bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic properties of the temozolomide perillyl alcohol conjugate (NEO212) in mice
Authors: Cho Hee-Yeon , Swenson Steve , Thein Thu Zan , Wang Weijun , Wijeratne Neloni R , Marín-Ramos Nagore I , Katz Jonathan E , Hofman Florence M , Schönthal Axel H , Chen Thomas C 
Published: December 2020

Abstract

Background
NEO212 is a novel small-molecule anticancer agent that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH) to the alkylating agent temozolomide (TMZ). It is undergoing preclinical development as a therapeutic for brain-localized malignancies. The aim of this study was to characterize metabolism and pharmacokinetic (PK) properties of NEO212 in preclinical models.

Methods
We used mass spectrometry (MS) and modified high-performance liquid chromatography to identify and quantitate NEO212 and its metabolites in cultured glioblastoma cells, in mouse plasma, brain, and excreta after oral gavage.

Results
Our methods allowed identification and quantitation of NEO212, POH, TMZ, as well as primary metabolites 5-aminoimidazole-4-carboxamide (AIC) and perillic acid (PA). Intracellular concentrations of TMZ were greater after treatment of U251TR cells with NEO212 than after treatment with TMZ. The half-life of NEO212 in mouse plasma was 94 min. In mice harboring syngeneic GL261 brain tumors, the amount of NEO212 was greater in the tumor-bearing hemisphere than in the contralateral normal hemisphere. The brain:plasma ratio of NEO212 was greater than that of TMZ. Excretion of unaltered NEO212 was through feces, whereas its AIC metabolite was excreted via urine.

Conclusions
NEO212 preferentially concentrates in brain tumor tissue over normal brain tissue, and compared to TMZ has a higher brain:plasma ratio, altogether revealing favorable features to encourage its further development as a brain-targeted therapeutic. Its breakdown into well-characterized, long-lived metabolites, in particular AIC and PA, will provide useful equivalents for PK studies during further drug development and clinical trials with NEO212.
Tocilizumab for the Treatment of COVID-19 Among Hospitalized Patients: A Matched Retrospective Cohort Analysis
Authors: Ignatius Elisa H , Wang Kunbo , Karaba Andrew , Robinson Matthew , Avery Robin K , Blair Paul , Chida Natasha , Jain Tania , Petty Brent G , Siddiqui Zishan , Melia Michael T , Auwaerter Paul G , Xu Yanxun , Garibaldi Brian T 
Published: December 2020

Abstract

Background
There is currently no single treatment that mitigates all harms caused by severe acute respiratory syndrome coronavirus 2 infection. Tocilizumab, an interleukin-6 antagonist, may have a role as an adjunctive immune-modulating therapy.

Methods
This was an observational retrospective study of hospitalized adult patients with confirmed coronavirus disease 2019 (COVID-19). The intervention group comprised patients who received tocilizumab; the comparator arm was drawn from patients who did not receive tocilizumab. The primary outcome was all-cause mortality censored at 28 days; secondary outcomes were all-cause mortality at discharge, time to clinical improvement, and rates of secondary infections. Marginal structural Cox models via inverse probability treatment weights were applied to estimate the effect of tocilizumab. A time-dependent propensity score–matching method was used to generate a 1:1 match for tocilizumab recipients; infectious diseases experts then manually reviewed these matched charts to identify secondary infections.

Results
This analysis included 90 tocilizumab recipients and 1669 controls. Under the marginal structural Cox model, tocilizumab was associated with a 62% reduced hazard of death (adjusted hazard ratio [aHR], 0.38; 95% CI, 0.21 to 0.70) and no change in time to clinical improvement (aHR, 1.13; 95% CI, 0.68 to 1.87). The 1:1 matched data set also showed a lower mortality rate (27.8% vs 34.4%) and reduced hazards of death (aHR, 0.47; 95% CI, 0.25 to 0.88). Elevated inflammatory markers were associated with reduced hazards of death among tocilizumab recipients compared with controls. Secondary infection rates were similar between the 2 groups.

