bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Drug Monitoring of Lamotrigine, Lacosamide, and Levetiracetam in Dried Capillary Blood—Determination of Conversion Factors for Serum-Based Reference Ranges
Authors: Klimpel Dennis , Hagemann Anne , Bien Christian G. , Dufaux Bertin , May Theodor W. , Brandt Christian 
Published: April 2021

Background:
Drug concentrations of antiepileptic drugs (AEDs) are routinely determined from blood serum or plasma at trough levels (before intake of morning dose). In capillary blood collection, blood is taken from the fingertip with the aid of a disposable tool and dried on absorbent material. The volumetric absorptive microsampling technique offers several advantages over the use of filter paper cards. The aim of this study was to determine conversion factors for the estimation of AED serum concentrations from capillary blood concentrations.

Methods:
Venous and capillary blood samples were collected from adult inpatients with epilepsy who were treated with lacosamide (LCM, n = 30), lamotrigine (LTG, n = 40), and/or levetiracetam (LEV, n = 36). A validated liquid chromatography-mass spectrometry (LC-MS) method for dried blood samples for these AEDs was compared with routine serum laboratory methods. Method agreement was evaluated using different regression techniques, and the conversion factors were calculated.

Results:
Regression analyses revealed a linear relationship between serum and capillary blood concentrations for all 3 AEDs (r ≥ 0.95). For LTG, the regression intercept was significantly different from 0, indicating that the relationship was linear, but not necessarily proportional. Although LEV and LCM concentrations tended to be lower in capillary blood than in serum (mean ratio of serum concentration to capillary blood concentration: 1.14 and 1.22, respectively), LTG concentrations were higher in capillary blood (mean ratio = 0.85).

Conclusions:
The estimation of serum concentrations from measured capillary blood concentrations is feasible for LCM, LTG, and LEV. A simple ratio approach using the mean ratio and Passing–Bablok regression showed the best results for all 3 AEDs. The volumetric absorptive microsampling technique facilitates the quantitative sample collection of capillary blood and overcomes the drawbacks associated with the classical dried blood spot technique.
Cost of Health Care–Associated Infections in the United States
Authors: Forrester Joseph D. , Maggio Paul M. , Tennakoon Lakshika 
Published: April 2021

Background
Health care–associated infections (HAIs) are costly, and existing national cost estimates are out-of-date.

Methods
We retrospectively analyzed the Agency for Healthcare Cost and Utilization Project’s 2016 National Inpatient Sample, the largest all-payer U.S. inpatient database. We included all inpatient encounters with primary or secondary International Classification of Disease, 10th Revision Clinical Modification diagnosis codes corresponding to infection with catheter-associated urinary tract infections (T85.511), catheter- and line-associated blood stream infections (T80.211), surgical site infections (SSIs; T81.49), ventilator-associated pneumonias (J95.851), and Infection with Clostridioides difficile (CDI; A04.7). We combined HAI incidence data from the National Inpatient Sample with additional hospital inpatient HAI cost estimates to create national cost estimates for HAI individually and collectively.

Results
In 2016, 7.2 to 14.9 billion U.S. dollars were spent on HAIs in the United States. For admissions with any diagnosis of HAI, the frequencies of HAI in descending order were as follows: CDI (n = 356,754 [56%]), SSI (n = 196,215 [31%]), catheter- and line-associated blood stream infection (n = 42,811 [7%]), catheter-associated urinary tract infection (n = 23,546 [4%]), and ventilator-associated pneumonia (n = 16,767 [3%]). Collectively, CDI and SSI accounted for 79% of the cost of HAI in the United States.

Conclusions
Health care–associated infections remain a significant economic burden for health care systems in the United States.
Analysis on Action Tracking Reports of COVID-19 Informs Control Strategies and Vaccine Delivery in Post-Pandemic Era
Authors: Sun Xiaofei , Guan Tianjia , Xue Tao , Fan Chun , Yang Meng , Meng Yuxian , Zhang Tianwei , Jiangtulu Bahabaike , Wu Fei , Li Jiwei 
Published: April 2021

