bluuebunny/crossref_metadata_2025 huggingface dataset:
The evening complex promotes maize flowering and adaptation to temperate regions
Authors: Zhao Yongping , Zhao Binbin , Xie Yurong , Jia Hong , Li Yongxiang , Xu Miaoyun , Wu Guangxia , Ma Xiaojing , Li Quanquan , Hou Mei , Li Changyu , Xia Zhanchao , He Gang , Xu Hua , Bai Zhijing , Kong Dexin , Zheng Zhigang , Liu Qing , Liu Yuting , Zhong Jinshun , Tian Feng , Wang Baobao , Wang Haiyang
Published: September 2022

Maize (Zea mays) originated in southern Mexico and has spread over a wide latitudinal range. Maize expansion from tropical to temperate regions has necessitated a reduction of its photoperiod sensitivity. In this study, we cloned a quantitative trait locus (QTL) regulating flowering time in maize and show that the maize ortholog of Arabidopsis thaliana EARLY FLOWERING3, ZmELF3.1, is the causal locus. We demonstrate that ZmELF3.1 and ZmELF3.2 proteins can physically interact with ZmELF4.1/4.2 and ZmLUX1/2, to form evening complex(es; ECs) in the maize circadian clock. Loss-of-function mutants for ZmELF3.1/3.2 and ZmLUX1/2 exhibited delayed flowering under long-day and short-day conditions. We show that EC directly represses the expression of several flowering suppressor genes, such as the CONSTANS, CONSTANS-LIKE, TOC1 (CCT) genes ZmCCT9 and ZmCCT10, ZmCONSTANS-LIKE 3, and the PSEUDORESPONSE REGULATOR (PRR) genes ZmPRR37a and ZmPRR73, thus alleviating their inhibition, allowing florigen gene expression and promoting flowering. Further, we identify two closely linked retrotransposons located in the ZmELF3.1 promoter that regulate the expression levels of ZmELF3.1 and may have been positively selected during postdomestication spread of maize from tropical to temperate regions during the pre-Columbian era. These findings provide insights into circadian clock-mediated regulation of photoperiodic flowering in maize and new targets of genetic improvement for breeding.
Conserved noncoding sequences and de novo Mutator insertion alleles are imprinted in maize
Authors: Li Tong , Yin Liangwei , Stoll Claire E , Lisch Damon , Zhao Meixia
Published: September 2022

Genomic imprinting is an epigenetic phenomenon in which differential allele expression occurs in a parent-of-origin-dependent manner. Imprinting in plants is tightly linked to transposable elements (TEs), and it has been hypothesized that genomic imprinting may be a consequence of demethylation of TEs. Here, we performed high-throughput sequencing of ribonucleic acids from four maize (Zea mays) endosperms that segregated newly silenced Mutator (Mu) transposons and identified 110 paternally expressed imprinted genes (PEGs) and 139 maternally expressed imprinted genes (MEGs). Additionally, two potentially novel paternally suppressed MEGs are associated with de novo Mu insertions. In addition, we find evidence for parent-of-origin effects on expression of 407 conserved noncoding sequences (CNSs) in maize endosperm. The imprinted CNSs are largely localized within genic regions and near genes, but the imprinting status of the CNSs are largely independent of their associated genes. Both imprinted CNSs and PEGs have been subject to relaxed selection. However, our data suggest that although MEGs were already subject to a higher mutation rate prior to their being imprinted, imprinting may be the cause of the relaxed selection of PEGs. In addition, although DNA methylation is lower in the maternal alleles of both the maternally and paternally expressed CNSs (mat and pat CNSs), the difference between the two alleles in H3K27me3 levels was only observed in pat CNSs. Together, our findings point to the importance of both transposons and CNSs in genomic imprinting in maize.
Homotopy epimorphisms and derived tate’s acyclicity for commutative C*-algebras
Authors: Bambozzi Federico , Mihara Tomoki
Published: September 2022

We study homotopy epimorphisms and covers formulated in terms of derived Tate’s acyclicity for commutative $C^*$-algebras and algebras of continuous functions valued in non-Archimedean valued fields. We prove that a homotopy epimorphism between commutative $C^*$-algebras precisely corresponds to a closed immersion between the compact Hausdorff topological spaces associated with them and a cover of a commutative $C^*$-algebra precisely corresponds to a topological cover of the compact Hausdorff topological space associated with it by closed immersions admitting a finite subcover. This permits us to prove derived and non-derived descent for Banach modules over commutative $C^*$-algebras.
Opinions as Facts
Authors: Bursztyn Leonardo , Rao Aakaash , Roth Christopher , Yanagizawa-Drott David
Published: September 2022

