bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility-value intervention promotes persistence and diversity in STEM
Authors: Asher Michael W. , Harackiewicz Judith M. , Beymer Patrick N. , Hecht Cameron A. , Lamont Liana B. , Else-Quest Nicole M. , Priniski Stacy J. , Thoman Dustin B. , Hyde Janet S. , Smith Jessi L.
Published: May 2023

We tested the long-term effects of a utility-value intervention administered in a gateway chemistry course, with the goal of promoting persistence and diversity in STEM. In a randomized controlled trial (N = 2,505), students wrote three essays about course content and its personal relevance or three control essays. The intervention significantly improved STEM persistence overall (74% vs. 70% were STEM majors 2.5 y later). Effects were larger for students from marginalized and underrepresented racial/ethnic groups, who were 14 percentage points more likely to persist in STEM fields in the intervention condition (69% vs. 55%). Mediation analysis suggests that the intervention promoted persistence for these students by bolstering their motivation to attain a STEM degree and by promoting engagement with course assignments. This theory-informed curricular intervention is a promising tool for educators committed to retaining students in STEM.
Angiotensin II receptor inhibition ameliorates liver fibrosis and enhances hepatocellular carcinoma infiltration by effector T cells
Authors: Gu Li , Zhu Yahui , Lee Maiya , Nguyen Albert , Ryujin Nicolas T. , Huang Jian Yu , Pandit Shusil K. , Chamseddine Shadi , Xiao Lianchun , Mohamed Yehia I. , Kaseb Ahmed O. , Karin Michael , Shalapour Shabnam
Published: May 2023

Although viral hepatocellular carcinoma (HCC) is declining, nonviral HCC, which often is the end stage of nonalcoholic or alcoholic steatohepatitis (NASH, ASH), is on an upward trajectory. Immune checkpoint inhibitors (ICIs) that block the T cell inhibitory receptor PD-1 were approved for treatment of all HCC types. However, only a minority of HCC patients show a robust and sustained response to PD-1 blockade, calling for improved understanding of factors that negatively impact response rate and duration and the discovery of new adjuvant treatments that enhance ICI responsiveness. Using a mouse model of NASH-driven HCC, we identified peritumoral fibrosis as a potential obstacle to T cell–mediated tumor regression and postulated that antifibrotic medications may increase ICI responsiveness. We now show that the angiotensin II receptor inhibitor losartan, a commonly prescribed and safe antihypertensive drug, reduced liver and peritumoral fibrosis and substantially enhanced anti-PD-1-induced tumor regression. Although losartan did not potentiate T cell reinvigoration, it substantially enhanced HCC infiltration by effector CD8
+
T cells compared to PD-1 blockade alone. The beneficial effects of losartan correlated with blunted TGF-β receptor signaling, reduced collagen deposition, and depletion of immunosuppressive fibroblasts.
Three years of COVID-19 and life satisfaction in Europe: A macro view
Authors: Easterlin Richard A. , O’Connor Kelsey J.
Published: May 2023

Every country in Europe experienced an adverse impact from the COVID-19 pandemic on life satisfaction, though on average, satisfaction with life in the summer of 2022 is about the same as the pre-pandemic value in the autumn of 2019. Typically, an upsurge in the severity of the pandemic (measured by the number of COVID-related deaths) is associated with declining life satisfaction and an ebbing, with increasing life satisfaction. Of the three waves of the pandemic between March 2020 and the autumn of 2022, the most severe impact typically occurred in 2021 during the second wave; in the third wave, the response declined due to the spread of effective vaccines and the takeover of omicron variants.
Intermediate-range order governs dynamics in dense colloidal liquids
Authors: Singh Navneet , Zhang Zhen , Sood A. K. , Kob Walter , Ganapathy Rajesh
Published: May 2023

