bluuebunny/crossref_metadata_2025_split huggingface dataset:
An international, interlaboratory ring trial confirms the feasibility of an open-source, extraction-less “direct” RT-qPCR method for reliable detection of SARS-CoV-2 RNA in clinical samples
Authors: Mills Margaret G. , Bruce Emily , Huang Meei-Li , Crothers Jessica W. , Hyrien Ollivier , Oura Christopher A. L. , Blake Lemar , Jordan Arianne Brown , Hester Susan , Wehmas Leah , Mari Bernard , Barby Pascal , Lacoux Caroline , Fassy Julien , Vial Pablo , Vial Cecilia , Martinez Jose R.W. , Oladipo Olusola Olalekan , Inuwa Bitrus , Shittu Ismaila , Meseko Clement A. , Chammas Roger , Santos Carlos Ferreira , José Dionísio Thiago , Garbieri Thais Francini , Parisi Viviane Aparecida , Mendes-Correa Maria Cassia , dePaula Anderson V. , Romano Camila M. , Góes Luiz Gustavo Bentim , Minoprio Paola , Campos Angelica C. , Cunha Marielton P. , Vilela Ana Paula P. , Nyirenda Tonney , Mkakosya Rajhab Sawasawa , Muula Adamson S. , Dumm Rebekah E. , Harris Rebecca M. , Mitchell Constance A. , Pettit Syril , Botten Jason , Jerome Keith R. 
Published: April 2021

AbstractReverse transcription–quantitative polymerase chain reaction (RT-qPCR) is used worldwide to test and trace the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). “Extraction-less” or “direct” real time–reverse transcription polymerase chain reaction (RT-PCR) is an open-access qualitative method for SARS-CoV-2 detection from nasopharyngeal or oral pharyngeal samples with the potential to generate actionable data more quickly, at a lower cost, and with fewer experimental resources than full RT-qPCR. This study engaged 10 global testing sites, including laboratories currently experiencing testing limitations due to reagent or equipment shortages, in an international interlaboratory ring trial. Participating laboratories were provided a common protocol, common reagents, aliquots of identical pooled clinical samples, and purified nucleic acids and used their existing in-house equipment. We observed 100% concordance across laboratories in the correct identification of all positive and negative samples, with highly similar cycle threshold values. The test also performed well when applied to locally collected patient nasopharyngeal samples, provided the viral transport media did not contain charcoal or guanidine, both of which appeared to potently inhibit the RT-PCR reaction. Our results suggest that open-access, direct RT-PCR assays are a feasible option for more efficient COVID-19 coronavirus disease testing as demanded by the continuing pandemic.
Plasma glial fibrillary acidic protein is an early marker of Aβ pathology in Alzheimer’s disease
Authors: Pereira Joana B. , Janelidze Shorena , Smith Ruben , Mattsson-Carlgren Niklas , Palmqvist Sebastian , Zetterberg Henrik , Stomrud Erik , Ashton Nicholas J. , Blennow Kaj , Hansson Oskar 
Published: April 2021

