bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polygenic risk scores in coronary artery disease
Authors: Christiansen Morten Krogh , Nyegaard Mette , Jensen Henrik Kjærulf 
Published: January 2023

Purpose of review
Recent advances in genetics have facilitated the calculation of polygenic risk scores (PRSs) based on common genetic risk variants of coronary artery disease (CAD). Here, we provide an explanation of the genetic basis for PRSs and review recent literature investigating PRSs and the clinical utility for different aspects of CAD.

Recent findings
CAD-based PRSs are strongly associated with atherosclerosis burden in the coronary arteries and other vascular beds. In multiple studies, PRSs have proven to be a measure of CAD risk, more powerful than most established risk factors alone, that can be used from early life to stratify individuals into varying trajectories of lifetime risk. When implemented in risk stratification models for primary prevention of cardiovascular disease, PRSs provide modest improvements in discrimination (C-index generally increasing 0–4% points) and reclassification, but yield significant clinical benefit as a risk enhancer. Additionally, data suggest possible value of PRSs for aiding decisions in other aspects of diagnostics and treatment in CAD.

Summary
Once genotyped, the genetic information may be used to calculate an infinite number of PRSs and contribute to personalize medicine providing clinical value for risk stratification, diagnostics and treatment in CAD as well as in other diseases.
Expanding heart transplantation in 2022 and beyond
Authors: Rivera Nina Thakkar , Baran David A. 
Published: January 2023

Purpose of review
Despite advances in the technology of mechanical circulatory support, the need for heart transplantation continues to grow. The longevity of heart transplants continues to be superior to mechanical solutions, though the short-term differences are shrinking. In this review, we cover three timely developments and summarize the recent literature.

Recent findings
After stagnant rates of heart transplant activity for some years, recently, transplant volume has increased. The developments that have ignited interest have been the use of hepatitis C infected donors, which can now be safely transplanted with the advent of curative oral regimens, and the worldwide use of donors following withdrawal of life support as opposed to traditional brain death donors. In addition, the recent experience of human cardiac xenotransplantation has been very exciting, and though it is not of clinical utility yet, it holds the promise for a virtually unlimited supply of organs at some time in the future.

Summary
Much work remains to be done, but together, all three of these developments are exciting and important to be aware of in the future. Each will contribute to additional donors for human heart transplantation and hopefully will alleviate suffering and death on the waiting list.
Prospective Observational Study of Pain Severity and Pain Interference Outcomes Following Percutaneous MRI-guided Laser Ablation or Cryoablation for Focal Painful Peripheral, Soft Tissue Vascular Malformations: 12-month Outcomes
Authors: Thompson Scott M. , Knavel Koepsel Erica M. , Powell Garret M. , Bendel Emily C. , Bjarnason Haraldur , Polites Stephanie F. , Adamo Daniel A. , Howe-Clayton Desirae L. , Favazza Christopher P. , Lu Aiming , Anderson Katelyn R. , Tollefson Megha M. , Woodrum David A. 
Published: January 2023

Background:
Percutaneous image-guided thermal ablation has emerged as a treatment option for vascular malformations (VM). However, prospective data on intermediate to long-term effectiveness with uniform follow-up are lacking.

Purpose:
To prospectively evaluate the 12-month pain severity and pain interference outcomes following percutaneous MRI-guided laser ablation and cryoablation of focal painful, peripheral soft tissue VM.

Materials and Methods:
Participants undergoing clinically indicated MRI-guided laser ablation and cryoablation for focal painful (worst pain ≥4 out of 10 on Visual Analog Scale), peripheral soft tissue vascular malformations (VM) were enrolled in an IRB-approved prospective, observational study after giving informed consent. Participants completed the Brief Pain Inventory questionnaire prior to ablation and 1, 3, 6, and 12-month postablation. Differences in pain severity and interference outcomes from baseline on a 0 to 10 scale were compared using a paired t-test.

Results:
Seventeen participants (15 female; mean age 28.3 ± 9.3 years) underwent 24 MRI-guided and monitored ablation sessions including laser (n = 21), cryoablation (n = 2), or both (n = 1) for treatment of painful slow-flow (n = 16) or high-flow (n = 1) VM. Median maximal VM diameter was 5.7 cm (range 1.1 to 31.0 cm). Mean (±SD) preablation worst pain score was 7.9 ± 1.4. There was a significant decrease in worst pain at 1-month postablation (–3.5 ± 2.9; P = .0007) that was sustained at 3 (–3.4 ± 3.2; P = .0007), 6 (–4.2 ± 3.6; P = .0003), and 12 months (–3.6 ± 3.9; P = .002), with similar results for average, current, and least pain scores. There was a significant improvement in pain interference outcomes at 12-month postablation: general activity (P = .018), walking ability (P = .008), work (P = .003), sleep (P = .007), and enjoyment of life (P = .033).

