bluuebunny/crossref_metadata_2025_split huggingface dataset:
Withdrawn as duplicate: Evaluation of discharge prescribing after rescheduling of gabapentin as a controlled substance
Authors: Robbins Melody J , Floroff Catherine , Ingemi Amanda , Kaplan Marcus C 
Published: July 2021

Abstract
This article has been withdrawn due to a publisher error that caused the article to be duplicated. The definitive version of this article is published under DOI 10.1093/ajhp/zxab293.
Differential Response in Ethanol Behaviors of Female Rats Given Various Weight Loss Surgeries
Authors: Orellana Elise R , Piscura Mary K , Horvath Nelli , Hajnal Andras 
Published: July 2021

AbstractAimsCurrently, the only effective treatment for morbid obesity and its comorbidities is weight loss surgery (WLS). Growing evidence suggests that different types of WLS, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), have differential effects on alcohol consumption in humans and rats. Thus, we aimed to directly compare the effects of these two surgical procedures, for the first time in female rats, and to determine whether presence or absence of the ghrelin-producing stomach tissue has critical influence on postoperative alcohol intake.MethodsWe performed two experiments using an identical behavioral protocol, a continuous-access two-bottle choice protocol for various concentrations of ethanol (EtOH). In Experiment 1, 23 high fat diet (HFD) obese, female rats were randomized to three groups: RYGB, SG or sham-operated food-restricted (Sham) controls. In Experiment 2, HFD obese female rats received either sham (n = 11) or a modified RYGB surgery where the remnant stomach was removed (RYGB-X; n = 12).ResultsSG rats drank significantly less than RYGB for 4, 6 and 8% and significantly less than Sham for 6, 8 and 8% reinstatement. RYGB-X consumed significantly less EtOH than Sham across all concentrations, reaching significance for 6 and 8% reinstatement.ConclusionThese findings confirm reduced EtOH consumption by female SG rats as opposed to increased intake following RYGB, and provide the first experimental evidence that the remnant stomach in the RYGB procedure is contributory. Future studies in rats and humans are warranted to confirm that ghrelin plays a critical role in susceptibility to AUD development following WLS.
A Multivariate Interpretation of the Spanish-Language NIH Toolbox Cognition Battery: The Normal Frequency of Low Scores
Authors: Karr Justin E , Mindt Monica Rivera , Iverson Grant L 
Published: July 2021

Abstract

Objective
The current study involved the preparation of multivariate base rates for the Spanish-language NIH Toolbox Cognition Battery (NIHTB-CB) based on the U.S. normative sample, quantifying the normal frequency of low scores among healthy adults.

Method
Participants included 250 healthy Latinx adults (M = 38.8 ± 13.7 years old, range: 19–80; 72.0% women; education: M = 11.5 ± 3.9 years) who completed the full Spanish-language NIHTB-CB, including two tests of crystallized cognition and five tests of fluid cognition. Multivariate base rates quantified the frequency at which participants obtained 1 or more fluid scores ≤25th, ≤16th, ≤9th, ≤5th, and ≤2nd percentile, per age-adjusted or demographically adjusted (age, gender, education) normed scores.

Results
A substantial minority of participants had 1 or more low scores (e.g., 40.4% had 1 or more age-adjusted score ≤16th percentile). The frequencies of low scores increased with fewer years of education and lower crystallized cognitive ability. Higher frequencies of low scores were observed among participants who were born and educated abroad, versus within the USA; monolingual Spanish speakers, versus bilingual Spanish/English speakers; and from households below the national median income, versus households above the national median.

Conclusion
Low scores were common and related to crystallized ability, education, and sociocultural variables. Although using demographically adjusted scores reduced group differences related to sociocultural variables, group differences were not eliminated, indicating that age, gender, and education score adjustments do not fully explain the associations between sociocultural variables and test performances. These stratified base rates may be useful when working with Spanish-speaking patients with diverse sociocultural characteristics.
Inhibition of GFAT1 in lung cancer cells destabilizes PD-L1 protein
Authors: Chen Wenshu , Saxton Bryanna , Tessema Mathewos , Belinsky Steven A 
Published: July 2021

