bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sterols of the aberrant plastid, Kareniacean dinoflagellate Asterodinium gracile: Chemotaxonomic overlap with amphisterol‐producing Amphidinium carterae
Authors: Leblond Jeffrey D. , Sabir Kyra , Ayoub Daniel , McKinnon Mackenzie B. , Myers Chelsea S. , Busari Tawakalit J. , Hollingsworth Braedyn E. 
Published: March 2024

SUMMARYDinoflagellates have a rich history of characterization of their membrane‐reinforcing sterols because of a structural diversity and chemotaxonomic utility uncommon to other classes of algae. The Kareniaceae are no exception in that they produce sterols, often containing a Δ8(14) nuclear unsaturation, which are rare in most other dinoflagellate groups. A continuing goal of our laboratory is to examine the sterols of previously uncharacterized dinoflagellates to assess their sterol‐based chemotaxonomy compared to other members of the Dinophyceae. Asterodinium gracile, a member of the Kareniaceae, has not been commercially available for study until recently. To this end, our objective was to characterize the sterols of A. gracile to determine whether they match the 4α‐methyl‐substituted, Δ8(14)‐nuclear‐unsaturated sterols, such as (24R)‐4α‐methyl‐5α‐ergosta‐8(14),22‐dien‐3β‐ol (gymnodinosterol; C29:2) and 27‐nor‐(24R)‐4α‐methyl‐5α‐ergosta‐8(14),22‐dien‐3β‐ol (brevesterol; C28:2), of most species within the canonical genera Karenia, Karlodinium and Takayama, or instead the 4‐desmethyl sterols, such as 27‐nor‐(24R)‐23‐methyl‐ergosta‐8(14),22‐dien‐3β‐ol (C28:2), of its chemotaxonomically atypical, yet closest phylogenetic relative, Karenia papilionacea. We have observed A. gracile to produce two 4α‐methyl‐substituted sterols with the suggested structures of 4α‐methyl‐5α‐ergosta‐8(14)‐en‐3β‐ol (C29:1) and 4α‐methyl‐5α‐ergosta‐8(14),24(28)‐dien‐3β‐ol (amphisterol, C29:2), as major sterols amongst five other minor sterols, which included the common dinoflagellate sterol cholest‐5‐en‐3β‐ol (cholesterol, C27:1), but did not include gymnodinosterol or brevesterol (as in most canonical Kareniaceae) or 27‐nor‐(24R)‐23‐methyl‐ergosta‐8(14),22‐dien‐3β‐ol (as found in K. papilionacea). Detection of amphisterol and 4α‐methyl‐5α‐ergosta‐8(14)‐en‐3β‐ol is notable because they are sterols associated with some species of Amphidinium, such as Amphidinium carterae, and, to our knowledge, have not been observed in a member of the Kareniaceae before. Discovery of these major sterols in A. gracile expands our knowledge of the range of sterols produced by the Kareniaceae and indicates a shared chemotaxonomy with some species of Amphidinium.
Nurses' organizational climate of perceived organizational support and its relationships with psychosocial working conditions and psychological contracts: A longitudinal questionnaire study
Authors: Larsman Pernilla , Pousette Anders , Törner Marianne 
Published: March 2024

ObjectiveThe aim of the present study was to investigate the longitudinal relationships between nurses' organizational climate of perceived organizational support (POS‐climate) and their psychosocial working conditions and psychological contracts.MethodsA two‐wave longitudinal cohort questionnaire study was carried out among registered nurses employed within six hospitals in two regions in Sweden (n = 711). Two cross‐lagged panel models were tested after ensuring scalar factorial invariance of the measurement models. The first model investigated longitudinal relationships between psychosocial working conditions and the POS‐climate, while the second model investigated such relationships between the psychological contracts and the POS‐climate.ResultsThe results indicated that influence at work and an ideology‐infused psychological contract had positive effects on the nurses' POS‐climate.ConclusionsThese results highlight the importance of providing nurses with such influence, and of a shared ideology within the entire health‐care organization, centered on the ethical values of the health‐care professions.
Pesticide exposure and risk of cholangiocarcinoma: A hospital‐based matched case–control study
Authors: Pugkhem Ake , Kamsa‐ard Supot , Kamsa‐ard Siriporn , Luvira Vor , Luvira Varisara , Bhudhisawasdi Vajarabhongsa 
Published: March 2024