AbstractUnderstanding the spread of SARS-CoV-2 provides important insights for control policies such as social-distancing interventions and vaccine delivery in the post-pandemic era. In this work, we take the advantage of action tracking reports of confirmed COVID-19 patients, which contain the mobility trajectory of patients. We analyzed reports of patients from April 2020 to January 2021 in China, a country where the residents are well-prepared for the “new normal” world following COVID-19 spread. We developed natural language processing (NLP) tools to transform the unstructured text of action-tracking reports to a structured network of social contacts. An epidemiology model was built on top of the network. Our analysis provides important insights for the development of control policies. Under the “new normal” conditions, we find that restaurants, locations less protected by mask-wearing, have a greater risk than any other location categories, including locations where people are present at higher densities (e.g., flight). We find that discouraging railway transports is crucial to avoid another wave of breakout during the Chunyun season (a period of travel in China with extremely high traffic load around the Chinese New Year). By formalizing the challenge of finding the optimal vaccine delivery among various different population groups as an optimization problem, our analysis helps to maximize the efficiency of vaccine delivery under the general situation of vaccine supply shortage. We are able to reduce the numbers of infections and deaths by 7.4% and 10.5% respectively with vaccine supply for only 1% of the population. Furthermore, with 10% vaccination rate, the numbers of infections and deaths further decrease by 52.6% and 78.1% respectively. Our work will be helpful in the design of effective policies regarding interventions, reopening, contact tracing and vaccine delivery in the “new normal” world following COVID-19 spread.
Two Distinct Dynamic Process Models of COVID-19 Spread with Divergent Vaccination Outcomes
Authors: Chang Ernie , Moselle Kenneth A. 
Published: April 2021

ABSTRACTKinematic models of contagion-based viral transmission describe patterns of events over time (e.g., new infections), relying typically on systems of differential equations to reproduce those patterns. By contrast, agent-based models of viral transmission seek to relate those events or patterns of events to causes, expressed in terms of factors (parameters) that determine the dynamics that give rise to those events.This paper is concerned with the dynamics of contagion-based spread of infection. Dynamics that reflect time homogeneous vs inhomogeneous transmission rates are generated via an agent-based infectious disease modeling tool (CovidSIMVL - github.com/ecsendmail/MultiverseContagion). These different dynamics are treated as causal factors and are related to differences in vaccine efficacy in an array of simulated vaccination trials. Visualizations of simulated trials and associated metrics illustrate graphically some cogent reasons for not effectively hard-coding assumptions of dynamic temporal homogeneity, which come ‘pre-packaged’ with the mass action incidence assumption that underpins typical equation-based models of infection spread.
Impacts of COVID-19 on sick leave
Authors: Skyrud Katrine , Telle Kjetil , Hernæs Kjersti , Magnusson Karin 
Published: April 2021

AimTo explore sick leave after COVID-19, by comparing doctor-certified sick leave for up to 6 months after testing for SARS-CoV-2 across employees who tested positive and negative.MethodsIn all persons (20-70 year of age) with an employment contract, who were tested for the SARS-CoV-2 in Norway from March 1st to November 1st 2020 (N=740 182 with mean [SD] age 39 [13] years, 44% men), we used a difference-in-difference design to contrast doctor-certified sick leave before and after testing, across employees with negative test and positive test by age and sex groups.ResultsSick leave for those testing positive (N=11 414) remained elevated for up to 2 months after testing when compared to those testing negative (N= 728 768), for men and women aged 20-44 and for men aged 45-70 years (relative increase in sick-leave ∼344-415%, (Ball strata=0.079, 95% CI=0.076, 0.082). The increase in sick leave was prolonged for women aged 45-70 years only, persisting for up to 4 months after testing positive (relative increase = 35%, B=0.010, 95% CI=0.004-0.035).ConclusionSick leave following COVID-19 is elevated for up to two to four months after initial infection, thereafter not elevated compared with employees who tested negative for COVID-19. Women aged 45-70 years tend to have a larger impact of COVID-19 on their work ability than men and younger women.
Analysis across Taiwan Biobank, Biobank Japan and UK Biobank identifies hundreds of novel loci for 36 quantitative traits
Authors: Chen Chia-Yen , Chen Tzu-Ting , Feng Yen-Chen Anne , Longchamps Ryan J. , Lin Shu-Chin , Wang Shi-Heng , Hsu Yi-Hsiang , Yang Hwai-I , Kuo Po-Hsiu , Daly Mark J. , Chen Wei J. , Huang Hailiang , Ge Tian , Lin Yen-Feng 
Published: April 2021