Conclusions:
These data suggest that MRI-guided and monitored thermal ablation is safe and provides early and sustained significant improvements in pain severity and pain interference outcomes during the first year of follow-up in participants with focal painful peripheral soft tissue VM.
Xenosterolemia in clinical practice: what is in a name?
Authors: Loh Wann Jia , Watts Gerald F. 
Published: January 2023

Purpose of review
The aim of this study was to assess the potential value of the measurement of plasma xenosterols (or phytosterols) concentrations in clinical practice.

Recent findings
Recent genetic studies suggest that individuals with elevated plasma phytosterol concentrations due to monogenic and polygenic variants are at an increased risk of coronary artery disease. This supports early observations that elevated plasma phytosterol concentrations are per se atherogenic.

Summary
Measurement of plasma phytosterols can identify individuals with xenosterolemia (or phytosterolemia). This may be clinically useful in four ways: Establishing a diagnosis and informing management of patients with homozygous phytosterolemia; Providing a comprehensive differential diagnosis for familial hypercholesterolemia; Providing an index of cholesterol absorption that may inform personalized pharmacotherapy; and Informing more precise assessment of risk of cardiovascular disease.
Mechanisms of leptin-induced endothelial dysfunction
Authors: Mellott Elisabeth , Faulkner Jessica L. 
Published: January 2023

Purpose of review
Endothelial dysfunction is a major risk factor for many cardiovascular diseases, notably hypertension. Obesity increases the risk of endothelial dysfunction in association with increasing production of the adipokine leptin. Preclinical studies have begun to unravel the mechanisms whereby leptin leads to the development of endothelial dysfunction, which are sex-specific. This review will summarize recent findings of mechanisms of leptin-induced endothelial impairment in both male and females and in pregnancy.

Recent findings
Leptin receptors are found in high concentrations in the central nervous system (CNS), via which leptin promotes appetite suppression and upregulates sympathetic nervous system activation. However, leptin receptors are expressed in many other tissues, including the vascular endothelial cells and smooth muscle cells. Recent studies in mice with vascular endothelial or smooth muscle-specific knockdown demonstrate that endothelial leptin receptor activation plays a protective role against endothelial dysfunction in male animals, but not necessarily in females. Clinical studies indicate that women may be more sensitive to obesity-associated vascular endothelial dysfunction. Emerging preclinical data indicates that leptin and progesterone increase aldosterone production and endothelial mineralocorticoid receptor activation, respectively. Furthermore, decades of clinical studies indicate that leptin levels increase in the hypertensive pregnancy disorder preeclampsia, which is characterized by systemic endothelial dysfunction. Leptin infusion in mice induces the clinical characteristics of preeclampsia, including endothelial dysfunction.

Summary
Novel preclinical data indicate that the mechanisms whereby leptin promotes endothelial dysfunction are sex-specific. Leptin-induced endothelial dysfunction may also play a role in hypertensive pregnancy as well.
Radiosynthesis, optimization and pharmacokinetic study of the 99mTc-labeled human epidermal growth factor receptor 2 affibody molecule probe 99mTc-(HE)3ZHER2:V2
Authors: Hu Xianwen , Liang Zhigang , Qi Lili , Li Fangming , Cai Xiaojia , Cai Jiong 
Published: January 2023

Objective
To prepare a single-photon molecular probe easily labeled with 99mTc for evaluating the expression status of the human epidermal growth factor receptor 2 (HER2) receptor in ovarian cancer.

Materials and methods
The HEHEHE tag was added to the amino terminus of the affibody ZHER2:V2 by the method of gene recombinant expression, and a new affibody was synthesized which was easy to be labeled with 99mTc. The newly prepared affibody was labeled with 99mTc, and pharmacokinetic studies were carried out.

