bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiology and Determinants of Survival for Primary Intestinal Non-Hodgkin’s Lymphoma – A Population Based Study
Authors: Singh Vinit , Gor Dhairya , Gupta Varsha , Jacob Aasems , Du Doantrang , Eltoukhy Hussam , Meghal Trishal 
Published: July 2022

AbstractIntroductionGastrointestinal tract is the most common site of extra nodal non-Hodgkin’s lymphoma (EN-NHL). Most of the published data have been on gastric NHL with limited studies on primary intestinal - Non-Hodgkin’s Lymphoma (PI-NHL) considering rare incidence. We performed epidemiological and survival analysis for PI-NHL from the Surveillance, Epidemiology, and End Results (SEER) 18 database.MethodsA total of 9143 PI-NHL cases of age ≥18 years were identified from the SEER 18 database for the period 2000-2015. 8568 Patients were included for survival analysis. Cause specific Survival (CSS) and overall survival analysis (OS) were done for PINHL and PI-diffuse large B-cell lymphoma (PI-DLBCL) using gender, age of onset, treatment, histology, stage, and Year of diagnosis. Survival analysis was done by using cox-proportional hazard model and Kaplan Meier plot with log-rank test.ResultsThe percentage of PI-NHL of all the intestinal cancers and extra nodal non-Hodgkin’s lymphoma were 1.35 %, and 10.52%, respectively. The age-adjusted incidence was 0.9145/100,000 population for the study population. PI-NHL was more common among patients aged≥60 Years, male and non-Hispanics whites. Majority of patients were diagnosed at stage 1 and 2 (74%), and DLBCL (44.8%) was the most common histology. In OS analysis, Significant increased risk of mortality was seen with T-cell NHLs vs. DLBCL (HR – 2.56), patients aged ≥60 vs <60 Years (HR – 2.87), stage 4 vs Stage 1 (HR – 1.93), male vs. female (HR- 1.17), with best outcome seen in patient treated with combination of chemotherapy and surgery vs. none (HR – 0.45). Similar results were seen in CSS and for primary intestinal DLBCL as well. Significant improvement in outcomes was observed for PI-DLBCL patients receiving chemotherapy with/without surgery.ConclusionFindings from our large, population-based study reveal PI-NHL is a rare type of intestinal malignancy with significant difference in survival based on histological and epidemiological characteristics.
A simple SEIR-V model to estimate COVID-19 prevalence and predict SARS-CoV-2 transmission using wastewater-based surveillance data
Authors: Phan Tin , Brozak Samantha , Pell Bruce , Gitter Anna , Mena Kristina D. , Kuang Yang , Wu Fuqing 
Published: July 2022

AbstractWastewater-based surveillance (WBS) has been widely used as a public health tool to monitor SARS-CoV-2 transmission. However, epidemiological inference from WBS data remains understudied and limits its application. In this study, we have established a quantitative framework to estimate COVID-19 prevalence and predict SARS-CoV-2 transmission through integrating WBS data into an SEIR-V model. We conceptually divide the individual-level viral shedding course into exposed, infectious, and recovery phases as an analogy to the compartments in population-level SEIR model. We demonstrated that the temperature effect on viral losses in the sewer can be straightforwardly incorporated in our framework. Using WBS data from the second wave of the pandemic (Oct 02, 2020 – Jan 25, 2021) in the Great Boston area, we showed that the SEIR-V model successfully recapitulates the temporal dynamics of viral load in wastewater and predicts the true number of cases peaked earlier and higher than the number of reported cases by 16 days and 8.6 folds (R = 0.93), respectively. This work showcases a simple, yet effective method to bridge WBS and quantitative epidemiological modeling to estimate the prevalence and transmission of SARS-CoV-2 in the sewershed, which could facilitate the application of wastewater surveillance of infectious diseases for epidemiological inference and inform public health actions.
Fluorescence spectroscopy of low-level endogenous β-adrenergic receptor expression at the plasma membrane of differentiating human iPSC-derived cardiomyocytes
Authors: Gmach Philipp , Bathe-Peters Marc , Telugu Narasimha , Lohse Martin J , Annibale Paolo 
Published: July 2022