The conventional wisdom is that liquids are completely disordered and lack nontrivial structure beyond nearest-neighbor distances. Recent observations have upended this view and demonstrated that the microstructure in liquids is surprisingly rich and plays a critical role in numerous physical, biological, and industrial processes. However, approaches to uncover this structure are either system-specific or yield results that are not physically intuitive. Here, through single-particle resolved three-dimensional confocal microscope imaging and the use of a recently introduced four-point correlation function, we show that bidisperse colloidal liquids have a highly nontrivial structure comprising alternating layers with icosahedral and dodecahedral order, which extends well beyond nearest-neighbor distances and grows with supercooling. By quantifying the dynamics of the system on the particle level, we establish that it is this intermediate-range order, and not the short-range order, which has a one-to-one correlation with dynamical heterogeneities, a property directly related to the relaxation dynamics of glassy liquids. Our experimental findings provide a direct and much sought-after link between the structure and dynamics of liquids and pave the way for probing the consequences of this intermediate-range order in other liquid state processes.
Tumoral macroglobulinosis of the skin: In situ release of IgM
Authors: Bonnetblanc JM , Bedane C , Fayol J , Labrousse F.
Published: May 2023

This article does not have an abstract.
2. Imiquimod: Mode of Action and Therapeutic Potential
Authors: Chosidow O , Dummer R
Published: May 2023

This article does not have an abstract.
3. Successful Management of Viral Infections and Other Dermatoses with Imiquimod 5% Cream
Authors: Berman B , Hengge U , Barton S
Published: May 2023

This article does not have an abstract.
4. Treatment of Non-Melanoma Skin Cancer: Immunotherapy as a Viable Option
Authors: Shumack S , Rigel D
Published: May 2023

This article does not have an abstract.
5. Imiquimod 5% Cream for the Treatment of Cutaneous Lesions in Immunocompromised Patients
Authors: Johnson R , Stockfleth E
Published: May 2023

This article does not have an abstract.
The role of leukotriene A4 hydrolase/aminopeptidase in transcellular leukotriene B4 synthesis in human epidermis
Authors: Iversen Lars
Published: May 2023

No abstract available
Type 𝐼𝐼 quantum subgroups of 𝔰𝔩_{𝔑}. ℑ: Symmetries of local modules
Authors: Edie-Michell Cain
Published: May 2023

This paper is the first of a pair that aims to classify a large number of the type

I
I

II

quantum subgroups of the categories

C

(

s
l

r
+
1

,
k
)

\mathcal {C}(\mathfrak {sl}_{r+1}, k)

. In this work we classify the braided auto-equivalences of the categories of local modules for all known type

I
I

quantum subgroups of

C

(

s
l

r
+
1

,
k
)

\mathcal {C}(\mathfrak {sl}_{r+1}, k)

. We find that the symmetries are all non-exceptional except for four cases (up to level-rank duality). These exceptional cases are the orbifolds

C

(

s
l

2

,
16

)

Rep
⁡
(

Z

2

)

0

\mathcal {C}(\mathfrak {sl}_{2}, 16)^0_{\operatorname {Rep}(\mathbb {Z}_{2})}

,

C

(

s
l

3

,
9

)

Rep
⁡
(

Z

3

)

0

\mathcal {C}(\mathfrak {sl}_{3}, 9)^0_{\operatorname {Rep}(\mathbb {Z}_{3})}

,

C

(

s
l

4

,
8

)

Rep
⁡
(

Z

4

)

0

\mathcal {C}(\mathfrak {sl}_{4}, 8)^0_{\operatorname {Rep}(\mathbb {Z}_{4})}

, and

C

(

s
l

5

,
5

)

Rep
⁡
(

Z

5

)

0

\mathcal {C}(\mathfrak {sl}_{5}, 5)^0_{\operatorname {Rep}(\mathbb {Z}_{5})}

.

We develop several technical tools in this work. We give a skein theoretic description of the orbifold quantum subgroups of

C

(

s
l

r
+
1

,
k
)

\mathcal {C}(\mathfrak {sl}_{r+1}, k)

. Our methods here are general, and the techniques developed will generalise to give skein theory for any orbifold of a braided tensor category. We also give a formulation of orthogonal level-rank duality in the type

D
D

-

D
D

case, which is used to construct one of the exceptionals. We uncover an unexpected connection between quadratic categories and exceptional braided auto-equivalences of the orbifolds. We use this connection to construct two of the four exceptionals.