Abstract
Immunotherapy using checkpoint blockers (antibodies) has been a major advance in recent years in the management of various types of solid cancers including lung cancer. One target of checkpoint blockers is programmed death ligand 1 (PD-L1) expressed by cancer cells, which engages programmed death 1 on T cells and Natural Killer (NK) cells resulting in suppression of their activation and cancer-killing function, respectively. Apart from antibodies, other clinically relevant agents that can inhibit PD-L1 are limited. PD-L1 protein stability depends on its glycosylation. Here we show that l-glutamine:d-fructose-6-phosphate amidotransferase 1 (GFAT1), a rate-limiting enzyme of the hexosamine biosynthesis pathway, which produces uridine diphosphate-N-acetyl-β-glucosamine, a precursor for glycosylation, is required for the stability of PD-L1 protein. Inhibition of GFAT1 activity markedly reduced interferon gamma (IFNγ)-induced PD-L1 levels in various lung cancer cell lines. GFAT1 inhibition suppressed glycosylation of PD-L1 and accelerated its proteasomal degradation. Importantly, inhibition of GFAT1 in IFNγ-treated cancer cells enhanced the activation of T cells and the cancer-killing activity of NK cells. These findings support using GFAT1 inhibitors to manipulate PD-L1 protein level that could augment the efficacy of immunotherapy for lung cancer.
Total Content of Piperidine Analysis in Artane by RP-HPLC Using Pre-Column Derivatization with 4-Toluene Sulfonyl Chloride
Authors: Zhou Guiyin , Chen Yao , Tang Ying 
Published: July 2021

Abstract
A simple, sensitive and accurate reversed-phase high-performance liquid chromatography (RP-HPLC) method was established for the determination of piperidine and piperidine hydrochloride in artane, using pre-column derivatization with 4-toluenesulfonyl chloride. The RP-HPLC method was carried out on a Inertsil C18 column (250 × 4.6 mm I.D.) maintained at 30°C. The mobile phase consisted of water with 0.1% phosphoric acid (phase A) and acetonitrile (phase B) (32:68, V:V) at a flow rate of 1.0 mL/min. Linearity of piperidine was found in the range of 0.44–53.33 μg/mL with R2 = 0.9996. The limit of detection was estimated to be 0.15 μg/mL, and the limit of quantitation was 0.44 μg/mL. The average recovery was 101.82% with relative standard deviations of 0.6% at three spiked levels. The developed method using HPLC-ultraviolet system was a rapid tool for routine analysis of piperidine in the bulk form with good accuracy.
Anogenital Human Papillomavirus (HPV) Infection, Seroprevalence, and Risk Factors for HPV Seropositivity Among Sexually Active Men Enrolled in a Global HPV Vaccine Trial
Authors: Tota Joseph E , Giuliano Anna R , Goldstone Stephen E , Dubin Brady , Saah Alfred , Luxembourg Alain , Velicer Christine , Palefsky Joel M 
Published: July 2021

Abstract

Background
In men, the incidence of human papillomavirus (HPV)–related cancer is rising, but data regarding male HPV infection and seroprevalence are available from only a few countries.

Methods
This analysis of a global HPV vaccine trial evaluated baseline data from 1399 human immunodeficiency virus–negative heterosexual men (HM) and men who have sex with men (MSM). Key objectives included assessment of HPV prevalence and risk factors for seropositivity to 9-valent HPV (9vHPV) vaccine types (6, 11, 16, 18, 31, 33, 45, 52, and 58), and concordance between seropositivity and prevalent HPV type.

Results
Overall, 455 of 3463 HM (13.1%) and 228 of 602 MSM (37.9%) were HPV DNA positive for any 9vHPV vaccine type at baseline. Infection prevalence and seroprevalence (≥1 9vHPV vaccine type) were 13.2% and 8.1%, respectively, among 333 HM from Europe, and 37.9% and 29.9%, respectively, among 335 MSM from Europe or North America. Among men with baseline infection, MSM had higher seroprevalence for concordant HPV types (39.5% vs 10.8% in HM). The seropositivity risk (irrespective of baseline infection status) was higher among MSM versus HM (age-adjusted odds ratio, 3.0 [95% confidence interval, 2.4–6.4]). Among MSM, statistically significant seropositivity risk factors included younger age at sexual debut, higher number of receptive anal sex partners, and less frequent condom use. No factors assessed were associated with seropositivity in HM.

