bluuebunny/crossref_metadata_2025 huggingface dataset:
The Alaska Native/American Indian experience of hepatitis C treatment with sofosbuvir-based direct-acting antivirals
Authors: Townshend-Bulson Lisa , Roik Elena , Barbour Youssef , Bruden Dana , Homan Chriss , Espera Hannah , Stevenson Tim , Hewitt Annette , Rhodes Wileina , Gove Jim , Plotnik Julia , Snowball Mary , McGilvray John , Simons Brenna C. , McMahon Brian
Published: September 2021

Background

Direct-acting antiviral (DAA) drugs have been effective in the treatment of chronic hepatitis C virus (HCV) infection. Limited data are available on safety, tolerability, and efficacy in American Indian or Alaska Native people. We aim to evaluate the treatment outcomes of sofosbuvir-based regimens for treatment of HCV in a real life setting in Alaska Native/American Indian (AN/AI) people.

Methods

AN/AI patients within the Alaska Tribal Health System with confirmed positive anti-HCV and HCV RNA, who were 18 years of age and older were included in the study. Pretreatment baseline patient characteristics, treatment efficacy based on sustained virologic response (SVR) 12 weeks after treatment completion, and adverse effects were assessed. The following treatments were given according to the American Association for the Study of Liver Diseases/Infectious Disease Society of America (AASLD/IDSA) HCV Guidance: ledipasvir/sofosbuvir, sofosbuvir plus weight-based ribavirin, and sofosbuvir/velpatasvir.

Results

We included 501 patients with a mean age of 54.3 (range 21.3 -78.3) in the study. Overall SVR was achieved in 95.2% of patients who received one of the three DAA regimens. For those with cirrhosis, overall SVR was 92.8% and for those with genotype 3 91.1% achieved SVR. The most common symptom experienced during treatment was headache. Joint pain was found to decrease during treatment. One person discontinued sofosbuvir plus ribavirin due to myocardial infarction and one discontinued sofosbuvir/velpatasvir due to urticaria.

Conclusions

In the real-world setting, sofosbuvir-based treatment is safe, effective, and well tolerated in AN/AI patients. Sustained virologic response was high regardless of HCV genotype or cirrhosis status.
Clozapine-induced myocarditis and patient outcomes after drug rechallenge following myocarditis: a systematic case review
Authors: Richardson Noah , Greenway Steven C. , Bousman Chad A.
Published: September 2021

Clozapine is underutilized due, in part, to concerns about rare but severe adverse drug reactions, including cardiac inflammation and injury (myocarditis). Risk factors for clozapine-induced myocarditis are limited and predictors for the successful rechallenge of clozapine after an episode of myocarditis are even more poorly understood. We conducted a systematic review, in accordance with the PRISMA recommendation, of published case reports to describe demographic and clinical characteristics of patients with clozapine-induced myocarditis and identify potential markers of clozapine rechallenge success. A total of 180 cases from 88 articles were evaluated. Male cases of clozapine-associated myocarditis were more frequently reported than female cases by a ratio of 6:1. Less than half of patients reported the presence of chest pain (35%) or flu-like symptoms (43%) but increases in troponin or C-reactive protein were present in 87% of cases. Clozapine rechallenge was carried out in 34 (2 female) cases, with successful reintroduction in 22 (2 female) cases (64.7%). Only chest pain during the initial trial was found to be significantly associated with rechallenge success (odds ratio = 6.87, 95% CI = 1.17 – 40.3). Standardized reporting of clozapine-induced myocarditis cases is needed to facilitate the identification of factors associated with successful rechallenge.
The Xer activation factor of TLCΦ expands the possibilities for Xer recombination
Authors: Miele Solange , Vergne Justine , Possoz Christophe , Ochsenbein Françoise , Barre François-Xavier
Published: September 2021

Many mobile elements take advantage of the highly-conserved chromosome dimer resolution system of bacteria, Xer. They participate in the transmission of antibiotic resistance and pathogenicity determinants. In particular, the toxin-linked cryptic satellite phage (TLCΦ) plays an essential role in the continuous emergence of new toxigenic clones of the Vibrio cholerae strain at the origin of the ongoing 7th cholera pandemic. The Xer machinery is composed of two chromosomally-encoded tyrosine recombinases, XerC and XerD. They resolve chromosome dimers by adding a crossover between sister copies of a specific 28 base pair site of bacterial chromosomes, dif. The activity of XerD depends on a direct contact with a cell division protein, FtsK, which spatially and temporally constrains the process. TLCΦ encodes for a XerD-activation factor (XafT), which drives the integration of the phage into the dif site of the primary chromosome of V. cholerae independently of FtsK. However, XerD does not bind to the attachment site (attP) of TLCΦ, which raised questions on the integration process. Here, we compared the integration efficiency of thousands of synthetic mini-TLCΦ plasmids harbouring different attP sites and assessed their stability in vivo. In addition, we compared the efficiency with which XafT and the XerD activation domain of FtsK drive recombination reactions in vitro. Taken together, our results suggest that XafT promotes the formation of synaptic complexes between canonical Xer recombination sites and imperfect sites.
An adjuvanted SARS-CoV-2 RBD nanoparticle elicits neutralizing antibodies and fully protective immunity in aged mice
Authors: Borriello Francesco , Nanishi Etsuro , Seo Hyuk-Soo , O’Meara Timothy R. , McGrath Marisa E. , Saito Yoshine , Haupt Robert E. , Chen Jing , Diray-Arce Joann , Song Kijun , Xu Andrew Z , Caradonna Timothy M. , Feldman Jared , Hauser Blake M. , Schmidt Aaron G. , Baden Lindsey R. , Ernst Robert K. , Dillen Carly , Weston Stuart M. , Johnson Robert M. , Hammond Holly L. , Yu Jingyou , Chang Aiquan , Hilgers Luuk , Platenburg Peter Paul , Dhe-Paganon Sirano , Barouch Dan H. , Ozonoff Al , Zanoni Ivan , Frieman Matthew B. , Dowling David J. , Levy Ofer
Published: September 2021