AbstractThe potential of human induced pluripotent stem cells (hiPSCs) to be differentiated into cardiomyocytes (CMs) mimicking the adult CMs functional morphology, marker genes and signaling characteristics has been investigated since over a decade. The evolution of the membrane localization of CM-specific G protein-coupled receptors throughout differentiation has received, however, only limited attention to date. We employ here advanced fluorescent spectroscopy, namely linescan Fluorescence Correlation Spectroscopy (FCS), to observe how the plasma membrane abundance of the β1- and β2-adrenergic receptors (β1/2-ARs), labelled using a bright and photostable fluorescent antagonist, evolves during long-term monolayer culture of hiPSC-derived CMs. We compare it to the kinetic of observed mRNA levels in wildtype (WT) hiPSCs and in two CRISPR/Cas9 knock-in clones. We conduct these observations against the backdrop of our recent report that β2-ARs, as opposed to β1-ARs, specifically segregate to the T-Tubular system of adult CMs.
Predatory fish preferentially target virtual prey with Lévy motion rather than Brownian motion
Authors: Ioannou Christos C. , Braga Carvalho Luis Arrochela , Budleigh Chessy , Ruxton Graeme D. 
Published: July 2022

AbstractOf widespread interest in animal behaviour and ecology is how animals search their environment for resources, and whether these search strategies are optimal. However, movement also affects predation risk through effects on encounter rates, the conspicuousness of prey, and the success of attacks. Here we use predatory fish attacking a simulation of virtual prey to test whether predation risk is associated with movement behaviour. Despite often being demonstrated to be a more efficient strategy for finding resources, we find that prey displaying Lévy motion are twice as likely to be targeted by predators than prey utilising Brownian motion. This result emphasises that costs of predation risk need to be considered alongside the foraging benefits when comparing different movement strategies.
Direct calculation of cryo EM and crystallographic model maps for real-space refinement
Authors: Urzhumtsev Alexandre , Urzhumtseva Ludmila , Lunin Vladimir Y. 
Published: July 2022

AbstractReal-space refinement of atomic models improves them by their fit to experimental scattering electrostatic potential maps in cryo electron microscopy and to electron density maps in crystallography. This procedure has a number of advantages in comparison with reciprocal-space refinement, is complementary to it in crystallographic studies and is the principal technique in cryo EM. An accurate real-space refinement of atomic models can be done by comparison of the model maps, calculated according to the respective theory, with the experimental ones, when the former mimic imperfections of the latter, mainly a limited resolution and an atomic disorder. Calculation of model maps as a sum of contributions of individual atoms means that these contributions - atomic images in the given map – should also be affected by the resolution and positional disorder. This blurs atomic images and surrounds their central peak by Fourier ripples. These ripples can be described by a specially designed function which allows combining both principal effects of map imperfection in an analytic way. The atomic images, at any resolution and with any value of the atomic displacement parameter, can be decomposed into a linear combination of such functions with the precalculated parameter values. As a consequence, each map value becomes an analytic function of atomic parameters including displacement parameter and a local resolution if required. Using the chain rule for the score function which compares the maps, such model results in analytic expressions for its partial derivatives with respect to all atomic parameters allowing an efficient real-space refinement. At the same time, for practical calculations atomic images are cut at some truncation distance, i.e., include a limited number of ripples. This introduced in the model maps errors which are not present in the experimental maps. Due to oscillating behavior of the atomic images, the choice of the value of this truncation distance is not straightforward and discussed in this work.SynopsisA new method is suggested to calculate maps of a limited and eventually inhomogeneous resolution as an analytic function of all atomic parameters, including local resolution.
Identification of novel antiviral drug candidates using an optimized SARS-CoV-2 phenotypic screening platform
Authors: Bojkova Denisa , Reus Philipp , Panosch Leona , Bechtel Marco , Rothenburger Tamara , Kandler Joshua , Pfeiffer Annika , Wagner Julian U.G. , Shumliakivska Mariana , Dimmeler Stefanie , Olmer Ruth , Martin Ulrich , Vondran Florian , Toptan Tuna , Rothweiler Florian , Zehner Richard , Rabenau Holger , Osman Karen L. , Pullan Steven T. , Carroll Miles , Stack Richard , Ciesek Sandra , Wass Mark N , Michaelis Martin , Cinatl Jindrich 
Published: July 2022