Conclusions
Higher proportions of MSM than HM were HPV DNA positive and seropositive, and concordance between HPV DNA positivity and seropositivity, a potential marker of true infection versus carriage, was higher in MSM. Most MSM and HM were seronegative for all 9vHPV vaccine types, suggesting the potential benefit of catch-up vaccination after sexual debut.
Clinical Trials Registration. NCT00090285.
External validation of a high-sensitive troponin I algorithm for rapid evaluation of acute myocardial infarction in a Danish cohort
Authors: Andersen Camilla Fuchs , Bang Camilla , Lauridsen Kasper Glerup , Frederiksen Christian Alcaraz , Schmidt Morten , Jensen Tage , Hornung Nete , Løfgren Bo 
Published: July 2021

Abstract

Aims
An accelerated diagnostic algorithm for ruling-in or ruling-out myocardial infarction (MI) after 1 hour (1 h) has recently been derived and internally validated for the Siemens ADVIA Centaur TNIH assay. We aimed to validate the diagnostic performance of the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in a Danish cohort.

Methods and results
Patients with chest pain suggestive of MI were prospectively enrolled. High-sensitive troponin I (TNIH) was measured at admission (0 h) and after 30 minutes (30 m), 1 h, and 3 hours (3 h). We externally validated the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in Danish patients. Moreover, we applied the algorithm using the second TNIH measurement at 30 m instead of 1 h. We enrolled 1003 patients: median (Q1–Q3) age 64 (52–74) years, 42% female, and 23% with previous MI. Myocardial infarction was the final diagnosis in 9% of patients. Median (Q1–Q3) times from admission to 30 m and 1 h blood draw were 35 min (30–37 min) and 67 min (62–75 min), respectively. Using the 0 h and 1 h results, 468 (47%) patients were assigned to rule-out, 104 (10%) to rule-in, and 431 (43%) to the observational zone. This resulted in a negative predictive value of 100% (95% confidence interval: 99.2–100%), sensitivity of 100% (95.9–100%), positive predictive value of 79.8 (70.8–87.0%), and specificity of 97.7% (96.5–98.6%). The diagnostic performance after 30 m was similar.

Conclusions
The TNIH 0 h/1 h algorithm ad modum Boeddinghaus performed excellently for rule-out of MI in a Danish cohort. The Boeddinghaus algorithm also performed excellently after only 30 m.

Trial registration number
NCT03634384.

Trial registry name and URL
Rapid Use of High-Sensitive Cardiac Troponin I for Ruling-in and Ruling-out Acute Myocardial Infarction (RACING-MI), https://clinicaltrials.gov/ct2/show/NCT03634384.
Spectrum bias in algorithms derived by artificial intelligence: a case study in detecting aortic stenosis using electrocardiograms
Authors: Tseng Andrew S , Shelly-Cohen Michal , Attia Itzhak Z , Noseworthy Peter A , Friedman Paul A , Oh Jae K , Lopez-Jimenez Francisco 
Published: July 2021

Abstract

Aims
Spectrum bias can arise when a diagnostic test is derived from study populations with different disease spectra than the target population, resulting in poor generalizability. We used a real-world artificial intelligence (AI)-derived algorithm to detect severe aortic stenosis (AS) to experimentally assess the effect of spectrum bias on test performance.

Methods and results
All adult patients at the Mayo Clinic between 1 January 1989 and 30 September 2019 with transthoracic echocardiograms within 180 days after electrocardiogram (ECG) were identified. Two models were developed from two distinct patient cohorts: a whole-spectrum cohort comparing severe AS to any non-severe AS and an extreme-spectrum cohort comparing severe AS to no AS at all. Model performance was assessed. Overall, 258 607 patients had valid ECG and echocardiograms pairs. The area under the receiver operator curve was 0.87 and 0.91 for the whole-spectrum and extreme-spectrum models, respectively. Sensitivity and specificity for the whole-spectrum model was 80% and 81%, respectively, while for the extreme-spectrum model it was 84% and 84%, respectively. When applying the AI-ECG derived from the extreme-spectrum cohort to patients in the whole-spectrum cohort, the sensitivity, specificity, and area under the curve dropped to 83%, 73%, and 0.86, respectively.