Conclusions
Tocilizumab may provide benefit in a subgroup of patients hospitalized with COVID-19 who have elevated biomarkers of hyperinflammation, without increasing the risk of secondary infection.
Clinical and Economic Burden of Valley Fever in Arizona: An Incidence-Based Cost-of-Illness Analysis
Authors: Grizzle Amy J , Wilson Leslie , Nix David E , Galgiani John N 
Published: December 2020

Abstract

Background
Coccidioidomycosis, ie, Valley fever, is an important fungal infection in the Southwest, with half to two thirds of all cases occurring in Arizona. This endemic respiratory disease can range from primary uncomplicated pneumonia to disseminated infection such as meningitis with chronic pulmonary complications. Valley fever diagnoses have risen over recent years and cause substantial morbidity and economic burden in Arizona.

Methods
We estimated the lifetime cost-of-illness associated with all cases of Valley fever diagnosed in 2019 in Arizona. Natural history of the disease was determined from literature and expert opinion and assigned costs from national data sources to determine lifetime direct and indirect costs (work loss).

Results
Total lifetime costs of $736 million were estimated for the 10 359 cases of Valley fever diagnosed in Arizona in 2019. Direct costs of $671 million accounted for over 90% of expenditures, with $65 million in indirect costs. Disseminated infection produces the highest economic burden at $1.26 million direct and $137 400 indirect costs per person. The lowest Valley fever lifetime costs were for cases of primary uncomplicated pneumonia with $23 200 in direct costs and $1300 in lost wages. The average lifetime direct costs across all Valley fever manifestations are $64 800 per person diagnosed in Arizona in 2019 and $6300 for indirect costs.

Conclusions
Valley fever is responsible for substantial economic burden in Arizona. Our estimates underscore the value of supporting research into developing more rapid diagnostic tests, better therapies, and ultimately a preventative vaccine to address this important public health problem in Arizona.
Occurrence of 4 Dengue Virus Serotypes and Chikungunya Virus in Kilombero Valley, Tanzania, During the Dengue Outbreak in 2018
Authors: Chipwaza Beatrice , Sumaye Robert David , Weisser Maja , Gingo Winfrid , Yeo Nicholas Kim-Wah , Amrun Siti Naqiah , Okumu Fredros O , Ng Lisa F P 
Published: December 2020

Abstract

Background
Dengue and Chikungunya viruses can cause large-scale epidemics, with attack rates of up to 80%. In Tanzania, there have been repeated outbreaks of dengue fever, the most recent in 2018 and 2019, mostly affecting the coastal areas. Despite the importance of these viruses, there is limited knowledge on the epidemiology of dengue (DENV) and Chikungunya (CHIKV) in Tanzania. This study was conducted to investigate the prevalence of DENV and CHIKV in Kilombero Valley, Tanzania.

Methods
A cross-sectional study was conducted at Kibaoni Health Center in Kilombero Valley, Southeastern Tanzania, in the rainy and dry seasons of 2018. Febrile patients of any age and gender were enrolled from the outpatient department. Blood samples were taken and screened for DENV and CHIKV viral RNA by real-time reverse transcription polymerase chain reaction assays.

Results
Overall, 294 patients were recruited. Most were females (65%), and one-third of patients were aged 14–25 years. DENV and CHIKV were detected in 29 (9.9%) and 3 (1.0%) patients, respectively. DENV was detected across all age groups during both the dry and rainy seasons. Although all 4 DENV serotypes were detected, serotypes 1 and 3 dominated and were present in 14 patients (42.4%) each. Additionally, the study showed DENV-1 and DENV-3 co-infections.

Conclusions
This study reveals the co-circulation of all 4 DENV serotypes and CHIKV in Kilombero. Importantly, we report the first occurrence of DENV-4 in Tanzania. Unlike previous DENV outbreaks caused by DENV-2, the 2018 outbreak was dominated by DENV-1 and DENV-3. The occurrence of all serotypes suggests the possibility of severe clinical outcomes in future DENV epidemics in Tanzania.
Risk of Clinical Severity by Age and Race/Ethnicity Among Adults Hospitalized for COVID-19—United States, March–September 2020
Authors: Pennington Audrey F , Kompaniyets Lyudmyla , Summers April D , Danielson Melissa L , Goodman Alyson B , Chevinsky Jennifer R , Preston Leigh Ellyn , Schieber Lyna Z , Namulanda Gonza , Courtney Joseph , Strosnider Heather M , Boehmer Tegan K , Mac Kenzie William R , Baggs James , Gundlapalli Adi V 
Published: December 2020

Abstract

Background
Older adults and people from certain racial and ethnic groups are disproportionately represented in coronavirus disease 2019 (COVID-19) hospitalizations and deaths.