AbstractAlthough recent clinical trials targeting amyloid-β (Aβ) in Alzheimer’s disease (AD) have shown promising results, there is increasing evidence suggesting that understanding alternative disease pathways that interact with Aβ metabolism and amyloid pathology might be important to halt the clinical deterioration. In particular, there is evidence supporting a critical role of astroglial activation and astrocytosis in AD. However, to this date, no studies have assessed whether astrocytosis is independently related to Aβ or tau pathology, respectively,in vivo. To address this question, we determined the levels of the astrocytic marker glial fibrillary acidic protein (GFAP) in plasma and cerebrospinal fluid (CSF) of 217 Aβ-negative cognitively unimpaired individuals, 71 Aβ-positive cognitively unimpaired individuals, 78 Aβ-positive cognitively impaired individuals, 63 Aβ-negative cognitively impaired individuals and 75 patients with a non-AD neurodegenerative disorder from the Swedish BioFINDER-2 study. Subjects underwent longitudinal Aβ (18F-flutemetamol) and tau (18F-RO948) positron emission tomography (PET) as well as cognitive testing. We found that plasma GFAP concentration was significantly increased in all Aβ-positive groups compared with subjects without Aβ pathology (p<0.01). In addition, there were significant associations between plasma GFAP with higher Aβ-PET signal in all Aβ-positive groups, but also in cognitively normal individuals with normal Aβ values (p<0.001), which remained significant after controlling for tau-PET signal. Furthermore, plasma GFAP could predict Aβ-PET positivity with an area under the curve of 0.76, which was greater than the performance achieved by CSF GFAP (0.69) and other glial markers (CSF YKL-40: 0.64, sTREM2: 0.71). Although correlations were also observed between tau-PET and plasma GFAP, these were no longer significant after controlling for Aβ-PET. In contrast to plasma GFAP, CSF GFAP concentration was significantly increased in non-AD patients compared to other groups (p<0.05) and correlated with Aβ-PET only in Aβ-positive cognitively impaired individuals (p=0.005). Finally, plasma GFAP was associated with both longitudinal Aβ-PET and cognitive decline, and mediated the effect of Aβ-PET on tau-PET burden, suggesting that astrocytosis secondary to Aβ aggregation might promote tau accumulation. Altogether, these findings indicate that plasma GFAP is an early marker associated with brain Aβ pathology but not tau aggregation, even in cognitively normal individuals with a normal Aβ status. This suggests that plasma GFAP should be incorporated in current hypothetical models of AD pathogenesis and be used as a non-invasive and accessible tool to detect early astrocytosis secondary to Aβ pathology.
Spread of the SARS-CoV-2 UK-variant in the South East of France: impact on COVID-19 patients’ age, comorbidity profiles and clinical presentation
Authors: Courjon Johan , Contenti Julie , Demonchy Elisa , Levraut Jacques , Barbry Pascal , Rios Géraldine , Dellamonica Jean , Chirio David , Bonnefoy Caroline , Giordanengo Valérie , Carles Michel 
Published: April 2021

AbstractObjectivesThe variant 20I/501Y.V1, associated to a higher risk of transmissibility, emerged in Nice city (South East of France, French Riviera) during January 2021. The pandemic has resumed late December 2020 in this aera. A high incidence rate together with a fast turn-over of the main circulating variants, provided us the opportunity to analyze modifications in clinical profile and outcome traits.MethodsObservational study in the University hospital of Nice from December 2020 to February 2021. We analyzed data of sequencing of SARS-CoV-2 from the sewage collector and PCR screening from all positive samples at the hospital. Then, we described the characteristics of all COVID-19 patients admitted in the emergency department (ED) (n=1247) and those hospitalized in the infectious diseases ward or ICU (n=232). Demographic data, clinical signs and severity were recorded by the NEWS-2, SAPS-2 and SOFA scores were recorded and analyzed.Resultsthe UK-variant was absent in the area in December, then increasingly spread in January representing 59% of the PCR screening performed mid-February. The rate of patients over 65 years admitted to the ED decreased from 63% to 50% (p=0.001). The mean age of hospitalized patients in the infectious diseases ward decreased from 70.7 to 59.2 (p<0.001) while the proportion of patients without comorbidity increased from 16% to 42% (p=0.007). Neither the NEWS-2 score nor the main signs of clinical severity have changed over time.ConclusionSpread of the UK-variant in the South East of France affects younger and healthier patients.
Predicting severe COVID-19 outcomes for triage and resource allocation
Authors: Morada Anthony Onde , Scheidel Caleb , Brown Jennifer , Albright Jeremy , Kolade Victor , Cagir Burt 
Published: April 2021

AbstractBackgroundWhile numerous studies have identified factors associated with severe COVID-19 outcomes, they have yet to quantify these characteristics. Therefore, our study’s purpose is to stratify these risk factors and use them to predict outcomes.Study DesignThis is a retrospective review of the CDC COVID-19 Surveillance Data. Logistic regression models calculated risk estimates for independent variables, and random forest models predicted the chance of severe outcomes.ResultsOur sample of 3,798,261 patients with COVID-19 consisted mainly of females (51.9%), 10-to 69-year-olds, and White/Non-Hispanics (34.9%). Most were not healthcare workers (90.6%) and did not have preexisting medical conditions (47.1%). Age had an increased risk of severe outcomes that grew every decade of life. White patients had a decreased occurrence of severe outcomes than Non-Whites, except for Pacific Islanders with comparable mortality. The variable selection algorithm detected that three outcomes were more accurate without healthcare worker classification: mechanical ventilation/intubation, pneumonia, and ARDS Acute respiratory distress. However, providers had a decreased risk of severe outcomes overall. Also, patients with preexisting conditions demonstrated an increased risk in all outcomes. Compared to the logistic regressions, the predictive models had a higher performance (AUC>0.8). The death model had the best metrics, followed by hospitalization and ventilation. We amassed these predictive models into the Severe COVID-19 Calculator web application that estimates the probability of severe outcomes.ConclusionsSeveral patient social and medical demographics recorded by the CDC significantly affect severe COVID-19 outcomes suggesting a multifactorial influence. To account for these variables, a generated Severe Covid-19 Calculator can accurately predict the chance of severe outcomes in citizens that may contract or have COVID-19.
Deep Neural Survival Networks for Cardiovascular Risk Prediction: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Hathaway Quincy A. , Yanamala Naveena , Budoff Matthew J. , Sengupta Partho P. , Zeb Irfan 
Published: April 2021

