bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urine Recirculation Improves Hemodynamics and Enhances Function in Normothermic Kidney Perfusion
Authors: Weissenbacher Annemarie , Voyce Daniel , Ceresa Carlo D.L. , Soares Maria F. , Roberts Ian S. , Hunter James P. , Cook Andrew , Ploeg Rutger J. , Coussios Constantin C. , Friend Peter J. 
Published: March 2020

Background.
The study compares urine recirculation (URC) to urine replacement (UR) with Ringer’s lactate in a porcine normothermic kidney machine perfusion (NMP) model using a preclinical prototype device.

Methods.
Kidney pairs were recovered uninjured (as live-donor nephrectomy) and perfused consecutively. Pig kidneys (n = 10) were allocated to either NMP with URC (n = 5) or NMP with volume replacement (n = 5). Cold ischemia time was either 2 or 27 hours for the first or second perfusion (URC or UR) of a kidney pair. An autologous blood-based perfusate, leukocyte-filtered, was used and NMP performed up to 24 hours. Perfusion parameters, biochemistry/metabolic parameters were monitored and samples collected.

Results.
Physiological mean arterial pressures and flows were achieved in both groups but were sustainable only with URC. Significantly higher arterial flow was observed with URC (326.7 ± 1.8 versus 242.5 ± 14.3 mL/min, P = 0.001). Perfusate sodium levels were lower with URC, 129.6 ± 0.7 versus 170.3±2.7 mmol/L, P < 0.001). Stable physiological pH levels were only observed with URC. Perfusate lactate levels were lower with URC (2.2 ± 0.1 versus 7.2 ± 0.5 mmol/L, P < 0.001). Furthermore, the hourly rate of urine output was lower with URC and closer to physiological levels (150 versus 548 mL/h, P = 0.008). Normothermic kidney perfusion with URC was associated with longer achievable durations of perfusion: the objective in all experiments was a 24-hour perfusion, but this was not achieved in every case. The mean perfusions were 17.3 ± 9.2 hours with URC versus 5.3 ± 1.3 hours NMP with UR; P = 0.02. There appeared to be no differences in baseline tubular condition with and without URC.

Conclusions.
URC facilitates long-term kidney NMP in a porcine model. Perfusate homeostasis and stability of renal arterial flow throughout the perfusion period was only achievable with URC, independent of cold ischemia time duration.
Scattering on a square lattice from a crack with a damage zone
Authors: Lal Sharma Basant , Mishuris Gennady 
Published: March 2020

A semi-infinite crack in an infinite square lattice is subjected to a wave coming from infinity, thereby leading to its scattering by the crack surfaces. A partially damaged zone ahead of the crack tip is modelled by an arbitrarily distributed stiffness of the damaged links. While an open crack, with an atomically sharp crack tip, in the lattice has been solved in closed form with the help of the scalar Wiener–Hopf formulation (Sharma 2015
SIAM J. Appl. Math.
,
75
, 1171–1192 (
doi:10.1137/140985093
); Sharma 2015
SIAM J. Appl. Math.
75
, 1915–1940. (
doi:10.1137/15M1010646
)), the problem considered here becomes very intricate depending on the nature of the damaged links. For instance, in the case of a partially bridged finite zone it involves a 2 × 2 matrix kernel of formidable class. But using an original technique, the problem, including the general case of arbitrarily damaged links, is reduced to a scalar one with the exception that it involves solving an auxiliary linear system of
N
×
N
equations, where
N
defines the length of the damage zone. The proposed method does allow, effectively, the construction of an exact solution. Numerical examples and the asymptotic approximation of the scattered field far away from the crack tip are also presented.
Decreased bioefficacy of long-lasting insecticidal nets and the resurgence of malaria in Papua New Guinea
Authors: Vinit Rebecca , Timinao Lincoln , Bubun Nakei , Katusele Michelle , Robinson Leanne , Kaman Peter , Sakur Muker , Makita Leo , Reimer Lisa , Schofield Louis , Pomat Willie , Mueller Ivo , Laman Moses , Freeman Tim , Karl Stephan 
Published: March 2020