Results
A new affibody (HE)3ZHER2:V2 was prepared by the method of gene recombination and expression, which is easy to be labeled with 99mTc. The 99mTc labeling of the affibody can reach about 95% at 90°C. The pharmacokinetic study has shown that the 99mTc-labeled molecular probe has a fast clearance time in the blood and little side effect, which may be a promising single-photon emission computed tomography (SPECT) imaging agent.

Conclusion
The affibody (HE)3ZHER2:V2 is easy to be labeled with 99mTc, has a high yield and has a suitable half-life in vivo, which is suitable for the next step in ovarian cancer model imaging research.
Hepatitis E Virus Infection in Pediatric Oncology
Authors: Lenglart Anna , Chappé Céline , Grulois Isabelle , Hervé Françoise , Gandemer Virginie , Robert Guillaume 
Published: January 2023

Background:
In the 2016 ESPGHAN recommendations on how to deal with hepatitis E virus infection in immunocompromised children, patients treated with chemotherapy were not specifically mentioned.

Observations:
Two teenagers treated with chemotherapy for acute leukemia and medulloblastoma, respectively, were diagnosed with hepatic cytolysis. After numerous investigations hepatitis E was found, limiting the good progress of the chemotherapy treatment.

Conclusion:
In the case of liver cytolysis in immunocompromised children treated with chemotherapy, hepatitis E virus infection has to be promptly diagnosed.
The Vitamin D Status in Children With Newly Diagnosed Acute Lymphoblastic Leukemia and Its Potential Impact on the Primary Symptoms of Leukemia and Course of Induction Treatment
Authors: Malecka Anna , Hennig Marcin , Jaworski Radoslaw , Irga-Jaworska Ninela 
Published: January 2023

Background:
Vitamin D deficiency is ubiquitous within the population of children. A similar problem is recognized among pediatric patients with acute lymphoblastic leukemia. The purpose of this study was to analyze the prevalence of vitamin D deficiency and to investigate the connection between vitamin D status and the course of induction treatment of ALL.

Materials and Methods:
A cross-sectional study including 59 patients with newly diagnosed ALL from May 2017 until November 2020.

Results:
Vitamin D deficiency was found in 39% of the patients. There were no seasonal differences in vitamin D status. Patients with optimal 25(OH)D concentration presented more profound thrombocytopenia (P=0.015) and required more frequent platelet transfusions (P=0.018). Good prognosis factors such as B phenotype and hyperdiploidy were also more frequent among children with higher 25(OH)D concentration (P=0.01 and 0.014, respectively).

Conclusions:
The study showed that patients with a higher serum concentration of 25(OH)D presented deeper thrombocytopenia and needed more frequent transfusions. Moreover, those patients showed higher rates of B-cell leukemia and hyperdiploid karyotype. We did not find any influence of the possible exposure to sunlight (defined as the season of the year on admission) on serum 25(OH)D concentration, which supports the argument for supplementing vitamin D all year round. Moreover, the supplementing of vitamin D seems to be safe and does not cause any renal complications connected to calcium and phosphorus imbalance as no correlation between their levels and 25(OH)D concentration was found.
Hypogammaglobulinemia in Children After Hematopoietic Stem Cell Transplantation and Rituximab Treatment: Relevance of B Cell Subsets
Authors: Marzollo Antonio , Serena Tiziana , Mainardi Chiara , Calore Elisabetta , Pillon Marta , Carraro Elisa , Tosato Francesca , Biffi Alessandra , Tumino Manuela 
Published: January 2023

Rituximab (RTX) is widely employed to treat Epstein-Barr virus reactivation in children undergoing Hematopoietic Cell Transplantation (HCT). The resulting loss of B cells may cause persistent hypogammaglobulinemia. This retrospective cross-sectional study aims to identify flow cytometry biomarkers associated with persistent hypogammaglobulinemia in patients receiving RTX after HCT. We analyzed 5 patients (cases group) requiring immunoglobulin substitution due to low level of IgG (IgG <5 g/L) detected after RTX treatment and 5 patients (controls group) not requiring long-term immunoglobulin (Ig) substitution. We investigated the B cell reconstitution, and in patients group we observed a significantly lower count in B total, IgD+CD27+ marginal B cells and IgD-CD27+ switched-memory B cells, after a median of 5 years from HCT, compared with the control group. Despite the importance limits of our study and the heterogeneity of our data (age of included patients, time of evaluation, interval between RTX dose and assessment) we conclude that RTX given early after HCT might cause a deranged B cell maturation, contributing to the delation in B cell recovery following HCT, and switched memory and marginal zone B cell counts could be a promising biomarker to identify patients requiring long-term Ig substitution.
A Comprehensive Review of Neuropsychologic Studies Supports the Concept That Adequate Folinic Acid Rescue Prevents Post Methotrexate Neurotoxicity
Authors: Sadeh Michelle , Toledano Helen , Cohen Ian J. 
Published: January 2023