AbstractBackgroundThere is growing interest in utilizing machine learning techniques for routine atherosclerotic cardiovascular disease (ASCVD) risk prediction. We investigated whether novel deep learning survival models can augment ASCVD risk prediction over existing statistical and machine learning approaches.Methods6,814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed over 16 years to assess incidence of all-cause mortality (mortality) or a composite of major adverse events (MAE). Features were evaluated within the categories of traditional risk factors, inflammatory biomarkers, and imaging markers. Data was split into an internal training/testing (four centers) and external validation (two centers). Both machine learning (COXPH, RSF, and lSVM) and deep learning (nMTLR and DeepSurv) models were evaluated.ResultsIn comparison to the COXPH model, DeepSurv significantly improved ASCVD risk prediction for MAE (AUC: 0.82 vs. 0.79, P≤0.001) and mortality (AUC: 0.86 vs. 0.80, P≤0.001) with traditional risk factors alone. Implementing non-categorical NRI, we noted a 65% increase in correct reclassification compared to the COXPH model for both MAE and mortality (P≤0.05). Assessing the relative risk of participants, DeepSurv was the only learning algorithm to develop a significantly improved risk score criteria, which outcompeted COXPH for both MAE (4.07 vs. 2.66, P≤0.001) and mortality (6.28 vs. 4.67, P=0.014). The addition of inflammatory or imaging biomarkers to traditional risk factors showed minimal/no significant improvement in model prediction.ConclusionDeepSurv can leverage simple office-based clinical features alone to accurately predict ASCVD risk and cardiovascular outcomes, without the need for additional features, such as inflammatory and imaging biomarkers.
How to tie dangerous surgical knots – easily. Can we avoid this?
Authors: Drabble E H , Spanopoulou S , Sioka E. , Politaki E , Paraskeva I K , Palla E , Stockley L , Zacharoulis D 
Published: April 2021

AbstractObjectiveSecure knots are essential. Previous publications have concentrated on security of different knot types, but could individual technique be important?Determine whether the technique of formation of each layer of a surgical knot is important to the security of the knot formed.Design studyProspective analysis of technique on knot securityMaterials and methodsSenior and resident surgeons, and medical students, tied knots with three techniques, using four study materials, 2/0 polyglactin 910 (vicryl), 3/0 polydioxanone (PDS), 4/0 poliglecaprone 25 (monocryl) and 1 nylon (Ethilon); a standard flat reef knot (FRK), knots tied under tension (TK), and knots laid without appropriate hand crossing (NHCK). Each knot technique was performed reproducibly, and security determined by distraction with increasing force, till each material broke, or the knot separated completely.Results20% of flat reef knots (FRK) tied with all suture materials slipped; all knots tied with the other two techniques, with all materials, slipped, TK (100%) and NHCK (100%). The quantitative degree of slip, was significantly less for FRK (mean 6.3% 95%CI 2.2-10.4%) than for TK (mean 312% 95%CI 280.0-344.0%) and NHCK (mean 113.0% 95%CI 94.3-131.0%).The mean lengths of suture in loops held within knots, tied under tension (TK mean 17.0mm 95%CI 16.3-17.7mm), and tied without appropriate hand crossing (NHCK mean 16.3mm 95%CI 15.9-16.7mm) were significantly lower than for flat reef knots (FRK mean 25.1mm 95%CI 24.2-26.0mm). The first two types of knot may have tightened more than anticipated, in comparison to flat reef knots, with potential undue tissue tension.ConclusionMeticulous technique of knot tying, is essential for secure knots, appropriate tissue tension, and the security of anastomoses and haemostasis effected.Strengths and limitationsThe study design was simple, with equal numbers of knots tied for each technique, and for each material.Only a small number of participants tied knots, limiting any assessment to the effect of the knot tying technique. No inference could be drawn regarding the effect of seniority of participant.A relatively small number of knots were tied with each of the materials limiting more detailed assessment of the effect of the suture material and size on knot security, or whether material and size had any significant influence.
Objective quantitation of EGFR protein levels using Quantitative Dot Blot (QDB) method for prognosis of gastric cancer patients
Authors: Xin Lei , Tang Fangrong , Song Bo , Yang Maozhou , Zhang Jiandi 
Published: April 2021