AbstractBackgroundPapua New Guinea (PNG) has the highest malaria transmission outside of Africa and long-lasting insecticidal nets (LLINs) are the only vector-control tool distributed country-wide. LLINs were introduced into PNG in about 2006 and have been attributed to have had a huge impact on malaria transmission, with reductions in observed average malaria prevalence from 15.7% (2008) to 1% (2014). However, since 2015 malaria indicators in PNG have risen significantly. Similar trends have been observed in several African nations. In the present study, we observed a drastic reduction in bioefficacy of LLINs collected both from households as used nets and prior to use in original, unopened packaging. We hypothesise that decreased bioefficacy of LLIN is a major contributor to the observed malaria resurgence in PNG and possibly in other parts of the world.MethodsNew LLINs in original and unopened packaging (n=192) manufactured between 2007-2019 were collected in 15 PNG provinces. Used LLIN (n=40) manufactured between 2008 and 2017 were collected in 2 provinces. LLIN were subjected to standard WHO cone bioassays using fully susceptible An. farauti mosquitoes. A subset of LLIN was re-tested using fully susceptible An. gambiae G3 mosquitoes in order to ensure reproducibility of results.ResultsOnly 7% (95% CI 4-12%) of new LLINs manufactured between 2013-2019 exhibited 100% mortality. However, 84% (95%CI: 65-84%) new nets manufactured in 2012 or before exhibited 100% mortality. Only 29 % of used LLIN less than 3 years old exhibited > 80% 24h-mortality. Results obtained in tests using An. farauti corresponded well with confirmatory tests conducted using An. gambiae.DiscussionBioefficacy of LLIN in PNG appears to have been highly variable since 2013, with few nets manufactured since 2013 meeting WHO standards. This time-frame coincides with malaria resurgence in the country. These results may have ramifications for LLIN-based malaria control that go beyond the local PNG scenario.
Deficient uracil base excision repair leads to persistent dUMP in HIV proviruses during infection of monocytes and macrophages
Authors: Meshesha Mesfin , Esadze Alexandre , Cui Junru , Churgulia Natela , Sahu Sushil Kumar , Stivers James T. 
Published: March 2020

AbstractNon-dividing cells of the myeloid lineage such as monocytes and macrophages are target cells of HIV that have low dNTP pool concentrations and elevated levels of dUTP, which leads to frequent incorporation of dUMP opposite to A during reverse transcription (“uracilation”). One factor determining the fate of dUMP in proviral DNA is the host cell uracil base excision repair (UBER) system. Here we explore the relative UBER capacity of monocytes (MC) and monocyte-derived macrophages (MDM) and the fate of integrated uracilated viruses in both cell types to understand the implications of viral dUMP on HIV diversification and infectivity. We find that monocytes are almost completely devoid of functional UBER, while macrophages are mainly deficient in the initial enzyme uracil DNA glycosylase (hUNG2). Accordingly, dUMP persists in viral DNA during the lifetime of a MC and can only be removed after differentiation of MC into MDM. Overexpression of human uracil DNA glycosylase in MDM prior to infection resulted in rapid removal of dUMP from HIV cDNA and near complete depletion of dUMP-containing viral copies. This finding establishes that the low hUNG2 expression level in these cells limits UBER but that hUNG2 is restrictive against uracilated viruses. In contrast, overexpression of hUNG2 after viral integration did not accelerate the excision of uracils, suggesting that they may poorly accessible in the context of chromatin. We found that viral DNA molecules with incorporated dUMP contained unique (+) strand transversion mutations that were not observed when dUMP was absent (G→T, T→A, T→G, A→C). These observations and other considerations suggest that dUMP introduces errors predominantly during (-) strand synthesis when the template is RNA. These mutations may arise from the increased mispairing and duplex destabilizing effects of dUMP relative to dTMP during reverse transcription. Overall, the likelihood of producing a functional virus fromin vitroinfection of MC is about 50-fold and 300-fold reduced as compared to MDM and activated T cells. The results implicate viral dUMP incorporation in MC and MDM as a potential viral diversification and restriction pathway during human HIV infection.
Germline and Tumor Whole Genome Sequencing as a Diagnostic Tool to Resolve Suspected Lynch Syndrome
Authors: Pope Bernard J. , Clendenning Mark , Rosty Christophe , Mahmood Khalid , Georgeson Peter , Joo Jihoon E. , Walker Romy , Hutchinson Ryan A. , Jayasekara Harindra , Joseland Sharelle , Como Julia , Preston Susan , Spurdle Amanda B. , Macrae Finlay A. , Win Aung K. , Hopper John L. , Jenkins Mark A. , Winship Ingrid M. , Buchanan Daniel D. 
Published: March 2020

