bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacometabolomics Identifies Candidate Predictor Metabolites of an L-carnitine Treatment Mortality Benefit in Septic Shock
Authors: Puskarich Michael A. , Jennaro Theodore S. , Gillies Christopher E. , Evans Charles R. , Karnovsky Alla , McHugh Cora E. , Flott Thomas L. , Jones Alan E. , Stringer Kathleen A. 
Published: February 2021

AbstractBackgroundSepsis-induced metabolic dysfunction contributes to organ failure and death. L-carnitine has shown promise for septic shock, but a recent study demonstrated a non-significant reduction in mortality.MethodsA pharmacometabolomics study of patients (n=250) in a Phase II trial of L-carnitine to identify metabolic profiles predictive of a 90-day mortality benefit from L-carnitine. The independent predictive value of each pre-treatment metabolite concentration, adjusted for L-carnitine dose, on 90-day mortality was determined by logistic regression. A grid-search analysis maximizing the Z-statistic from a binomial proportion test identified specific metabolite threshold levels that discriminated L-carnitine responsive patients. Threshold concentrations were further assessed by hazard-ratio and Kaplan-Meier estimate.FindingsAccounting for L-carnitine treatment and dose, 11 1H-NMR metabolites and 12 acylcarnitines were independent predictors of 90-day mortality. Based on the grid-search analysis numerous acylcarnitines and valine were identified as candidate metabolites of drug response. Acetylcarnitine emerged as highly viable for the prediction of an L-carnitine mortality benefit due to its abundance and biological relevance. Using its most statistically significant threshold concentration, patients with acetylcarnitine ≥35µM were less likely to die at 90 days if treated with L-carnitine (18 g) versus placebo (p=0.01 by log rank test).InterpretationMetabolomics identified independent predictors of 90-day sepsis mortality. Our proof-of-concept approach shows how pharmacometabolomics may be useful for tackling the heterogeneity of sepsis and informing clinical trial design. Also, metabolomics can help understand mechanisms of sepsis heterogeneity and variable drug response, since sepsis induces alterations in numerous metabolite concentrations.
Resource Allocation for Different Types of Vaccines against COVID-19: Tradeoffs and Synergies between Efficacy and Reach
Authors: Kim Daniel , Pekgün Pelin , Yildirim İnci , Keskinocak Pınar 
Published: February 2021

AbstractObjectiveVaccine shortage and supply-chain challenges have caused limited access by many resource-limited countries during the COVID-19 pandemic. One of the primary decisions for a vaccine-ordering decision-maker is how to allocate the limited resources between different types of vaccines effectively. We studied the tradeoff between efficacy and reach of the two vaccine types that become available at different times.MethodsWe extended a Susceptible-Infected-Recovered-Deceased (SIR-D) model with vaccination, ran extensive simulations with different settings, and compared the level of infection attack rate (IAR) under different reach ratios between two vaccine types under different resource allocation decisions.ResultsWe found that when there were limited resources, allocating resources to a vaccine with high efficacy that became available earlier than a vaccine with lower efficacy did not always lead to a lower IAR, particularly if the former could vaccinate less than 42.5% of the population (with the selected study parameters) who could have received the latter. Sensitivity analyses showed that this result stayed robust under different study parameters.ConclusionsOur results showed that a vaccine with lower resource requirements (wider reach) can significantly contribute to reducing IAR, even if it becomes available later in the pandemic, compared to a higher efficacy vaccine that becomes available earlier but requires more resources. Limited resource in vaccine distribution is significant challenge in many parts of the world that needs to be addressed to improve the global access to life-saving vaccines. Understanding the tradeoffs between efficacy and reach is critical for resource allocation decisions between different vaccine types for improving health outcomes.
TIME TO LUNG VOLUME STABILITY AFTER PRESSURE CHANGE DURING HIGH-FREQUENCY OSCILLATORY VENTILATION
Authors: Tingay David G , Kiraly Nicholas , Mills John F , Dargaville Peter A 
Published: February 2021