BackgroundOne causing factor underlying failures of several clinical trials of anti-EGFR therapies is the lack of effective method to select patients overexpressing EGFR protein. Quantitative Dot Blot method (QDB) is proposed here to measure EGFR protein levels objectively and quantitatively. Its feasibility was evaluated for prognosis of overall survival (OS) of gastric cancer patients.MethodsFormalin Fixed Paraffin Embedded (FFPE) slices of 2×5 μm from gastric and Lung cancer specimens were used to extract total tissue lysate for QDB measurement. Absolutely quantitated EGFR protein levels were used for Kaplan-Meier Overall Survival (OS) analysis of gastric cancer patients.ResultsEGFR protein levels ranged from 0 to 772 pmole/g (n=246) for gastric, and from 0 to 2695 pmole/g (n=81) for lung cancer patients. Poor correlation was observed between quantitated EGFR levels and immunohistochemistry (IHC) scores with r=0.018, p=0.786 from Spearman’s correlation analysis. EGFR was identified as an independent negative prognostic biomarker for gastric patients only through absolute quantitation, with HR at 2.29 (95%CI:1.23-4.26, p=0.0089) from multivariate cox regression OS analysis. A cutoff of 207.7 pmole/g was proposed to stratify gastric cancer patients, with 5-year survival probability at 37% for those whose EGFR levels were above the cutoff, and at 64% those below the cutoff based on Kaplan-Meier OS analysis. p=0.0057 from Log Rank test.ConclusionA QDB-based assay was developed for both gastric and Lung cancer specimens to measure EGFR protein levels absolutely, quantitatively and objectively. This assay should facilitate clinical trials aiming to evaluate anti-EGFR therapies retrospectively and prospectively.
A comprehensive analysis of outcomes between COVID-19 patients with an elevated serum lipase compared to those with pancreatitis
Authors: Benias Petros C , Inamdar Sumant , Wee Diana , Liu Yan , Buscaglia Jonathan M , Satapathy Sanjaya K , Trindade Arvind J ,   Northwell COVID-19 Research Consortium.
Published: April 2021

ABSTRACTBackground and AimsCOVID-19 patients may have asymptomatic hyperlipasemia without abdominal imaging findings or abdominal pain. In addition, primary and secondary pancreatitis have been described in COVID-19 patients. There is limited information on how the groups compare in outcomes. The aim is to compare outcomes among these groups.MethodsThis is a retrospective study from 12 hospitals within one healthcare system examining outcomes between hospitalized COVID-19 patients with a lipase <3x upper limit of normal (ULN), asymptomatic hyperlipasemia (>3x ULN), secondary pancreatitis (typical respiratory COVID-19 symptoms and found to have pancreatitis), and primary pancreatitis (presenting with pancreatitis).ResultsOf 11,883 patients admitted with COVID-19, 1,560 patients were included: 1,155 COVID-19 patients with a normal serum lipase (control group), 270 with an elevated lipase <3x ULN, 46 patients with asymptomatic hyperlipasemia with a lipase 3xULN, 57 patients with secondary pancreatitis, and 32 patients with primary pancreatitis. On adjusted multivariate analysis, the elevated lipase <3x ULN and asymptomatic hyperlipasemia groups had worse outcomes. The mortality was OR1.6 (95% CI 1.2-2.2) and 1.1 (95% CI 0.5-2.3), respectively. The need for mechanical ventilation was OR 2.8 (95% CI 1.2-2.1) and 2.8 (95% CI 1.5-5.2), respectively. Longer length of stay was OR 1.5 (95%CI 1.1-2.0) and 3.16 (95%CI 1.5-6.5), respectively.ConclusionCOVID-19 patients with an elevated lipase< 3x ULN and asymptomatic hyperlipasemia have generally worse outcomes than those with pancreatitis. This could be attributed to extrapancreatic causes (liver failure, renal failure, enteritis, etc), which may signify a more severe course of clinical disease.
Ornithine Decarboxylase (ODC1) gene variant (rs2302615) is associated with gastric cancer independently of Helicobacter pylori CagA serostatus
Authors: Miller Anna K , Tavera Gloria , Dominguez Ricardo L , Camargo M Constanza , Waterboer Tim , Wilson Keith T , Williams Scott M , Morgan Douglas R 
Published: April 2021

