bluuebunny/crossref_metadata_2025 huggingface dataset:
The Link Between Childhood Adversity and Cardiovascular Disease Risk: Role of Cerebral and Systemic Vasculature
Authors: Rodriguez-Miguelez Paula , Looney Jacob , Blackburn Marsha , Thomas Jeffrey , Pollock Jennifer S , Harris Ryan A
Published: May 2022

Adverse childhood experiences (ACEs) are traumatic events during the first years of life that are associated with a higher risk of developing cardiovascular disease (CVD) during adulthood. The medial prefrontal cortex (mPFC) is a core region in the brain that modulates emotions and is directly involved in the cardiovascular response to stress by increasing vascular resistance. In the present study we examined the relationship between ACEs, mPFC and peripheral vascular function. Forty-five, adults (33±5 yrs.) participated in the present study to evaluate cerebral hemodynamics and peripheral vascular function. The impact of adverse experiences was evaluated through the ACE questionnaire. Among those that experienced ACEs (ACE group, n = 22), there was a significantly (P < 0.001) reduced activation of the mPFC as well as greater peripheral vascular resistance observed in the small (P ≤ 0.035), conduit (P ≤ 0.042) and large (P ≤ 0.001) blood vessels, when compared to those that did not report ACEs (Control group, n = 23). In addition, relationships between the number of ACEs and mPFC activation (rs = −0.428; P = 0.003) and peripheral vascular function (rs≤ −0.373; P ≤ 0.009) were observed. Findings from the present study support that adults who experienced ACEs exhibit a reduced activation of the mPFC along with systemic vascular dysfunction. In addition, individuals exposed to more childhood traumatic events exhibited a progressively greater inactivation of the mPFC and an increased peripheral vasoconstriction in a dose-dependent manner. These findings provide novel insights into the potential role that the brain and the peripheral vasculature may have in connecting adverse childhood events to the increased risk of CVD.
Genomic signatures of the evolution of a diurnal lifestyle in Strigiformes
Authors: Espíndola-Hernández Pamela , Mueller Jakob C , Kempenaers Bart
Published: May 2022

Understanding the targets of selection associated with changes in behavioral traits represents an important challenge of current evolutionary research. Owls (Strigiformes) are a diverse group of birds, most of which are considered nocturnal raptors. However, a few owl species independently adopted a diurnal lifestyle in their recent evolutionary history. We searched for signals of accelerated rates of evolution associated with a diurnal lifestyle using a genome-wide comparative approach. We estimated substitution rates in coding and noncoding conserved regions of the genome of seven owl species, including three diurnal species. Substitution rates of the noncoding elements were more accelerated than those of protein-coding genes. We identified new, owl-specific conserved noncoding elements as candidates of parallel evolution during the emergence of diurnality in owls. Our results shed light on the molecular basis of adaptation to a new niche and highlight the importance of regulatory elements for evolutionary changes in behavior. These elements were often involved in the neuronal development of the brain.
Genome Assembly and Evolutionary Analysis of the Mandarin Duck Aix galericulata Reveal Strong Genome Conservation among Ducks
Authors: Ng Chen Siang , Lai Cheng-Kuo , Ke Huei-Mien , Lee Hsin-Han , Chen Chih-Feng , Tang Pin-Chi , Cheng Hsu-Chen , Lu Meiyeh J. , Li Wen-Hsiung , Tsai Isheng Jason
Published: May 2022

The mandarin duck, Aix galericulata, is popular in East Asian cultures and displays exaggerated sexual dimorphism, especially in feather traits during breeding seasons. We generated and annotated the first mandarin duck de novo assembly, which was 1.08 Gb in size and encoded 16,615 proteins. Using a phylogenomic approach calibrated with fossils and molecular divergences, we inferred that the last common ancestor of ducks occurred 13.3–26.7 Ma. The majority of the mandarin duck genome repetitive sequences belonged to the chicken repeat 1 (CR1) retroposon CR1-J2_Pass, which underwent a duck lineage-specific burst. Synteny analyses among ducks revealed infrequent chromosomal rearrangements in which breaks were enriched in LINE retrotransposons and DNA transposons. The calculation of the dN/dS ratio revealed that the majority of duck genes were under strong purifying selection. The expanded gene families in the mandarin duck are primarily involved in olfactory perception as well as the development and morphogenesis of feather and branching structures. This new reference genome will improve our understanding of the morphological and physiological characteristics of ducks and provide a valuable resource for functional genomics studies to investigate the feather traits of the mandarin duck.
Bidirectional Associations Between Adiposity and Cognitive Function: A Prospective Analysis of the Canadian Longitudinal Study on Aging (CLSA)
Authors: Nazmus Sakib Mohammad , Best John R , Ramezan Reza , Thompson Mary E , Hall Peter A
Published: May 2022

Background

Theoretical perspectives suggest that adiposity and cognitive function may be bidirectionally associated, but this has not been examined in a large-scale data set. The current investigation aims to fill this gap using a large, representative sample of middle-aged and older adults.

Methods

Using data from the Canadian Longitudinal Study on Aging (N = 25 854), the bidirectional hypothesis was examined with 3 indicators of cognitive function (ie, executive function, processing speed, and verbal fluency) and adiposity (ie, waist circumference [WC], body mass index [BMI], and total fat mass). We used multivariate multivariable regression and structural equation modeling to assess the prospective associations between adiposity and cognitive indicators.