Development of affordable and effective vaccines that can also protect vulnerable populations such as the elderly from COVID-19-related morbidity and mortality is a public health priority. Here we took a systematic and iterative approach by testing several SARS-CoV-2 protein antigens and adjuvants to identify a combination that elicits neutralizing antibodies and protection in young and aged mice. In particular, SARS-CoV-2 receptorbinding domain (RBD) displayed as a protein nanoparticle (RBD-NP) was a highly effective antigen, and when formulated with an oil-in-water emulsion containing Carbohydrate fatty acid MonoSulphate derivative (CMS) induced the highest levels of cross-neutralizing antibodies compared to other oil-in-water emulsions or AS01B. Mechanistically, CMS induced antigen retention in the draining lymph node (dLN) and expression of cytokines, chemokines and type I interferon-stimulated genes at both injection site and dLN. Overall, CMS:RBD-NP is effective across multiple age groups and is an exemplar of a SARS-CoV-2 subunit vaccine tailored to the elderly.
Successful, coasting and low-performing school principals in Israel: an explanatory model
Authors: Tubin Dorit , Farchi Talmor Rachel
Published: September 2021

Purpose

The purpose of this paper is to present the successful school and principal (SSP) model, which has developed over 13 years of Israeli involvement in the ISSPP study.

Design/methodology/approach

This is a conceptual paper summarizing the findings of more than 20 case studies of successful, coasting and low-performing schools and their principals, into the SSP model. In all the cases, ISSPP protocols were used to collect the data, and the findings were analyzed in accordance with the organizational approach and organizational routine theory.

Findings

The explanatory SSP model comprises three cyclical phases that explain cause–effect relationships and presents intervention points for school improvement toward success. The first phase is an organizational restructuring of two core routines: the school schedule routine and the school tracking routine, which shape and affect school staff behavior. The second phase is the priorities and values revealed in these behaviors and which shape the school as a learning environment. The third phase in school improvement is the institutional legitimacy derived from and reflecting the school’s priorities and values. All these phases are based on the principal as a crucial key player who turns the wheel.

Originality/value

Theoretically, the SSP model explains cause–effect relationships and indicates possible interventions and improvements. Practically, the SSP model can influence principal preparation programs, novice principal mentoring and serve as a roadmap for school improvement.
Dubious or decisive? Digging deeper into the unchartered path of academic ghostwriting
Authors: Svirina Anna , Anand Amitabh
Published: September 2021

Purpose

The aim of this paper is to investigate the journey of academic professors who have engaged in ghostwriting.

Design/methodology/approach

This study adopts qualitative exploratory methods to investigate the ghostwriters' journey into academic ghostwriting. To achieve the goal, the authors interviewed academic ghostwriters, who were working for a diploma mill company, specifically focused on PhD thesis writing in the NIS setting.

Findings

This study revealed several interesting insights from ghostwriter perspective such as the origins and motivation of ghostwriters, ghostwriters life, ghostwriters' careers and impediments faced by them.

Originality/value

Given the dispersed and sensitive nature of the topic, this is one of the few studies to investigate ghostwriting and offer implications.
Sustainability and its challenges in destinations that highly depend on tourism: a thematic literature review
Authors: Dembovska Iveta , Zvaigzne Anda
Published: September 2021

Purpose

This article aims to adopt a thematic approach to a review of the literature relating to sustainability and its challenges in destinations that highly depend on tourism.

Design/methodology/approach

The paper provides a review of scientific and theoretical research studies on the concept and principles of sustainable tourism, the effects of tourism on society and sustainable tourism strategy.

Findings

The basic principles of sustainable tourism development apply to all destinations, including Cyprus. The development of tourism is associated with the observance of the principles of sustainable tourism development, which takes the form of balanced environmental and economic development and involves the observance of public interest.

Originality/value

The paper offers a broad-ranging review-based perspective on sustainable tourism and the principles and development thereof.
Relatedness modulates density‐dependent cannibalism rates in Drosophila
Authors: Fisher Adam M. , Le Page Sally , Manser Andri , Lewis Daniel R. , Holwell Gregory I. , Wigby Stuart , Price Tom A. R.
Published: September 2021

Cannibalism is taxonomically widespread and can have large impacts on individual fitness and population‐level processes. As such, identifying how cannibalism rates vary in response to ecological cues is important for predicting species evolution and population dynamics.

In this study, we aimed to identify several eco‐evolutionary factors that affect cannibalism rate and measure how they interacted with one another.

