bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of implementing a guideline-based approach to achieve target LDL-C levels in very high risk patients. The PENELOPE study one year follow-up results
Authors: Van Der Brug S J , Khader A O , Atazadah M , Liem A H , Groenemeijer B E , Schut A , Martens F A M , Dunselman P H J M , Alings A M W 
Published: November 2023

Abstract

Background/introduction
Hyperlipidemia is a major modifiable risk factor for developing cardiovascular disease. Lowering LDL-C reduces the risk for coronary heart disease (1,2). The PENELOPE study implemented an ESC-guideline-based, stepwise strategy of lipid-lowering therapy (LLT) to achieve target LDL-C levels in very high-risk patients, with a mean duration of 61 days.

Purpose
This paper demonstrates the legacy effect after one year.

Methods
Nine hundred and ninety-nine (999) patients with a myocardial infarction and a history of atherosclerotic cardiovascular disease and/or diabetes mellitus were included in PENELOPE for stepwise intensified LLT (high intensity statin (HIST) monotherapy, HIST + ezetimibe, HIST + ezetimibe + PCSK9i) until reaching target LDL-C level (≤1.8mmol/L). The primary objective was to assess the prevalence of maintained LDL-C ≤1.8 mmol/L and therapy-adherence after one year.

Results
For the one year follow up visit, 738 patients (73%) were available. Thirty patients had died, 45 were lost to follow up and from 178 patients no signed informed reconsent was obtained. The per protocol cohort included six hundred and seventy-one (671) patients. In this cohort, a non-participation bias cannot be excluded.
After one year, in four-hundred forty-nine (449) patients target LDL-C level (66,9%) was maintained. Mean LDL-C level after one year was 1.67 mmol/L and the adherence rate to LLT was 94,5%. The major treatment regimens were statin monotherapy (61,7%), statin + ezetimibe (28,3%) and PCK9i + ezetimibe (+ statin) (5,8%). Maintained target (LDL-C ≤1.8mmol/L) was 64%, 77% and 82%, respectively. The large percentage loss of patients on target after one year could be explained by the cut-off at 1.8 mmol/L (only 0.28 mmol/L increase in mean LDL-C level), the short-term effect of heart rehabilitation and a treatment change in 20,4% of patients. Therapy adherence was high and did not differ between treatment regimen.

Conclusion
Using an ESC-guideline-based flowchart with quick, stepwise intensification of LLT leads to a 99% success rate (LDL-C ≤1.8mmol/L) within 3 months and 67% after one year. The mean LDL-C level increases with 0.28 mmol/L.
Contribution of Lipoprotein(a) to polygenic risk of coronary artery disease: A prospective UK Biobank analysis
Authors: Arsenault B , Manikpurage H D , Paulin A , Girard A , Eslami A , Mathieu P , Theriault S 
Published: November 2023

Abstract

Background
Lipoprotein(a) (Lp[a]) is a highly atherogenic lipoprotein subfraction that may contribute to polygenic risk of coronary artery disease (CAD), but the extent of this contribution is unknown.

Purpose
Our objective was to estimate the contribution of Lp(a) to polygenic risk of CAD and to evaluate the respective contributions of Lp(a) and a CAD polygenic risk score (PRS) to CAD.

Methods
372,385 UK Biobank participants of European ancestry free of CAD at baseline were included. Plasma Lp(a) levels were measured and a CAD-PRS was calculated using LDpred2. Over the median follow-up of 12.6 years, 13,538 participants had incident CAD (myocardial infarction, coronary artery bypass grafting or coronary angioplasty).

Results
The LPA region contribution to the CAD-PRS-mediated CAD risk was modest (6.5%). Lp(a) levels significantly increased the predictive performance of a CAD-PRS including age and sex in Cox regression (C-statistic 0.751 versus 0.746, difference = 0.005 (95% CI, 0.004-0.006). Compared to participants in the top CAD-PRS quintile with Lp(a) levels ≥125 nmol/L (CAD event rate 6.6%), the hazard ratio for incident CAD in participants in the bottom CAD-PRS quintile with Lp(a) levels &lt;25 nmol/L was 0.18 (95% CI, 0.17-0.20, p=6.41e-241, CAD event rate 2.0%).

Conclusions
Compared to individuals with a high genetic risk of CAD (high CAD-PRS and high Lp(a) levels), those with a low genetic risk had an 82% lower CAD risk. These results highlight a substantial contribution of genetic risk factors to CAD and that accurate estimation of genetic risk of CAD should consider blood levels of Lp(a).
Hospitals’ electronic access to information needed to treat COVID-19
Authors: Richwine Chelsea , Everson Jordan , Patel Vaishali 
Published: November 2023

Abstract

Objective
To understand whether hospitals had electronic access to information needed to treat COVID-19 patients and identify factors contributing to differences in information availability.