Results

Analyses revealed that higher baseline WC was associated with higher Stroop interference at follow-up for both middle-aged (standardized estimate, β = 0.08, 95% confidence interval [CI] 0.06, 0.10) and older adults (β = 0.07, 95% CI 0.04, 0.09). Similarly, higher baseline Stroop interference was also associated with higher follow-up WC in middle-aged (β = 0.08, 95% CI 0.06, 0.10) and older adults (β = 0.03, 95% CI 0.01, 0.06). Effects involving semantic fluency and processing speed were less consistent. The earlier effects were similar to those observed using other adiposity indicators (eg, BMI and total fat mass) and were robust to adjustment for demographics and other cofounders, and when using latent variable modeling of the adiposity variable.

Conclusion

Evidence for a bidirectional relationship between adiposity and cognitive function exists, though the associations are most reliable for executive function and primarily evident at midlife.
Anti-inflammatory and Chondroprotective Effects of Platelet-derived Growth Factor-BB on Osteoarthritis Rat Models
Authors: Cai Yu , Wang Zhengchao , Liao Bokai , Sun Zhenxing , Zhu Pengfei
Published: May 2022

Osteoarthritis (OA) is a common and challenging joint disease that mainly affects the diarthrodial joints. Traditionally, except for surgery for severe cases, treatments for OA mainly focus on relieving pain and improving joint function. However, these treatments are not effective for cartilage repair and induce only symptomatic relief. Platelet-derived growth factor (PDGF)-BB, a member of the PDGF cytokine family, has been proved to have effects on protecting the chondrocytes via multiple mechanisms. In this study, we further focused on the effects of PDGF-BB on OA and found that PDGF-BB could attenuate OA development by inhibiting inflammation and enhancing cell proliferation via JAK2/STAT3, PI3K/AKT, and p38 signaling pathways and PKA-mediated regulation of SOX-9/RunX-2. This article demonstrates the feasibility of PDGF-BB application as a treatment for OA. This is the first article that reports that PDGF-BB attenuates OA development via PKA-mediated regulation of SOX-9 and RunX-2.
The WALLET Study: Examining Early Memory Loss and Personal Finance
Authors: Lichtenberg Peter A , Tarraf Wassim , Rorai Vanessa O , Roling Matthew , Moray Juno , Gross Evan Z , Boyle Patricia A
Published: May 2022

Background and Objectives

This feasibility study tests a new approach for assessing personal finance in older persons with early memory loss. The project examines 2 primary outcomes that gauge the financial viability and well-being of older adults: wealth loss and financial exploitation. The overall objective is to determine the association of financial literacy and management, financial decision-making, and cognition with wealth loss and financial exploitation.

Research Design and Methods

This cross-sectional study recruited 46 participants who were 60 years of age or older. Participants were classified as having mild cognitive impairment, perceived cognitive impairment, or no cognitive impairment. The study coordinator arranged with each participant to obtain copies of their main checking account statements for 12 consecutive months within the previous 2 years and, if appropriate, credit card statements. All statements were de-identified and assigned a random ID number. Participants then completed 2 telephone interviews.

Results

The average participant age was 72 years (standard deviation [SD] = 7.7); 84% were female, 39% White, and 35% currently married. Average education was 16.2 years (SD = 2.4); mean yearly household income was almost $42,000 (SD = 25,752); and monthly social security payments averaged $1,446 (SD = 1,244). Our results indicate that the methods used to analyze checking account statements, followed by telephone interviews to verify identified trends, were useful in developing a financial behavior index to measure wealth loss.

Discussion and Implications

We demonstrate an alternative method for assessing personal finance using person-centered principles, which we believe are critical in the presence of diminished or impaired cognition. Our findings offer an innovative method for assessing the risk for wealth loss and financial exploitation.
Do Latino Older Adults and Service Providers Agree on Positive Aging? Using Concept Mapping to Compare Perspectives
Authors: Piedra Lissette M , Howe Melissa J K , Ridings John , Gutwein Melissa
Published: May 2022

Background and Objectives

In the United States, Latino adults are a growing segment of the aging population who will need research-informed interventions to help them age successfully. Arguably, how Latino older adults and service providers understand “positive aging” serves as an important precursor for the cultivation of such interventions. This investigation explored whether Latino older adults’ conceptualizations of positive aging aligned with those of service providers.

Research Design and Methods

We compared how Latino older adults (n = 93) and service providers (n = 45) rated 85 positive aging statements produced by Latino older adults. These 85 items were used to generate a concept map, which displays those items thematically by clusters and overarching regions of meaning.

Results

We found divergences at each level of the map—statements, clusters, and regions—which illuminate differences between how service providers and Latino older adults think about Latino positive aging. For example, whereas Latino older adults prioritized the cluster containing items related to internal well-being, service providers rated it seventh of 11 clusters. The region comprising clusters related to relationships garnered the highest agreement between groups, but also a notable departure; compared to Latino older adults, service providers rated community and social involvement as less important.