To do this, we conducted two experiments using complimentary methods to measure how cannibalism rates varied among larval Drosophila melanogaster and Drosophila simulans in response to changes in conspecific relatedness, social familiarity and density.

We found that larvae were more likely to cannibalise non‐related larval victims in both species, and that this effect increased at high densities in D. simulans. We found no evidence that Drosophila larvae use social familiarity to assess relatedness. Finally, in D. melanogaster, cannibalistic larvae prefer to cannibalise larvae that are being attacked by a greater number of conspecifics, implying that cues linked to conspecific abundance encourage cooperative cannibalism.

By showing that cannibalism frequency in Drosophila spp. is sensitive to relatedness and several other factors, we reveal the complex relationship between cannibalism frequency and species ecology. Also, by showing that the effect of relatedness on cannibalism frequency is density dependent, we advance the current understanding of how ecological variables interact to affect kin selection.

A free Plain Language Summary can be found within the Supporting Information of this article.
The unusual microbiota of the traditional Bulgarian dairy product Krokmach – A pilot metagenomics study
Authors: Dimov Svetoslav G
Published: September 2021

Krokmach is a traditional Bulgarian fermented dairy product. The microbiota composition was investigated for the first time by next‐generation sequencing. The results revealed a quite specific constitution comprising several bacterial species never reported before for fermented dairy products. It resembles those of soft and smear cheeses rather than that of yoghurt. The dominant species was Lactococcus lactis subsp. lactis (75% of the operational taxonomic unit (OTU) counts). The overall composition was quite unusual with 8.5% of Exiguobacterium sp. OTU counts, as well as the presence of Apiactobacillus kunkeei, Megamonas sp. and Kluyvera georgiana among the dominant and subdominant species and genera.
Vascular injury is an infrequent finding following non‐fatal strangulation in two Australian trauma centres
Authors: Williamson Frances , Collins Sarah , Dehn Anja , Doig Shaela
Published: September 2021

Objective

Non‐fatal strangulation assessment is challenging for clinicians as clear guidelines for evaluation are limited. The prevalence of non‐fatal strangulation events, clinical findings, frequency of injury on computed tomography angiogram (CTA) and outcomes across two trauma centres will be used to improve this assessment process.

Methods

This is a retrospective observational study of adult presentations during 2‐year period to two major‐trauma referral hospitals and subsequent 12 months to identify delayed vascular injury. Patients included using standardised search terms. Demographic data, clinical findings, radiological reports and outcomes were included for review.

Results

A total of 425 patients were included for analysis. Self‐inflicted injury comprised 62.1%, with domestic violence (28.5%) and assault (9.4%) the remainder. Manual strangulation events 36.7% of overall presentations and 63.3% following ligature strangulation (ligature strangulation, incomplete and complete hanging). On examination soft signs present in 133 (31.2%) cases, commonly neck tenderness in isolation. No hard signs suggesting vascular damage. Vascular injury was demonstrated in three cases (0.7% of the total cohort and 1.5% of CTA scans completed), and all occurred in ligature strangulation events as a result of hanging. No patients had delayed vascular injury in the 12‐month period post‐initial presentation.

Conclusions

In non‐fatal strangulation presentations, the majority have subtle signs of neck injury on examination with inconsistent documentation of findings. Low rate of vascular injury overall (0.7%), and entirely in hanging events. No longer‐term vascular sequalae identified. Improving documentation focusing on hypoxic insult and evidence of airway trauma is warranted, rather than a reliance on computed tomography imaging to delineate a traumatic event in non‐fatal strangulation.
Measuring Agenda Setting in Interactive Political Communication
Authors: Rossiter Erin L.
Published: September 2021

Although strategies exist to measure actors' efforts to set policy, media, and lawmaking agendas, political scientists lack a method for identifying and accurately measuring another form of agenda setting that lies under the surface anytime two people talk. Within interactions, such as debates, deliberations, and discussions, actors can set the agenda by shifting others' attention to their preferred topics. In this article, I use a topic model that locates where topic shifts occur within an interaction in order to measure the relative agenda‐setting power of actors. Validation exercises show that the model accurately identifies topic shifts and infers coherent topics. Three empirical applications also validate the agenda‐setting measure within different political settings: U.S. presidential debates, in‐person deliberations, and online discussions. These applications show that successfully setting the agenda can shape an interaction's outcomes, demonstrating the importance of continued research on this form of agenda setting.
In utero exposure to antiretroviral drugs and pregnancy outcomes: Analysis of the French ANRS pharmacovigilance database
Authors: Saint‐Lary Laura , Diallo Alpha , de Monteynard Laure‐Amélie , Paul Christelle , Marchand Lucie , Tubiana Roland , Warszawski Josiane , Mandelbrot Laurent , Rekacewicz Claire , Petrov‐Sanchez Ventzislava , Faye Albert , Sibiude Jeanne , Dabis François , Sommet Agnès , Leroy Valériane
Published: September 2021

Aims

In 2018, 1.07 million pregnant women received antiretroviral drugs, raising whether this affects pregnancy outcomes. We assessed the adverse pregnancy outcomes associated with prenatal antiretroviral drug exposure, notified to the French ANRS pharmacovigilance system.