AbstractGenome-wide association studies (GWAS) have identified tens of thousands of genetic loci associated with human complex traits and diseases1,2. However, the majority of GWAS were conducted in individuals of European ancestry3. Failure to capture global genetic diversity has limited biological discovery and impeded equitable delivery of genomic knowledge to diverse populations4. Here we report findings from 102,900 individuals across 36 human quantitative traits in the Taiwan Biobank (TWB), a major biobank effort that broadens the population diversity of genetic studies in East Asia (EAS). We identified 979 novel genetic loci, pinpointed novel causal variants through fine-mapping, compared the genetic architecture across TWB, Biobank Japan (BBJ)5–7 and UK Biobank (UKBB)8,9, and evaluated the utility of cross-phenotype, cross-population polygenic risk scores (PRS) in disease risk prediction. These results demonstrated the potential to advance genomic discovery through increasing and diversifying GWAS populations, and provided insights into the common genetic background for human complex traits in East Asian populations.
Breakpoint modelling of temporal associations between non-pharmaceutical interventions and the incidence of symptomatic COVID-19 in the Republic of Ireland
Authors: Boudou M , ÓhAiseadha C , Garvey P , O’Dwyer J , Hynds P 
Published: April 2021

AbstractBackgroundTo constrain propagation and mitigate the burden of COVID-19, most countries initiated and continue to implement several non-pharmaceutical interventions (NPIs), including national and regional lockdowns. In the Republic of Ireland, the first national lockdown was decreed on 23rdof March 2020, followed by a succession of restriction increases and decreases (phases) over the the following year. To date, the effects of these interventions remain unclear, and particularly within differing population subsets. The current study sought to assess the impact of individual NPI phases on COVID-19 transmission patterns within delineated population subgroups in the Republic of Ireland.Methods and FindingsConfirmed, anonymised COVID-19 cases occurring between the 29thof February 2020 and 30thNovember 2020 (n= 72,654) were obtained. Segmented modelling via breakpoint regression with multiple turning points was employed to identify structural breaks across sub-populations, including primary/secondary infections, age deciles, urban/commuter/rural areas, patients with underlying health conditions, and socio-demographic profiles. These were subsequently compared with initiation dates of eight overarching NPI phases.Five distinct breakpoints were identified. The first breakpoint, associated with a decrease in the daily COVID-19 incidence, was reported within 14 days of the first set of restrictions in mid-March 2020 for most population sub-groups. Results suggest that moderately strict NCIs were more effective than the strictest Phase 5 (National Lockdown). Divergences were observed across population sub-groups; lagged response times were observed among populations >80 years, residents of rural/ commuter regions, and cases associated with a below-median deprivation score.ConclusionsStudy findings suggest that many NPIs have been successful in decreasing COVID-19 incidence rates, however the strictest Phase 5 NPI was not. Moreover, NPIs were not equally successful across all sub-populations, with differing response times noted. Mitigation strategies and interventions may need to be increasingly bespoke, based on sub-population profiles and required responses.
Seroepidemiology among Employees of New York City Health and Hospitals during the First Wave of the SARS-CoV-2 Epidemic
Authors: Bryan Alexander D. , Tatem Kathleen , Diuguid-Gerber Jillian , Cooke Caroline , Romanoff Anya , Choudhury Nandini , Scanlon Michael , Kishore Preeti , Sydney Elana , Masci Joseph , Bakshi Parampreet , Pemmasani Sahithi , Davis Nichola J. , Maru Duncan 
Published: April 2021