ABSTRACTObjectivesClinicians have little guidance on the time needed before assessing the effect of a mean airway pressure (PAW) change during high-frequency oscillatory ventilation (HFOV). We aimed to determine 1) time to stable lung volume after a PAW change during HFOV and, 2) the relationship between time to volume stability and the volume state of the lung.MethodsContinuous lung volume measurements (respiratory inductive plethysmography) after 1-2 cmH2O PAW changes made every 10 minutes during an open lung strategy (n=13 infants) were analysed with a bi-exponential model. Time to stable lung volume (extrapolated to maximum 3600s) was calculated if the model R2 was >0.6.Results196 PAW changes were made, with no volume change in 33 (17%) occurrences. 125 volume signals met modelling criteria for inclusion; median (IQR) R2 0.96 (0.91, 0.98). The time to stable lung volume was 1131 (718, 1959)s (PAW increases) and 647 (439, 1309)s (PAW decreases), with only 17 (14%) occurring within 10 minutes and time to stability being longer when the lung was atelectatic.ConclusionsDuring HFOV, the time to stable lung volume after a PAW change is variable, often requires more than 10 minutes and is dependent on the preceding volume state.Impact StatementIn infants without preterm respiratory distress syndrome the time to achieve lung volume stability after a PAW change during HFOV is usually greater than 10 minutes.The volume state of the lung at the time of PAW change influences the time required to achieve a stable new lung volume; being shorter when the lung is well recruited and longer when the lung is already atelectatic.Clinicians should be aware that it may require least 10 minutes before assessing the clinical response to a change in PAW during HFOV
Metastatic risk stratification of leiomyosarcoma patients using transcription- and replication-associated chromosomal instability mechanisms
Authors: Benhaddou Ataaillah , Gaston Laetitia , Pérot Gaëlle , Desplat Nelly , Leroy Laura , Guellec Sophie Le , Haddou Mohamed Ben , Rochaix Philippe , Valentin Thibaud , Ferron Gwenaël , Chevreau Christine , Bui Binh , Stoeckle Eberhard , Cesne Axel Le , Piperno-Neumann Sophie , Colin Françoise , Firmin Nelly , De Pinieux Gonzague , Coindre Jean-Michel , Blay Jean-Yves , Chibon Frédéric 
Published: February 2021

AbstractLeiomyosarcoma (LMS) is an aggressive smooth muscle cancer with few therapeutic options. LMSs show a high level of genomic instability (GI) and the mechanisms underlying their oncogenic processes are poorly understood. While the level of GI influences treatment efficacy and resistance, an accurate measure of it is lacking. Current measures of GI are based on counts of specific structural variation (SV) and mutational signatures. Here, we present a holistic approach to measuring GI based on the quantification of the steady-state equilibrium between DNA damage and repair as assessed by the residual breakpoints (BP) remaining after repair, irrespective of SV type. We use the notion of Hscore, a BP “hotspotness” magnitude scale, to measure the propensity of genomic structural or functional DNA elements to break more than expected by chance. We then derived new measures of transcription- and replication-associated GI that we call iTRAC (Transcription-Associated Chromosomal instability index (iTRAC) and iRACIN (Replication-Associated Chromosomal INstability index). We show that iTRAC and iRACIN are predictive of metastatic relapse in LMS and that they may be combined to form a new classifier called MAGIC (Mixed transcription-and replication-Associated Genomic Instability Classifier). MAGIC outperforms the gold standards FNCLCC and CINSARC in stratifying metastatic risk in LMS. Furthermore, iTRAC stratifies chemotherapeutic response in LMS. We finally show that this approach is applicable to other cancers.
Differential Cytokine Signatures of SARS-CoV-2 and Influenza Infection Highlight Key Differences in Pathobiology
Authors: Karaba Andrew H. , Zhou Weiqiang , Hsieh Leon L. , Figueroa Alexis , Massaccesi Guido , Rothman Richard E. , Fenstermacher Katherine Z.J. , Sauer Lauren , Shaw-Saliba Kathryn , Blair Paul W. , Leung Sherry , Wesson Russell , Alachkar Nada , El-Diwany Ramy , Ji Hongkai , Cox Andrea L. 
Published: February 2021