The rise of opinion programs has transformed television news. Because they present anchors’ subjective commentary and analysis, opinion programs often convey conflicting narratives about reality. We experimentally document that people across the ideological spectrum turn to opinion programs over “straight news”, even when provided large incentives to learn objective facts. We then examine the consequences of diverging narratives between opinion programs in a high-stakes setting: the early stages of the COVID-19 pandemic in the US. We find stark differences in the adoption of preventative behaviours among viewers of the two most popular opinion programs, both on the same network, which adopted opposing narratives about the threat posed by the COVID-19 pandemic. We then show that areas with greater relative viewership of the program downplaying the threat experienced a greater number of COVID-19 cases and deaths. Our evidence suggests that opinion programs may distort important beliefs and behaviours.
Systemic sclerosis associated interstitial lung disease: a conceptual framework for subclinical, clinical and progressive disease
Authors: Roofeh David , Brown Kevin K , Kazerooni Ella A , Tashkin Donald , Assassi Shervin , Martinez Fernando , Wells Athol U , Raghu Ganesh , Denton Christopher P , Chung Lorinda , Hoffmann-Vold Anna-Maria , Distler Oliver , Johannson Kerri A , Allanore Yannick , Matteson Eric L , Kawano-Dourado Leticia , Pauling John D , Seibold James R , Volkmann Elizabeth R , Walsh Simon L F , Oddis Chester V , White Eric S , Barratt Shaney L , Bernstein Elana J , Domsic Robyn T , Dellaripa Paul F , Conway Richard , Rosas Ivan , Bhatt Nitin , Hsu Vivien , Ingegnoli Francesca , Kahaleh Bashar , Garcha Puneet , Gupta Nishant , Khanna Surabhi , Korsten Peter , Lin Celia , Mathai Stephen C , Strand Vibeke , Doyle Tracy J , Steen Virginia , Zoz Donald F , Ovalles-Bonilla Juan , Rodriguez-Pinto Ignasi , Shenoy Padmanabha D , Lewandoski Andrew , Belloli Elizabeth , Lescoat Alain , Nagaraja Vivek , Ye Wen , Huang Suiyuan , Maher Toby , Khanna Dinesh
Published: September 2022

Objectives

To establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD).

Methods

A conceptual framework for subclinical, clinical and progressive ILD was provided to 83 experts, asking them to use the framework and classify actual SSc-ILD patients. Each patient profile was designed to be classified by at least four experts in terms of severity and risk of progression at baseline; progression was based on 1-year follow-up data. A consensus was reached if ≥75% of experts agreed. Experts provided information on which items were important in determining classification.

Results

Forty-four experts (53%) completed the survey. Consensus was achieved on the dimensions of severity (75%, 60 of 80 profiles), risk of progression (71%, 57 of 80 profiles) and progressive ILD (60%, 24 of 40 profiles). For profiles achieving consensus, most were classified as clinical ILD (92%), low risk (54%) and stable (71%). Severity and disease progression overlapped in terms of framework items that were most influential in classifying patients (forced vital capacity, extent of lung involvement on high resolution chest CT [HRCT]); risk of progression was influenced primarily by disease duration.

Conclusions

Using our proposed conceptual framework, international experts were able to achieve a consensus on classifying SSc-ILD patients along the dimensions of disease severity, risk of progression and progression over time. Experts rely on similar items when classifying disease severity and progression: a combination of spirometry and gas exchange and quantitative HRCT.
Neighborhood disadvantage, race/ethnicity and neural sensitivity to social threat and reward among adolescents
Authors: Jorgensen Nathan A , Muscatell Keely A , McCormick Ethan M , Prinstein Mitchell J , Lindquist Kristen A , Telzer Eva H
Published: September 2022

Experiences within one’s social environment shape neural sensitivity to threatening and rewarding social cues. However, in racialized societies like the USA, youth from minoritized racial/ethnic backgrounds can have different experiences and perceptions within neighborhoods that share similar characteristics. The current study examined how neighborhood disadvantage intersects with racial/ethnic background in relation to neural sensitivity to social cues. A racially diverse (59 Hispanic/Latine, 48 White, 37 Black/African American, 15 multi-racial and 6 other) and primarily low to middle socioeconomic status sample of 165 adolescents (88 female; Mage = 12.89) completed a social incentive delay task while undergoing functional magnetic resonance imaging (fMRI) scanning. We tested for differences in the association between neighborhood disadvantage and neural responses to social threat and reward cues across racial/ethnic groups. For threat processing, compared to White youth, neighborhood disadvantage was related to greater neural activation in regions involved in salience detection (e.g. anterior cingulate cortex) for Black youth and regions involved in mentalizing (e.g. temporoparietal junction) for Latine youth. For reward processing, neighborhood disadvantage was related to greater brain activation in reward, salience and mentalizing regions for Black youth only. This study offers a novel exploration of diversity within adolescent neural development and important insights into our understanding of how social environments may ‘get under the skull’ differentially across racial/ethnic groups.
Anti-transparency within the EU shift to open science
Authors: Nelhans Gustaf , Nolin Jan
Published: September 2022

In 2014, the European Commission initiated a process to strengthen science 2.0 as a core research policy concept. However, this turned into a substantial ideational shift. The concept of science 2.0 was dropped. Instead, open science became established as one of the three pillars of the €94 billion research framework programme Horizon Europe. This article scrutinises the official narrative regarding the shift of concepts, identifying transparency issues, specifically misrepresentation of concepts and data, and the redaction of key material. This can be characterised as problems of input legitimacy. A public consultation did take place, but numerous transparency issues can be found. From science 2.0 to open science, the ideational shift was portrayed as simply a matter of exchanging two synonymous concepts. However, science 2.0 is a descriptive concept referring to science being transformed by digitalisation. In contrast, open science involves normative assumptions about how science should work and be governed.
IIOld English
Authors: Burns Rachel A , Kehoe Niamh , Knowles Emma , Pascual Rafael J , Ponirakis Eleni , Tedford Margaret
Published: September 2022