Materials and methods
Using 2021 data from the American Hospital Association IT Supplement, we produced national estimates on the electronic availability of information needed to treat COVID-19 at US non-federal acute care hospitals (N = 1976) and assessed differences in information availability by hospital characteristics and engagement in interoperable exchange.

Results
In 2021, 38% of hospitals electronically received information needed to effectively treat COVID-19 patients. Information availability was significantly higher among higher-resourced hospitals and those engaged in interoperable exchange (44%) compared to their counterparts. In adjusted analyses, hospitals engaged in interoperable exchange were 140% more likely to receive needed information electronically compared to those not engaged in exchange (relative risk [RR]=2.40, 95% CI, 1.82-3.17, P&lt;.001). System member hospitals (RR = 1.62, 95% CI, 1.36-1.92, P&lt;.001) and major teaching hospitals (RR = 1.35, 95% CI, 1.10-1.64, P=.004) were more likely to have information available; for-profit hospitals (RR = 0.14, 95% CI, 0.08-0.24, P&lt;.001) and hospitals in high social deprivation areas (RR = 0.83, 95% CI, 0.71-0.98, P = .02) were less likely to have information available.

Discussion
Despite high rates of hospitals’ engagement in interoperable exchange, hospitals’ electronic access to information needed to support the care of COVID-19 patients was limited.

Conclusion
Limited electronic access to patient information from outside sources may impede hospitals’ ability to effectively treat COVID-19 and support patient care during public health emergencies.
The prognostic and predictive effect of body mass index in hormone receptor-positive breast cancer
Authors: Lammers Senna W M , Geurts Sandra M E , van Hellemond Irene E G , Swinkels Astrid C P , Smorenburg Carolien H , van der Sangen Maurice J C , Kroep Judith R , de Graaf Hiltje , Honkoop Aafke H , Erdkamp Frans L G , de Roos Wilfred K , Linn Sabine C , Imholz Alexander L T , Smidt Marjolein L , Vriens Ingeborg J H , Tjan-Heijnen Vivianne C G 
Published: November 2023

Abstract

Background
Obesity has been associated with an adverse prognosis and reduced efficacy of endocrine therapy in patients with hormone receptor-positive (HR+) breast cancer (BC). This study determines the prognostic and predictive effect of body mass index (BMI) on the disease-free survival (DFS) of postmenopausal HR+ BC patients.

Methods
Patients were identified from the DATA study (NCT00301457), a randomized controlled trial evaluating the efficacy of 6 vs 3 years of anastrozole after 2 to 3 years of adjuvant tamoxifen in postmenopausal women with HR+ BC. Patients were classified as normal weight (BMI: 18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), or obese (≥30.0 kg/m2). The primary endpoint was DFS, evaluated from randomization (prognostic analyses) or 3 years after randomization onwards (predictive analyses; aDFS) using multivariable Cox regression analyses. P-values were 2-sided.

Results
This study included 678 normal weight, 712 overweight, and 391 obese patients. After a median follow-up of 13.1 years, overweight and obesity were identified as negative prognostic factors for DFS (hazard ratio (HR) = 1.16; 95% confidence interval (CI) = 0.97 to 1.38 and HR = 1.26; 95% CI = 1.03 to 1.54, respectively). The adverse prognostic effect of BMI was observed in women aged younger than 60 years, but not in women aged 60 years or older (P-interaction = .009). The effect of extended anastrozole on aDFS was similar in normal weight (HR = 1.00; 95% CI = 0.74 to 1.35), overweight (HR = 0.74; 95% CI = 0.56 to 0.98), and obese patients (HR = 0.97; 95% CI = 0.69 to 1.36) (P-interaction = .24).

Conclusion
In this study among 1781 HR+ BC patients, overweight and obesity were adverse prognostic factors for DFS. BMI did not impact the efficacy of extended anastrozole.
Isolation, phytochemistry, characterization, biological activity, and application of Morinda officinalis How oligosaccharide: a review
Authors: Yue Jiahui , Xia Wenxin , Wang Yushu , Zhang Yuanyuan , Zhang Yan , Li Yuxin , Wang Lulu , Li Cunbing , Li Tingting , Fu Xueyan 
Published: November 2023