In the sequel to this paper we will use the classified braided auto-equivalences to construct the corresponding type

I
I

II

quantum subgroups of the categories

C

(

s
l

r
+
1

,
k
)

\mathcal {C}(\mathfrak {sl}_{r+1}, k)

. This will essentially finish the type

I
I

II

classification for

s
l

n

\mathfrak {sl}_n

modulo type

I
I

classification. When paired with Gannon’s type

I
I

classification for

r
≤
6

r\leq 6

, our results will complete the type

I
I

II

classification for these same ranks.

This paper includes an appendix by Terry Gannon, which provides useful results on the dimensions of objects in the categories

C

(

s
l

r
+
1

,
k
)

\mathcal {C}(\mathfrak {sl}_{r+1}, k)

.
Matching single cells across modalities with contrastive learning and optimal transport
Authors: Gossi Federico , Pati Pushpak , Chouvardas Panagiotis , Martinelli Adriano Luca , Kruithof-de Julio Marianna , Rapsomaniki Maria Anna
Published: May 2023

Understanding the interactions between the biomolecules that govern cellular behaviors remains an emergent question in biology. Recent advances in single-cell technologies have enabled the simultaneous quantification of multiple biomolecules in the same cell, opening new avenues for understanding cellular complexity and heterogeneity. Still, the resulting multimodal single-cell datasets present unique challenges arising from the high dimensionality and multiple sources of acquisition noise. Computational methods able to match cells across different modalities offer an appealing alternative towards this goal. In this work, we propose MatchCLOT, a novel method for modality matching inspired by recent promising developments in contrastive learning and optimal transport. MatchCLOT uses contrastive learning to learn a common representation between two modalities and applies entropic optimal transport as an approximate maximum weight bipartite matching algorithm. Our model obtains state-of-the-art performance on two curated benchmarking datasets and an independent test dataset, improving the top scoring method by 26.1% while preserving the underlying biological structure of the multimodal data. Importantly, MatchCLOT offers high gains in computational time and memory that, in contrast to existing methods, allows it to scale well with the number of cells. As single-cell datasets become increasingly large, MatchCLOT offers an accurate and efficient solution to the problem of modality matching.
STMHCpan, an accurate Star-Transformer-based extensible framework for predicting MHC I allele binding peptides
Authors: Ye Zheng , Li Shaohao , Mi Xue , Shao Baoyi , Dai Zhu , Ding Bo , Feng Songwei , Sun Bo , Shen Yang , Xiao Zhongdang
Published: May 2023

Peptide-major histocompatibility complex I (MHC I) binding affinity prediction is crucial for vaccine development, but existing methods face limitations such as small datasets, model overfitting due to excessive parameters and suboptimal performance. Here, we present STMHCPan (STAR-MHCPan), an open-source package based on the Star-Transformer model, for MHC I binding peptide prediction. Our approach introduces an attention mechanism to improve the deep learning network architecture and performance in antigen prediction. Compared with classical deep learning algorithms, STMHCPan exhibits improved performance with fewer parameters in receptor affinity training. Furthermore, STMHCPan outperforms existing ligand benchmark datasets identified by mass spectrometry. It can also handle peptides of arbitrary length and is highly scalable for predicting T-cell responses. Our software is freely available for use, training and extension through Github (https://github.com/Luckysoutheast/STMHCPan.git).
Sulbactam-durlobactam: A Step Forward in Treating Carbapenem-Resistant Acinetobacter baumannii (CRAB) Infections
Authors: Watkins Richard R , Bonomo Robert A
Published: May 2023

Antimicrobial resistance in gram-negative pathogens, such as Acinetobacter baumannii, is a serious threat to human health. Sulbactam-durlobactam, a unique β-lactam and a β-lactamase inhibitor combination, is a novel agent targeted against carbapenem-resistant A. baumannii. This supplement provides a summary of the development of SUL-DUR, discussing its unique features and role in treating infections caused by CRAB pathogens.
The Pharmacokinetics/Pharmacodynamic Relationship of Durlobactam in Combination With Sulbactam in In Vitro and In Vivo Infection Model Systems Versus Acinetobacter baumannii-calcoaceticus Complex
Authors: O’Donnell John P , Bhavnani Sujata M
Published: May 2023