This chapter has ten sections: 1. Manuscript Studies; 2. Cultural and Intellectual Contexts; 3. Literature: General; 4. The Poems of the Exeter Book; 5. The Poems of the Vercelli Book; 6. The Poems of the Junius Manuscript; 7. Beowulf and the Beowulf Manuscript; 8. Other Poems; 9. Prose; 10. Reception. Section 1 is by Rachel A. Burns; sections 2 and 9 are by Margaret Tedford; section 3 is by Margaret Tedford with contributions by Rachel A. Burns; section 4 is by Niamh Kehoe; sections 5 and 7 are by Rafael J. Pascual; section 6 is by Emma Knowles; sections 8 and 10 are by Eleni Ponirakis.
IXThe Seventeenth Century, Part I
Authors: Martin Catherine Gimelli , Urban David V , Gwynn Lucy , Stelzer Emily , Dyck Paul , James Anne
Published: September 2022

This chapter has seven sections: 1. General; 2. Bacon; 3. Browne; 4. Burton; 5. Herbert; 6. Donne; 7. Milton. Section 1 is by Catherine Gimelli Martin; section 2 is by David V. Urban; section 3 is by Lucy Gwynn; section 4 is by Emily Stelzer; section 5 is by Paul Dyck; section 6 is by Anne James; section 7 is by David V. Urban.
Monitoring Spore Dispersal and Early Infections of Diplocarpon coronariae Causing Apple Blotch Using Spore Traps and a New qPCR Method
Authors: Boutry Clémence , Bohr Anne , Buchleither Sascha , Ludwig Mathias , Oberhänsli Thomas , Tamm Lucius , Schärer Hans-Jakob , Flury Pascale
Published: September 2022

Apple blotch (AB) is a major disease of apple in Asia and recently emerged in Europe and the United States. It is caused by the fungus Diplocarpon coronariae (formerly Marssonina coronaria; teleomorph: Diplocarpon mali) and leads to severe defoliation of apple trees in late summer, resulting in reduced yield and fruit quality. To develop effective disease management strategies, a sound knowledge of the pathogen's biology is crucial. Data on the early phase of disease development are scarce: No data on spore dispersal in Europe are available. We developed a highly sensitive TaqMan qPCR method to quantify D. coronariae conidia in spore trap samples. We monitored temporal and spatial dispersal of conidia of D. coronariae and the progress of AB in spring and early summer in an extensively managed apple orchard in Switzerland in 2019 and 2020. Our results show that D. coronariae overwinters in leaf litter, and spore dispersal and primary infections occur in late April and early May. We provide the first results describing early-season dispersal of conidia of D. coronariae, which, combined with the observed disease progress, helps to understand the disease dynamics and will be a basis for improved disease forecast models. Using the new qPCR method, we detected D. coronariae in buds, on bark, and on fruit mummies, suggesting that several apple tissues might serve as overwintering habitats for the fungus, in addition to fallen leaves.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Impact of Virtual Interviewing During the COVID-19 Pandemic on the Residency Application Process: One Institution’s Experience
Authors: Nilsen Kari , Walling Anne , Johnson Mariah , Curran Maggie , Irwin Gretchen , Meyer Mark , Unruh Greg
Published: September 2022

Purpose

To assess the impact of virtual interviewing during the COVID-19 pandemic on the residency application process and to compare applicant costs and time spent interviewing during the 2020–2021 application cycle with prior years.

Method

Fourth-year medical students at the University of Kansas School of Medicine applying for first-year residency positions via the National Resident Matching Program Match completed an electronic 46-item survey after submitting their rank lists during each application cycle from 2015–2016 to 2020–2021. The authors used descriptive statistics and t tests to analyze and compare responses to demographics questions and questions regarding number of submitted applications, offered and completed interviews, ranked programs, costs, and time spent interviewing. They used thematic analysis to code respondents’ narrative comments about the virtual interviewing experience.

Results

From 2015–2016 to 2020–2021, 994 (of 1,190; 83.5%) respondents completed the survey. From 2019–2020 to 2020–2021, the average total cost of applying to residency per applicant dropped by $3,566 (P < .001) and the average time spent interviewing dropped by 13.3 days (P < .001). At the same time, the average number of applications per applicant dropped by 3.4, and applicants completed the same number of interviews and ranked 2.3 fewer programs, none of which were statistically significant differences. Narrative comments from 113 (79%) respondents in 2020–2021 revealed 4 themes related to virtual interviewing: convenience of time and cost, positive aspects of the process, negative aspects of the process, and overall impressions of the program.