AbstractBackgroundCholangiocarcinoma (CCA) caused by Opisthorchis viverrini is a well‐known and significant public health issue in northeastern Thailand; however, a link between pesticide exposure (PE) and CCA risk has not yet been established. Therefore, our research objective was to investigate the relationship between PE and CCA risk.MethodsA hospital‐based matched case–control study was carried out. All cases (in‐patients) and controls (out‐patients) were volunteers at a tertiary hospital in northeast Thailand. Between 2015 and 2019, 178 incident cases of pathologically‐confirmed CCA and 356 controls were selected from the check‐up clinic from the Srinagarind Hospital outpatient database (two controls per case). The recruited controls were individually‐matched to the CCA cases based on sex, age (±5 years) and admission date (±3 months). During face‐to‐face interviews, a standardised pre‐tested questionnaire was used to collect data. Multivariable conditional logistic regression was used to analyse the data.ResultsThe respective frequency of PE between the 178 CCA cases and 356 controls was 77.0% versus 87.6% for never used, 14.6% versus 5.3% for have used but stopped and 8.4% versus 7.0% for currently using. After adjusting for the highest educational attainment, smoking behaviour, alcohol use and family history of cancer, PE was not significantly associated with CCA (p‐value = 0.086). Using volunteers who have never used PE as the reference group, the respective odds of developing CCA for those who have ever used but have since stopped and are currently using was 2.04 (adjusted OR = 2.04; 95% CI: 1.03–4.04) versus 0.83 (adjusted OR = 0.83; 95% CI: 0.39–1.76) times more likely to develop CCA than those who had never used PE.ConclusionThere is no association between PE and the risk of CCA. Notwithstanding the finding, future research should focus on enhancing PE assessment methods that consider complex chemical mixtures, chemicals of interest, historical exposure and exposure pathways. Moreover, there is need for more extensive and longer population‐based cohort studies that include younger, non‐occupationally exposed individuals during periods of developmental susceptibility.
Decreasing parvovirus B19 and hepatitis A nucleic acid test positivity rates in Canadian plasma donors following the initiation of COVID‐19 restriction in March 2020
Authors: Drews Steven J. , Charlton Carmen , O'Brien Sheila F. , Burugu Samantha , Denomme Gregory A. 
Published: March 2024

AbstractBackground and ObjectivesIn Canada, plasma sent for fractionation is tested for both parvovirus B19 (B19V) and hepatitis A virus (HAV). This study compared positivity rates of B19 and HAV nucleic acid tests (NATs) in Canadian plasma samples for the pre‐COVID‐19 restriction era (2015 to end of February 2020 [Q1] 2020) and the post‐COVID‐19 restriction era.Materials and MethodsPooled EDTA plasma specimens were tested within 24 months of blood draw using the Procleix Panther System (Grifols Diagnostic Solutions Inc, San Diego, CA, USA) for B19V and HAV detection. Reactive pools were resolved by individual specimen testing.ResultsBetween 1 January 2015, and 31 March 2022, 3,928,619 specimens from Canadian plasma donors were tested for B19V. For the same period, 3,922,954 specimens were tested for HAV. To account for a lag in specimen testing for up to 24 months, the data were divided into: (1) a pre‐pandemic period (1 January 2015–31 March 2020; B19V tested n = 2,412,701, B19V NAT‐positive n = 240 [0.01%], HAV tested n = 2,407,036, HAV NAT‐positive n = 26 [0.001%]); (2) a two‐year mixed‐impact period (1 April 2020–31 March 2022; B19V tested n = 968,250, B19V NAT‐positive n = 14 [0.001%], HAV tested n = 968,250, HAV NAT‐positive n = 2 [0.0002%]); and (3) a pandemic‐impact period (1 April 2022–31 March, 2023; B19V tested n = 597,668, B19V NAT‐positive n = 3 [0.0005%], HAV tested n = 597,668, HAV NAT‐positive n = 1 [0.0002%]).ConclusionThe percentage of B19V‐ and HAV‐positive donations was significantly reduced from the pre‐pandemic period to the pandemic‐impact period.
Spatio‐temporal epidemiology of Japanese encephalitis virus infection in pig populations of eastern Uttar Pradesh, India, 2013–2022
Authors: Dhanze Himani , Singh Balbir B. , Walsh Michael , Kumar M. Suman , Kumar Amit , Bhilegaonkar Kiran N. , Brookes Victoria J. 
Published: March 2024