Discussion and Implications

Understanding such differences can help providers tailor services consistent with the interests of Latino older adults. Future studies should examine the extent to which stakeholders believe various aspects of positive aging are modifiable.
Genotype–phenotype correlation of T-cell subtypes reveals senescent and cytotoxic genes in Alzheimer’s disease
Authors: Dressman Dallin , Buttrick Thomas , Cimpean Maria , Bennett David , Menon Vilas , Bradshaw Elizabeth M , Vardarajan Badri , Elyaman Wassim
Published: May 2022

Recent studies identifying expression quantitative trait loci (eQTLs) in immune cells have uncovered important links between disease risk alleles and gene expression trends in monocytes, T cells and other cell types. However, these studies are generally done with young, healthy subjects, limiting the utility of their findings for age-related conditions such as Alzheimer’s disease (AD). We have performed RNA sequencing on four T-cell subsets in genome-wide genotyped and well-characterized AD subjects and age- and sex-matched controls from the Religious Orders Study/Memory and Aging Project. We correlated gene expression data with AD neuropathological traits and with single-nucleotide polymorphisms to detect eQTLs. We identified several significant genes involved in T-cell senescence and cytotoxicity, consistent with T-cell RNA sequencing studies in aged/AD cohorts. We identified unexpected eQTLs previously associated with neuropsychiatric disease traits. Finally, we discovered that pathways related to axon guidance and synaptic function were enriched among trans-eQTLs in coding regions of the genome. Our data strengthen the potential link between T-cell senescence and age-related neurodegenerative disease. In addition, our eQTL data suggest that T-cell phenotypes may influence neuropsychiatric disorders and can be influenced by genes involved in neurodevelopmental processes.
Fertilization signatures as biomarkers of embryo quality
Authors: Coticchio Giovanni , Borini Andrea , Zacà Carlotta , Makrakis Evangelos , Sfontouris Ioannis
Published: May 2022

Fertilization underpins the vital transition from gametic meiosis to embryonic mitosis. For decades, in human IVF, microscopic observation at a single time point has limited our appreciation of the morphokinetic complexity of this process. More recently, the introduction of time lapse technology—also enhanced by combination with artificial intelligence—has revealed the finest morphokinetic details of the beginning of human development. Overall, a picture has finally emerged in which the precise timing, morphology and geometry of several fertilization events offer clues to predict the fate of the embryo—a key aspect of assisted reproduction. In this scenario, correct unfolding of intra- and interpronuclear rearrangements emerge as a crucial factor to create a platform able to preserve genetic and cellular integrity at the first mitotic cleavage.
Na+/K+ ATPase α1 and β3 subunits are localized to the basolateral membrane of trophectoderm cells in human blastocysts
Authors: Hirakawa T , Goto M , Takahashi K , Iwasawa T , Fujishima A , Makino K , Shirasawa H , Sato W , Sato T , Kumazawa Y , Terada Y
Published: May 2022

STUDY QUESTION

Is there a relation between specific Na+/K+ ATPase isoform expression and localization in human blastocysts and the developmental behavior of the embryo?

SUMMARY ANSWER

Na+/K+ ATPase α1, β1 and β3 are the main isoforms expressed in human blastocysts and no association was found between the expression level of their respective mRNAs and the rate of blastocyst expansion.

WHAT IS KNOWN ALREADY

In mouse embryos, Na+/K+ ATPase α1 and β1 are expressed in the basolateral membrane of trophectoderm (TE) cells and are believed to be involved in blastocoel formation (cavitation).

STUDY DESIGN, SIZE, DURATION

A total of 20 surplus embryos from 11 patients who underwent IVF and embryo transfer at a university hospital between 2009 and 2018 were analyzed.

PARTICIPANTS/MATERIALS, SETTING, METHODS

After freezing and thawing Day 5 human blastocysts, their developmental behavior was observed for 24 h using time-lapse imaging, and the expression of Na+/K+ ATPase isoforms was examined using quantitative RT-PCR (RT-qPCR). The expressed isoforms were then localized in blastocysts using fluorescent immunostaining.

MAIN RESULTS AND THE ROLE OF CHANCE

RT-qPCR results demonstrated the expression of Na+/K+ ATPase α1, β1 and β3 isoforms in human blastocysts. Isoforms α1 and β3 were localized to the basolateral membrane of TE cells, and β1 was localized between TE cells. A high level of β3 mRNA expression correlated with easier hatching (P = 0.0261).

LARGE SCALE DATA

N/A.

LIMITATIONS, REASONS FOR CAUTION

The expression of mRNA and the localization of proteins of interest were verified, but we have not been able to perform functional analysis.

WIDER IMPLICATIONS OF THE FINDINGS

Of the various Na+/K+ ATPase isoforms, expression levels of the α1, β1 and β3 mRNAs were clearly higher than other isoforms in human blastocysts. Since α1 and β3 were localized to the basolateral membrane via fluorescent immunostaining, we believe that these subunits contribute to the dilation of the blastocoel. The β1 isoform is localized between TE cells and may be involved in tight junction formation, as previously reported in mouse embryos.

STUDY FUNDING/COMPETING INTEREST(S)

This work was supported by the JSPS KAKENHI (https://www.jsps.go.jp/english/index.html), grant number 17K11215. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no conflicts of interest.
A single-centre, retrospective study of mid-term outcomes of aortic arch repair using a standardized resection and patch augmentation technique
Authors: Patukale Aditya , Shikata Fumiaki , Marathe Shilpa S , Patel Pervez , Marathe Supreet P , Colen Timothy , Venugopal Prem ,   QPCR Group, Suna Jessica , Betts Kim , Karl Tom R , Johnson Janelle , Versluis Kathryn , Alphonso Nelson
Published: May 2022

OBJECTIVES

The aim of this study was to evaluate the mid-term outcomes after the repair of aortic arch using a standard patch augmentation technique.