ABSTRACTBackgroundSeveral inflammatory cytokines are upregulated in severe COVID-19. We compared cytokines in COVID-19 versus influenza in order to define differentiating features of the inflammatory response to these pathogens and their association with severe disease. Because elevated body mass index (BMI) is a known risk factor for severe COVID-19, we examined the relationship of BMI to cytokines associated with severe disease.MethodsThirty-seven cytokines and chemokines were measured in plasma from 145 patients with COVID-19, 57 patients with influenza, and 30 healthy controls. Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was utilized to determine the cytokines most important in distinguishing severe COVID-19 and influenza. Mediation analysis was utilized to identify cytokines that mediate the effect of BMI on disease severity.ResultsIL-18, IL-1β, IL-6, and TNF-α were significantly increased in COVID-19 versus influenza patients while GM-CSF, IFN-γ, IFN-λ1, IL-10, IL-15, and MCP-2 were significantly elevated in the influenza group. In subgroup analysis based on disease severity, IL-18, IL-6, and TNF-α were elevated in severe COVID-19, but not severe influenza. Random forest analysis identified high IL-6 and low IFN-λ1 levels as the most distinct between severe COVID-19 and severe influenza. Finally, IL-1RA was identified as a potential mediator of the effects of BMI on COVID-19 severity.ConclusionsThese findings point to activation of fundamentally different innate immune pathways in SARS-CoV-2 and influenza infection, and emphasize drivers of severe COVID-19 to focus both mechanistic and therapeutic investigations.SummarySevere COVID-19 is marked by dysregulated inflammation and is associated with elevated BMI. By comparing cytokines and chemokines in patients with either COVID-19 or influenza, we identified distinct inflammatory pathways and a cytokine mediator of the effect of BMI.
Hot days and Covid-19 – unusual heat stress for nursing professions in Germany
Authors: Jegodka Yvette , Lagally Lena , Mertes Hanna , Deering Katharina , Schoierer Julia , Buchberger Barbara , Bose-O’Reilly Stephan 
Published: February 2021

AbstractObjectivesOur aim was to identify whether working during hot days alongside with Covid-19 related personal protective equipment causes heat stress for nursing professionals in Germany.MethodsUsing an online survey, we assessed the impact of hot weather on nursing staff performing in personal protective equipment. A random selection of nursing staff from hospitals, nursing homes and outpatient care participated in the survey.ResultsOut of 428 participants, 6.3% were between 16 and 25 years old, 22.8% between 26 and 35 years, 21.9% between 36 and 45 years, 30.5% between 45 and 55 years, 18.2% between 56 and 65 years, and 0.3% were older than 65 years. Out of all participants, 18.2% were male and 82.5% female. The results of the survey showed that 48.3% had more than 20 years of experience in nursing and 46.2% cardiac, pulmonary, or other pre-existing conditions. Work was found exhaustive while working in PPE by 96.5% of the participants, and 93% complained of worse breathing. We found out that 85.8% reported difficulties to focus. Many workplaces turned out to lack adequate heat protection, with distinct differences concerning the amount of prophylactic and heat mitigating measures across institutions.ConclusionsOur results clearly show that employers must make more of an effort to provide adequate heat protection for their nursing staff. In order to secure the public health care, there is a need for action, especially in the case of previous conditions of caregivers.What is already known about this subject?►Working in personal protective equipment is often needed during pandemics, to protect nurses, doctors and staff from an infection.►However, the equipment can also hamper efficiency and productivity of healthcare workers and lead to personal discomfort, for example, during heat waves.What are the new findings?►According to our study, nurses and nursing assistants in Germany are often older than 45 years and, in many cases, suffer from pre-existing conditions, which exacerbate the problems with personal protective equipment during periods of hot temperatures.►Many healthcare institutions do not offer adequate ways to mitigate heat stress for their staff.How might this impact on policy or clinical practice in the foreseeable future?►The results from this study can inform policy makers and clinical practitioners to modify their protocols to include better protective measures during extreme heat or other adverse environmental conditions.
Impact of public sentiments on the transmission of COVID-19 across a geographical gradient
Authors: Agusto Folashade B. , Numfor Eric , Srinivasan Karthik , Iboi Enahoro , Fulk Alexander , Saint Onge Jarron M. , Peterson Townsend 
Published: February 2021