Methods

An exhaustive case report series has been performed using the ANRS pharmacovigilance database. All ANRS‐sponsored HIV clinical research studies using antiretroviral drugs either in pregnant women or women of childbearing age were eligible from 2004 to 2019. We analysed the following pregnancy outcomes: abortion, ectopic pregnancy, stillbirth, prematurity (<37 weeks of gestational age), low birth weight (<2500 g) and congenital abnormalities. A logistic regression was performed to assess the odds ratio (OR) for each outcome separately (if occurrence >50) compared to the outcome observed when exposed to non‐nucleoside‐reverse‐transcriptase‐inhibitor (NNRTI)‐based regimen as the reference.

Results

Among the 34 studies selected, 918 deliveries occurred, of whom 88% had pregnancy outcomes documented. Pregnant women were mainly exposed to PI (n = 387, 48.6%), NNRTI (n = 331, 41.5%) and INI‐based combinations (n = 40, 5.0%, 18 on dolutegravir). Compared to NNRTI‐based combinations, there was no significant association observed with exposure to other antiretroviral combination for spontaneous abortion, prematurity or low birth weight, except an increased risk of low birth weight in new‐born exposed to exclusive nucleoside‐reverse‐transcriptase‐inhibitor (NRTI) combinations (n = 4; OR 7.50 [1.49–37.83]).

Conclusions

Our study, mainly based on protease inhibitor (PI) and NNRTI‐based regimens, is overall reassuring on the risk of adverse pregnancy outcomes, except for NRTI which should be interpreted cautiously (small number, indication bias). In this study, the number of integrase inhibitor (INI)‐based combinations was too low to draw any conclusions.
Ferroptosis‐related gene signature associates with immunity and predicts prognosis accurately in patients with osteosarcoma
Authors: Lei Ting , Qian Hu , Lei Pengfei , Hu Yihe
Published: September 2021

Osteosarcoma has been the most common malignant bone tumor in children and adolescents, while the 5‐y survival of osteosarcoma patients gained no significant improvement over the past decades. This study aimed to explore the role of ferroptosis‐related genes (FRGs) in the development and prognosis of osteosarcoma. The datasets of osteosarcoma patients including RNA sequencing data and clinical information were acquired from the TRGET and Gene Expression Omnibus (GEO) databases. The identification of molecular subgroups with different FRG expression patterns was achieved through nonnegative matrix factorization (NMF) clustering. The prognostic model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression analysis. The ESTIMATE algorithm was applied for determining the stromal score, immune score, ESTIMA score, and tumor purity of osteosarcoma patients. Functional analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) were conducted to explore the underlying mechanisms in the development and prognosis of osteosarcoma. Two molecular subgroups with different FRGs expression patterns were identified. The molecular subgroups with higher immune score and more active immune status showed better prognostic survival. On the basis of FRGs, a prognostic model and a nomogram integrating clinical characteristics were constructed and their prediction efficiency for osteosarcoma prognosis were well validated. Gene functional enrichment analysis showed that these differentially expressed FRGs were mainly enriched in immunity‐related signaling pathways, indicating that FRGs may affect the development and prognosis of osteosarcoma by regulating the immune microenvironment. The expression profiles of FRGs were closely related to the immunity status and prognostic survival of osteosarcoma patients. The interaction between ferroptosis and immunity in the development of osteosarcoma could provide a new insight into the exploration of molecular mechanisms and targeted therapies of osteosarcoma patients.
Kidney transplant recipients vaccinated before transplantation maintain superior humoral response to SARS‐CoV‐2 vaccine
Authors: Grupper Ayelet , Katchman Eugene , Ben‐Yehoyada Merav , Rabinowich Liane , Schwartz Doron , Schwartz Idit F. , Shashar Moshe , Halperin Tami , Turner Dan , Goykhman Yaacov , Shibolet Oren , Levy Sharon , Houri Inbal , Baruch Roni , Katchman Helena
Published: September 2021

Majority of transplant recipients did not develop an appreciable humoral response following SARS‐CoV‐2 vaccine, in contrast to dialysis patients and healthy individuals. We analyzed the serologic response to BNT162b2 (Pfizer‐BioNTech) vaccine in a cohort of 19 kidney transplant recipients, vaccinated prior to transplantation, compare to 109 recipients vaccinated after transplantation, and to 39 healthcare workers, by determining the level of anti‐spike antibodies after transplantation. All controls and 17 of 19 (90%) of recipients vaccinated before transplant were seropositive, while only 49 of 109 (45%) recipients vaccinated post‐transplant had positive serology (P < .001). Median anti‐spike IgG in the group of kidney transplant recipients vaccinated after transplantation (10.7 AU/ml, [IQR 0–62.5]) was lower than the patients vaccinated before transplantation (66.2 AU/ml [21.6–138]), which was significantly lower than in the controls (156 AU/ml [99.7–215.5]). Negative humoral response was associated with vaccination post transplantation (odds ratio 22.4), older age (OR = 1.04), and longer time on dialysis (OR = 1.02), while higher lymphocyte count at time of vaccination was protective (OR = .52). Our findings of sustained superior humoral response to SARS‐CoV‐2 vaccine in kidney transplant recipients vaccinated prior to transplantation strongly support the recommendations of SARS‐CoV‐2 vaccination of transplant candidates, especially those younger than 60 years.
Lateral preoptic area neurons signal cocaine self‐administration behaviors
Authors: Coffey Kevin R. , Venkat Vaishnavi , West Mark O. , Barker David J.
Published: September 2021