Methods
Using data from the Premier Healthcare Database on 181 813 hospitalized adults diagnosed with COVID-19 during March–September 2020, we applied multivariable log-binomial regression to assess the associations between age and race/ethnicity and COVID-19 clinical severity (intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], and death) and to determine whether the impact of age on clinical severity differs by race/ethnicity.

Results
Overall, 84 497 (47%) patients were admitted to the ICU, 29 078 (16%) received IMV, and 27 864 (15%) died in the hospital. Increased age was strongly associated with clinical severity when controlling for underlying medical conditions and other covariates; the strength of this association differed by race/ethnicity. Compared with non-Hispanic White patients, risk of death was lower among non-Hispanic Black patients (adjusted risk ratio, 0.96; 95% CI, 0.92–0.99) and higher among Hispanic/Latino patients (risk ratio [RR], 1.15; 95% CI, 1.09–1.20), non-Hispanic Asian patients (RR, 1.16; 95% CI, 1.09–1.23), and patients of other racial and ethnic groups (RR, 1.13; 95% CI, 1.06–1.21). Risk of ICU admission and risk of IMV were elevated among some racial and ethnic groups.

Conclusions
These results indicate that age is a driver of poor outcomes among hospitalized persons with COVID-19. Additionally, clinical severity may be elevated among patients of some racial and ethnic minority groups. Public health strategies to reduce severe acute respiratory syndrome coronavirus 2 infection rates among older adults and racial and ethnic minorities are essential to reduce poor outcomes.
North American Breeding Bird Survey status and trend estimates to inform a wide range of conservation needs, using a flexible Bayesian hierarchical generalized additive model
Authors: Smith Adam C , Edwards Brandon P M 
Published: December 2020

AbstractThe status and trend estimates derived from the North American Breeding Bird Survey (BBS) are critical sources of information for bird conservation. However, the estimates are partly dependent on the statistical model used. Therefore, multiple models are useful because not all of the varied uses of these estimates (e.g., inferences about long-term change, annual fluctuations, population cycles, and recovery of once-declining populations) are supported equally well by a single statistical model. Here we describe Bayesian hierarchical generalized additive models (GAMs) for the BBS, which share information on the pattern of population change across a species’ range. We demonstrate the models and their benefits using data from a selection of species, and we run full cross-validation of the GAMs against 2 other models to compare the predictive fit. The GAMs have a better predictive fit than the standard model for all species studied here and comparable predictive fit to an alternative first difference model. In addition, one version of the GAM described here (GAMYE) estimates a population trajectory that can be decomposed into a smooth component and the annual fluctuations around that smooth component. This decomposition allows trend estimates based only on the smooth component, which are more stable between years and are therefore particularly useful for trend-based status assessments, such as those by the International Union for the Conservation of Nature. It also allows for the easy customization of the model to incorporate covariates that influence the smooth component separately from those that influence annual fluctuations (e.g., climate cycles vs. annual precipitation). For these reasons and more, this GAMYE model is a particularly useful model for the BBS-based status and trend estimates.
The Equivalence of Definitions of Algorithmic Randomness†
Authors: Porter Christopher 
Published: December 2020

ABSTRACT
In this paper, I evaluate the claim that the equivalence of multiple intensionally distinct definitions of random sequence provides evidence for the claim that these definitions capture the intuitive conception of randomness, concluding that the former claim is false. I then develop an alternative account of the significance of randomness-theoretic equivalence results, arguing that they are instances of a phenomenon I refer to as schematic equivalence. On my account, this alternative approach has the virtue of providing the plurality of definitions of randomness with conceptual unity and a rationale for certain investigations that are carried out in the field.
Spatial patterns in planktonic cnidarian distribution in the western boundary current system of the tropical South Atlantic Ocean
Authors: Tosetto Everton Giachini , Bertrand Arnaud , Neumann-Leitão Sigrid , Costa da Silva Alex , Nogueira Júnior Miodeli 
Published: December 2020