Purpose:
To review all studies providing evidence of the correlation between folinic acid (FA) rescue inadequacy and long-term cognitive damage in neuropsychological studies of children with acute lymphoblastic leukemia or osteogenic sarcoma treated under protocols using high-dose methotrexate and FA rescue.

Methods:
A comprehensive literature search was performed of all databases of the Web of Science Citation Index, during 1990–2020, for the terms: neuropsychological, neurocognitive, and cognitive, together with acute lymphoblastic (and lymphocytic) leukemia and osteogenic sarcoma. English-language peer-reviewed articles on neuropsychological assessments of children who had been treated with high-dose methotrexate without irradiation, and which included details of methotrexate and FA schedules, were selected. In addition, a personal database of over 500 reprints of articles from over 130 journals was reviewed on the subjects of methotrexate and FA and their side effects.

Results:
Three groups of studies were found and analyzed, with (1) no evidence of cognitive deterioration, (2) evidence of cognitive deterioration, and (3) more than 1 protocol grouped together, preventing separate analysis of any protocols, Protocols without cognitive deterioration reported adequate FA rescue, and those with cognitive deterioration reported inadequate FA rescue.

Conclusion:
Neuropsychological evaluation supported inadequate FA being the cause of neurocognitive damage after high-dose methotrexate and that adequate FA rescue prevents this complication.
Development of Distance Simulation Educator Guidelines in Healthcare
Authors: Bajwa Maria , Ahmed Rami , Lababidi Hani , Morris Melissa , Morton Alex , Mosher Cynthia , Wawersik Dawn , Herx-Weaver Anne , Gross Isabel T. , Palaganas Janice C. 
Published: January 2023

Introduction
The abrupt disruption of in-person instruction in health care during the COVID-19 pandemic resulted in the rapid adoption of distance simulation as an immediate alternative to providing in-person simulation-based education. This massive instructional shift, combined with the lack of educator training in this domain, led to challenges for both learners and educators. This study aimed to disseminate the first set of competencies required of and unique to effective distance simulation educators.

Methods
This was a multiphasic and iterative modified Delphi study validating the content of carefully and rigorously synthesized literature. Experts were invited from around the globe to participate in this study with mandatory attendance at an annual health care simulation conference to openly discuss the guidelines presented as competencies in this document. We divided each competency into “Basic” and “Advanced” levels, and agreement was sought for these levels individually. The experts provided their opinion by choosing the options of “Keep, Modify, or Delete.” A free-marginal kappa of 0.60 was chosen a priori.

Results
At the conclusion of the Delphi process, the number of competencies changed from 66 to 59, basic subcompetencies from 216 to 196, and advanced subcompetencies from 179 to 182.

Conclusions
This article provides the first set of consensus guidelines to distance simulation educators in health care, and paved the way for further research in distance simulation as a modality.
Nirmatrelvir Resistance in SARS-CoV-2 Omicron_BA.1 and WA1 Replicons and Escape Strategies
Authors: Lan Shuiyun , Neilsen Grace , Slack Ryan L. , Cantara William A. , Castaner Andres Emanuelli , Lorson Zachary C. , Lulkin Nicole , Zhang Huanchun , Lee Jasper , Cilento Maria E. , Tedbury Philip R. , Sarafianos Stefan G. 
Published: January 2023