The lateral preoptic area is implicated in numerous aspects of substance use disorder. In particular, the lateral preoptic area is highly sensitive to the pharmacological properties of psychomotor stimulants, and its activity promotes drug‐seeking in the face of punishment and reinstatement during abstinence. Despite the lateral preoptic area's complicity in substance use disorder, how precisely lateral preoptic area neurons signal the individual components of drug self‐administration has not been ascertained. To bridge this gap, we examined how the firing of single lateral preoptic area neurons correlates with three discrete elements of cocaine self‐administration: (1) drug‐seeking (pre‐response), (2) drug‐taking (response) and (3) receipt of the cocaine infusion. A significant subset of lateral preoptic area neurons responded to each component with a mix of increases and decreases in firing‐rate. A majority of these neurons signal the operant response with increases in spiking, though responses during the drug‐seeking, taking and reciept windows were highly correlated.
Naked mole‐rats (Heterocephalus glaber) do not specialise in cooperative tasks
Authors: Siegmann Susanne , Feitsch Romana , Hart Daniel W. , Bennett Nigel C. , Penn Dustin J. , Zöttl Markus
Published: September 2021

It has been proposed that naked mole‐rat (Heterocephalus glaber) societies resemble those of eusocial insects by showing a division of labour among non‐breeding individuals. Earlier studies suggested that non‐breeders belong to distinct castes that specialise permanently or temporarily in specific cooperative tasks. In contrast, recent research on naked mole‐rats has shown that behavioural phenotypes are continuously distributed across non‐breeders and that mole‐rats exhibit considerable behavioural plasticity suggesting that individuals may not specialise permanently in work tasks. However, it is currently unclear whether individuals specialise temporarily and whether there is a sex bias in cooperative behaviour among non‐breeders. Here, we show that non‐breeding individuals vary in overall cooperative investment, but do not specialise in specific work tasks. Within individuals, investment into specific cooperative tasks such as nest building, food carrying and burrowing is positively correlated, and there is no evidence that individuals show trade‐offs between these cooperative behaviours. Non‐breeding males and females do not differ in their investment in cooperative behaviours and show broadly similar age and body mass related differences in cooperative behaviours. Our results suggest that non‐breeding naked mole‐rats vary in their overall contribution to cooperative behaviours and that some of this variation may be explained by differences in age and body mass. Our data provide no evidence for temporary specialisation, as found among some eusocial insects and suggest that the behavioural organisation of naked mole‐rats resembles that of other cooperatively breeding vertebrates more than that of eusocial insect species.
Variability of disease activity in patients with hereditary angioedema type 1/2: longitudinal data from the Icatibant Outcome Survey
Authors: Maurer M. , Caballero T. , Aberer W. , Zanichelli A. , Bouillet L. , Bygum A. , Grumach A.S. , Botha J. , Andresen I. , Longhurst H.J. ,   for the IOS Study Group
Published: September 2021

Background

Hereditary angioedema due to C1 inhibitor deficiency (HAE‐1/2) is a chronic and debilitating disease. The unpredictable clinical course represents a significant patient burden.

Objective

To analyse longitudinal registry data from the Icatibant Outcome Survey (IOS) in order to characterize temporal changes in disease activity in patients with HAE‐1/2.

Methods

Icatibant Outcome Survey (NCT01034969) is an international observational registry monitoring the clinical outcomes of patients eligible for icatibant treatment. The current analyses are based on data collected between July 2009 and July 2019. Retrospective data for attacks recorded in the 12 months prior to IOS enrolment and for each 12‐month period up to 7 years were analysed.

Results

Included patients reported angioedema attacks without long‐term prophylaxis (LTP; n = 315) and with LTP (n = 292) use at the time of attack onset. Androgens were the most frequently used LTP option (80.8%). At the population level, regardless of LTP use, most patients (52–80%) reporting <5 attacks in Year 1 continued experiencing this rate; similarly, many patients (25–76%) who reported high attack frequency continued reporting ≥10 attacks/year. However, year on year, 31–51% of patients experienced notable changes (increase/decrease of ≥5 attacks) in annual attack frequency. Of patients who reported an absolute change of ≥10 attacks from Year 1 to 2, 17–50% continued to experience a change of this magnitude in subsequent years.

Conclusion

At the population level, attack frequency was generally consistent over 7 years. At the small group level, 28.8–34.5% of patients reported a change in attack frequency of ≥5 attacks from Year 1 to Year 2; up to half of these patients continued to experience this magnitude of variation in disease activity in later years, reflecting high intra‐patient variability.
Children with familial hypercholesterolemia display changes in LDL and HDL function: A cross‐sectional study
Authors: Christensen Jacob J. , Narverud Ingunn , Ruuth Maija , Heier Martin , Jauhiainen Matti , Ulven Stine M. , Bogsrud Martin P. , Kovanen Petri T. , Halvorsen Bente , Oda Michael N. , Wium Cecilie , Retterstøl Kjetil , Öörni Katariina , Holven Kirsten B.
Published: September 2021

Background

The functional status of lipoprotein particles contributes to atherogenesis. The tendency of plasma low‐density lipoprotein (LDL) particles to aggregate and the ability of igh‐density lipoprotein (HDL) particles to induce and mediate reverse cholesterol transport associate with high and low risk for cardiovascular disease in adult patients, respectively. However, it is unknown whether children with familial hypercholesterolemia (FH) display lipoprotein function alterations.