Abstract
In marine western boundary systems, strong currents flowing coastward spread oceanic water masses over the continental shelves. Here we propose to test the hypothesis according to which oceanic cnidarian species may dominate western boundary system regions even in coastal waters. For that purpose we use a set of data collected above the shelf, slope and around oceanic seamounts and islands in the Western Tropical South Atlantic. Samples were acquired with a plankton net with 300 μm mesh size over 34 stations during an oceanographic cruise carried out in October 2015. Results reveal a diverse cnidarian assemblage in the area, extending the known distribution of many species. In addition, the Fernando de Noronha Chain and most of the narrow continental shelf presented a typical oceanic cnidarian community, dominated by holoplanktonic siphonophores. In this western boundary system, this condition was likely driven by the strong currents, which carry the oceanic tropical water and associated planktonic fauna toward the coast. A specific area with reduced influence of oceanic currents presented typical coastal species. The pattern we observed with the dominance of oceanic plankton communities up to coastal areas may be typical in western boundary systems characterized by a narrow continental shelf.
D5-brane on topological black holes
Authors: Nagasaki Koichi 
Published: December 2020

Abstract
Our interest is in finding the difference in behavior between black holes with three different topologies. These black holes have spherical, hyperbolic and toroidal structures. We study in this paper the behavior of probe D5-branes in this nontrivial black hole spacetime. We would like to find the solution that describes the embedding of a probe D5-brane. This system realizes an “interface” solution, a kind of non-local operators, on the boundary gauge theories. These operators are important to deepen understanding of AdS/CFT correspondence.
Portfolio Liquidity and Security Design with Private Information
Authors: DeMarzo Peter M , Frankel David M , Jin Yu 
Published: December 2020

Abstract
A privately informed seller seeks to liquidate a portfolio to raise cash. Each asset’s liquidity thus depends on the impact of its sale on the value of the entire portfolio. We demonstrate the importance of cross-signaling and derive sufficient conditions for a liquidity “pecking order” that determines the order of sale. For assets backed by a common pool, liquidity naturally aligns with seniority. Finally, we extend the portfolio liquidation game to consider security design and demonstrate the optimality of pooling securities and selling senior tranches or debt secured by the pool, with retention increasing in asset quality or informational asymmetry.
Comparison of a Point-of-Care Testing with Enzyme-Multiplied Immunoassay Technique and Liquid Chromatography Combined With Tandem Mass Spectrometry Methods for Therapeutic Drug Monitoring of Mycophenolic Acid: A Preliminary Study
Authors: Zhou Hong , Xiang Hongping , Cai Jie , Wang Yirong , Zhang Min , Han Yong , Zhang Yu 
Published: December 2020

Background:
For mycophenolic acid (MPA), therapeutic drug monitoring is an essential tool for dosage optimization in transplant recipients and autoimmune diseases. In China, a new commercial kit using an immunochromatographic assay (FICA) with a point-of-care testing system was approved for therapeutic drug monitoring of MPA. However, corroboration between FICA and clinically used assays remains unknown. The authors evaluated MPA concentrations in heart transplant recipients obtained by FICA, high-performance liquid chromatography combined with tandem mass spectrometry (LC-MS/MS), and enzyme-multiplied immunoassay technique (EMIT).

Methods:
Nine heart transplant recipients administered a single mycophenolate mofetil (MMF) dose, and 4 administered multiple MMF doses were enrolled. MPA samples were collected before administration, and after 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours, and assessed by 2 immunoassays (EMIT and FICA) and LC-MS/MS. Consistency between methods was evaluated using Passing–Bablok regression and Bland–Altman analysis.