ABSTRACTThe primary cause of gastric cancer is chronic infection with Helicobacter pylori (H. pylori), particularly the high-risk genotype cagA, and risk modification by human genetic variants. We studied 94 variants in 54 genes for association with gastric cancer, including rs2302615 in ornithine decarboxylase (ODC1), which may affect response to chemoprevention with the ODC inhibitor, eflornithine (difluoromethylornithine; DFMO). Our population-based, case-control study included 1366 individuals (664 gastric cancer cases and 702 controls) from Western Honduras, a high incidence region of Latin America. CagA seropositivity was strongly associated with cancer (OR = 3.6; 95% CI: 2.6, 5.1). The ODC1 variant rs2302615 was associated with gastric cancer (OR = 1.36; p = 0.018) in a model adjusted for age, sex, and CagA serostatus. Two additional single nucleotide polymorphisms (SNPs) in CASP1 (rs530537) and TLR4 (rs1927914) genes were also associated with gastric cancer. The ODC1 SNP association with gastric cancer was stronger in individuals who carried the TT genotype at the associating TLR4 polymorphism, rs1927914 (OR = 1.77; p = 1.85 × 10−3). In conclusion, the ODC1 variant, rs2302615, is associated with gastric cancer and supports chemoprevention trials with DFMO, particularly in individuals homozygous for the risk allele, C, at rs2302615.
Covid-19: Early evening curfews are not effective and may backfire
Authors: Georganas Sotiris , Velias Alina , Vandoros Sotiris 
Published: April 2021

AbstractBackgroundDuring the COVID-19 pandemic, some countries have introduced early evening curfews. Several studies try measure the effectiveness of such measures across different countries, but clear identification of effects is elusive.ObjectiveWe examined the impact of an early evening curfew on mobility by studying a shift in curfews from 9pm to 6pm in Greece.Data and MethodsWe took advantage of a natural experiment in Greece, where curfews shifted from 9pm to 6pm in one Region, but not in another. We followed a difference-in-differences econometric approach, where we compared trends in mobility in groceries and pharmacies as well as residential spaces before and after the introduction of the 6pm curfew, in the two regions.ResultsThe relative difference in the time spent in groceries and pharmacies between the two regions before and after the intervention, is statistically insignificant [coeff: −9.95; 95%CI −44.358 to 24.458]. The relative increase in time spent at residential spaces after the 6pm curfew was only 4.625 percentage points [coeff: 4.625; 95%CI 1.412 to 7.838].ConclusionsWe found that the 6pm instead of 9pm curfew in Athens led to a 4.63 percentage point relative increase in time spent at home and had no effect on time spent in groceries and pharmacies. Considering that this was a result of a 18.75% reduction in hours where people were allowed to leave home, it seems that the early evening curfew led to more crowding in indoor spaces – which may facilitate the spread of disease. Interventions should be based on a thorough analysis of human behaviour, that anticipates substitution of activities.
Do people reduce compliance with COVID-19 guidelines following vaccination? A longitudinal analysis of matched UK adults
Authors: Wright Liam , Steptoe Andrew , Mak Hei Wan , Fancourt Daisy 
Published: April 2021

AbstractIntroductionCOVID-19 vaccines do not confer immediate immunity and vaccinated individuals may still be at risk of transmitting the virus. Governments have not exempted vaccinated individuals from behavioural measures to reduce the spread of COVID-19, such as practicing social distancing. However, vaccinated individuals may have reduced compliance with these measures, given lower perceived risks.MethodsWe used monthly panel data from October 2020 – March 2021 in the UK COVID-19 Social Study to assess changes in compliance following vaccination. Compliance was measured with two items on compliance with guidelines in general and compliance with social distancing. We used matching to create comparable groups of individuals by month of vaccination (January, February, or not vaccinated by February) and fixed effects regression to estimate changes in compliance over the study period.ResultsCompliance increased between October 2020 – March 2021, regardless of vaccination status or month of vaccination. There was no clear evidence that vaccinated individuals decreased compliance relative to those who were not yet vaccinated.ConclusionThere was little evidence that sample members vaccinated in January or February reduced compliance after receiving vaccination for COVID-19. Continued monitoring is required as younger individuals receive the vaccine, lockdown restrictions are lifted and individuals receive second doses of the vaccine.