AbstractCOVID-19 is a respiratory disease caused by a recently discovered, novel coronavirus, SARS-COV2. The disease has led to over 81 million confirmed cases of COVID-19, with close to 2 million deaths. In the current social climate, the risk of COVID-19 infection is driven by individual and public perception of risk and sentiments. A number of factors influences public perception, including an individual’s belief system, prior knowledge about a disease and information about a disease. In this paper, we develop a model for COVID-19 using a system of ordinary differential equations following the natural history of the infection. The model uniquely incorporates social behavioral aspects such as quarantine and quarantine violation. The model is further driven by people’s sentiments (positive and negative) which accounts for the influence of disinformation. People’s sentiments were obtained by parsing through and analyzing COVID-19 related tweets from Twitter, a social media platform across six countries. Our results show that our model incorporating public sentiments is able to capture the trend in the trajectory of the epidemic curve of the reported cases. Furthermore, our results show that positive public sentiments reduce disease burden in the community. Our results also show that quarantine violation and early discharge of the infected population amplifies the disease burden on the community. Hence, it is important to account for public sentiment and individual social behavior in epidemic models developed to study diseases like COVID-19.
Standardization of a flow cytometry SARS-CoV-2 serologic test
Authors: Simard Carl , Richard Jonathan , Bazin Renée , Finzi Andrés , Trépanier Patrick 
Published: February 2021

AbstractThe SARS-CoV-2 virus is the causing agent of the coronavirus disease 2019 (COVID-19) pandemic which is responsible for millions of deaths worldwide. The development of the humoral response to the virus has been the subject of intensive research and development. A flow cytometry-based assay using native full-length SARS-CoV-2 Spike protein expressed in 293T cells was recently proposed as a complementary seropositivity determination assay.The aim of our study was to further develop the flow cytometry assay for potential use as a confirmatory test and to standardize its parameters and results for reliable inter-laboratory use. We have optimized the protocol, established the Receiving Operating Characteristic (ROC) curve and tested reproducibility using pre-COVID plasma samples and convalescent, SARS-CoV-2 individual plasma samples.The flow-based assay was simplified and standardized by cultivating the 293T cells in suspension and expressing results in Mean Equivalent Soluble Fluorochrome (MESF) using an internal antibody positive control. The ROC curve was determined with an area under the curve (AUC) of 0.996 and the assay specificity and sensitivity were established at 100% and 97.7% respectively. Reproducibility was good as determined on multiple cytometers, on different days, and with data acquisition as far as 72h post-staining. The optimized and standardized assay could be used as a high throughput confirmation confirmatory assay in flow cytometry laboratories involved in serological testing.
Sensitive extraction-free SARS-CoV-2 RNA virus detection using a novel RNA preparation method
Authors: Guan Bin , Frank Karen M. , Maldonado José O. , Beach Margaret , Pelayo Eileen , Warner Blake M. , Hufnagel Robert B. 
Published: February 2021

AbstractCurrent conventional detection of SARS-CoV-2 involves collection of a patient sample with a nasopharyngeal swab, storage of the swab during transport in a viral transport medium, extraction of RNA, and quantitative reverse transcription PCR (RT-qPCR). We developed a simplified and novel preparation method using a Chelex resin that obviates RNA extraction during viral testing. Direct detection RT-qPCR and digital-droplet PCR was compared to the current conventional method with RNA extraction for simulated samples and patient specimens. The heat-treatment in the presence of Chelex markedly improved detection sensitivity as compared to heat alone, and lack of RNA extraction shortens the overall diagnostic workflow. Furthermore, the initial sample heating step inactivates SARS-CoV-2 infectivity, thus improving workflow safety. This fast RNA preparation and detection method is versatile for a variety of samples, safe for testing personnel, and suitable for standard clinical collection and testing on high throughput platforms.
COVID-19 Prevention Beliefs and Practices in College Students
Authors: Cassimatis Caitlyn , Kreitner Liga , Njai Abdoulie , Leary Emily , Gray Aaron 
Published: February 2021