AbstractBackgroundPeople who develop mismatch repair (MMR) deficient cancer in the absence of a germline MMR gene pathogenic variant or hypermethylation of theMLH1gene promoter in their tumor are classified as having suspected Lynch syndrome (SLS). We applied germline whole genome sequencing (WGS) and targeted and genome-wide tumor sequencing approaches to identify the underlying cause of tumor MMR-deficiency in SLS.MethodsGermline WGS was performed on 14 cancer-affected people with SLS, including two sets of first-degree relatives. Tumor tissue was sequenced for somatic MMR gene mutations by targeted, whole exome sequencing or WGS. Germline pathogenic variants, including complex structural rearrangements and non-coding variants, were assessed for the MMR genes. Tumor mutation burden and mutational signatures.ResultsGermline WGS identified pathogenic MMR variants in 3 of the 14 (21.4%) SLS cases including a 9.5Mb inversion disrupting exons 1-7 ofMSH2in a mother and daughter. Excluding these 3 MMR carriers, tumor sequencing identified at least two somatic MMR gene mutations in 8/11 (72.7%) tumors tested, supporting a non-inherited cause of tumor MMR-deficiency. In the second mother-daughter pair, the combined analysis of germline and tumor by WGS supported a somatic rather than inherited cause of their tumor MMR-deficiency, through presence of double somaticMSH2mutations in their respective tumors.ConclusionGermline WGS of people with SLS improved the identification of Lynch syndrome. When coupled with tumor sequencing, >70% of the people with SLS were resolved as having double somatic MMR mutations and a non-inherited cause for their tumor MMR-deficiency.
From work stress to disease: A computational model
Authors: de Grave Remco Benthem , Hasselman Fred , Bijleveld Erik 
Published: March 2020

AbstractIn modern society, work stress is highly prevalent. Problematically, work stress can cause disease. To help understand the causal relationship between work stress and disease, we present a computational model of this relationship. That is, drawing from allostatic load theory, we captured the link between work stress and disease in a set of mathematical formulas. With simulation studies, we then examined our model’s ability to reproduce key findings from previous empirical research. Specifically, results from Study 1 suggested that our model could accurately reproduce established findings on daily fluctuations in cortisol levels (both on the group level and the individual level). Results from Study 2 suggested that our model could accurately reproduce established findings on the relationship between work stress and cardiovascular disease. Finally, results from Study 3 yielded new predictions about the relationship between workweek configurations (i.e., how working hours are distributed over days) and the subsequent development of disease. Together, our studies suggest a new, computational approach to studying the causal link between work stress and disease. We suggest that this approach is fruitful, as it aids the development of falsifiable theory, and as it opens up new ways of generating predictions about why and when work stress is (un)healthy.
The effects of border control and quarantine measures on global spread of COVID-19
Authors: Hossain M. Pear , Junus Alvin , Zhu Xiaolin , Jia Pengfei , Wen Tzai-Hung , Pfeiffer Dirk , Yuan Hsiang-Yu 
Published: March 2020

AbstractThe rapid expansion of coronavirus (COVID-19) has been observed in many parts of the world. Many newly reported cases of this new coronavirus during early outbreak phases have been associated with travel history from an epidemic region (identified as imported cases). For those cases without travel history, the risk of wider spreads through community contact is even higher. However, most population models assume a homogeneous infected population without considering that the imported and secondary cases contracted by the imported cases can pose a different risk to community spread.We have developed an “easy-to-use” mathematical framework extending from a meta-population model embedding city-to-city connections to stratify the dynamics of transmission waves caused by imported, secondary, and others from an outbreak source region when control measures are considered. Using the dynamics of the secondary cases, we are able to determine the probability of community spread.Using the top 10 visiting cities from Wuhan in China as an example, we first demonstrated that the arrival time and the dynamics of the outbreaks at these cities can be successfully predicted under the reproductive number R0 = 2.92 and latent period τ = 5.2 days. Next, we showed that although control measures can gain extra 32.5 and 44.0 days in arrival time through a high intensive border control measure and a shorter time to quarantine under a low R0 (1.4), if the R0 is higher (2.92), only 10 extra days can be gained for each of the same measures. This suggests the importance of lowering the incidence at source regions together with infectious disease control measures in susceptible regions. The study allows us to assess the effects of border control and quarantine measures on the emergence and the global spread in a fully connected world using the dynamics of the secondary cases.
Serological immunochromatographic approach in diagnosis with SARS-CoV-2 infected COVID-19 patients
Authors: Pan Yunbao , Li Xinran , Yang Gui , Fan Junli , Tang Yueting , Zhao Jin , Long Xinghua , Guo Shuang , Zhao Ziwu , Liu Yinjuan , Hu Hanning , Xue Han , Li Yirong 
Published: March 2020