AbstractAimsJapanese encephalitis (JE) is endemic in India. Although pigs are considered important hosts and sentinels for JE outbreaks in people, limited information is available on JE virus (JEV) surveillance in pigs.Methods and ResultsWe investigated the spatio‐temporal distribution of JEV seroprevalence and its association with climate variables in 4451 samples from pigs in 10 districts of eastern Uttar Pradesh, India, over 10 years from 2013 to 2022. The mean seroprevalence of IgG (2013–2022) and IgM (2017–2022) was 14% (95% CI 12.8–15.2) and 10.98% (95% CI 9.8–12.2), respectively. Throughout the region, higher seroprevalence from 2013 to 2017 was observed and was highly variable with no predictable spatio‐temporal pattern between districts. Seroprevalence of up to 60.8% in Sant Kabir Nagar in 2016 and 69.5% in Gorakhpur district in 2017 for IgG and IgM was observed, respectively. IgG seroprevalence did not increase with age. Monthly time‐series decomposition of IgG and IgM seroprevalence demonstrated annual cyclicity (3–4 peaks) with seasonality (higher, broader peaks in the summer and monsoon periods). However, most variance was due to the overall trend and the random components of the time series. Autoregressive time‐series modelling of pigs sampled from Gorakhpur was insufficiently predictive for forecasting; however, an inverse association between humidity (but not rainfall or temperature) was observed.ConclusionsDetection patterns confirm seasonal epidemic periods within year‐round endemicity in pigs in eastern Uttar Pradesh. Lack of increasing age‐associated seroprevalence indicates that JEV might not be immunizing in pigs which needs further investigation because models that inform public health interventions for JEV could be inaccurate if assuming long‐term immunity in pigs. Although pigs are considered sentinels for human outbreaks, sufficient timeliness using sero‐surveillance in pigs to inform public health interventions to prevent JEV in people will require more nuanced modelling than seroprevalence and broad climate variables alone.
Generating the homology of covers of surfaces
Authors: Boggi Marco , Putman Andrew , Salter Nick 
Published: March 2024

AbstractPutman and Wieland conjectured that if is a finite branched cover between closed oriented surfaces of sufficiently high genus, then the orbits of all nonzero elements of under the action of lifts to of mapping classes on are infinite. We prove that this holds if is generated by the homology classes of lifts of simple closed curves on . We also prove that the subspace of spanned by such lifts is a symplectic subspace. Finally, simple closed curves lie on subsurfaces homeomorphic to 2‐holed spheres, and we prove that is generated by the homology classes of lifts of loops on lying on subsurfaces homeomorphic to 3‐holed spheres.
Estimating the economic burden of stroke in China: a cost-of-illness study
Authors: Ma Jingdong , Tian Zeshi , Chai Peipei , Wan Quan , Zhai Tiemin , Guo Feng , Li Yan 
Published: March 2024

ObjectivesStroke imposes a heavy economic burden and loss of productivity on individuals and society. This study assessed a range of crucial factors, including direct costs and indirect costs, to gauge the economic implications of stroke in China. These outcomes were evaluated with specific reference to the year 2018, using the Chinese yuan (¥) as the unit of measurement and providing the corresponding purchasing power parity dollar ($PPP) currency value.MethodsA cost-of-illness methodology was used to ascertain the economic implications of stroke in 2018. Within the constraints of this approach, economic costs were defined as ‘direct costs’ or ‘indirect costs’. We estimated direct costs from sample data, the National Health Service Survey and theNational Health Account and Health Statistical Yearbook. A human capital method was used to conservatively estimate indirect costs.ResultsIn 2018, of the economic burden of stroke in China, the direct costs were ¥247.8 billion ($PPP 58.6 billion) and indirect costs were ¥704.4 billion ($PPP 166.5 billion). The curative care expenditure for stroke was ¥193.1 billion ($PPP 45.7 billion), consuming nearly 5.5% of curative expenditure. The cost of stroke treatment relied heavily on public financing, with 58% from social health insurance and 14% from government sources.ConclusionsA significant economic burden is imposed by stroke on China’s economy, and there is a risk of underestimating this burden if indirect costs are not comprehensively considered. The importance of implementing effective preventive measures and screening strategies for stroke, with a particular focus on high-risk populations, is underscored by this study’s findings. Such investments in public health have the potential to yield substantial benefits.
Low-value MRI of the knee in Norway: a register-based study to identify the proportion of potentially low-value MRIs and estimate the related costs
Authors: Hofmann Bjørn , Håvik Vegard , Andersen Eivind Richter , Brandsæter Ingrid Øfsti , Kjelle Elin 
Published: March 2024