METHODS

The study included all patients who underwent repair of a hypoplastic/interrupted aortic arch (IAA) in a single institute from June 2012 to December 2019 by a standardized patch augmentation (irrespective of concomitant intra-cardiac lesions). End points evaluated were reintervention for arch obstruction and persistent/new-onset hypertension.

RESULTS

The study included 149 patients [hypoplastic aortic arch, n = 92 (62%), IAA, n = 9 (6%), Norwood procedure, n = 48 (32%)]. The patch material used for augmentation of the aortic arch included pulmonary homograft (n = 120, 81%), homograft pericardium (n = 18, 12%), CardioCel® (n = 9, 6%) and glutaraldehyde-treated autologous pericardium (n = 2, 1%). The median age and weight at surgery were 7 days [interquartile range (IQR) 5–17 days] and 3.5 kg (IQR 3–3.9 kg), respectively. The median follow-up was 3.27 years (IQR 1.28, 5.08), range (0.02, 8.76). Freedom from reintervention at 1, 3 and 5 years was 95% [95% confidence interval (CI) = 89%, 98%], 93% (95% CI = 86%, 96%) and 93% (95% CI = 86%, 96%) respectively. One patient (0.6%) had persistent hypertension 8 years after correction for interrupted arch with truncus arteriosus.

CONCLUSIONS

Repair of hypoplastic/IAA by transection and excision of all ductal tissue and standardized patch augmentation provide good mid-term durability. The freedom from reintervention at 5 years is >90%. The incidence of persistent systemic hypertension following arch reconstruction is low. The technique is reproducible and applicable irrespective of underlying arch anatomy.
Early and late results of mitral valve repair with anterior leaflet patch augmentation
Authors: Kehara Hiromu , Minakata Kenji , McCarthy James , Sunagawa Gengo , Mangukia Chirantan , Brann Stacey , Zhao Huaqing , Boova Robert , Toyoda Yoshiya
Published: May 2022

OBJECTIVES

The aim of this study was to determine the long-term results of mitral valve (MV) repair with anterior leaflet patch augmentation.

METHODS

Between 2012 and 2015, 45 patients underwent MV repair using the anterior leaflet patch augmentation technique at our institution. The mean age of the patients was 65.9 ± 13.0 years (16 males). We reviewed the MV pathology and the surgical techniques used and assessed the early and late results.

RESULTS

In terms of MV pathology, 43 patients (95.6%) had pure mitral regurgitation (MR) and 2 patients (4.4%) had mixed mitral stenosis and MR. Rheumatic changes were seen in 18 patients (40.0%). Postoperative echocardiography showed that 95.6% of patients had none to mild MR. During a median follow-up period of 5.5 years (range 0.1–8.3 years), there were 8 late deaths. Nine patients (20%) required reoperation. The mean interval between the initial operation and redo operation was 3.7 ± 3.1 years (range: 0.4–7.8 years). The causes of reoperation included patch dehiscence (n = 4), progression of mitral stenosis (n = 2), band dehiscence (n = 1), patch enlargement (n = 1) and unknown (n = 1). Eight patients underwent MV replacement and 1 underwent repeat MV repair. The freedom from reoperation at 3 and 5 years was 85.7 ± 6.7% and 81.2 ± 7.7%, respectively.

CONCLUSIONS

Anterior leaflet patch augmentation can provide excellent early results in the majority of the patients even in the presence of rheumatic pathology; however, we observed late reoperation in 20% of patients. Thus, this technique should be used with caution and careful follow-up with serial echocardiography is essential.
Normothermic blood polarizing versus depolarizing cardioplegia in a porcine model of cardiopulmonary bypass
Authors: Kramer Anne-Margarethe , Kiss Attila , Heber Stefan , Chambers David J , Hallström Seth , Pilz Patrick M , Podesser Bruno K , Santer David
Published: May 2022

OBJECTIVES

We have previously demonstrated beneficial cardiac protection with hypothermic polarizing cardioplegia compared to a hyperkalemic depolarizing cardioplegia. In this study, a porcine model of cardiopulmonary bypass was used to compare the protective effects of normothermic blood-based polarizing and depolarizing cardioplegia during cardiac arrest.

METHODS

Thirteen pigs were randomized to receive either normothermic polarizing (n = 8) or depolarizing (n = 5) blood-based cardioplegia. After initiation of cardiopulmonary bypass, normothermic arrest (34°C, 60 min) was followed by 60 min of on-pump and 90 min of off-pump reperfusion. Primary outcome was myocardial injury measured as arterial myocardial creatine kinase concentration. Secondary outcome was haemodynamic function and the energy state of the hearts.

RESULTS

During reperfusion, release of myocardial creatine kinase was comparable between groups (P = 0.36). In addition, most haemodynamic parameters showed comparable results between groups, but stroke volume (P = 0.03) was significantly lower in the polarizing group. Adenosine triphosphate levels were significantly (18.41 ± 3.86 vs 22.97 ± 2.73 nmol/mg; P = 0.03) lower in polarizing hearts, and the requirement for noradrenaline administration (P = 0.002) and temporary pacing (6 vs 0; P = 0.02) during reperfusion were significantly higher in polarizing hearts.