Conclusion
While the algorithm performed robustly in identifying severe AS, this study shows that limiting datasets to clearly positive or negative labels leads to overestimation of test performance when testing an AI algorithm in the setting of classifying severe AS using ECG data. While the effect of the bias may be modest in this example, clinicians should be aware of the existence of such a bias in AI-derived algorithms.
Absolute and relative risk prediction in cardiovascular primary prevention with a modified SCORE chart incorporating ceramide-phospholipid risk score and diabetes mellitus
Authors: Hilvo Mika , Jylhä Antti , Lääperi Mitja , Jousilahti Pekka , Laaksonen Reijo 
Published: July 2021

Abstract

Aims
A risk score, CERT2, based on distinct ceramide and phosphatidylcholine lipid species, has shown robust performance in predicting cardiovascular risk in secondary prevention. Here, our aim was to investigate the predictive value of CERT2 in primary prevention compared to classical lipid biomarkers and its compatibility with clinical characteristics used in the SCORE risk chart.

Methods and results
Four ceramides [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), Cer(d18:1/24:1)] and three phosphatidylcholines [PC(14:0/22:6), PC(16:0/22:5), PC(16:0/16:0)] were analysed by targeted tandem liquid chromatography–mass spectrometry method in FINRISK 2002, which is a population-based risk factor survey investigating men and women aged 25–74 years. Primary prevention subjects (N = 7324) were followed up for 10 years for the following outcomes: incident coronary heart disease (CHD), cardiovascular disease (CVD), major adverse cardiovascular event (MACE), stroke, and heart failure. Hazard ratios per standard deviation obtained from adjusted Cox proportional hazard models were significant for all these endpoints, and the highest for fatal ones, i.e. fatal CHD [1.45 (95% confidence interval 1.07–1.97)], CVD [1.39 (1.06–1.83)], and MACE [1.39 (1.07–1.80)]. The categorical net reclassification improvement was 0.051 for the 10-year risk of incident CVD. Incidence of fatal events was over 10-fold more frequent in the highest CERT2 category compared to the lowest risk category and modified SCORE risk charts, utilizing CERT2 and diabetes mellitus, increased granularity of risk assessment compared to a chart utilizing total cholesterol.

Conclusion
CERT2 is a significant predictor of incident cardiovascular outcomes and risk charts utilizing this score provide an easy tool to estimate relative and absolute risk for incident CVD.
De novo genome assembly of the marine teleost, bluefin trevally (Caranx melampygus)
Authors: Pickett Brandon D , Glass Jessica R , Ridge Perry G , Kauwe John S K 
Published: July 2021

Abstract
The bluefin trevally, Caranx melampygus, also known as the bluefin kingfish or bluefin jack, is known for its remarkable, bright-blue fins. This marine teleost is a widely prized sportfish, but few resources have been devoted to the genomics and conservation of this species because it is not targeted by large-scale commercial fisheries. Population declines from recreational and artisanal overfishing have been observed in Hawai‘i, USA, resulting in both an interest in aquaculture and concerns about the long-term conservation of this species. Most research to-date has been performed in Hawai‘i, raising questions about the status of bluefin trevally populations across its Indo-Pacific range. Genomic resources allow for expanded research on stock status, genetic diversity, and population demography. We present a high quality, 711 Mb nuclear genome assembly of a Hawaiian bluefin trevally from noisy long-reads with a contig NG50 of 1.2 Mb and longest contig length of 8.9 Mb. As measured by single-copy orthologs, the assembly was 95% complete, and the genome is comprised of 16.9% repetitive elements. The assembly was annotated with 33.1 K protein-coding genes, 71.4% of which were assigned putative functions, using RNA-seq data from eight tissues from the same individual. This is the first whole-genome assembly published for the carangoid genus Caranx. Using this assembled genome, a multiple sequentially Markovian coalescent model was implemented to assess population demography. Estimates of effective population size suggest population expansion has occurred since the Late Pleistocene. This genome will be a valuable resource for comparative phylogenomic studies of carangoid fishes and will help elucidate demographic history and delineate stock structure for bluefin trevally populations throughout the Indo-Pacific.
Accuracy of GEBV of sires based on pooled allele frequency of their progeny
Authors: Vargas Jurado Napoleón , Kuehn Larry A , Keele John W , Lewis Ronald M 
Published: July 2021