Conclusions

Virtual interviewing during the 2020–2021 application cycle resulted in an approximately 80% reduction in cost for applicants and an approximately 50% decrease in time spent interviewing compared with previous years but was not associated with large increases in number of submitted applications, completed interviews, or ranked programs. Applicants generally perceived virtual interviewing as positive although they raised notable concerns.
A Review of Double Kissing Crush Stenting in Coronary Bifurcation Lesions
Authors: Kwan Tak W. , Lin Patricia
Published: September 2022

Double kissing (DK) crush stenting for coronary bifurcation lesions has gain popularity worldwide because of its superior randomized studies data and excellent clinical outcomes. This review evaluates all DK crush clinical trials and studies. It also reveals the contemporary technique steps by steps as well as the trouble shooting with illustrated clinical scenarios. Among all the available evidence, the DK crush technique is superior when compared to the provisional stenting technique for complex bifurcation lesion. DK crush stenting provides the best evidence-based approach to complex bifurcation lesions especially the left main coronary artery bifurcation lesions. Future direction of how to make this DK crush technique better is also proposed.
A Case Report on Application of Multimodal Imaging to an Alcoholic Cardiomyopathic Patient Undergoing Heart Transplantation
Authors: Li Zhiming , Wang Yu , Duan Bingsong , Han Dan , Chen Wei
Published: September 2022

Alcoholic cardiomyopathy (ACM) is a dilated cardiomyopathy induced by excessive alcohol consumption that causes progressive cardiac dysfunction and chamber dilatation, leading to arrhythmias, heart failure, and death. Cardiac transplantation is the final measure for end-stage ACM. In this case, we used multimodal imaging for ACM diagnosis in a patient with refractory heart failure. The patient received a heart transplant with a good prognosis, and his pathological results after the transplant confirmed our suspected diagnosis. End-stage ACM may lead to refractory heart failure and multimodal imaging may play an important role in the diagnosis, prognosis prediction, and follow-up study of suspected ACM.
Provisional Stenting: A Contemporary Relook at the Strategy and Lingering Issues
Authors: Choo Gim-Hooi , Gurupparan Kumara
Published: September 2022

Bifurcation lesions are encountered and treated in up to 1 in 5 cases of percutaneous coronary intervention (PCI). Such lesions pose a technical challenge to PCI, leading to lower procedural success and a higher rate of long-term adverse events. However, each bifurcation is unique in terms of anatomy and pathological presentation. There is no “one size fits all” strategy for coronary bifurcation PCI. Nevertheless, in most scenarios, provisional stenting is the preferred technique. This method is easy to apply and involves a logical stepwise escalation approach that is highly successful and safe.
Impact of Side Branch Lesion Length on Clinical Outcome after Coronary Stenting Techniques in Patients with Coronary Artery Bifurcation Disease: A Meta-Analysis
Authors: Kan Junyan , Luo Shuai , Wang Dongchen , Cai Dandan , Zhang Xiaojuan , Kan Jing
Published: September 2022

Objective:

The optimal percutaneous coronary intervention (PCI) technique for bifurcation lesions remains controversial, especially considering the variability of the side branch (SB). A provisional stenting technique is currently recommended in most cases. This meta-analysis aimed to compare outcomes of different bifurcation PCI strategies, clarifying their scope of application.

Methods:

Randomized controlled trials comparing PCI strategies for coronary bifurcation lesions were systematically retrieved from PubMed, Cochrane, Web of Science, and EBSCO literature databases without limitations on published date or language. Major adverse cardiovascular events (MACEs) were stipulated as main outcomes. Secondary outcomes of interest were all-cause mortality, cardiovascular mortality, target lesion revascularization (TLR), target vessel revascularization, myocardial infarction (MI), and stent thrombosis. Both pooled analysis and sub-group analysis were performed.

Results:

Twenty-three randomized controlled trials with 6380 participants were included. Eighteen studies compared the provisional strategy with 2-stent approaches. No significant difference in MACEs (relative risk (RR), 1.16; 95% confidence interval (CI), 0.90–1.48; I2
= 62%) was found between 1-stent and 2-stent techniques. However, when SB lesion length was used as the separation condition, the 2-stent strategy was associated with fewer MACEs (RR, 1.87; 95% CI, 1.46–2.41; I2
= 70%), TLRs (RR, 2.13; 95% CI, 1.50–3.02; I2
= 59%), and MIs (RR, 2.17; 95% CI, 1.19–3.95; I2
= 52%) than the provisional strategy in those where SB lesions measured >10 mm long.

Conclusions:

In the current work, there was no significant difference between 1-stent and 2-stent techniques in terms of MACEs or secondary outcomes. However, 2-stent approaches have clinical advantages over the provisional strategy in bifurcation when the SB lesion length is >10 mm due to fewer cases of TLR and MI.
Long-term Outcomes after Second-Generation Cryoballoon Ablation of Atrial Fibrillation and Analysis of Risk Factors Related to Recurrence
Authors: Dai Yufan , Wang Chenyuan , Wang Zulu , Liang Ming , Yang Guitang , Jin Zhiqing , Ding Jian , Zhang Ping , Han Yaling
Published: September 2022

Objective:

This study is aimed to analyze the long-term safety and effectiveness of second-generation cryoballoon (CB2) ablation in the treatment of atrial fibrillation (AF).

Methods:

Data from 760 consecutive patients in the Department of Cardiology, General Hospital of Northern Theater Command from August 2016 to December 2018 with drug-refractory symptomatic AF undergoing pulmonary vein isolation (PVI) using CB2 were assessed. Procedure-related safety and freedom from AF and atrial flutter/atria tachycardia through 3 years were determined. The risk factors related to atrial tachyarrhythmia recurrence were analyzed.