Abstract
Morinda officinalis How oligosaccharide (MOO) stands as one of the principal active constituents of M. officinalis How, widely employed in traditional Chinese medicine. The methods for MOO extraction predominantly encompass hot water extraction, ethanol extraction, ultrasonic-assisted extraction, and microwave-assisted extraction. Distinct extraction techniques yield varying MOO quantities. MOO encompasses a diversity of oligosaccharides, including bajijiasu, sucrose, 1-kestose, nystose, mannose, 1F-fructofuranosylnystose, 1,1,1,1-kestohexose, fructoheptasaccharide, inulin-type hexasaccharide, inulin-type heptasaccharide, inulotriose, inulotetraose, inulopentaose, and mannose. MOO exhibits a wide spectrum of biological activities, exerting specific effects on the nervous system, cardiovascular system, motor system, reproductive system, and immune system. It demonstrates antidepressant properties, offers potential in mitigating Alzheimer’s disease, stimulates angiogenesis, and possesses anti-osteoporotic and other pharmacological effects. Clinically, when combined with various antidepressants, MOO exhibits specific therapeutic efficacy across multiple forms of depression. As a naturally occurring plant oligosaccharide, MOO holds diverse pharmaceutical applications. This article conducts a review of the latest extraction and purification methodologies, structural characterization analysis, biological activity assessment, and clinical applications of MOO. Such a comprehensive analysis yields innovative insights for advancing the research and application of MOO in the future.
Synchronous colonal and jejunal adenocarcinomas leading to intussusception in an adult female suffering from celiac disease
Authors: Sadeghi Mirsalim Seyyed , Haghshenas Negin , Khanghah Ali Samady 
Published: November 2023

Abstract
Coeliac disease, a relatively rare gluten-sensitive enteropathy, correlates with small intestinal malignancies, especially lymphoma and adenocarcinoma. Any kind of masses, whether malignant or benign, in the way of natural peristaltic action may increase the probability of intussusception, telescoping invagination of the proximal segment into the distal one causing an obstruction. We report a case of synchronous adenocarcinomas of the colon and jejunum in a 3-year-old female presenting as bowel obstruction. She also had coeliac disease. During laparotomy, the surgical team encountered jejunojejunal intussusception as the cause of obstruction. There are direct relationships among coeliac disease, increased risk of adenocarcinoma, and repeated intussusceptions in the absence of mass in adults. The intussusception phenomenon in an adult necessitates investigating a more severe lead point than simple mesenteric lymphadenopathy.
Multiband cross-correlated radio variability of the blazar 3C 279
Authors: Mohana A Krishna , Gupta Alok C , Marscher Alan P , Sotnikova Yulia V , Jorstad S G , Wiita Paul J , Cui Lang , Aller Margo F , Aller Hugh D , Kovalev Yu A , Kovalev Y Y , Liu Xiang , Mufakharov T V , Popkov A V , Mingaliev M G , Erkenov A K , Nizhelsky N A , Tsybulev P G , Zhao Wei , Weaver Z R , Morozova D A 
Published: November 2023

ABSTRACT
We present the results of our study of cross-correlations between long-term multiband observations of the radio variability of the blazar 3C 279. More than a decade (2008–2022) of radio data were collected at seven different frequencies ranging from 2 to 230 GHz. The multiband radio light curves show variations in flux, with the prominent flare features appearing first at higher-frequency and later in lower-frequency bands. This behaviour is quantified by cross-correlation analysis, which finds that the emission at lower-frequency bands lags that at higher-frequency bands. Lag versus frequency plots are well fit by straight lines with negative slope, typically ∼−30 day GHz−1. We discuss these flux variations in conjunction with the evolution of bright moving knots seen in multiepoch Very Long Baseline Array maps to suggest possible physical changes in the jet that can explain the observational results. Some of the variations are consistent with the predictions of shock models, while others are better explained by a changing Doppler beaming factor as the knot trajectory bends slightly, given a small viewing angle to the jet.
Vibrio chanodichtyis sp. nov., isolated from the intestine of swordfish Chanodichthys dabryi
Authors: Wu Ningning , Liu Le , Liu Kai , Shao Jiahui , Nie Zhijuan , He Jian , Shen Qirong 
Published: November 2023

A Gram-stain-negative, facultatively anaerobic, motile, curved-rod-shaped flagellated bacterium, designated DSL-7T, was isolated from the intestine of Chanodichthys dabryi in the Yangtze river, PR China. The strain grew optimally in tryptone soy broth medium at 37 °C, pH 7.0 and with 1 % (w/v) NaCl. Strain DSL-7T showed less than 96.2 % 16S rRNA gene sequence similarity to type strains of the genus

Vibrio

. Phylogenetic analysis based on genomes indicated that strain DSL-7T belonged to the genus