Sulbactam-durlobactam is a β-lactam/β-lactamase inhibitor combination currently in development for the treatment of infections caused by Acinetobacter, including multidrug-resistant (MDR) isolates. Although sulbactam is a β-lactamase inhibitor of a subset of Ambler class A enzymes, it also demonstrates intrinsic antibacterial activity against a limited number of bacterial species, including Acinetobacter, and has been used effectively in the treatment of susceptible Acinetobacter-associated infections. Increasing prevalence of β-lactamase–mediated resistance, however, has eroded the effectiveness of sulbactam in the treatment of this pathogen. Durlobactam is a rationally designed β-lactamase inhibitor within the diazabicyclooctane (DBO) class. The compound demonstrates a broad spectrum of inhibition of serine β-lactamase activity with particularly potent activity against class D enzymes, an attribute which differentiates it from other DBO inhibitors. When combined with sulbactam, durlobactam effectively restores the susceptibility of resistant isolates through β-lactamase inhibition. The present review describes the pharmacokinetic/pharmacodynamic (PK/PD) relationship associated with the activity of sulbactam and durlobactam established in nonclinical infection models with MDR Acinetobacter baumannii isolates. This information aids in the determination of PK/PD targets for efficacy, which can be used to forecast efficacious dose regimens of the combination in humans.
Pathogen-Targeted Clinical Development to Address Unmet Medical Need: Design, Safety, and Efficacy of the ATTACK Trial
Authors: Watkins Richard R , Du Bin , Isaacs Robin , Altarac David
Published: May 2023

There is a crucial need for novel antibiotics to stem the tide of antimicrobial resistance, particularly against difficult to treat gram-negative pathogens like Acinetobacter baumannii-calcoaceticus complex (ABC). An innovative approach to addressing antimicrobial resistance may be pathogen-targeted development programs. Sulbactam-durlobactam (SUL-DUR) is a β-lactam/β-lactamase inhibitor combination antibiotic that is being developed to specifically target drug-resistant ABC. The development of SUL-DUR culminated with the Acinetobacter Treatment Trial Against Colistin (ATTACK) trial, a global, randomized, active-controlled phase 3 clinical trial that compared SUL-DUR with colistin for treating serious infections due to carbapenem-resistant ABC. SUL-DUR met the primary noninferiority endpoint of 28-day all-cause mortality. Furthermore, SUL-DUR had a favorable safety profile with a statistically significant lower incidence of nephrotoxicity compared with colistin. If approved, SUL-DUR could be an important treatment option for infections caused by ABC, including carbapenem-resistant and multidrug-resistant strains. The development program and the ATTACK trial highlight the potential for pathogen-targeted development programs to address the challenge of antimicrobial resistance.
A Systematic Review and Meta-Analysis of Tuberculous Preventative Therapy Adverse Events
Authors: Melnychuk Luca , Perlman-Arrow Sara , Lisboa Bastos Mayara , Menzies Dick
Published: May 2023

Background

Tuberculosis preventative therapy (TPT) is a key part of the World Health Organization’s (WHO) end tuberculosis (TB) strategy. However, the occurrence of potentially serious adverse events (AE) is a limitation of TPT regimens. We conducted a systemic review and meta-analysis to estimate the incidence of AE and hepatotoxicity with various TPT regimens to help inform clinical decision making.

Methods

We searched MEDLINE, Cochrane, Health Star, and EMBASE from 1952 to April 2021 for studies reporting AE associated with TPT. Included studies reported AE stratified by regimen and provided the number of participants receiving each regimen. We used a random-effect model to meta-analyze the cumulative incidence of AE.

Results

We included 175 publications describing TPT-related AE in 277 cohorts. Among adults, the incidence of any AE, and hepatotoxicity leading to drug discontinuation was 3.7% and 1.1%, respectively, compared to 0.4% and 0.02%, respectively, in children. The highest incidence of any AE, and AE leading to drug discontinuation was with 3 months isoniazid and rifapentine (3HP), and the lowest was with 4 months rifampin (4R). 4R also had the lowest incidence of hepato-toxic AE and drug discontinuation due to hepato-toxic AE. 3HP also had a low incidence of hepato-toxic AE.

