganglion cell-inner plexiform layer (GCIPL) and the retinal nerve fiber layer (RNFL) thickness of non-glaucomatous eyes and 2) to elucidate whether this effect is related to crossing the lower limit of retinal blood flow (RBF) autoregulation.DesignCross-sectional, case-control.SubjectsWe included 96 eyes of 96 ophthalmologically healthy subjects (age 50-65). Participants were prospectively recruited from a large-scale cohort study in the northern Netherlands (n=167,000; Lifelines Biobank). They were allocated to four groups (low BP, normal BP [controls], treated AHT, untreated AHT), based on information from previous visits and strict distribution criteria.MethodsInner retinal layer thicknesses were obtained with optical coherence tomography (OCT). Fractal dimension of the superficial microvasculature was quantified with OCT-angiography and customized software. Central retinal vessel diameters were obtained from fundus images. BP and intraocular pressure measurements were also acquired. Measurements were combined with a validated physiological model to estimate vascular outcome measures. Structural and vascular metrics were compared across groups and mediation analysis was performed.Main outcome measuresStructural: macular GCIPL and RNFL (mRNFL), peripapillary RNFL (pRNFL) thickness. Vascular: RBF, retinal vascular resistance (RVR), autoregulatory reserve (AR).ResultsCompared to controls, GCIPL was thinner in the low BP group (P=0.013), treated hypertensives (P=0.007), and untreated hypertensives (P=0.007). Treated hypertensives exhibited the thinnest mRNFL (P=0.001), temporal pRNFL (P=0.045), and inferior pRNFL (P=0.034). In multivariable analysis, RBF was mediating the association of GCIPL thickness with BP within the combined low BP group and controls (P=0.003), RVR together with AR were mediating the same association within the combined treated hypertensives and controls (P=0.001 and P=0.032), and RVR was mediating the association within the combined untreated antihypertensives and controls (P=0.022).ConclusionsWe uncovered GCIPL and RNFL thinning related to both tails of the BP distribution. GCIPL thinning was associated with reduced RBF autoregulatory capacity. This predisposition to glaucomatous damage could explain the frequent epidemiological finding of increased glaucoma risk in certain subgroups, such as subjects with nocturnal BP dipping or aggressively treated AHT. Longitudinal studies could confirm this postulation.
Heart rate and heart rate variability in patients with chronic inflammatory joint disease: The role of pain duration and the insular cortex
Authors: Buschmann Leona Katharin , Spindler Melanie , Sörös Peter , Bantel Carsten 
Published: January 2021

AbstractChronic inflammatory joint diseases (CIJD) have been linked to increased cardiovascular morbidity and mortality. A decisive reason could be a dysregulation of the autonomic nervous system (ANS), which is responsible for the control of cardio-vascular function. So far, the cause of changes in ANS functions remains elusive. In this study, we investigate the role of chronic pain and the insular cortex in autonomic control of cardiac functioning in patients with CIJD. We studied the sympathetic and parasympathetic branch of the ANS through the assessment of heart rate and heart rate variability (HRV) at rest and under cognitive stimulation. Furthermore, we investigated insular cortex volume by performing surface-based brain morphometry with FreeSurfer. For this study, 22 individual age- and sex-matched pairs for the magnetic resonance imaging analyses and 14 for the HRV analyses were recruited. Pain duration was negatively correlated with the resting heart rate in patients with chronic inflammatory joint diseases (n = 19). In a multiple linear regression model including only CIJD patients with HR at rest as a dependent variable, we found a significant positive relationship between HR at rest and the volume of the left insular cortex and a significant negative relationship between HR at rest and the volume of the right insular cortex. However, we found no significant differences in HRV parameters or insular cortex volumes between both groups. In this study we provide evidence to suggest insular cortex involvement in the process of ANS changes due to chronic pain in CIJD patients.
Innate lymphoid cells and disease tolerance in SARS-CoV-2 infection
Authors: Silverstein Noah J. , Wang Yetao , Manickas-Hill Zachary , Carbone Claudia , Dauphin Ann , Boribong Brittany P. , Loiselle Maggie , Davis Jameson , Leonard Maureen M. , Kuri-Cervantes Leticia ,   MGH COVID-19 Collection & Processing Team, Meyer Nuala J. , Betts Michael R. , Li Jonathan Z. , Walker Bruce , Yu Xu G. , Yonker Lael M. , Luban Jeremy 
Published: January 2021