AbstractReliable, easy-to-handle phenotypic screening platforms are needed for the identification of anti-SARS-CoV-2 compounds. Here, we present caspase 3/7 activity as a read-out for monitoring the replication of SARS-CoV-2 isolates from different variants, including a remdesivir-resistant strain, and of other coronaviruses in a broad range of cell culture models, independently of cytopathogenic effect formation. Compared to other cell culture models, the Caco-2 subline Caco-2-F03 displayed superior performance, as it possesses a stable SARS-CoV-2 susceptible phenotype and does not produce false-positive hits due to drug-induced phospholipidosis. A proof-of-concept screen of 1796 kinase inhibitors identified known and novel antiviral drug candidates including inhibitors of PHGDH, CLK-1, and CSF1R. The activity of the PHGDH inhibitor NCT-503 was further increased in combination with the HK2 inhibitor 2-deoxy-D-glucose, which is in clinical development for COVID-19. In conclusion, caspase 3/7 activity detection in SARS-CoV-2-infected Caco-2F03 cells provides a simple phenotypic high-throughput screening platform for SARS-CoV-2 drug candidates that reduces false positive hits.
Identification of long non-coding RNAs as substrates for cytoplasmic capping enzyme
Authors: Mukherjee Avik , Islam Safirul , Kieser Rachel E. , Kiss Daniel L. , Mukherjee Chandrama 
Published: July 2022

AbstractCytoplasmic capping returns a cap to specific mRNAs thus protecting uncapped RNAs from decay. Prior to the identification of cytoplasmic capping, uncapped mRNAs were thought to be degraded. Here, we test whether long non-coding RNAs (lncRNAs) are cytoplasmic capping enzyme (cCE) substrates. The subcellular localization of fourteen lncRNAs associated with sarcomas were examined in U2OS osteosarcoma cells. We used 5’ rapid amplification of cDNA ends (RACE) to assay uncapped forms of these lncRNAs. Inhibiting cytoplasmic capping elevated uncapped forms of selected lncRNAs indicating a plausible role of cCE in targeting them. Analysis of published cap analysis of gene expression (CAGE) data shows increased prevalence of certain 5’-RACE cloned sequences suggesting that these uncapped lncRNAs are cytoplasmic capping targets.
Structure of Geobacter OmcZ filaments suggests extracellular cytochrome polymers evolved independently multiple times
Authors: Wang Fengbin , Chan Chi H. , Suciu Victor , Mustafa Khawla , Si Dong , Hochbaum Allon I. , Egelman Edward H. , Bond Daniel R. 
Published: July 2022

AbstractWhile early genetic and low resolution structural observations suggested that extracellular conductive filaments on metal reducing organisms such as Geobacter were composed of Type IV pili, it has now been established that bacterial c-type cytochromes can polymerize to form extracellular filaments capable of long-range electron transport. Atomic structures exist for two such cytochrome filaments, formed from the hexaheme cytochrome OmcS and the tetraheme cytochrome OmcE. Due to the highly conserved heme packing within the central OmcS and OmcE cores, and shared pattern of heme coordination between subunits, it has been suggested that these polymers have a common origin. We have now used cryo-EM to determine the structure of a third extracellular filament, formed from the Geobacter sulfurreducens octaheme cytochrome, OmcZ. In contrast to the linear heme chains in OmcS and OmcE, the packing of hemes, heme:heme angles, and between-subunit heme coordination is quite different in OmcZ. A branched heme arrangement within OmcZ leads to a highly surface exposed heme in every subunit, which may account for the formation of conductive biofilm networks, and explain the higher measured conductivity of OmcZ filaments. This new structural evidence suggests that conductive cytochrome polymers arose independently on more than one occasion from different ancestral multiheme proteins.
Pandemic modelling for regions implementing an elimination strategy
Authors: Hurford Amy , Martignoni Maria M. , Loredo-Osti J.C. , Anokye Francis , Arino Julien , Husain Bilal Saleh , Gaas Brian , Watmough James 
Published: July 2022