Results:

Acute PVI was achieved in 100% of the 760 patients. Radiofrequency application for additional focal ablation was needed in 11 (1.4%) patients and for 14 pulmonary veins (0.5%, 14/(760 × 4)) to achieve PVI. A total of 748 patients, including 539 with paroxysmal AF (PAF) and 209 with persistent AF (SAF) completed the follow-up, and only 12 (1.6%) patients were lost. The mean follow-up duration was (19 ± 8) months. The rate of major complications was 0.9%, including 0.8% of right phrenic nerve injury, which resolved before discharge. Freedom from all tachyarrhythmias was achieved in 75.0%, 69.4%, and 63.2% of patients with PAF, respectively, at 12-, 24-, and 36-month follow-up, and in 75.1%, 67.4%, and 60.9% for SAF, with no significant differences between the PAF and SAF groups. AF course and the rate of body weight gain were independent risk factors for recurrence at 12 months after ablation (P = 0.001 and P = 0.009, respectively).

Conclusion:

PVI using CB2 has a high acute success rate and good safety in the treatment of PAF and SAF. Long course of AF and weight gain after ablation were independent risk factors for recurrence.
Women's Prodromal Myocardial Infarction Symptom Perception, Attribution, and Care Seeking
Authors: Blakeman John R. , Woith Wendy M. , Astroth Kim S. , Jenkins Sheryl H. , Stapleton Stephen J.
Published: September 2022

Background

Most women experience prodromal myocardial infarction (MI) symptoms, but more information is needed about the perception, attribution, and care-seeking behaviors related to these prodromal symptoms.

Objectives

We aimed to describe women's perceptions, attributions, and care-seeking behaviors related to prodromal MI symptoms.

Method

We used a qualitative, multiple case study approach, recruiting participants during summer 2019 from a large hospital in the Midwestern United States. Data were collected from interviews with the women who experienced MI and some of their family members, journals, and electronic health records. An inductive, comparative analysis procedure was applied.

Results

Ten women, ages 42 to 84, participated in the study. The women experienced a mixture of certainty and uncertainty related to their symptoms and engaged in several cognitive processes to conceptualize and act upon their symptoms. Although all the women retrospectively reported at least 4 prodromal symptoms, they lacked knowledge of prodromal MI symptoms and often responded to prodromal sensations that they experienced using emotion- and avoidance-based strategies. It was difficult for the women to establish a symptom pattern that was attributable to heart disease.

Discussion

The findings of this study may be used as evidence to support interventions that would facilitate women's care seeking for and health care providers' recognition of prodromal MI symptoms. Additional research is necessary to more fully characterize the cognitive processes at play for women of many different sociocultural backgrounds who experience prodromal MI symptoms.
A Systematic Review of Nursing Practice Workarounds
Authors: McCord Jennifer Lynn , Lippincott Cynthia Russell , Abreu Eduardo , Schmer Carol
Published: September 2022

Background

Nursing practice workarounds (NPWs) are a significant problem for health care organizations. Identified NPWs serve as a catalyst for innovation to improve efficiency, patient safety, and system design. To date, a systematic review of NPW literature has not been performed.

Objectives

The aim of this systematic review was to synthesize evidence of NPW definitions, context, and prevention strategies, utilizing previous research to develop a framework that examines the current state of this phenomenon and implications for clinical practice, while highlighting the need for future research.

Methods

A systematic review of the literature was conducted using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Academic Search, Ovid MEDLINE, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Google Scholar databases were reviewed for eligible studies from 2013 to 2020. Results were further screened and sorted by relevance and scored for quality.

Results

Thirteen studies were included. Studies lacked the use of theory, and NPW definitions were varied. Nursing workarounds occurred most frequently when implementing new technology (46%) and when administering medications (31%). Contributing factors were workplace stressors and obstructions in workflow environment. Workaround prevention strategies include open communication and a proactive approach addressing conditions, situations, and processes. Overall study quality was low.

Discussion

This systematic review provides valuable information for critical care nurses and administrators regarding NPW. Implications for practice include the need for proactive and open communication between nurses and administrators when new technology and/or patient care processes require NPW. Administrative considerations include process and environmental improvement strategies to remove perceived workflow barriers. Future research to examine causes and consequences of NPW is needed to identify interventions for NPW prevention. Specific nursing considerations include workload, staffing and time constraints, and impacts of work-related stress levels. Critical care nursing processes should be examined for common NPW challenges. Interventions developed to address these challenges should then be tested to further advance evidence-based critical care nursing care.
Evidence-Based Recommendations
Authors: Toufic El Hussein Mohamed , Mikhail Marianne
Published: September 2022

One of the potential complications of acute myocardial infarction is left ventricular thrombus (LVT). The incidence of LVT following acute myocardial infarction has decreased dramatically with early invasive reperfusion techniques or fibrinolysis. However, the risk of LVT formation remains significant and is associated with an increased risk of systemic embolism, stroke, cardiovascular events, and even death. Current guidelines indicate that dual antiplatelet therapy and anticoagulation therapy for at least 3 months can reduce the risk of these events. While vitamin K antagonist is the preferred oral anticoagulant, there is growing evidence to support the use of direct-acting oral anticoagulants in LVT management. Cardiac magnetic resonance has shown the highest diagnostic accuracy for LVT assessment, followed by echocardiography with contrast agents. This article serves as a general review of the pathophysiology, diagnosis, and management of LVT.
Pharmacist-Driven Therapeutic Infliximab Monitoring at the Point of Care Using Rapidly Assessed Drug Levels in Patients with Inflammatory Bowel Disease
Authors: Rentsch Clarissa A. , Ward Mark G. , Luber Raphael P. , Taylor Kirstin M. , Gibson David J. , Headon Belinda , Rosella Ourania , Su Heidi Y. , Friedman Antony B. , Dooley Michael , Sparrow Miles P. , Gibson Peter R.
Published: September 2022