Hypothesis

We hypothesized that FH children had disrupted lipoprotein functions.

Methods

We analyzed LDL aggregation susceptibility and HDL‐apoA‐I exchange (HAE), and activity of four proteins that regulate lipoprotein metabolism (cholesteryl ester transfer protein, lecithin–cholesterol acyltransferase, phospholipid transfer protein, and paraoxonase‐1) in plasma samples derived from children with FH (n = 47) and from normocholesterolemic children (n = 56). Variation in lipoprotein functions was further explored using an nuclear magnetic resonance‐based metabolomics profiling approach.

Results

LDL aggregation was higher, and HAE was lower in FH children than in normocholesterolemic children. LDL aggregation associated positively with LDL cholesterol (LDL‐C) and negatively with triglycerides, and HAE/apoA‐I associated negatively with LDL‐C. Generally, the metabolomic profile for LDL aggregation was opposite of that of HAE/apoA‐I.

Conclusions

FH children displayed increased atherogenicity of LDL and disrupted HDL function. These newly observed functional alterations in LDL and HDL add further understanding of the risk for atherosclerotic cardiovascular disease in FH children.
Super‐resolution reconstruction of T2‐weighted thick‐slice neonatal brain MRI scans
Authors: Askin Incebacak N. Ceren , Sui Yao , Gui Levy Laura , Merlini Laura , Sa de Almeida Joana , Courvoisier Sebastien , Wallace Tess E. , Klauser Antoine , Afacan Onur , Warfield Simon K. , Hüppi Petra , Lazeyras Francois
Published: September 2021

Background and Purpose

Super‐resolutionreconstruction (SRR) can be used to reconstruct 3‐dimensional (3D) high‐resolution (HR) volume from several 2‐dimensional (2D) low‐resolution (LR) stacks of MRI slices. The purpose is to compare lengthy 2D T2‐weighted HR image acquisition of neonatal subjects with 3D SRR from several LR stacks in terms of image quality for clinical and morphometric assessments.

Methods

LR brain images were acquired from neonatal subjects to reconstruct isotropic 3D HR volumes by using SRR algorithm. Quality assessments were done by an experienced pediatric radiologist using scoring criteria adapted to newborn anatomical landmarks. The Wilcoxon signed‐rank test was used to compare scoring results between HR and SRR images. For quantitative assessments, morphology‐based segmentation was performed on both HR and SRR images and Dice coefficients between the results were computed. Additionally, simple linear regression was performed to compare the tissue volumes.

Results

No statistical difference was found between HR and SRR structural scores using Wilcoxon signed‐rank test (p = .63, Z = .48). Regarding segmentation results, R2 values for the volumes of gray matter, white matter, cerebrospinal fluid, basal ganglia, cerebellum, and total brain volume including brain stem ranged between .95 and .99. Dice coefficients between the segmented regions from HR and SRR ranged between .83 ± .04 and .96 ± .01.

Conclusion

Qualitative and quantitative assessments showed that 3D SRR of several LR images produces images that are of comparable quality to standard 2D HR image acquisition for healthy neonatal imaging without loss of anatomical details with similar edge definition allowing the detection of fine anatomical structures and permitting comparable morphometric measurement.
Exploration of an effective method to determine the relative sweetness of natural alternative sweeteners: Comparison of two‐alternative forced‐choice test and generalized labeled magnitude scale
Authors: Lee Soo‐Hyun , Kim Min‐Ji , Hong Jae‐Hee
Published: September 2021

The relative sweetness (RS) of natural alternative sweeteners is influenced by their distinct flavors and temporal profiles but also by the determination method. This study investigated the reported RS of natural alternative sweeteners using two methods—the two‐alternative forced‐choice (2‐AFC) test and generalized labeled magnitude scale (g‐LMS). The 2‐AFC test and g‐LMS were applied to determine the RS of rebaudioside A, luo han guo extract, and xylo‐oligosaccharide to 5% sucrose. The RS values were verified by comparison to those obtained from descriptive analysis (DA). The 2‐AFC test produced RS values more similar to those of the DA, whereas the g‐LMS yielded much higher RS values. The results suggest that the 2‐AFC test, which compares the integrated perception of samples directly to that of a reference, yields a more accurate RS value than the g‐LMS, which asks panelists to rate sweetness separately from other sensations that might influence perception.

Practical applications

Replacing sugar with alternative sweeteners is one sugar reduction strategy widely used in the food industry. It is important to accurately identify RS values because an accurate replacement ratio based on the RS is necessary for successful sugar replacement that does not change the original sensory profile. However, the unique sensory characteristics and temporal profiles of natural alternative sweeteners can make it difficult to determine RS values accurately. This study compared the performances of the 2‐AFC test and g‐LMS, which use different evaluation strategies, to provide researchers with insights on the efficacy of the methods. It is expected that the outcomes of this study will aid in the research and development of sugar replacement strategies in both academia and industry.
Moving toward responsible value creation: Business model challenges faced by organizations producing responsible health innovations
Authors: Lehoux Pascale , Silva Hudson P. , Denis Jean‐Louis , Miller Fiona A. , Pozelli Sabio Renata , Mendell Marguerite
Published: September 2021