AbstractAn outbreak of new coronavirus SARS-CoV-2 was occurred in Wuhan, China and rapidly spread to other cities and nations. The standard diagnostic approach that widely adopted in the clinic is nuclear acid detection by real-time RT-PCR. However, the false-negative rate of the technique is unneglectable and serological methods are urgently warranted. Here, we presented the colloidal gold-based immunochromatographic (ICG) strip targeting viral IgM or IgG antibody and compared it with real-time RT-PCR. The sensitivity of ICG assay with IgM and IgG combinatorial detection in nuclear acid confirmed cases were 11.1%, 92.9% and 96.8% at the early stage (1-7 days after onset), intermediate stage (8-14 days after onset), and late stage (more than 15 days), respectively. The ICG detection capacity in nuclear acid-negative suspected cases was 43.6%. In addition, the consistencies of whole blood samples with plasma were 100% and 97.1% in IgM and IgG strips, respectively. In conclusion, serological ICG strip assay in detecting SARS-CoV-2 infection is both sensitive and consistent, which is considered as an excellent supplementary approach in clinical application.
Clinical Characteristics and Durations of Hospitalized Patients With COVID-19 in Beijing: A Retrospective Cohort Study
Authors: Zhao Wen , Zha Xiangyi , Wang Ning , Li Dongzeng , Li Aixin , Yu Shikai 
Published: March 2020

AbstractObjectiveTo give the information on clinical characteristics and different durations of COVID-19 and to identify the potential risk factors for longer hospitalization duration.MethodsIn this retrospective study, we enrolled 77 patients (mean age: 52±20 years; 44.2% males) with laboratory-confirmed COVID-19 admitted to Beijing YouAn Hospital during 21st Jan and 8th February 2020. Epidemiological, clinical, and radiological data on admission were collected; complications and outcomes were followed up until 26th February 2020. The study’s endpoint was the discharge within two weeks. Cox proportional-hazards regression was performed to identify risk factors for longer hospitalization duration.ResultsOf 77 patients, there were 34 (44.2%) males, 24 (31.2%) with comorbidities, 22 (28.6%) lymphopenia, 20 (26.0%) categorized as severe patients, and 28 (36.4%) occurred complications. By the end of follow-up, 64 (83.1%) patients were discharged home, 8 remained in hospital and 5 died. 36 (46.8%) patients were discharged within 14 days and thus reached the study endpoint, including 34 (59.6%) of 57 non-severe patients and 2 (10%) of 20 severe patients. The overall cumulative probability of the endpoint was 48.3%. Hospital length of stay and duration of exposure to discharge for 64 discharged patients were 13 (10-16.5) and 23 (18-24.5) days, respectively. Multivariable stepwise Cox regression model showed that bilateral pneumonia on CT scan, shorter time from the illness onset to admission, severity of disease and lymphopenia were independently associated with longer duration of hospitalization.ConclusionsCOVID-19 has significantly shorter duration of disease and hospital length of stay than SARS. Bilateral pneumonia on CT scan, shorter period of illness onset to admission, lymphopenia, severity of disease are the risk factors for longer hospitalization duration of COVID-19.Significance StatementIn this study, we reported that the average hospital length of stay for discharged patients with COVID-19 is 13 days and the average time of clinical course of COVID-19 is 23 days, both of which are significantly shorter than that of SARS. The risk factors for longer hospitalization duration of COVID-19 include bilateral pneumonia on CT scan, shorter period of illness onset to admission, lymphopenia, and severity of disease. There findings might be helpful for the countries or territories facing the threat of COVID-19 to well prepare and rebalance their medical resources.
Lower DNA methylation levels in CpG island shores of CR1, CLU, and PICALM genes in the blood of Alzheimer’s disease patients
Authors: Mitsumori Risa , Sakaguchi Kazuya , Niida Shumpei , Shimoda Nobuyoshi 
Published: March 2020