AbstractThe antiviral component of Paxlovid, nirmatrelvir (NIR), forms a covalent bond with Cys145 of SARS-CoV-2 nsp5. To explore NIR resistance we designed mutations to impair binding of NIR over substrate. Using 12 Omicron (BA.1) and WA.1 SARS-CoV-2 replicons, cell-based complementation and enzymatic assays, we showed that in both strains, E166V imparted high NIR resistance (∼55-fold), with major decrease in WA1 replicon fitness (∼20-fold), but not BA.1 (∼2-fold). WA1 replicon fitness was restored by L50F. These differences may contribute to a potentially lower barrier to resistance in Omicron than WA1. E166V is rare in untreated patients, albeit more prevalent in paxlovid-treated EPIC-HR clinical trial patients. Importantly, NIR-resistant replicons with E166V or E166V/L50F remained susceptible to a) the flexible GC376, and b) PF-00835231, which forms additional interactions. Molecular dynamics simulations show steric clashes between the rigid and bulky NIR t-butyl and β-branched V166 distancing the NIR warhead from its Cys145 target. In contrast, GC376, through “wiggling and jiggling” accommodates V166 and still covalently binds Cys145. PF-00835231 uses its strategically positioned methoxy-indole to form a β-sheet and overcome E166V. Drug design based on strategic flexibility and main chain-targeting may help develop second-generation nsp5-targeting antivirals efficient against NIR-resistant viruses.
Subjective survival probabilities by employment category and job satisfaction among the fifty-plus population in Japan
Authors: Wels Jacques 
Published: January 2023

AbstractBackgroundSubjective Survival Probabilities (SSP) are known to be associated with mortality but little is known about the relationship they might have with employment categories and job satisfaction. We assess such a relationship looking at the fifty-plus population in Japan that is characterized by a stratified labour market for the older workers and high working time intensity.MethodWe use the four waves (2007-2013) of the Japanese Study of Aging and Retirement (JSTAR), a panel dataset tracking 7,082 50-plus respondents in 10 Japanese prefectures. We use a mixed-effects quantile regression model to investigate the relationship between SSP and employment status (model 1) and job satisfaction (model 2). Both models additively control for demographic and socio-economic cofounders as well as other health measurements. Multiple imputations are used to correct sample attrition.ResultsIn model 1, retirement (−0.27, 95%CI =-0.51;-0.03) and contract work (−0.51, 95%CI=-0.79;-0.23) are negatively associated with SSP in comparison with full-time employment. In model 2, low job satisfaction appears to be strongly associated with SSP (−1.37, 95%CI=-1.84;-0.91) in comparison with high job satisfaction. The same trend is observed regardless of the way job satisfaction is calculated. Both working time and employment category are not significantly associated with SSP after controlling for job satisfaction which indicates that job satisfaction is a main driver of SSP discrepancies.DiscussionSSP variations can be explained by employment category with contract work more at risk. Job dissatisfaction is a main explanation of low SSP. Both work and employment explain SSP variations.
Nanoparticle-Conjugated TLR9 Agonists Improve the Potency, Durability, and Breadth of COVID-19 Vaccines
Authors: Ou Ben S. , Baillet Julie , Picece Vittoria C.T.M. , Gale Emily C. , Powell Abigail E. , Saouaf Olivia M. , Yan Jerry , Nejatfard Anahita , Hernandez Hector Lopez , Appel Eric A. 
Published: January 2023

ABSTRACTDevelopment of effective vaccines for infectious diseases has been one of the most successful global health interventions in history. Though, while ideal subunit vaccines strongly rely on antigen and adjuvant(s) selection, the mode and timescale of exposure to the immune system has often been overlooked. Unfortunately, poor control over the delivery of many adjuvants, which play a key role in enhancing the quality and potency of immune responses, can limit their efficacy and cause off-target toxicities. There is critical need for new adjuvant delivery technologies to enhance their efficacy and boost vaccine performance. Nanoparticles have been shown to be ideal carriers for improving antigen delivery due to their shape and size, which mimic viral structures, but have been generally less explored for adjuvant delivery. Here, we describe the design of self-assembled poly(ethylene glycol)-b-poly(lactic acid) nanoparticles decorated with CpG, a potent TLR9 agonist, to increase adjuvanticity in COVID-19 vaccines. By controlling the surface density of CpG, we show that intermediate valency is a key factor for TLR9 activation of immune cells. When delivered with the SARS-CoV-2 spike protein, CpG nanoparticle (CpG-NP) adjuvant greatly improve the magnitude and duration of antibody responses when compared to soluble CpG, and result in overall greater breadth of immunity against variants of concern. Moreover, encapsulation of CpG-NP into injectable polymeric-nanoparticle (PNP) hydrogels enhance the spatiotemporal control over co-delivery of CpG-NP adjuvant and spike protein antigen such that a single immunization of hydrogel-based vaccines generates comparable humoral responses as a typical prime-boost regimen of soluble vaccines. These delivery technologies can potentially reduce the costs and burden of clinical vaccination, both of which are key elements in fighting a pandemic.