ObjectivesThe objective of this study is to investigate the proportion of potentially low-value knee MRI in Norway and to provide an estimate of the related costs.DesignRegister study based on conditional data extraction and analysis of data from Control and Reimbursement of Healthcare Claims registry in Norway.SettingMRI in public specialist healthcare with universal health coverage (Norway).Participants48 212 MRIs for 41 456 unique patients and 45 946 reimbursement claims.Outcome measuresProportion of MRIs of the knee that (1) did not have a relevant tentative diagnosis prior to the knee MRI, (2) did not have a relevant alternative image of the knee before the MRI or (3) did not have a relevant code from the specialist care within 6 months after the MRI, and those that had combinations of 1, 2 and 3. Estimated costs for those that had combinations of 1, 2 and 3.ResultsVery few patients (6.4%) had a relevant diagnosis code or prior imaging examination when having the MRI and only 14.6% got a knee-related diagnosis code from the specialist care within 6 months after the MRI. 21.8% of the patients had knee X-ray, CT or ultrasound within 6 months before the MRI. Between 58% and 85% of patients having knee MRIs in Norway have no relevant examinations or diagnoses six months prior to or after the MRI examination. These examinations are unlikely to benefit patients and they correspond to between 24 108 and 35 416 MRIs at a cost of €6.7–€9.8 million per year.ConclusionA substantial proportion of MRIs of the knee in Norway have no relevant examinations or diagnoses before or after the MRI and are potentially of low value. Reducing low-value MRIs could free resources for high-value imaging, reduce waiting times, improve the quality of care and increase patient safety and professional integrity.
Cost-effectiveness of the top 100 drugs by public spending in Canada, 2015–2021: a repeated cross-sectional study
Authors: Gaudette Étienne , Rizzardo Shirin , Zhang Yvonne , Pothier Kevin R , Tadrous Mina 
Published: March 2024

ObjectivesTo assess the distribution and spending by cost-effectiveness category among those drugs with the highest public spending levels in Canada.DesignRepeated cross-sectional study.SettingThe Canadian provinces of Manitoba, Ontario, New Brunswick, Nova Scotia, Prince Edward Island and Newfoundland.Main outcomes and measuresCost-effectiveness assessments by the Canadian Agency for Drugs and Technologies in Health (CADTH) for top-100 brand-name outpatient drugs by gross public plan spending in any year between 2015 and 2021 in Canada Institute for Health Information’s National Prescription Drug Utilization Information System data. Gross public plan spending by cost-effectiveness category.ResultsFrom 2015 to 2021, 152 brand-name drugs occupied a top-100 rank and were included in the analysis. Of those, 117 had been assessed by CADTH. During the 7-year period, there was an increase in both top-100 drugs with cost-effective (from 18 to 24) and cost-ineffective (from 29 to 41) assessments, while drugs not assessed or with an unclear assessment declined (from 31 to 19 and from 22 to 16, respectively). As a share of spending on top-100 drugs with an assessment, spending on cost-effective drugs was mostly stable at 40%–46% from 2015 to 2021, while spending on cost-ineffective drugs increased from 30% to 45%.ConclusionA large and growing share of public drug spending has been allocated to cost-ineffective drugs in Canada. Dedicating large budgets to such treatments prevents spending with greater health impact elsewhere in the healthcare system and could restrain the capacity to pay for groundbreaking pharmaceutical innovation in the future.
Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Outcomes in histopathologic subgroups from the randomized, double-blind, phase 3 KEYNOTE-716 trial
Authors: Schadendorf Dirk , Luke Jason John , Ascierto Paolo A , Long Georgina V , Rutkowski Piotr , Khattak Adnan , Del Vecchio Michele , de la Cruz-Merino Luis , Mackiewicz Jacek , Sileni Vanna Chiarion , Kirkwood John M , Robert Caroline , Grob Jean-Jacques , Dummer Reinhard , Carlino Matteo S , Zhao Yujie , Kalabis Mizuho , Krepler Clemens , Eggermont Alexander , Scolyer Richard A 
Published: March 2024