ABSTRACTBackgroundAs college students in the United States return to university campuses, it is important to understand their beliefs and practices on coronavirus disease 2019 (COVID-19) prevention.PurposeTo assess beliefs and practices regarding COVID-19 prevention among college students in the United StatesMethodsAn online, self-administered survey was developed that collected information on COVID-19 preventative practice and beliefs. Survey responses were collected between July 13, 2020 and July 31, 2020.ResultsA total of 4,834 college students participated in the survey with a response rate of 22.9%. Compared to males, more female college students practiced COVID-19 preventative measures, includingalwayswearing masks or face coverings in public (52% vs. 44%, p<0.001) andalwaysoroftenobserving social distancing (70% vs. 63%, p<0.001). In contrast to students from larger population areas, fewer college students from rural areas reported practicing prevention measures, such asalwayswearing a mask (24% rural v. 45% towns vs. 55% cities, p<0.001) andalwayssocial distancing (20% rural vs. 21% towns vs. 29% cities, p<0.001). Additionally, more students from rural areas have becomemuch lessworried about personally contracting COVID-19 over the last 3 months when compared to students from towns and cities (21% vs. 16% vs. 11%, p<0.001). Fewer white college students compared to other racial groups thought it wasvery importantto wear masks (55% white vs. 76% Black vs. 82% Asian vs. 63% American Indian or Alaskan native (AIAN) & Native Hawaiian or Other Pacific Islander (NHOPI), p<0.001) andvery importantto practice social distancing (29% white vs. 50% Black vs. 53% Asian vs. 36% AIAN/NHOPI, p <0.001). Compared to Non-Hispanic students, more Hispanic students thought it wasvery importantto practice preventative measures, including wearing a mask (71% vs. 58%, p<0.001), social distancing (37% vs. 32%, p=0.017), and good hand hygiene (77% vs. 67%, p=0.013).ConclusionCOVID-19 prevention beliefs and practices differ between sexes, the size of town one lives, race, and ethnicity. In general, female students followed Center for Disease Control and Prevention (CDC) COVID-19 prevention guidelines more closely than male students. Students who reside in areas of larger populations have more strict COVID-19 prevention beliefs and practices than students from areas with smaller populations. Asian and Black/African American students adhered closer to CDC COVID-19 prevention guidelines and had stronger beliefs for infection prevention measures than white or AIAN/NHOPI students. Hispanic/Latino students were more stringent in COVID-19 prevention beliefs and practices than non-Hispanic/Latino students.
Identification of B.1.346 lineage of SARS-CoV-2 in Japan: Genomic evidence of re-entry of Clade 20C
Authors: Abe Kodai , Shimura Takako , Takenouchi Toshiki , Iwasaki Yuka W. , Ishizu Hirotsugu , Uwamino Yoshifumi , Uno Shunsuke , Gotoh Jun , Tachikawa Natsuo , Takeuchi Yuriko , Katayama Junpei , Nozaki Hiroyuki , Fujii Susumu , Seki Shikou , Nakamura Morio , Uda Kazuhiro , Misumi Takahiko , Ishihara Jun , Yamada Kenichiro , Kanai Toshio , Murai Shinji , Araki Kazuhiro , Ebihara Tamotsu , Shiomi Haruhiko , Hasegawa Naoki , Kitagawa Yuko , Amagai Masayuki , Suematsu Makoto , Kosaki Kenjiro 
Published: February 2021

AbstractObjectivesWhole SARS-CoV-2 genome sequencing from COVID-19 patients is useful for infection control and regional trends evaluation. We report a lineage data collected from hospitals in the Kanto region of Japan.MethodsWe performed whole genome sequencing in specimens of 198 COVID-19 patients at 13 collaborating hospitals in the Kanto region. Phylogenetic analysis and fingerprinting of the nucleotide substitutions underwent to differentiate and classify the viral lineages.ResultsMore than 90% of the strains belonged to Clade 20B and two lineages (B.1.1.284 and B.1.1.214) have been detected predominantly in the Kanto region. However, one sample from a COVID-19 patient in November 2020, belonged to the B.1.346 lineage of Clade 20C, which has been prevalent in western United States. The patient had no history of overseas travel and no contact with anyone who had travelled abroad, suggesting that this strain appeared likely to have been imported from western United States, across the strict quarantine barrier.ConclusionB.1.1.284 and B.1.1.214 have been identified predominantly in the Kanto region and B.1.346 of clade 20C in one patient was probably imported from western United States. These results illustrate that a decentralized network of hospitals can be significantly advantageous for monitoring regional molecular epidemiologic trends.Highlights· Whole SARS-CoV-2 genome sequencing is useful for infection control· B.1.1.284 and B.1.1.214 have been identified predominantly in the Kanto region· B.1.346 of Clade 20C was detected in one COVID-19 patient in November· Molecular genomic data sharing provides benefits to public health against COVID-19