Abstract
Despite decreasing genotyping costs, in some cases individually genotyping animals is not economically feasible (e.g., in small ruminants). An alternative is to pool DNA, using the pooled allele frequency (PAF) to garner information on performance. Still, the use of PAF for prediction (estimation of genomic breeding values; GEBVs) has been limited. Two potential sources of error on accuracy of GEBV of sires, obtained from PAF of their progeny themselves lacking pedigree information, were tested: (i) pool construction error (unequal contribution of DNA from animals in pools), and (ii) technical error (variability when reading the array). Pooling design (random, extremes, K-means), pool size (5, 10, 25, 50, and 100 individuals), and selection scenario (random, phenotypic) also were considered. These factors were tested by simulating a sheep population. Accuracy of GEBV—the correlation between true and estimated values—was not substantially affected by pool construction or technical error, or selection scenario. A significant interaction, however, between pool size and design was found. Still, regardless of design, mean accuracy was higher for pools of 10 or less individuals. Mean accuracy of GEBV was 0.174 (SE 0.001) for random pooling, and 0.704 (SE 0.004) and 0.696 (SE 0.004) for extreme and K-means pooling, respectively. Non-random pooling resulted in moderate accuracy of GEBV. Overall, pooled genotypes can be used in conjunction with individual genotypes of sires for moderately accurate predictions of their genetic merit with little effect of pool construction or technical error.
Efficient construction of a linkage map and haplotypes for Mentha suaveolens using sequence capture
Authors: Tsai Helen , Kippes Nestor , Firl Alana , Lieberman Meric , Comai Luca , Henry Isabelle M 
Published: July 2021

Abstract
The sustainability of many crops is hindered by the lack of genomic resources and a poor understanding of natural genetic diversity. Particularly, application of modern breeding requires high-density linkage maps that are integrated into a highly contiguous reference genome. Here, we present a rapid method for deriving haplotypes and developing linkage maps, and its application to Mentha suaveolens, one of the diploid progenitors of cultivated mints. Using sequence-capture via DNA hybridization to target single nucleotide polymorphisms (SNPs), we successfully genotyped ∼5000 SNPs within the genome of &gt;400 individuals derived from a self cross. After stringent quality control, and identification of nonredundant SNPs, 1919 informative SNPs were retained for linkage map construction. The resulting linkage map defined a total genetic space of 942.17 cM divided among 12 linkage groups, ranging from 56.32 to 122.61 cM in length. The linkage map is in good agreement with pseudomolecules from our preliminary genome assembly, proving this resource effective for the correction and validation of the reference genome. We discuss the advantages of this method for the rapid creation of linkage maps.
Engineering threshold-based selection systems
Authors: Pedone Katherine H , González-Pérez Vanessa , Leopold Luciana E , Rasmussen Neal R , Der Channing J , Cox Adrienne D , Ahmed Shawn , Reiner David J 
Published: July 2021

Abstract
Using model organisms to identify novel therapeutic targets is frequently constrained by pre-existing genetic toolkits. To expedite positive selection for identification of novel downstream effectors, we engineered conditional expression of activated CED-10/Rac to disrupt Caenorhabditis elegans embryonic morphogenesis, titrated to 100% lethality. The strategy of engineering thresholds for positive selection using experimental animals was validated with pharmacological and genetic suppression and is generalizable to diverse molecular processes and experimental systems.
Differences in temperature-sensitive expression of PcG-regulated genes among natural populations of Drosophila melanogaster
Authors: Voigt Susanne , Kost Luise 
Published: July 2021

Abstract
Environmental temperature can affect chromatin-based gene regulation, in particular in ectotherms such as insects. Genes regulated by the Polycomb group (PcG) vary in their transcriptional output in response to changes in temperature. Expression of PcG-regulated genes typically increases with decreasing temperatures. Here, we examined variations in temperature-sensitive expression of PcG target genes in natural populations from different climates of Drosophila melanogaster, and differences thereof across different fly stages and tissues. Temperature-induced expression plasticity was found to be stage- and sex-specific with differences in the specificity between the examined PcG target genes. Some tissues and stages, however, showed a higher number of PcG target genes with temperature-sensitive expression than others. Overall, we found higher levels of temperature-induced expression plasticity in African tropical flies from the ancestral species range than in flies from temperate Europe. We also observed differences between temperate flies, however, with more reduction of expression plasticity in warm-temperate than in cold-temperate populations. Although in general, temperature-sensitive expression appeared to be detrimental in temperate climates, there were also cases in which plasticity was increased in temperate flies, as well as no changes in expression plasticity between flies from different climates.