Responsible Research and Innovation (RRI) seeks to steer innovation toward important societal challenges and, by doing so, calls for entrepreneurial activities that create economic, social, and environmental value. Nonetheless, little is known about the way different types of organization can produce responsible products and services and the challenges they face when implementing new business models remain largely uncharted. By linking the RRI and the business model literatures, the aim of this article is to generate a better understanding of the challenges underlying responsible value creation. To do so, we approach the business model as a dynamic construct that crosses organizational boundaries and develop an empirically grounded multilevel model that links entrepreneurs' practices (micro‐level), organizational management (meso‐level), and innovation system dynamics (macro‐level). Our multiple case studies include for‐profit and not‐for‐profit Canadian and Brazilian organizations (n = 16) engaged in the production of responsible health innovations and explore the following research questions: “What business model challenges do these organizations face in their attempt to produce responsible innovations? How do these challenges affect the implementation of their business model and capacity to achieve responsible value creation?” Our findings focus on cross‐case commonalities that clarify how specific business model components are dynamically adapted in response to eight micro‐, meso‐, and macro‐level business model challenges, while the organizations' capacity to adequately align these components remains precarious. Our study provides innovation management scholars with an empirically grounded model that brings conceptual clarity to responsible value creation. This groundwork may foster cumulative knowledge growth on the way RRI‐oriented organizations can orchestrate their activities toward responsible value creation, which simultaneously requires individual entrepreneurial skills, organizational capacities, and the support of other innovation stakeholders.
Rural‐urban differences in HPV testing for cervical cancer screening
Authors: Locklar Lindsay R. B. , Do D. Phuong
Published: September 2021

Purpose

Rural preventable cancer disparities are often attributed in part to lower screening rates secondary to compromised health care access. When considering higher cervical cancer incidence and mortality, existing analyses primarily consider differences in Pap testing rather than the preferred method of HPV testing, which is more sensitive in identifying severe cases of cervical dysplasia.

Methods

Logistic regression using data from the 2016 and 2018 Behavioral Risk Factor Surveillance System was used to examine urban and rural rates of cervical cancer screening according to national guidelines. Propensity score weighting was used to account for baseline sociodemographic differences between rural and urban populations in the 2016 landline sample.

Findings

In 2016 and 2018, rural women were less likely than urban women to have current cervical cancer screening. This disparity was explained by sociodemographic variables in 2016. Among women with current cervical cancer screening, rural women were significantly less likely than urban women to undergo HPV testing in both 2016 and 2018.

Conclusion

Rural women with current cervical cancer screening were significantly less likely than their urban counterparts to have HPV testing. It is possible that updates to preventive care guidelines may be slower to reach rural providers, rural patients may be unaware that HPV testing was completed, or rural practice configuration may complicate the integration of HPV testing into clinical practice. Failure to undergo HPV testing may lead to delayed cervical dysplasia diagnosis, missed opportunities for early intervention, and contribute to rural/urban disparities in cervical cancer incidence and mortality.
Integration of multiple volatile cues into plant defense responses
Authors: Hu Lingfei
Published: September 2021

The ability to predict future risks is essential for many organisms, including plants. Plants can gather information about potential future herbivory by detecting volatiles that are emitted by herbivore‐attacked neighbors. Several individual volatiles have been identified as active danger cues. Recent work has also shown that plants may integrate multiple volatiles into their defense responses. Here, I discuss how the integration of multiple volatiles can increase the capacity of plants to predict future herbivore attack. I propose that integration of multiple volatile cues does not occur at the perception stage, but may through downstream early defense signaling and then be further consolidated by hormonal crosstalk. Exploring plant volatile cue integration can facilitate our understanding and utilization of chemical information transfer.
Shifting seasonal patterns of water availability: ecosystem responses to an unappreciated dimension of climate change
Authors: Hajek Olivia L. , Knapp Alan K.
Published: September 2021

Seasonal patterns of water availability can differ dramatically among ecosystems, with well‐known consequences for ecosystem structure and functioning. Less appreciated is that climate change can shift the seasonality of water availability (e.g. to wetter springs, drier summers), resulting in both subtle and profound ecological impacts. Here we (1) review evidence that the seasonal availability of water is being altered in ecosystems worldwide, (2) explore several mechanisms potentially driving these changes, and (3) highlight the breadth of ecological consequences resulting from shifts in the seasonality of water availability. We conclude that seasonal patterns of water availability are changing globally, but in regionally specific ways requiring more rigorous and nuanced assessments of ecosystem vulnerability as well as the ecological consequences.
Cannabis use disorder among atrial fibrillation admissions, 2008–2018
Authors: Chouairi Fouad , Miller P. Elliott , Guha Avirup , Clarke John‐Ross , Reinhardt Samuel W. , Ahmad Tariq , Freeman James V. , Desai Nihar R. , Friedman Daniel J.
Published: September 2021

Background

Despite changes inthe legality of cannabis use and the increasing prevalence of cannabis use disorder (CUD), there is little data investigating the association between CUD and inpatient atrial fibrillation (AF) hospitalizations.

Methods

Using the National Inpatient Sample, we identified Atrial Fibrillation (AF) hospitalizations with and without a codiagnosis of CUD using International Classification of Diseases diagnosis codes and compared demographics, socioeconomics, comorbidities, outcomes, and trends between cohorts.