AbstractDuring the COVID-19 pandemic, some countries, such as Australia, China, Iceland, New Zealand, Thailand, and Vietnam successfully implemented an elimination strategy, enacting strict border control and periods of lockdowns to end community transmission. Atlantic Canada and Canada’s territories implemented similar policies, and reported long periods with no community cases. In Newfoundland and Labrador (NL), Nova Scotia, and Prince Edward Island a median of 80% or more of daily reported cases were travel-related from July 1, 2020 to May 31, 2021. With increasing vaccination coverage, it may be appropriate to exit an elimination strategy, but most existing epidemiological frameworks are applicable only to situations where most cases occur in the community, and are not appropriate for regions that have implemented an elimination strategy. To inform the pandemic response in regions that are implementing an elimination strategy, we extend importation modelling to consider post-arrival travel restrictions, and pharmaceutical and non-pharmaceutical interventions in the local community. We find that shortly after the Omicron variant had begun spreading in Canada, the expected daily number of spillovers, infections spread to NL community members from travelers and their close contacts, was higher than any time previously in the pandemic. By December 24, 2021, the expected number of spillovers was 44% higher than the previous high, which occurred in late July 2021 shortly after travel restrictions were first relaxed. We develop a method to assess the characteristics of potential future community outbreaks in regions that are implementing an elimination strategy. We apply this method to predict the effect of variant and vaccination coverage on the size of hypothetical community outbreaks in Mount Pearl, a suburb of the St. John’s metropolitan area in NL. Our methodology can be used to evaluate alternative plans to relax public health restrictions when vaccine coverage is high in regions that have implemented an elimination strategy. This manuscript was submitted as part of a theme issue on“Modelling COVID-19 and Preparedness for Future Pandemics”.
Slow waning of antibodies following a third dose of BNT162b2 in adults who had previously received two doses of inactivated vaccine
Authors: Cowling Benjamin J. , Cheng Samuel M. S. , Martín-Sánchez Mario , Au Niki Y. M. , Chan Karl C. K. , Li John K. C. , Luk Leo L. H. , Tsang Leo C. H. , Ip Dennis K. M. , Poon Leo L. M. , Leung Gabriel M. , Peiris J. S. Malik , Leung Nancy H. L. 
Published: July 2022

ABSTRACTIntroductionThird doses of COVID-19 vaccination provide an important boost to immunity, reducing the risk of symptomatic infection and the risk of severe disease. Third doses have been particularly important for improving protection against variants. However, waning of clinical protection particularly against Omicron has been noted after receipt of third doses.MethodsWe administered BNT162b2 as a third dose to adults aged ≥30 years who had previously received two doses of inactivated vaccination. We collected blood before the third dose and again after one month and six months, and tested sera using a spike receptor binding domain IgG enzyme-linked immunosorbent assay, a surrogate virus neutralization test, and live virus plaque reduction neutralization assay against ancestral virus and Omicron BA.2.ResultsWe administered BNT162b2 as a third dose to 314 adults. We found robust antibody responses to the ancestral strain at six months after receipt of BNT162b2. Antibody responses to Omicron BA.2 were weaker after the third dose and had declined to a low level by six months. From a small number of participants we observed that natural infection or a fourth dose of vaccination generated similar antibody levels against ancestral virus, but infection generated higher antibody level against Omicron BA.2 than vaccination, suggesting a potential advantage in the breadth of antibody response from hybrid immunity.ConclusionsWhile antibody levels against the ancestral strain remained robust at six months after the third dose, antibody levels against Omicron BA.2 had fallen to low levels suggesting the potential benefits of a fourth dose.
Comparing methods to predict baseline mortality for excess mortality calculations
Authors: Ferenci Tamás 
Published: July 2022