Background:

Therapeutic monitoring of infliximab is limited by the time lag between drug-level measurement and dose adjustment, along with the cost of dose escalation. Strategies for dose reduction in stable patients on maintenance infliximab at supratherapeutic levels are uncertain. This study determined the feasibility of a pharmacist-driven strategy for immediate dose adjustment using a sliding scale at the point of care in stable patients with inflammatory bowel disease on maintenance therapy.

Methods:

Adult patients with stable disease undergoing maintenance therapy with infliximab infusions, 5 mg/kg every 8 weeks, were prospectively studied. Trough drug levels were assessed by a rapid assay (and later by ELISA) at all infusions for up to 12 months with immediate but quantitatively small dose adjustment according to a sliding scale targeting a therapeutic range of 3–7 mcg/mL. Disease activity was assessed both clinically and biochemically.

Results:

The rapid assay and ELISA detected similar infliximab levels, and the strategy added approximately 30 minutes to the duration of infusion events. Only 20% of 48 patients (77% with Crohn disease) had baseline trough infliximab concentrations within the therapeutic range. This value increased 3-fold after 24 and 48 weeks of interventions. One in 2 patients had baseline supratherapeutic levels, and most were brought into the therapeutic range without a discernible impact on disease activity by 1 dose adjustment, but 2 or 3 adjustments were generally needed for 29% of patients with subtherapeutic levels. Overall, drug costs were reduced by 4%.

Conclusions:

Immediate dose adjustment after infliximab rapid assay performed by a pharmacist using a sliding scale is a feasible strategy. Supratherapeutic infliximab levels can be safely and quickly brought into the therapeutic range using small dose adjustments without affecting disease activity, offsetting (at least partly) costs associated with dose escalation.
Assessment of microcirculatory function during hemodialysis
Authors: Penny Jarrin D. , Moradshahi Mehrshad , McIntyre Christopher W.
Published: September 2022

Purpose of review

Patients with chronic kidney disease characteristically exhibit microcirculatory dysfunction, in combination with vascular damage. Hemodialysis superimposes additional circulatory stress to the microvasculature (repetitive ischemic insults/cumulative damage) resulting in high mortality. Intradialytic monitoring and hemodialysis delivery is currently limited to macrovascular/systemic assessment and detection of intradialytic systemic hypotension. Monitoring of the microcirculation has the potential to provide valuable information on hemodialysis-induced circulatory stress likely to result in end-organ ischemia (with/without systemic hypotension) generating an opportunity to intervene before tissue injury occurs.

Recent findings

Various noninvasive technologies have been used assessing the microcirculation in hemodialysis patients at rest. Some technologies have also been applied during hemodialysis studying the effects of treatment on the microcirculation. Despite the approach used, results are consistent. Hemodialysis patients have impaired microcirculations with treatment adding additional stress to inadequately regulated vascular beds. Utility/practicality/clinical relevance vary significantly between methodologies.

Intradialytic monitoring of the microcirculation can provide additional insights into a patient's individual response to treatment. However, this valuable perspective has not been adopted into clinical practice. A microcirculatory view could provide a window of opportunity to enable a precision medicine approach to treatment delivery improving current woefully poor subjective and objective clinical outcomes.
Frailty, multimorbidity and sarcopaenia in haemodialysis patients
Authors: Eldehni Mohamed Tarek
Published: September 2022

Purpose of review

It is well recognised that haemodialysis patients have higher levels of multimorbidity, frailty and sarcopaenia. This review examines the current understanding of the three concepts in relation to the general population and haemodialysis patients, and the methods used to quantify them. It also looks at the interaction between multimorbidity, frailty and sarcopaenia in this patient group and proposes a new model that utilises muscle mass index and fat mass index as a surrogate representation of the three concepts.

Recent findings

Multimorbidity in on the rise in the general population and this is one of the contributing factors to higher rates of chronic kidney disease, progression to end-stage renal disease and multimorbidity in haemodialysis patients. Malnutrition and haemodialysis induced end organ damage further contributes to muscle loss and frailty in this patient group. There is a significant overlap and interaction between multimorbidity, frailty and sarcopaenia in haemodialysis and their presence carries a significant impact on quality of life and survival. There are multiple scores for measuring multimorbidity, frailty and sarcopenia and there is no consensus on their utilisation in haemodialysis patients. We propose the use of fat mass index and muscle mass index model as a surrogate method for clinically quantifying multimorbidity, frailty and sarcopaenia.