Results:
For Passing–Bablok regression between FICA and LC-MS/MS, FICA = 0.784 LC-MS/MS + 0.360 (95% CI slope: 0.739 to 0.829, 95% CI intercept: 0.174–0.545). Regardless of a significant observed correlation coefficient (R2 = 0.9126), statistical analyses revealed a significant difference between FICA and the reference LC-MS/MS method. The mean absolute bias was 0.69 mcg/mL between FICA and LC-MS/MS. Bland–Altman plots showed a mean bias of −0.23 mcg/mL (±1.96 SD, −2.19 to 1.72 mcg/mL) and average relative bias of 14.73% (±1.96 SD, −67.91% to 97.37%) between FICA and LC-MS/MS. Unsatisfactory consistency was observed between EMIT and LC-MS/MS, and FICA and EMIT. Differences between pharmacokinetic parameters after a single or 7 days of MMF administration, by LC-MS/MS and FICA, were not statistically significant.

Conclusions:
The consistency of the new FICA using a point-of-care testing device with LC-MS/MS and EMIT was inadequate, and the accuracy of EMIT and LC-MS/MS was inappropriate. Clinicians should be informed when switching MPA detection methods to avoid misleading results.
Identification of potential core genes in hepatoblastoma via bioinformatics analysis
Authors: Vastrad Basavaraj , Vastrad Chanabasayya , Kotturshetti Iranna 
Published: December 2020

AbstractHepatoblastoma is the childhood liver cancer. Profound efforts have been made to illuminate the pathology, but the molecular mechanisms of hepatoblastoma are still not well understood. To identify the candidate genes in the carcinogenesis and progression of hepatoblastoma, microarray dataset GSE131329 was downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and pathway and Gene Ontology (GO) enrichment analysis were performed. The protein-protein interaction network (PPI), module analysis, target gene - miRNA regulatory network and target gene - TF regulatory network were constructed and analyzed. A total of 996 DEGs were identified, consisting of 499 up regulated genes and 497 down regulated genes. The pathway and Gene Ontology (GO) enrichment analysis of the DEGs include proline biosynthesis, superpathway of tryptophan utilization, chromosome organization and organic acid metabolic process. Twenty-four hub genes were identified and biological process analysis revealed that these genes were mainly enriched in cell cycle, chromosome organization, lipid metabolic process and oxidation-reduction process. Validation of hub genes showed that TP53, PLK1, AURKA, CDK1, ANLN, ESR1, FGB, ACAT1, GOT1 and ALAS1 may be involved in the carcinogenesis, invasion or recurrence of hepatoblastoma. In conclusion, DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the carcinogenesis and progression of hepatoblastoma, and provide candidate targets for diagnosis and treatment of hepatoblastoma.
Characteristics of SARS-CoV-2 Testing for Rapid Diagnosis of COVID-19 during the Initial Stages of a Global Pandemic
Authors: Guthrie Jennifer L. , Chen Allison J. , Budhram Dalton R. , Cronin Kirby , Peci Adriana , Nelson Paul , Mallo Gustavo V. , Broukhanski George , Murti Michelle , Majury Anna , Mazzulli Tony , Allen Vanessa G. , Patel Samir N. , Kus Julianne V. , Tran Vanessa , Gubbay Jonathan B. 
Published: December 2020

ABSTRACTAccurate SARS-CoV-2 diagnosis is essential to guide prevention and control of COVID-19. From January 11 – April 22, 2020, Public Health Ontario conducted SARS-CoV-2 testing of 86,942 specimens collected from 80,354 individuals, primarily using real-time reverse-transcription polymerase chain reaction (rRT-PCR) methods. We analyzed test results across specimen types and for individuals with multiple same-day and multi-day collected specimens. Nasopharyngeal compared to throat swabs had a higher positivity (8.8% vs. 4.8%) and an adjusted estimate 2.9 Ctlower (SE=0.5,p<0.001). Same-day specimens showed high concordance (98.8%), and the median Ctof multi-day specimens increased over time. Symptomatic cases had rRT-PCR results with an adjusted estimate 3.0 Ct(SE=0.5,p<0.001) lower than asymptomatic/pre-symptomatic cases. Overall test sensitivity was 84.6%, with a negative predictive value of 95.5%. Molecular testing is the mainstay of SARS-CoV-2 diagnosis and testing protocols will continue to be dynamic and iteratively modified as more is learned about this emerging pathogen.