CONCLUSIONS

Under normothermic conditions, polarizing blood cardioplegia was associated with similar myocardial injury to depolarizing blood cardioplegia. Reduced haemodynamic and metabolic outcome and a higher need for temporary pacing with polarized arrest may be associated with the blood-based dilution of this solution.
Functional Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Variants in Children With Coronavirus Disease 2019, Multisystem Inflammatory Syndrome in Children, and After Two Doses of BNT162b2 Vaccination
Authors: Rostad Christina A , Chen Xuemin , Sun He ying , Hussaini Laila , Lu Austin , Perez Maria A , Hsiao Hui Mien , Anderson Larry J , Anderson Evan J
Published: May 2022

Background

Although neutralizing antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) correlate with protection against coronavirus disease 2019 (COVID-19), little is known about the neutralizing and antibody-dependent cell-mediated cytotoxicity (ADCC) responses to COVID-19, multisystem inflammatory syndrome in children (MIS-C), and COVID-19 vaccination in children.

Methods

We enrolled children 0–21 years of age with a history of COVID-19 (n = 13), MIS-C (n = 13), or 2 doses of BNT162b2 vaccination (n = 14) into a phlebotomy protocol. We measured pseudovirus neutralizing and functional ADCC antibodies to SARS-CoV-2 variants, including Omicron (B.1.1.529).

Results

The primary BNT162b2 vaccination series elicited higher neutralizing and ADCC responses with greater breadth to SARS-CoV-2 variants than COVID-19 or MIS-C, although these were diminished against Omicron.

Conclusions

Serologic responses were significantly reduced against variants, particularly Omicron.
Heterogeneity in Staphylococcus aureus Bacteraemia Clinical Trials Complicates Interpretation of Findings
Authors: Dolby Heather W , Clifford Sarah A , Laurenson Ian F , Fowler Vance G , Russell Clark D
Published: May 2022

We systematically evaluated randomized-controlled trials (RCTs) for Staphylococcus aureus bacteremia (SAB). There was intertrial heterogeneity in cohort characteristics, including bacteremia source, complicated SAB, and comorbidities. Reporting of cohort characteristics was itself variable, including bacteremia source and illness severity. Selection bias was introduced by exclusion criteria relating to comorbidities, illness severity, infection types, and source control. Mortality was lower in RCT control arms compared with observational cohorts. Differences in outcome definitions impedes meta-analysis. These issues complicate the interpretation and application of SAB RCT results. The value of these trials should be maximized by a standardized approach to recruitment, definitions, and reporting.
The Arabidopsis Framework Model version 2 predicts the organism-level effects of circadian clock gene mis-regulation
Authors: Chew Yin Hoon , Seaton Daniel D , Mengin Virginie , Flis Anna , Mugford Sam T , George Gavin M , Moulin Michael , Hume Alastair , Zeeman Samuel C , Fitzpatrick Teresa B , Smith Alison M , Stitt Mark , Millar Andrew J
Published: May 2022

Predicting a multicellular organism’s phenotype quantitatively from its genotype is challenging, as genetic effects must propagate across scales. Circadian clocks are intracellular regulators that control temporal gene expression patterns and hence metabolism, physiology and behaviour. Here we explain and predict canonical phenotypes of circadian timing in a multicellular, model organism. We used diverse metabolic and physiological data to combine and extend mathematical models of rhythmic gene expression, photoperiod-dependent flowering, elongation growth and starch metabolism within a Framework Model for the vegetative growth of Arabidopsis thaliana, sharing the model and data files in a structured, public resource. The calibrated model predicted the effect of altered circadian timing upon each particular phenotype in clock-mutant plants under standard laboratory conditions. Altered night-time metabolism of stored starch accounted for most of the decrease in whole-plant biomass, as previously proposed. Mobilization of a secondary store of malate and fumarate was also mis-regulated, accounting for any remaining biomass defect. The three candidate mechanisms tested did not explain this organic acid accumulation. Our results link genotype through specific processes to higher-level phenotypes, formalizing our understanding of a subtle, pleiotropic syndrome at the whole-organism level, and validating the systems approach to understand complex traits starting from intracellular circuits.
Oridonin suppresses particulate-induced NLRP3-independent IL-1α release to prevent crystallopathy in the lung
Authors: Ikoma Kenta , Takahama Michihiro , Kimishima Atsushi , Pan Yixi , Taura Manabu , Nakayama Akiyoshi , Arai Masayoshi , Takemura Naoki , Saitoh Tatsuya
Published: May 2022

The human body is exposed to various particulates of industrial, environmental, or endogenous origin. Invading or intrinsic particulates can induce inflammation by aberrantly activating the immune system, thereby causing crystallopathies. When immune cells such as macrophages phagocytose the particulates, their phagolysosomal membranes undergo mechanical damage, eventually leading to pyroptotic cell death accompanied by the release of inflammatory cytokines, including interleukin (IL)-1α and IL-1β. The nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is responsible for particulate-induced IL-1β release and is therefore regarded as a potential therapeutic target for inflammation-mediated crystallopathies. However, IL-1α is released after particulate stimulation in an NLRP3 inflammasome-independent manner and plays a critical role in disease development. Therefore, drugs that exert potent anti-inflammatory effects by comprehensively suppressing particulate-induced responses, including IL-1β release and IL-1α release, should be developed. Here, we found that oridonin, a diterpenoid isolated from Isodon japonicus HARA, strongly suppressed particulate-induced cell death, accompanied by the release of IL-1α and IL-1β in mouse and human macrophages. Oridonin reduced particulate-induced phagolysosomal membrane damage in macrophages without affecting phagocytosis of particulates. Furthermore, oridonin treatment markedly suppressed the symptoms of silica particle-induced pneumonia, which was attributed to the release of IL-1α independently of NLRP3. Thus, oridonin is a potential lead compound for developing effective therapeutics for crystallopathies attributed to NLRP3-dependent as well as NLRP3-independent inflammation.
Sustaining Capitalism and Democracy: Lessons from Global Competition Policy
Authors: Allen Michael O , Scheve Kenneth
Published: May 2022