AbstractBackgroundThe World Health Organization (WHO)’s excess mortality estimates presented in May 2022 stirred controversy, due in part to the high estimate provided for Germany, which was later attributed to the spline model used. This paper aims to reproduce the problem using synthetic datasets, thus allowing the investigation of its sensitivity to parameters, both of the mortality curve and of the used method, thereby shedding light on the conditions that gave rise to this error and identifying possible remedies.MethodsA negative binomial model was used accounting for long-term change, seasonality, flu seasons, and heat waves. Simulated mortality curves from this model were then analysed using simple methods (mean, linear trend), the WHO method, and the method of Acosta and Irizarry.ResultsThe performance of the WHO’s method with its original parametrization was indeed very poor, however it can be profoundly improved by a better choice of parameters. The Acosta–Irizarry method outperformed the WHO method despite being also based on splines, but it was also dependent on its parameters. Linear extrapolation could produce very good results, but was highly dependent on the choice of the starting year, while the average was the worst in almost all cases.ConclusionsSplines are not inherently unsuitable for predicting baseline mortality, but caution should be taken. In particular, the results suggest that the key issue is that the splines should not be too flexible to avoid overfitting. Even after having investigated a limited number of scenarios, the results suggest that there is not a single method that outperforms the others in all situations. As the WHO method on the German data illustrates, whatever method is chosen, it remains important to visualize the data, the fit, and the predictions before trusting any result. It will be interesting to see whether further research including other scenarios will come to similar conclusions.
COVID-19 vaccine effectiveness against progression to in-hospital mortality — Zambia, 2021-2022
Authors: Chanda Duncan , Hines Jonas Z , Itoh Megumi , Fwoloshi Sombo , Minchella Peter A , Zyambo Khozya D. , Sivile Suilanji , Kampamba Davies , Chirwa Bob , Chanda Raphael , Mutengo Katongo , Kayembe Mazinga F. , Chewe Webster , Chipimo Peter , Mweemba Aggrey , Agolory Simon , Mulenga Lloyd B. 
Published: July 2022

AbstractBackgroundCOVID-19 vaccines are highly effective for reducing severe disease and mortality. However, vaccine effectiveness data is limited from sub-Saharan Africa, where SARS-CoV-2 epidemiology has differed from other regions. We report COVID-19 vaccine effectiveness against progression to in-hospital mortality in Zambia.MethodsWe conducted a retrospective cohort study among admitted patients at eight COVID-19 treatment centers across Zambia during April 2021 through March 2022. Patient demographic and clinical information including vaccination status and hospitalization outcome (discharged or died) werecollected. Multivariable logistic regression was used to assess the odds of in-hospital mortality by vaccination status, adjusted for age, sex, number of comorbid conditions, disease severity, and COVID-19 treatment center. Vaccine effectiveness of ≥1 vaccine dose was calculated from the adjusted odds ratio.ResultsAmong 1,653 patients with data on their vaccination status and hospitalization outcome, 365 (22.1%) died. Overall, 236 (14.3%) patients had received ≥1 vaccine dose before hospital admission. For patients who had received ≥1 vaccine dose, 22 (9.3%) died compared with 343 (24.2%) among unvaccinated patients (p <0.01). The median time since receipt of a first vaccine dose was 52.5 days (IQR: 28-107). Vaccine effectiveness for progression to in-hospital mortality among hospitalized patients was 64.8% (95% CI: 42.3-79.4%).ConclusionsAmong patients admitted to COVID-19 treatment centers in Zambia, COVID-19 vaccination was associated with lower progression to in-hospital mortality. These data are consistent with evidence from other countries demonstrating benefit of COVID-19 vaccination against severe complications. Vaccination is a critical tool for reducing the consequences of COVID-19 in Zambia.Key points-Receipt of ≥1 COVID-19 vaccine dose reduced progression to in-hospital mortality in Zambia by 64.8%-Mortality benefit of COVID-19 vaccines was sustained during the period of omicron transmission in Zambia