AbstractRisk of severe COVID-19 increases with age, is greater in males, and is associated with lymphopenia, but not with higher burden of SARS-CoV-2. It is unknown whether effects of age and sex on abundance of specific lymphoid subsets explain these correlations. This study found that the abundance of innate lymphoid cells (ILCs) decreases more than 7-fold over the human lifespan — T cell subsets decrease less than 2-fold — and is lower in males than in females. After accounting for effects of age and sex, ILCs, but not T cells, were lower in adults hospitalized with COVID-19, independent of lymphopenia. Among SARS-CoV-2-infected adults, the abundance of ILCs, but not of T cells, correlated inversely with odds and duration of hospitalization, and with severity of inflammation. ILCs were also uniquely decreased in pediatric COVID-19 and the numbers of these cells did not recover during follow-up. In contrast, children with MIS-C had depletion of both ILCs and T cells, and both cell types increased during follow-up. In both pediatric COVID-19 and MIS-C, ILC abundance correlated inversely with inflammation. Blood ILC mRNA and phenotype tracked closely with ILCs from lung. Importantly, blood ILCs produced amphiregulin, a protein implicated in disease tolerance and tissue homeostasis, and the percentage of amphiregulin-producing ILCs was higher in females than in males. These results suggest that, by promoting disease tolerance, homeostatic ILCs decrease morbidity and mortality associated with SARS-CoV-2 infection, and that lower ILC abundance accounts for increased COVID-19 severity with age and in males.
Understanding COVID-19 dynamics and the effects of interventions in the Philippines: A mathematical modelling study
Authors: Caldwell Jaime M. , Lara-Tuprio Elvira de , Teng Timothy Robin , Estuar Maria Regina Justina E. , Sarmiento Raymond Francis R. , Abayawardana Milinda , Leong Robert Neil F. , Gray Richard T. , Wood James G. , McBryde Emma S. , Ragonnet Romain , Trauer James M. 
Published: January 2021

ABSTRACTObjectiveCOVID-19 appears to have caused less severe outbreaks in many low- and middle-income countries (LMIC) compared with high-income countries, possibly because of differing demographics, socio-economics, surveillance, and policy responses. Here, we investigate the role of multiple factors on COVID-19 dynamics in the Philippines, a LMIC that has had a relatively severe COVID-19 outbreak.MethodsWe applied an age-structured compartmental model that incorporated time-varying mobility, testing, and personal protective behaviors (through a “Minimum Health Standards” policy, MHS) to represent the Philippines COVID-19 epidemic nationally and for three highly affected regions (Calabarzon, Central Visayas, and the National Capital Region). We estimated effects of control measures, key epidemiological parameters, and interventions.FindingsPopulation age structure, contact rates, mobility, testing, and MHS were sufficient to explain the Philippines epidemic based on the good fit between modelled and reported cases, hospitalisations, and deaths. Several of the fitted epidemiological parameters were consistent with those reported in high-income settings. The model indicated that MHS reduced the probability of transmission per contact by 15-26%. The February 2021 case detection rate was estimated at ∼9%, population recovered at ∼12%, and scenario projections indicated high sensitivity to MHS adherence.ConclusionsCOVID-19 dynamics in the Philippines are driven by age, contact structure, mobility, and MHS adherence, and the epidemic can be understood within a similar framework as for high-income settings. Continued compliance with low-cost MHS should allow the Philippines to maintain epidemic control until vaccines are widely distributed, but disease resurgence could occur due to low population immunity and detection rates.
An Estimation of Reproduction Number of SARS-CoV-2 by Age Class for Age Classes in Japan
Authors: Kurita Junko , Hata Takahide , Sugawara Tamie , Ohkusa Yasushi , Hata Atsuko 
Published: January 2021

AbstractBackgroundInfectiousness of COVID-19 by age class inferred from the infection source and by infected people might be different. However, studies of such infectiousness have not been reported.ObjectThe object of this study was estimation of reproduction numbers by age class of the source of infection and the infected persons. To do so, after examining a new procedure for reproduction number estimation, we checked infected places by age class of the source of infection and the infected persons.MethodWe ignore patients who infected no one because their reliability might be lower than that of patients who infected more than one person. We estimated the reproduction number from the histogram of the number of the infected people by the same patient, assuming that the histogram follows an exponential distribution.Discussion and ConclusionThe obtained results demonstrated that the effective reproduction numbers for infection from children were very low. They were higher among adult and elderly people than among the same age class. Moreover, although the highest and second-highest infected places were ‘other’ and ‘at home’ with some exceptions, the data for infection at hospitals were remarkable among adults and elderly people. Among elderly people, infection at facilities for elderly was also high. Infections at nursing schools, schools, restaurants, and entertainment venues at night were negligible.