Vibrio

and formed a subclade with

Vibrio mimicus

NCTC 11435T,

Vibrio metoecus

OP3HT,

Vibrio cholerae

ATCC 14035T,

Vibrio albensis

ATCC14547T,

Vibrio paracholerae

OP3HEDC-792T and Vibrio tarriae 2521-89T. The average nucleotide identity (ANI) and in digital DNA–DNA hybridization (dDDH) values between DSL-7T and closely related type strains were below the accepted threshold to delineate a new species of 95 and 70 %, respectively. The major cellular fatty acids were summed feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c), C16 : 0, summed feature 8 (C18 : 1
ω7c and/or C18 : 1
ω6c) and C14 : 0. The genomic DNA G+C content was 47.6 mol%. Based on the phenotypic, chemotaxonomic, phylogenetic and genomic data, strain DSL-7T represents a novel species of the genus

Vibrio

, for which the name Vibrio chanodichtyis sp. nov. is proposed, with strain DSL-7T (=KCTC 92851T=CCTCC AB 2022396T) as the type strain.
Hematologic abnormalities after COVID-19 vaccination: A large Korean population-based cohort study
Authors: Choi Hye Sook , Kim Min-Ho , Choi Myeong Geun , Park Joo Hun , Chun Eun Mi 
Published: November 2023

AbstractAdverse hematologic events have been reported after COVID-19 vaccination. The objective of this study was to investigate whether hematologic abnormalities develop after COVID-19 vaccination. Retrospective cohort analyses of data from the Korean National Health Insurance Service (KNHIS) database were conducted from July 2022 to August 2023. We randomly selected data of half of those living in Seoul City as of January 1, 2021 with their diagnostic records up to December 31, 2021. The included participants were vaccinated and nonvaccinated persons aged 20 years or older (n= 4,203,887). Hematologic abnormalities after COVID-19 vaccination were identified as nutritional anemia, hemolytic anemia, aplastic anemia, coagulation defects, and neutropenia using International Classification of Diseases, Tenth Revision codes after index date. Incidence rates of hematologic abnormalities in the vaccination group 3 months after vaccination were significantly higher than those in the nonvaccinated group: 14.79 vs. 9.59 (P<.001) for nutritional anemia, 7.83 vs. 5.00 (P<.001) for aplastic anemia, and 4.85 vs. 1.85 (P<.001) for coagulation defects. COVID-19 mRNA vaccine was associated with higher development of nutritional anemia (odds ratio [OR], 1.230 [95% CI, 1.129-1.339], P<.001) and aplastic anemia (OR, 1.242 [95% CI, 1.110-1.390], P<.001) than the viral vector vaccine. The risk of coagulation defects was increased (OR, 1.986 [95% CI, 1.523-2.589], P<.001) after vaccination, and there was no risk difference between mRNA vaccine and viral vector vaccine (OR, 1.075 [95% CI, 0.936-1.233], P=.306). In conclusions, COVID-19 vaccination increased the risk of hematologic abnormalities. When administering the COVID-19 vaccine, careful observation will be necessary after vaccination.
ERBB2 R599C variant is associated with left ventricular outflow tract obstruction defects in human
Authors: Ampuja M , Selenius S , Paatero I , Chowdhury I , Villman J , Broberg M , Ranta A , Ojala T , Chong JX , Bamshad M , Priest JR , Varjosalo M , Kivelä R , Helle E 
Published: November 2023

AbstractBackground and aimsNon-syndromic congenital heart defects (CHD) are occasionally familial and left ventricular out flow tract obstruction (LVOTO) defects are among the subtypes with the highest hereditability. The aim of this study was to evaluate the pathogenicity of a heterozygousERBB2variant R599C identified in three families with LVOTO defects.MethodsVariant detection was done with exome sequencing. Western blotting, digital PCR, mass spectrometry (MS), MS-microscopy and flow cytometry were used to study the function of theERBB2variant R599C. Cardiac structure and function were studied in zebrafish embryos expressing humanERBB2WT or R599C. Patient-derived human induced pluripotent stem cell cardiomyocytes (hiPS-CM) and endothelial cells (hiPS-ECs) were used for transcriptomic analyses.ResultsWhile phosphorylation of the ERBB2 R599C receptor was not altered, the variant affected dramatically the binding partners of the protein and lead to mislocalization of ERBB2 from plasma membrane to ER and mitochondria. Expression of human ERBB2 R599C in zebrafish embryos resulted in cardiomyocyte hypertrophy, increased cardiac wall thickness, and impaired fractional shortening, demonstrating that the mutant receptor induces functional and structural defects during heart development. Transcriptomic analyses of hiPS-ECs and hiPS-CMs from a patient with the R599C variant indicated aberrant expression of genes related to cardiovascular system development and abnormal response to oxidative stress in both cell types.ConclusionThe heterozygous variantERBB2R599C leads to abnormal cellular localization of the ERBB2 receptor inducing structural changes and dysfunction in the zebrafish embryo heart. This evidence suggests ERBB2 as a novel disease gene for CHD.
Phenotype Execution and Modelling Architecture (PhEMA) to support disease surveillance and real-world evidence studies: English sentinel network evaluation
Authors: Jamie Gavin , Elson William , de Lusignan Simon , Kar Debasish , Wimalaratna Rashmi , Hoang Uy , Meza-Torres Bernardo , Forbes Anna , Hinton Will , Anand Sneha , Ferreira Filipa , Ordonez-Mena Jose , Agrawal Utkarsh , Byford Rachel 
Published: November 2023