Results

Between 2008 and 2018, we identified 5,155,789 admissions for AF of which 31,768 (0.6%) had a codiagnosis of CUD. The proportion of admissions with a history of CUD increased from 0.3% in 2008 to 1.0% in 2018 (p < .001). Hospital discharges of patients with CUD were significantly younger (53 vs. 72 years, p < .001), had a higher proportion of black race (CUD: 26.6% vs. 8.0%, p < .001), and had a higher proportion of income in the lowest income quartile than without a codiagnosis of CUD (CUD: 40.5% vs. 26.2%, p < .001).

Conclusions

CUD is increasingly prevalent among AF hospitalizations, particularly among young patients. Codiagnosis of CUD in AF hospitalizations is also more common in underserved patients. As a result, it is important for future research to examine and understand the impact of CUD on this population, particularly in the light of changing legislation surrounding the legality of cannabis.
Pneumatosis cystoides intestinalis: A rare complication after hematopoietic stem cell transplantation
Authors: Arman Bilir Özlem , Demir Arzu Meltem , Akçabelen Yunus Murat , Ok Bozkaya İkbal , Gürlek Gökçebay Dilek , Güneş Altan , Özbek Namık Yaşar , Yaralı Neşe
Published: September 2021

Background

Pneumatosis cystoides intestinalis (PCI) is a disorder in which widespread air sacs are present in mucosa, submucosa, subserosa, and intraabdominal area of the intestinal wall. It has a heterogeneous clinical presentation as a rare complication of intestinal graft‐versus‐host disease (GVHD). Computed tomography is the preferred imaging method for the diagnosis. Since the air sacs could be ruptured spontaneously, the presence of free air in the peritoneal cavity does not confirm intestinal perforation. The conservative treatment approach is sufficient in cases that do not require urgent surgical intervention, such as perforation or obstruction.

Case

Here, we present a 2.5‐year‐old patient diagnosed with primary hemophagocytic lymphohistiocytosis (pHLH), who underwent allogeneic hematopoietic stem cell transplantation from a matched unrelated donor (MUD) and developed PCI secondary to intestinal GVHD 14th months after HSCT.

Conclusions

Pneumatosis cystoides intestinalis, which is a rare complication, should be kept in mind, especially in patients with intestinal GVHD and receiving intensive immunosuppressive, octreotide, and steroid treatment after HSCT.
Barriers to Advance Care Planning Implementation in Health care: An Umbrella Review with Implications for Evidence‐Based Practice
Authors: Poveda‐Moral Silvia , Falcó‐Pegueroles Anna , Ballesteros‐Silva Mónica Patricia , Bosch‐Alcaraz Alejandro
Published: September 2021

Background

Advance care planning (ACP) refers to a process of discussions between professionals, patients, and their families, which allows the patient to define and communicate their care and treatment preferences. Understanding the barriers to advance care planning is the first step on the way to overcoming them and to improving person‐centred care and attention.

Aims

To identify the barriers perceived by professionals, patients, and family members when implementing ACP in a clinical context and to analyse the methodological quality of the evidence.

Methods

An umbrella review guided by the Joanna Briggs Institute and a systematic review in accordance with PRISMA 2015 were utilized. Data were obtained from MEDLINE, Cochrane Library, The Joanna Briggs Institute, CINAHL, Scopus, and EMBASE in November 2018.

Results

Fourteen systematic reviews were included. The main barriers reported by professionals were lack of knowledge and skills to carry out ACP, a certain fear of starting conversations about ACP, and a lack of time for discussions. Patients and family members considered that the main barriers were fear of discussing their relative’s end of life, lack of ability to carry out ACP, and not knowing who was responsible for initiating conversations about ACP.

Linking Evidence to Action

This review has examined the barriers presented by health professionals, patients, and family members, so that future lines of research can develop preventive or decisive measures that encourage the implementation of ACP in health care.
Model Based Design of a Low Cost and Compliant Low Profile Prosthetic Foot
Authors: Bartlett Harrison L. , King Shane T. , Goldfarb Michael , Lawson Brian E.
Published: September 2021

This paper describes the design of a simple and low-cost compliant low-profile prosthetic foot based on a cantilevered beam of uniform strength. The prosthetic foot is developed such that the maximum stress experienced by the beam is distributed approximately evenly across the length of the beam. Due to this stress distribution, the prosthetic foot exhibits compliant behavior not achievable through standard design approaches (e.g., designs based on simple cantilevered beams). Additionally, due to its simplicity and use of flat structural members, the foot can be manufactured at low cost. An analytical model of the compliant behavior of the beam is developed that facilitates rapid design changes to vary foot size and stiffness. A characteristic prototype was designed and constructed to be used in both a benchtop quasi-static loading test as well as a dynamic walking test for validation. The model predicted the rotational stiffness of the prototype with 5% error. Furthermore, the prototype foot was tested alongside two commercially available prosthetic feet (a low profile foot and an energy storage and release foot) in level walking experiments with a single study participant. The prototype foot displayed the lowest stiffness of the three feet (6.0, 7.1, and 10.4 Nm/deg for the prototype foot, the commercial low profile foot, and the energy storage and release foot, respectively). This foot design approach and accompanying model may allow for compliant feet to be developed for individuals with long residual limbs.