Effective public health policies are likely to have an impact on reducing the prevalence of multimorbidity and the development of end stage renal disease. Future research is required to develop interventions that are targeted at maintaining muscle mass and function in haemodialysis patients.
Skin autofluorescence as tool for cardiovascular and diabetes risk prediction
Authors: Smit Andries Jan , van de Zande Saskia Corine , Mulder Douwe Johannes
Published: September 2022

Purpose of review

Advanced glycation endproducts (AGE) have an important role in the development of chronic complications in diabetes mellitus and in renal failure. Skin autofluorescence (SAF) is a simple noninvasive optical technique to estimate AGE levels in the dermis. SAF increases with age, but rises more rapidly in diabetes and renal failure, and is also associated with, and a predictor of their complications.

Recent findings

In recent large population studies, SAF is a strong predictor of development of type 2 diabetes (T2D), and in persons with known diabetes of its complications. SAF also predicts new cardiovascular disease (CVD) and mortality not only in individuals with known type 2 diabetes but also in the general population.

SAF is a simple, powerful and independent predictor for development of type 2 diabetes (T2D), and also for cardiovascular disease and mortality in both persons with diabetes, and in the general population.
Comparison of Hand-Held Doppler and Indocyanine Green Angiography in Preoperative Design of Expanded Forehead Flaps for Nasal Reconstruction
Authors: Song Zhen , Zhang Xulong , Wang Huan , You Jianjun , Zheng Ruobing , Xu Yihao , Guo Junsheng , Tian Le , Fan Fei
Published: September 2022

Background:

Despite the different approaches for detection of perforators, methods of vascular mapping of the expanded forehead flap for nasal reconstruction are rarely described. This article aimed to present our experience in the preoperative design of the expanded forehead flap for nasal reconstruction and to compare the clinical practice of hand-held Doppler and indocyanine green angiography (ICGA) in vascular mapping for nasal reconstruction with the expanded forehead flap.

Methods:

From October 2019 to April 2022, 26 patients underwent nasal reconstruction using expanded forehead flap. The authors performed preoperative vascular mapping on 16 patients by hand-held Doppler alone, and on 10 patients by hand-held Doppler and ICGA primary outcomes considered were the visualization of the main vascular course of the flap obtained by hand-held Doppler or ICGA, intraoperative observation of the flap, and its postoperative complications.

Results:

Indocyanine green angiography provides a better detection in distal flap and the branches of the supratrochlear artery. Vein detection by ICGA generally corresponds to the results obtained by the combination of hand-held Doppler and transillumination test. In the group that only used hand-held Doppler, 2 patients presented hemodynamic complications in the margin of the flap and 1 patient presented partial necrosis postoperatively. No complication was found in the group that used ICGA.

Conclusions:

It is recommended to use the ICGA for preoperative planning, as it yields highly accurate vascular courses. As an alternative to other methods, hand-held Doppler is also an effective tool.

Level of Evidence:

IV.
Extended Superficial Musculoaponeurotic System Face-Lift With Vertical Vector for Asian Patients: A 3-Dimensional Analysis of Facial Contour
Authors: Kim Young Chul , Choi Jin-Mi , Oh Tae-Suk
Published: September 2022

In this study, the authors report the experience of extended superficial musculoaponeurotic system (SMAS) face-lift with the vertical vector in Asian ethnicity and investigate the 3-dimensional change of facial contour. A total of 32 patients with Korean ethnicity underwent extended SMAS face-lift with vertical vector from 2015 to 2018. Patients with aging face were included for the study subjects, whereas those who were diagnosed with any craniofacial deformity were excluded. Using 3-dimensional photogrammetry, surface contour analysis was performed in the cheek region to calculate the mean, maximal, and minimal difference of surface projection and global root mean square error between the preoperative and 1-year postoperative period. The change of horizontal facial widths and jawline angle was evaluated. In contour analysis, the mean difference of surface contour was highest in anterior, followed by lateral cheek and lower face, sequentially. The maximal difference of surface contour was highest in anterior cheek, followed by lateral cheek and lower face, whereas the minimal difference of surface contour was lowest in lower face, followed by anterior cheek and lateral cheek, sequentially. No significant differences in the midfacial and lower facial distances were observed between the preoperative and postoperative periods. There was significant increase of jawline angle, from 20.78 to 23.14 degree of mean value (P=0.001). In conclusion, the extended SMAS face-lift with vertical vector can be an optimal option for Asian subjects in terms of the midfacial volumetric shift, sharpening of jawline and avoidance of midfacial widening.
Multi-Omics Assessment of Genetic Risk for Celiac Disease in Down Syndrome
Authors: Stahl Marisa Gallant , Shaw Jessica R , Eduthan Neetha Paul , Rachubinski Angela L , Smith Keith P , Estrada Belinda Enriquez , Galbraith Matthew D , Sokol Ronald J , Chavan Sameer , Leaton Laura Ann , Kichula Katherine M , Norman Paul J , Norris Jill M , Liu Edwin , Espinosa Joaquin M
Published: September 2022

Objectives

Individuals with Down syndrome (DS) display high risk of celiac disease (CD), but the mechanisms underlying this increased susceptibility await elucidation. Here, we examined the prevalence of HLA genotypes associated with CD risk in the general population and tested a previously developed genetic risk score (GRS) for CD in people with DS.

Methods

HLA genotypes were obtained for 204 individuals with DS in the Human Trisome Project cohort study, of whom 9% had CD. We compared HLA genotype frequencies in those with and without CD against frequencies observed in the general population. CD permissive HLA haplotypes explored were DQ2.5, DQ2.2, DQ8.1, and DQ7.5. We also analyzed 38 non-HLA-DQ alleles used to generate the CD GRS.