AbstractObjectiveTo evaluate Phenotype Execution and Modelling Architecture (PhEMA), to express sharable phenotypes using Clinical Query Language (CQL) and intensional SNOMED CT Fast Healthcare Interoperability Resources (FHIR) valuesets, for exemplar chronic disease, sociodemographic risk factor and surveillance phenotypes.MethodWe curated three phenotypes: Type 2 diabetes (T2DM), excessive alcohol use and incident influenza-like illness (ILI) using CQL to define clinical and administrative logic. We defined our phenotypes with valuesets, using SNOMED’s hierarchy and expression constraint language (ECL), and CQL, combining valuesets and adding temporal elements where needed. We compared the count of cases found using PhEMA with our existing approach using convenience datasets.ResultsThe T2DM phenotype could be defined as two intensionally defined SNOMED valuesets and a CQL script. It increased the prevalence from 7.2% to 7.3%. Excess alcohol phenotype was defined by valuesets that added qualitative clinical terms to the quantitative conceptual definitions we currently use; this change increased prevalence by 58%, from 1.2% to 1.9%. We created an ILI valueset with SNOMED concepts, adding a temporal element using CQL to differentiate new episodes. This increased the weekly incidence in our convenience sample (weeks 26 to 38) from 0.95 cases to 1.11 cases per 100,000 people.ConclusionsPhenotypes for surveillance and research can be described fully and comprehensibly using CQL and intensional FHIR valuesets. Our use case phenotypes identified a greater number of cases, whilst anticipated from excessive alcohol this was not for our other variable. This may have been due to our use of SNOMED CT hierarchy.
An electronic cigarette pod system delivering 6-methyl nicotine, a synthetic nicotine analog, marketed in the United States as “PMTA exempt”
Authors: Jordt Sven E. , Jabba Sairam V. , Silinski Peter , Berman Micah L. 
Published: November 2023

ABSTRACTAs of April 14, 2022, the United States Food and Drug Administration (FDA) has been authorized to regulate tobacco products containing nicotine from any source, including synthetic, requiring manufacturers to submit a premarket tobacco product application (PMTA). A recent report by the World Health Organization (WHO) warned that non-nicotine tobacco alkaloids or other synthetic nicotine analogs could be used by manufacturers to bypass regulatory schemes focusing on nicotine alone. From October 2023 on, vape stores in the United States started selling a new electronic cigarette pod system, named Spree Bar, advertised as “PMTA exempt”, with youth-appealing flavors and advertising. The products are marketed as containing “Metatine”, a trademarked name for 6-methyl nicotine, a synthetic nicotine analog patented by a Chinese electronic cigarette manufacturer. Here we used liquid chromatography-mass spectrometry (LCMS) to confirm the presence of a chemical species with the molecular weight of 6-methyl nicotine in Spree Bar e-liquids. The FDA needs to determine whether, in its view, 6-methyl nicotine is a form of “nicotine” within the meaning of the Tobacco Control Act, or whether 6-methyl nicotine can be regulated as a drug under the Federal Food, Drug, and Cosmetic Act (FDCA).
Hi-C2B: Optimised detection of chromosomal contacts within synchronised meioticS. cerevisiaecells
Authors: Wright Ellie M. , Schalbetter S. , Neale Matthew J. 
Published: November 2023

AbstractHi-C, a genome-wide chromosome conformation capture assay is a powerful tool used to study three-dimensional genome organisation by converting physical pairwise interactions into counts of pairwise interaction. To study the many temporally regulated facets of meiotic recombination inS. cerevisiaethe Hi-C assay must be robust such that fine- and wide-scale comparisons between genetic datasets can be made. Here we describe an updated protocol for Hi-C (Hi-C2B) that generates reproducible libraries of interaction data with low noise and for a relatively low cost.