ABSTRACTObjectiveEstimate the seroprevalence of SARS-CoV-2 antibodies among New York City Health + Hospitals healthcare workers, and identify demographic and occupational factors associated with SARS-CoV-2 antibodies among healthcare workers.MethodsThis was an observational, cross-sectional study using data from SARS-CoV-2 serological tests accompanied by a demographic and occupational survey administered to healthcare workers. Participants were employed by New York City Health + Hospitals (NYC H+H) and either completed serologic testing at NYC H+H between April 30 and June 30, 2020, or completed SARS-CoV-2 antibody testing outside of NYC H+H and were able to self-report results.ResultsSeven hundred twenty-seven survey respondents were included in analysis. Participants had a mean age of 46 years (SD= 12.19) and 543 (75%) were women. Two hundred fourteen (29%) participants tested positive or reported testing positive for the presence of SARS-CoV-2 antibodies (IgG+). Characteristics associated with positive SARS-CoV-2 serostatus were Black race (25% IgG+ vs. 15% IgG-, p=0.001), having someone in the household with COVID symptoms (49% IgG+ vs. 21% IgG-, p<0.001), or having a confirmed COVID-19 case in the household (25% IgG+ vs 5% IgG-, p<0.001). Characteristics associated with negative SARS-CoV-2 serostatus included working on a COVID patient floor (27% IgG+ vs. 36% IgG-, p=0.02), working in the ICU (20% IgG+ vs. 28% IgG-, p=0.03), or having close contact with a patient with COVID-19 (51% IgG+ vs. 62% IgG-, p=0.03).ConclusionsResults underscore the significance of community factors and inequities might have on SARS-CoV-2 exposure for healthcare workers.What is already known about this subject?Healthcare workers are at risk of occupational transmission of SARS-CoV-2, and the risk of infection varies by demographic characteristics and work location.What are the new findings?Healthcare worker race and household contacts were significantly associated with SARS-CoV-2 seropositivity, while working on a COVID patient floor or ICU was associated with seronegativity.How might this impact on policy or clinical practice in the foreseeable future?Results underscore the significance of community factors and inequities on healthcare worker exposure to SARS-CoV-2, and the need to address these inequities at the community level where healthcare workers live.
Stress related network activity in the intact adrenal medulla
Authors: Ruiz Jose R. Lopez , Ernst Stephen A. , Holz Ronald W. , Stuenkel Edward L. 
Published: April 2021

AbstractThe adrenal medulla has long been recognized as playing a critical role in mammalian homeostasis and the stress response. The adrenal medulla is populated by clustered chromaffin cells that secrete epinephrine or norepinephrine along with other peptides into the general bloodstream affecting multiple distant target organs. Although the sympatho-adrenal pathway has been heavily studied, detailed knowledge on the central control and in-situ spatiotemporal responsiveness remains poorly understood. For this work we implemented electrophysiological techniques originally developed to elucidate CNS circuitry to characterize the functional micro-architecture of the adrenal medulla. To achieve this, we continuously monitored the electrical activity inside the adrenal medulla in the living anesthetized rat under basal conditions and under physiological stress. Under basal conditions, chromaffin cells fired action potentials with frequencies between ∼0.2 and 4 Hz. Activity was exclusively driven by sympathetic inputs coming through the splanchnic nerve. Furthermore, chromaffin cells were organized into arrays of independent local networks in which cells fire in a specific order, with latencies from hundreds of microseconds to few milliseconds. Electrical stimulation of the splanchnic nerve evoked the exact same spatiotemporal firing patterns that occurred spontaneously. Induction of hypoglycemic stress by administration of insulin resulted in an increase in the activity of a subset of the chromaffin cell networks. In contrast, respiratory arrest induced by anesthesia overdose resulted in an increase in the activity of the entire adrenal medulla before cessation of all activity when the animal died. The results suggest the differential activation of specific networks inside the adrenal gland depending on the stressor. These results revealed a surprisingly complex electrical organization and circuitry of the adrenal medulla that likely reflects the dynamic nature of its neuroendocrine output during basal conditions and during different types of physiological stress. To our knowledge, these experiments are the first to use multi-electrode arraysin vivoto examine the electrical and functional architecture of any endocrine gland.Significance StatementStress from extrinsic (environmental, psychological) and intrinsic (biological) challenges plays a critical role in disturbing the homeostatic balance. While the body’s responses to stress are designed to ameliorate these imbalances, prolonged and dysregulated stress often drives adverse health consequences in many chronic illnesses. The better understanding of the sympatho-adrenal stress response, will potentially impact and improve the treatment of several stress related illnesses. This work focusses on the study of the functional architecture of the adrenal medulla, a key component in neuronal stress response.
Laminar perfusion imaging with zoomed arterial spin labeling at 7 Tesla
Authors: Shao Xingfeng , Guo Fanhua , Shou Qinyang , Wang Kai , Jann Kay , Yan Lirong , Toga Arthur W. , Zhang Peng , Wang Danny JJ 
Published: April 2021