Results

Frequencies of risk genotypes were different for CD in DS versus CD in the general population. For example, we observed lower frequency of DQ2.5/DQ2.5 and higher prevalence of DQ7.5/X and X/X in CD in DS. Although GRS values were significantly increased in those with CD and DS, their predictive power was decreased relative to the general population. Transcriptome analysis revealed dysregulated expression of many genes composing the GRS in DS. Proteomics analysis showed that GRS values correlate with elevation of specific immune factors in DS.

Conclusions

The genetic risk profile of CD in DS is different relative to the general population, which is likely due to dysregulation of immune pathways in DS. Larger studies are needed to elucidate pathogenic mechanisms and to develop a validated GRS for CD in DS.

What is Known

Celiac disease is more common in individuals with Down syndrome, but the impact of HLA risk genotypes in this population is unclear.

A celiac disease genetic risk score incorporating HLA-DQ and non-HLA SNPs has been developed with good predictive accuracy in the general population.

What is New

Individuals with DS may still develop CD even without the traditional HLA-DQ risk factors.

A modified CD genetic risk score may be applied to individuals with DS with good accuracy and specificity.

The immune dysregulation characteristic of DS involves dysregulated expression of many genes involved in CD etiology.
Natural language supervision with a large and diverse dataset builds better models of human high-level visual cortex
Authors: Wang Aria Y. , Kay Kendrick , Naselaris Thomas , Tarr Michael J. , Wehbe Leila
Published: September 2022

Advances in neural networks have been catalyzed by joint training on images and natural language, increased dataset sizes, and data diversity. We explored whether the same factors support similar improvements in predicting visual responses in the human brain. We used models pre-trained with Contrastive Language-Image Pre-training (CLIP) – which learns image embeddings that best match text embeddings of image captions from diverse, large-scale datasets – to study visual representations. We built voxelwise encoding models based on CLIP image features to predict brain responses to real-world images. ResNet50 with CLIP explained up toR2= 79% of variance in individual voxel responses in held-out test data, a significant increase from models trained only with image/label pairs (ImageNet trained ResNet) or text (BERT). Comparisons across different model backbones ruled out network architecture as a factor in performance improvements. Comparisons across models that controlled for dataset size and data diversity demonstrated that language feedback along with data diversity in larger datasets are important factors in explaining neural responses in high-level visual brain regions. Visualizations of model embeddings and Principal Component Analysis (PCA) revealed that our models capture both global and fine-grained semantic dimensions represented within human visual cortex.
Genome-wide regulatory effects of STRs stabilized by elevated expression of antioxidant genes in C. elegans
Authors: Zhang Gaotian , Andersen Erik C.
Published: September 2022

Genetic variation can cause significant differences in gene expression among individuals. Although quantitative genetic mapping techniques provide ways to identify genome-wide regulatory loci, they almost entirely focus on single nucleotide variants (SNVs). Short tandem repeats (STRs) represent a large source of genetic variation with potential regulatory effects. Here, we leverage the recently generated expression and STR variation data among wild Caenorhabditis elegans strains to conduct a genome-wide analysis of how STRs affect gene expression variation. We identify thousands of expression STRs (eSTRs) showing regulatory effects and demonstrate that they explain missing heritability beyond SNV-based expression quantitative trait loci. We illustrate specific regulatory mechanisms such as how eSTRs affect splicing sites and alternative splicing efficiency. We also show that differential expression of antioxidant genes might affect STR variation systematically. Overall, we reveal the interplay between STRs and gene expression variation in a tractable model system to ultimately associate STR variation with differences in complex traits.
IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding
Authors: Bolton Marcus J. , Arevalo Claudia P. , Griesman Trevor , Li Shuk Hang , Bates Paul , Wilson Patrick C. , Hensley Scott E.
Published: September 2022

The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2 or IgG3. We found that many influenza virus-specific mAbs have altered binding and neutralization capacity depending on the IgG subclass encoded, and that these differences result from unique bivalency capacities of the subclasses. Importantly, subclass differences in antibody binding and neutralization were greatest when the affinity for the target antigen was reduced through antigenic mismatch. We found that antibodies expressed as IgG3 bound and neutralized antigenically drifted influenza viruses more effectively. We obtained similar results using a panel of SARS-CoV-2-specific mAbs and the antigenically advanced B.1.351 strain of SARS-CoV-2. We found that a licensed therapeutic mAb retained neutralization breadth against SARS-CoV-2 variants when expressed as IgG3, but not IgG1. These data highlight that IgG subclasses are not only important for fine-tuning effector functionality, but also for binding and neutralization of antigenically drifted viruses.

Significance

Influenza viruses and coronaviruses undergo continuous change, successfully evading human antibodies elicited from prior infections or vaccinations. It is important to identify features that allow antibodies to bind with increased breadth. Here we examined the effect that different IgG subclasses have on monoclonal antibody binding and neutralization. We show that IgG subclass is a determinant of antibody breadth, with IgG3 affording increased neutralization of antigenically drifted variants of influenza virus and SARS-CoV-2. Future studies should evaluate IgG3 therapeutic antibodies and vaccination strategies or adjuvants that may skew antibody responses toward broadly reactive isotypes.