Conclusions

Although our study was limited by variability in methods and quality of AE reporting in the studies reviewed, pediatric populations had a very low incidence of AE with all TPT regimens reviewed. In adults, compared to mono-H regimens all rifamycin-based regimens were safer, although 4R had the lowest incidence of TPT-related AE of all types and of hepatotoxicity.
The Impact of COVID-19 on Insurgency and Rebel Governance: Lessons from India's Northeast
Authors: Newman Edward , Saikia Jaideep , Waterman Alex
Published: May 2023

Emerging research has suggested that the COVID-19 pandemic has generally favored rebel organizations—rather than states—in situations of intrastate conflict. This article challenges this perspective by analyzing the pandemic's impact on three dimensions of rebel activity—armed activity, popular support and recruitment, and rebel governance. It does so by using illustrative evidence from long-running insurgencies in Northeast India, characterized by long-term rebel weakness and minimal, if any, territorial control. The article finds that during the early, acute phase of the pandemic in 2020, state-imposed lockdowns, rebels’ own restrictions, and disruptions to supply chains constrained most dimensions of rebel activity. The easing of restrictions in 2021 revealed complex and multidimensional impacts on different armed groups, which often hinged on pre-existing positions such as armed group strength, strategy, relations with the state, and operational circumstances. These experiences of low-level insurgencies lacking territorial control add important qualifiers to the notion that rebels are inherently best placed to capitalize on stochastic shocks such as pandemics. Beyond the case of Northeast India, these findings make a number of contributions to the analysis of counterinsurgency and rebel governance.
Inferring cell diversity in single cell data using consortium-scale epigenetic data as a biological anchor for cell identity
Authors: Sun Yuliangzi , Shim Woo Jun , Shen Sophie , Sinniah Enakshi , Pham Duy , Su Zezhuo , Mizikovsky Dalia , White Melanie D , Ho Joshua W K , Nguyen Quan , Bodén Mikael , Palpant Nathan J
Published: May 2023

Methods for cell clustering and gene expression from single-cell RNA sequencing (scRNA-seq) data are essential for biological interpretation of cell processes. Here, we present TRIAGE-Cluster which uses genome-wide epigenetic data from diverse bio-samples to identify genes demarcating cell diversity in scRNA-seq data. By integrating patterns of repressive chromatin deposited across diverse cell types with weighted density estimation, TRIAGE-Cluster determines cell type clusters in a 2D UMAP space. We then present TRIAGE-ParseR, a machine learning method which evaluates gene expression rank lists to define gene groups governing the identity and function of cell types. We demonstrate the utility of this two-step approach using atlases of in vivo and in vitro cell diversification and organogenesis. We also provide a web accessible dashboard for analysis and download of data and software. Collectively, genome-wide epigenetic repression provides a versatile strategy to define cell diversity and study gene regulation of scRNA-seq data.
RNA binding protein PRRC2B mediates translation of specific mRNAs and regulates cell cycle progression
Authors: Jiang Feng , Hedaya Omar M , Khor EngSoon , Wu Jiangbin , Auguste Matthew , Yao Peng
Published: May 2023