AbstractThe aim of the present study was to (1) investigate the relationship between late onset AD and DNA methylation levels in the top six Alzheimer’s disease (AD)-related genes in blood and (2) examine its applicability to the diagnosis of AD. We examined methylation differences at CpG island shores in the top six genes using Sanger sequencing, and one of two groups of 48 AD patients and 48 elderly controls was used for a test or replication analysis. We found that methylation levels in three out of the six genes, CR1, CLU, and PICALM, were lower in AD subjects. The combination of CLU methylation levels and the APOE genotype classified AD patients with AUC=0.84 and 0.80 in the test and replication analyses, respectively. Our results implicate methylation differences at the CpG island shores of AD-related genes in the onset of AD and suggest their diagnostic value.
Excess cases of Influenza like illnesses in France synchronous with COVID19 invasion
Authors: Boëlle Pierre-Yves ,   the Sentinelles syndromic and viral surveillance group
Published: March 2020

AbstractSeveral French regions where COVID19 has been reported currently show a renewed increase in ILI cases in the general practice based Sentinelles network. Here we computed the number of excess cases by region and found correlation with the number of reported COVID19 cases so far. These data suggest larger circulation of SARS-CoV-2 in the French population than apparent from confirmed cases.
Expected impact of COVID-19 outbreak in a major metropolitan area in Brazil
Authors: Rocha Filho Tarcísio M. , dos Santos Fabiana Sherine Ganem , Gomes Victor Bertollo , Rocha Thiago Augusto Hernandes , Croda Julio Henrique Rosa , Ramalho Walter Massa , de Araújo Wildo Navegantes 
Published: March 2020

AbstractIn January 2020 China reported to the World Health Organization an outbreak of pneumonia of undetermined origin in the city of Wuhan, Hubei. In January 30, 2020, the World Health Organization declared the outbreak of COVID-19 as a Public Health Emergency of International Interest (PHEI).ObjectivesThe aim of this study is to assess the impact of a COVID-19 epidemic in the metropolitan region of São Paulo, Brazil.MethodsWe used a generalized SEIR (Susceptibles, Exposed, Infectious, Recovered) model, with additional Hospitalized variables (SEIHR model) and age-stratified structure to analyze the expected time evolution during the onset of the epidemic in the metropolitan area of São Paulo. The model allows to determine the evolution of the number of cases, the number of patients admitted to hospitals and deaths caused by COVID-19. In order to investigate the sensibility of our results with respect to parameter estimation errors we performed Monte Carlo analysis with 100 000 simulations by sampling parameter values from an uniform distribution in the confidence interval.ResultsWe estimate 1 368 (IQR: 880, 2 407) cases, 301 (22%) in older people (≥60 years), 81 (50, 143) hospitalizations, and 14 (9, 26) deaths in the first 30 days, and 38 583 (IQR: 16 698, 113, 163) cases, 8 427 (21.8%) in older people (≥60 years), 2181 (914, 6392) hospitalizations, and 397(166, 1205) deaths in the first 60 days.LimitationsWe supposed a constant transmission probability Pc among different age-groups, and that every severe and critic case will be hospitalized, as well as that the detection capacity in all the primary healthcare services does not change during the outbreak.ConclusionSupposing the reported parameters in the literature apply in the city of São Paulo, our study shows that it is expected that the impact of a COVID-19 outbreak will be important, requiring special planning from the authorities. This is the first study for a major metropolitan center in the south hemisphere, and we believe it can provide policy makers with a prognosis of the burden of the pandemic not only in Brazil, but also in other tropical zones, allowing to estimate total cases, hospitalization and deaths, in support to the management of the public health emergence caused by COVID-19.
Indications for healthcare surge capacity in European countries facing an exponential increase in COVID19 cases
Authors: Verelst Frederik , Kuylen Elise , Beutels Philippe 
Published: March 2020

AbstractEuropean healthcare systems face extreme pressure from COVID-19. We estimate such pressure by relating both country-specific accumulated COVID-19 deaths (intensity-approach) and active COVID-19 cases (magnitude-approach) to measures of healthcare system capacity: hospital beds, healthcare workers and healthcare expenditure. On March 25, 2020 - relative to Italy on March 11- we found Spain, The Netherlands and France to experience the highest pressure using the intensity-approach with a composite measure for healthcare capacity. For updates see www.covid-hcpressure.org
Propagation analysis and prediction of the COVID-19
Authors: Li Lixiang , Yang Zihang , Dang Zhongkai , Meng Cui , Huang Jingze , Meng Hao Tian , Wang Deyu , Chen Guanhua , Zhang Jiaxuan , Peng Haipeng 
Published: March 2020

AbstractBased on the official data modeling, this paper studies the transmission process of the Corona Virus Disease 2019 (COVID-19). The error between the model and the official data curve is within 3%. At the same time, it realized forward prediction and backward inference of the epidemic situation, and the relevant analysis help relevant countries to make decisions.