Competition policy has been a central forum for contesting the uneasy relationship between capitalism and democracy since the late nineteenth century. From the earliest policy debates, concerns that robust competition policies aimed at limiting economic concentration would disadvantage domestic producers featured prominently. This dynamic creates an international cooperation problem over competition policy that has intensified with the dramatic increases in globalization over the last several decades. Understanding the causes and consequences of this cooperation problem is central to understanding global governance of the world economy, including the ability of democratic states to manage global capitalism in a manner that sustains democracy. This essay frames the challenge that global competition policy has posed over the last hundred years and argues that democratic major powers have played a critical role in shaping the limited cooperation that has been achieved. A research agenda that develops integrated theories of domestic and international competition policymaking as well as a multi-method empirical agenda for describing and explaining policy outcomes and their consequences for economic inequality, growth, and democracy is an essential task for international relations scholars.
Rediscovering Epistemic Coalitions Twenty Years Later: Using the International Olympic Committee to Build toward A Literature on Epistemic Institutionalism
Authors: Espino Giuliano
Published: May 2022

This article aims to help the literature on global governance and international professionalism move beyond a myopic focus on epistemic communities by unpacking the underutilized term epistemic coalition. Epistemic coalitions are an international nonstate actor that employ a broadened notion of expertise to incorporate business and political advocates alongside technical experts. I differentiate epistemic coalitions from epistemic communities by synthesizing the international relations, organizational theory, and public policy literatures. These organizations differ in the breadth of their policy agendas, dynamics of internal cohesion, and capabilities to engage in global policy transfer. However, I note that it is still unclear how epistemic coalitions coordinate member action along different professions and what are the conditions under which epistemic coalitions’ membership balances will be viewed by national elites as professionally legitimate. I then examine the role of the International Olympic Committee in US steroid policy to induce two preliminary hypotheses that can potentially address these gaps. First, epistemic coalitions use a foundational narrative to coordinate action among professions. Second, perceptions of equitable membership balance stem from an ideational congruence between national and international elites. I conclude with how these hypotheses can be tested in the future.
Trends in human intestinal carriage of ESBL- and carbapenemase-producing Enterobacterales among food handlers in Tunisia: emergence of C1-M27-ST131 subclades, blaOXA-48 and blaNDM
Authors: Sallem Nesrine , Hammami Adnene , Mnif Basma
Published: May 2022

Objectives

To determine the prevalence of community intestinal carriage of ESBL-producing Enterobacterales (ESBL-E), acquired-AmpC-producing Enterobacterales (aAmpC-E) and carbapenemase-producing Enterobacterales (CPE) in Tunisia.

Methods

From November 2012 to September 2017, stool samples from food handlers in Sfax, Tunisia, were screened for ESBL-E, AmpC-E and CPE using antibiotic-containing media. The genes encoding these β-lactamases were characterized by PCR, sequencing, and transfer assays. ST131 clonal groups were detected by PCR and characterized for antibiotic resistance, virulence genes and PFGE patterns.

Results

Of 2135 participants, ESBL-E, aAmpC-E, and CPE carriage were detected in 419 (19.63%), 35 (1.63%) and 7 (0.33%) participants, respectively. CTX-M-15 (60%), CTX-M-1 (16.8%) and CTX-M-27 (12.8%) were the most common ESBL determinants. The ESBL-E carriage was significantly higher in summer (33%) and autumn (25.7%) than in winter (12.1%) and spring (11.4%). ST131 was detected in 50 (13.2%) of the 378 ESBL-producing Escherichia coli isolates; most of them (35; 70%) belonged to subclade C1 (cluster C1-M27: 23 isolates, 46%; cluster C1-non-M27: 12 isolates, 24%) followed by those belonging to subclade C2 (11; 22%). Although subclade C2 isolates, all harbouring blaCTX-M-15, had the highest resistance rates and virulence factor and addiction system scores, the subclade C1 isolates, mainly harbouring blaCTX-M-27 (94%), were predominant since 2015. The most frequently detected carbapenemase-encoding gene was blaOXA-48-like (85%) and acquired AmpC-encoding genes were blaDHA-1 (54%) and blaCMY-2 (46%).

Conclusions

This is the first large Tunisian study to reveal a high faecal ESBL carriage rate, a low CPE carriage rate, and the predominance of CTX-M-27-producing subclade C1 among faecal ESBL-ST131 isolates in the Tunisian community.
Critical loss in market definition: methods and court decisions
Authors: Coate Malcolm B , Ulrick Shawn W , Yun John M
Published: May 2022

Critical loss analysis is an empirical tool used to define relevant markets in antitrust law. The existence of two different critical loss methodologies, however, complicates its application. Harris and Simons introduced the first approach, which focused on evaluating the market-level effect of a small, but significant and non-transitory increase in price (‘SSNIP’). Later, O’Brien and Wickelgren, along with Katz and Shapiro, introduced a firm-level approach to critical loss to derive a test that applies mathematical models of demand systems, foundationally based on a single-firm SSNIP, to proxy for a market-level price increase. A critical loss controversy evolved as the two tests can, but do not necessarily, generate different relevant markets. This article examines the choice between the two methods, reviews recent court decisions, and guides practitioners and courts as to when each approach makes the most sense.
Relationship between electronic health records strategy and user satisfaction: a longitudinal study using clinicians’ online reviews
Authors: Srivastava Ankita , Ayyalasomayajula Surya , Bao Chenzhang , Ayabakan Sezgin , Delen Dursun
Published: May 2022

Objective

We investigated how the electronic health records (EHRs) strategies concerning EHR sourcing and vendor switching impact user satisfaction over time.