BackgroundAdjuvant pembrolizumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) versus placebo in the phase 3 KEYNOTE-716 study of resected stage IIB or IIC melanoma. At the prespecified third interim analysis (data cut-off, January 4, 2022), the HR for RFS in the overall population was 0.64 (95% CI, 0.50 to 0.84) and the HR for DMFS was 0.64 (95% CI, 0.47 to 0.88). We present a post hoc analysis of efficacy by subtypes defined by histopathologic characteristics.MethodsPatients aged ≥12 years with newly diagnosed, resected stage IIB or IIC melanoma were randomly assigned (1:1) to pembrolizumab 200 mg every 3 weeks (2 mg/kg up to 200 mg for pediatric patients) or placebo. The primary end point was RFS per investigator review; DMFS per investigator review was secondary. Subgroups of interest were melanoma subtype (nodular vs non-nodular), tumor thickness (≤4 mm vs >4 mm), presence of ulceration (yes vs no), mitotic rate (<5 per mm2(median) vs ≥5 per mm2), and presence of tumor-infiltrating lymphocytes (TILs; absent vs present).ResultsBetween September 23, 2018, and November 4, 2020, 976 patients were assigned to pembrolizumab (n=487) or placebo (n=489). Median follow-up was 27.4 months (range, 14.0–39.4). The HR (95% CI) for RFS was 0.54 (0.37 to 0.79) for nodular and 0.77 (0.53 to 1.11) for non-nodular melanoma; 0.57 (0.37 to 0.89) for thickness ≤4 mm and 0.69 (0.50 to 0.96) for >4 mm; 0.66 (0.50 to 0.89) for ulceration and 0.57 (0.32 to 1.03) for no ulceration; 0.57 (0.35 to 0.92) for mitotic rate <5 per mm2and 0.57 (0.40 to 0.80) for ≥5 per mm2; and 0.89 (0.52 to 1.54) for TILs absent and 0.51 (0.34 to 0.76) for TILs present. DMFS results were similar. In a Cox multivariate analysis, treatment arm, tumor thickness, and mitotic rate were significant independent factors for RFS, and treatment arm and mitotic rate were significant independent factors for DMFS.ConclusionsIn this post hoc analysis, the benefit of pembrolizumab was largely consistent with the overall study population regardless of histopathologic characteristics. These results support the use of adjuvant pembrolizumab in patients with resected stage IIB or IIC melanoma.Trial registration numberClinicalTrials.gov,NCT03553836.
Overlapping Batch Confidence Intervals on Statistical Functionals Constructed from Time Series: Application to Quantiles, Optimization, and Estimation
Authors: Su Ziwei , Pasupathy Raghu , Yeh Yingchieh , Glynn Peter 
Published: March 2024

We propose a general purpose confidence interval procedure (CIP) for statistical functionals constructed using data from a stationary time series. The procedures we propose are based on derived distribution-free analogues of the χ
2
and Student’s
t
random variables for the statistical functional context and hence apply in a wide variety of settings including quantile estimation, gradient estimation, M-estimation, Conditional Value at Risk (CVaR) estimation, and arrival process rate estimation, apart from more traditional statistical settings. Like the method of subsampling, we use overlapping batches (OB) of time-series data to estimate the underlying variance parameter; unlike subsampling and the bootstrap, however, we assume that the implied point estimator of the statistical functional obeys a central limit theorem (CLT) to help identify the weak asymptotics (called OB-x limits, x = I, II, III) of batched Studentized statistics. The OB-x limits, certain functionals of the Wiener process parameterized by the size of the batches and the extent of their overlap, form the essential machinery for characterizing dependence and, consequently, the correctness of the proposed CIPs. The message from extensive numerical experimentation is that in settings where a functional CLT on the point estimator is in effect, using
large overlapping batches
alongside OB-x critical values yields confidence intervals that are often of significantly higher quality than those obtained from more generic methods like subsampling or the bootstrap. We illustrate using examples from CVaR estimation, ARMA parameter estimation, and non-homogeneous Poisson process rate estimation; R and MATLAB code for OB-x critical values is available at
web.ics.purdue.edu/∼pasupath
.