AbstractLaminar fMRI based on BOLD and CBV contrast at ultrahigh magnetic fields has been applied for studying the dynamics of mesoscopic brain networks. However, the quantitative interpretations of BOLD/CBV fMRI results are confounded by different baseline physiology across cortical layers. Here we introduce a novel 3D zoomed pseudo-continuous arterial spin labeling technique at 7T that offers the unique capability for quantitative measurements of laminar cerebral blood flow (CBF) both at rest and during task activation with high spatial specificity and sensitivity. We found arterial transit time in superficial layers is ∼100 msec shorter than in middle/deep layers revealing the dynamics of labeled blood flowing from pial arteries to downstream microvasculature. Resting state CBF peaked in the middle layers which is highly consistent with microvascular density measured from human cortex specimens. Finger tapping induced a robust two-peak laminar profile of CBF increases in the superficial (somatosensory and premotor input) and deep (spinal output) layers of M1, while finger brushing task induced a weaker CBF increase in superficial layers (somatosensory input). We further demonstrated that top-down attention induced a predominant CBF increase in deep layers and a smaller CBF increase on top of the lower baseline CBF in superficial layers of V1 (feedback cortical input), while bottom-up stimulus driven activity peaked in the middle layers (feedforward thalamic input). These quantitative laminar profiles of perfusion activity suggest an important role of M1 superficial layers for the computation of finger movements, and that visual attention may amplify deep layer output to the subcortex.Significance StatementCBF or microvascular perfusion measured by arterial spin labeling (ASL) is a key parameter forin vivoassessment of neurovascular function. Compared to BOLD or VASO fMRI, ASL perfusion contrast offers the unique capability for quantitative CBF measurements both at baseline and during task activation, which is critical for quantitative estimation of metabolic activities tightly related to neuronal activation. We proposed a zoomed 3D ASL technique at 7T for laminar perfusion imaging with high spatial specificity and sensitivity. This technique is able to differentiate and quantify the input/output and feedforward/feedback activities of human motor and visual cortex, thereby providing an important tool for quantitative assessment of neurovascular function and metabolic activities of neural circuits across cortical layers.
Disparities in SARS-CoV-2 Vaccination-to-Infection Risk, Massachusetts 2020-2021
Authors: Dryden-Peterson Scott , Velásquez Gustavo E. , Stopka Thomas J. , Davey Sonya , Gandhi Rajesh T. , Lockman Shahin , Ojikutu Bisola O. 
Published: April 2021

AbstractBackgroundEffective vaccine-based containment strategies for SARS-CoV-2 require equitable coverage of communities at greatest risk of infection. We sought to examine the alignment of vaccination and SARS-CoV-2 risk in Massachusetts to inform public health response.MethodsWe aggregated cumulative SARS-CoV-2 testing and vaccination data from the Massachusetts Department of Public Health and the Boston Public Health Commission from January 29, 2020 to April 9, 2021. We used two approaches to assess vaccination equity: vaccination-to-infection risk (VIR) ratio and Lorenz curves. The VIR ratio was calculated for each community as the quotient of the number of fully vaccinated individuals divided by the cumulative number of confirmed SARS-CoV-2 infections. Lorenz curves were used to describe vaccination relative to COVID-19 burden. A multivariable Poisson model was used to assess predictors of VIR ratio.ResultsA total of 607,120 (8.9%) SARS-CoV-2 infections were confirmed in Massachusetts residents and 1,485,266 (21.8%) residents were fully vaccinated. Communities with increased socioeconomic vulnerability had lower VIR ratios indicating less equitable vaccination relative to infection risk. In multivariable analysis, decreased vaccination relative to infection risk was independently associated with increasing socioeconomic vulnerability (aRR 0.82 per quartile increase, 95% CI 0.77 to 0.87) and with greater than 20% of the community identified as Black and/or Latinx (aRR 0.67, 95% CI 0.56 to 0.81). Improved community vaccine delivery was associated with higher community proportion of residents aged 65 or older (aRR 1.23 per 5% increase in proportion, 95% CI 1.15 to 1.31). Lorenz curves indicated considerable inequity (Gini 0.46 between communities). An estimated 330,000 full vaccination courses would need to be diverted to under-vaccinated communities to achieve equity.ConclusionIn conclusion, disparities in vaccine delivery highlight ongoing inequities in our approach to COVID-19 and imperil efforts to control the pandemic.