Materials and Methods

This study used a novel longitudinal dataset created by scraping clinicians’ Glassdoor.com reviews on 109 US health systems from 2012 to 2017 and combining it with the Healthcare Information and Management Systems Society (HIMSS) database. We performed sentiment analysis of clinician reviews to construct our main dependent variable, user satisfaction. Our main independent variables, EHR single sourcing and vendor switching, were constructed using the HIMSS database.

Results

Our fixed effects model showed that as health systems gain more experience with EHR, a single vendor sourcing strategy was associated with higher user satisfaction. Further, there was no significant impact of vendor switching on user satisfaction.

Conclusion

This work adds to the current understanding of EHR-driven clinician burnout using a novel longitudinal dataset. We show how organizational-level EHR strategy can impact user satisfaction and that providers and EHR vendors can mine clinician reviews online to understand their evolving needs and sentiments.
Evaluation of an online text simplification editor using manual and automated metrics for perceived and actual text difficulty
Authors: Leroy Gondy , Kauchak David , Haeger Diane , Spegman Douglas
Published: May 2022

Objective

Simplifying healthcare text to improve understanding is difficult but critical to improve health literacy. Unfortunately, few tools exist that have been shown objectively to improve text and understanding. We developed an online editor that integrates simplification algorithms that suggest concrete simplifications, all of which have been shown individually to affect text difficulty.

Materials and Methods

The editor was used by a health educator at a local community health center to simplify 4 texts. A controlled experiment was conducted with community center members to measure perceived and actual difficulty of the original and simplified texts. Perceived difficulty was measured using a Likert scale; actual difficulty with multiple-choice questions and with free recall of information evaluated by the educator and 2 sets of automated metrics.

Results

The results show that perceived difficulty improved with simplification. Several multiple-choice questions, measuring actual difficulty, were answered more correctly with the simplified text. Free recall of information showed no improvement based on the educator evaluation but was better for simplified texts when measured with automated metrics. Two follow-up analyses showed that self-reported education level and the amount of English spoken at home positively correlated with question accuracy for original texts and the effect disappears with simplified text.

Discussion

Simplifying text is difficult and the results are subtle. However, using a variety of different metrics helps quantify the effects of changes.

Conclusion

Text simplification can be supported by algorithmic tools. Without requiring tool training or linguistic knowledge, our simplification editor helped simplify healthcare related texts.
Optimization of Solid-Phase Extraction of a Degradation Product of Novichok (A234) and Its Application to Environmental Samples
Authors: Lee Jin Young , Shin Ji Young , Kim Hyun Suk
Published: May 2022

There have been no detailed investigations regarding solid-phase-extraction (SPE) optimization and screening for the degradation products of ethyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A234) in various environmental samples. Therefore, as a first step in the selective SPE of the degradation products of A234, we optimized the SPE adsorption and extraction parameters for the A234 degradation product ethylhydrogen (1-(diethylamino)ethylidene)phosphoramidate (cpd 1). Among various SPE cartridges, the Si cartridge (500 mg, 3 mL) selectively extracted cpd 1 using an elution volume of 4 mL of 25% H2O in acetonitrile, which eliminated most interference without cpd 1 loss during loading and washing. In addition, the sorbent capacity is also critical in the adsorption of cpd 1. The Si cartridge (500 mg, 3 mL) retained cpd 1 in the concentration range 1–10 µg/mL. The linearity of detector response of cpd 1 in deionized H2O was studied in the range of 1.0–100 ng/mL and showed good linearity with γ2 ranging from 0.9979 to 0.996. The limits of detection for cpd 1 are 10 ng/mL in the product-scan mode and 100 ng/mL in the full-scan mode. Also, after we optimized the SPE method, we validated the precision and accuracy of the Si-cartridge extraction method in real soil samples with diverse concentrations. The precision ranged from 2.5% to 5.3%. This newly developed SPE is applicable to the analysis of a degradation product of Novichok A234 in various environmental matrices, such as water, soil and sand, in the Organization for the Prohibition of Chemical Weapons (OPCW) proficiency test and unknown samples collected from suspected sites.
Polyamines produced by an extreme thermophile are essential for cell growth at high temperature
Authors: Sakamoto Akihiko , Tamakoshi Masatada , Moriya Toshiyuki , Oshima Tairo , Takao Koichi , Sugita Yoshiaki , Furuchi Takemitsu , Niitsu Masaru , Uemura Takeshi , Igarashi Kazuei , Kashiwagi Keiko , Terui Yusuke
Published: May 2022

An extreme thermophile, Thermus thermophilus grows at an optimum temperature of around 70°C and produces 16 different polyamines including long-chain and branched-chain polyamines. We found that the composition of polyamines in the thermophile cells changes with culture temperature. Long-chain and branched-chain polyamines (unusual polyamines) were increased in the cells grown at high temperature such as 80°C, but they were minor components in the cells grown at relatively lower temperature such as 60°C. The effects of polyamines on cell growth were studied using T. thermophilus HB8 ΔspeA deficient in arginine decarboxylase. Cell growth of this mutant strain was significantly decreased at 70°C. This mutant strain cannot produce polyamines and grows poorly at 75°C. It was also determined whether polyamines are directly involved in protecting DNA from DNA double-strand breaks (DSBs) induced by heat. Polyamines protected DNA against double-strand breaks. Therefore, polyamines play essential roles in cell growth at extremely high temperature through maintaining a functional conformation of DNA against DSBs and depurination.
Radiologic-Pathologic Correlation of Fibroepithelial Lesions: A Pictorial Review
Authors: Zhang Meng , Compton Lindsay , Hwang Helena , Hayes Jody C
Published: May 2022

Fibroepithelial lesions (FEL) of the breast encompass a spectrum of masses ranging from benign to malignant. Although these lesions are on the same biologic spectrum, differences in their clinical behaviors necessitate different management approaches. While imaging features are nonspecific, small size (less than 3 cm), oval shape, circumscribed margins, growth in diameter less than 20% in six months, and homogeneous echotexture on US favor fibroadenoma (FA). Conversely, larger size (3 cm or larger), rapid growth, irregular shape, noncircumscribed margins, and heterogeneous echotexture suggest possible phyllodes tumor (PT). Histopathologically, increased stromal cellularity, stromal atypia, and mitotic activity characterize PT, while FA typically lack these features. In this review, we summarize the imaging and pathology characteristics of nonmalignant FEL, including simple, juvenile, and complex FA, and benign and borderline PT and highlight the collaborative role of radiologists and pathologists in informing diagnosis and clinical management.
Hiding in Plain Sight: An Abundant and Widespread North American Horse Fly (Diptera: Tabanidae) in the Tabanus sulcifrons Group, Tabanus variegatus Fabricius, Redescribed
Authors: Mullens Bradley A , Trout Fryxell Rebecca , Masonick Paul K , Yanega Douglas A , Davis Travis M
Published: May 2022

Tabanus variegatus F. 1805 has been called by the name Tabanus sulcifronsMacquart 1855 for over 80 yr; T. variegatus is one of the most common large horse flies attacking livestock in much of the southeastern U.S. Morphological, ecological, and molecular evidence indicates that T. variegatus is a distinct species, and we redescribe the female and describe the male. The Fabricius holotype, heavily damaged after over nearly 220 yr, is nevertheless taxonomically sound. Morphology (size, color, palp shape, and r5 wing cell shape) can usually distinguish T. variegatus from T. sulcifrons, but some specimens remain difficult to separate, especially in and west of the Mississippi River Valley. Using geometric morphometric analyses of the wing vein arrangement and palp shape the two species are significantly different. The wings of T. variegatus females also have more microsetae and sometimes a “frosty” appearance. Where they are common and sympatric, as in eastern Tennessee, they are temporally separated such that T. variegatus flies later (August-October) than T. sulcifrons (June-August), minimizing opportunity for gene flow. Museum specimens allow the approximate range of T. variegatus to be compared with that of T. sulcifrons s.l.; T. variegatus is particularly abundant from the coast of the Carolinas and Georgia east to central Tennessee and south to about central Alabama. DNA evidence (COI gene) recovers T. variegatus and T. sulcifrons s.s. in separate clades. Further studies on the T. sulcifrons complex are needed to fully resolve the range of both species, assess the degree of genetic substructuring, and examine relationships with other members of the T. sulcifrons complex.
Effect of Larval Diets on House Fly (Diptera: Muscidae) Production and Host Suitability for a Pupal House Fly Parasitoid (Spalangia gemina) (Hymenoptera: Pteromalidae)
Authors: Ardburi Waranya , Tangkawanit Ubon
Published: May 2022

A larval medium for house fly (Musca domestica L.) suitable for house fly parasitoid production was developed from locally available and inexpensive food ingredients. Biological parameters and life table parameters were estimated for house flies treated with five different diets. It was found that percentage survival of 1st–3rd instar larvae of house fly, percentage of pupation, percentage of hatching adults, growth index, and life table parameters (net reproductive rate [R0] the cohort generation time [T], intrinsic rate of increase [r], and finite rate of increase [λ]) were significantly highest on larvae produced on diet 5 (composed of rice barn and chicken feed). Diet composition and performance of house fly larvae in larval medium are discussed, based on the results. The results of Spalangia gemina Bouček (Hymenoptera, Pteromalidae) parasitization on house fly pupae revealed that the number of total parasitized pupa and number of parasitoids hatched from pupa reared with diet 5 (rice bran and chicken feed) were greater than with diet 1 (rice bran, powdered milk, dry yeast, fish meal, soybean meal, and chicken feed). Additionally, S. gemina offspring from diet 5 treatment had a higher proportion of females. Our results indicated that pupal size resulting from larval diet was an important factor for parasitization.
A functional platform for remote use of electron microscopes using web conferencing systems
Authors: Sugiura-Nakazato Makoto , Takase Hiroshi , Nakazato Takeru
Published: May 2022

We propose a useful system for remote sharing of transmission electron microscope (TEM) images by connecting three computers: a computer connected to a TEM, a computer distributing images and a computer receiving images. Then, we confirmed the performance of three web conferencing systems, Microsoft Teams, Zoom and Google Meet, to evaluate the usefulness of their remote use based on the clarity of images, smoothness of movement and time lag in images on each computer in the system. Display image of operation computer for TEM can be captured using the following two methods: a virtual camera of a video distribution software that provided a good reaction speed to transfer images and the screen sharing by conference system software that could share high-quality images.