Accumulating evidence suggests that posttranscriptional control of gene expression, including RNA splicing, transport, modification, translation and degradation, primarily relies on RNA binding proteins (RBPs). However, the functions of many RBPs remain understudied. Here, we characterized the function of a novel RBP, Proline-Rich Coiled-coil 2B (PRRC2B). Through photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation and sequencing (PAR-CLIP-seq), we identified transcriptome-wide CU- or GA-rich PRRC2B binding sites near the translation initiation codon on a specific cohort of mRNAs in HEK293T cells. These mRNAs, including oncogenes and cell cycle regulators such as CCND2 (cyclin D2), exhibited decreased translation upon PRRC2B knockdown as revealed by polysome-associated RNA-seq, resulting in reduced G1/S phase transition and cell proliferation. Antisense oligonucleotides blocking PRRC2B interactions with CCND2 mRNA decreased its translation, thus inhibiting G1/S transition and cell proliferation. Mechanistically, PRRC2B interactome analysis revealed RNA-independent interactions with eukaryotic translation initiation factors 3 (eIF3) and 4G2 (eIF4G2). The interaction with translation initiation factors is essential for PRRC2B function since the eIF3/eIF4G2-interacting defective mutant, unlike wild-type PRRC2B, failed to rescue the translation deficiency or cell proliferation inhibition caused by PRRC2B knockdown. Altogether, our findings reveal that PRRC2B is essential for efficiently translating specific proteins required for cell cycle progression and cell proliferation.
dbCAN3: automated carbohydrate-active enzyme and substrate annotation
Authors: Zheng Jinfang , Ge Qiwei , Yan Yuchen , Zhang Xinpeng , Huang Le , Yin Yanbin
Published: May 2023

Carbohydrate active enzymes (CAZymes) are made by various organisms for complex carbohydrate metabolism. Genome mining of CAZymes has become a routine data analysis in (meta-)genome projects, owing to the importance of CAZymes in bioenergy, microbiome, nutrition, agriculture, and global carbon recycling. In 2012, dbCAN was provided as an online web server for automated CAZyme annotation. dbCAN2 (https://bcb.unl.edu/dbCAN2) was further developed in 2018 as a meta server to combine multiple tools for improved CAZyme annotation. dbCAN2 also included CGC-Finder, a tool for identifying CAZyme gene clusters (CGCs) in (meta-)genomes. We have updated the meta server to dbCAN3 with the following new functions and components: (i) dbCAN-sub as a profile Hidden Markov Model database (HMMdb) for substrate prediction at the CAZyme subfamily level; (ii) searching against experimentally characterized polysaccharide utilization loci (PULs) with known glycan substates of the dbCAN-PUL database for substrate prediction at the CGC level; (iii) a majority voting method to consider all CAZymes with substrate predicted from dbCAN-sub for substrate prediction at the CGC level; (iv) improved data browsing and visualization of substrate prediction results on the website. In summary, dbCAN3 not only inherits all the functions of dbCAN2, but also integrates three new methods for glycan substrate prediction.
Screening for functional regulatory variants in open chromatin using GenIE-ATAC
Authors: Cooper Sarah , Schwartzentruber Jeremy , Coomber Eve L , Wu Qianxin , Bassett Andrew
Published: May 2023

Understanding the effects of genetic variation in gene regulatory elements is crucial to interpreting genome function. This is particularly pertinent for the hundreds of thousands of disease-associated variants identified by GWAS, which frequently sit within gene regulatory elements but whose functional effects are often unknown. Current methods are limited in their scalability and ability to assay regulatory variants in their endogenous context, independently of other tightly linked variants. Here, we present a new medium-throughput screening system: genome engineering based interrogation of enhancers assay for transposase accessible chromatin (GenIE-ATAC), that measures the effect of individual variants on chromatin accessibility in their endogenous genomic and chromatin context. We employ this assay to screen for the effects of regulatory variants in human induced pluripotent stem cells, validating a subset of causal variants, and extend our software package (rgenie) to analyse these new data. We demonstrate that this methodology can be used to understand the impact of defined deletions and point mutations within transcription factor binding sites. We thus establish GenIE-ATAC as a method to screen for the effect of gene regulatory element variation, allowing identification and prioritisation of causal variants from GWAS for functional follow-up and understanding the mechanisms of regulatory element function.
Extraordinary long-stem confers resistance of intrinsic terminators to processive antitermination
Authors: Miguel-Arribas Andrés , Martín-María Ana , Alaerds Eef C W , Val-Calvo Jorge , Yuste Luis , Rojo Fernando , Abia David , Wu Ling Juan , Meijer Wilfried J J
Published: May 2023

Many prokaryotic operons encode a processive antitermination (P-AT) system. Transcription complexes associated with an antitermination factor can bypass multiple transcription termination signals regardless of their sequences. However, to avoid compromising transcriptional regulation of downstream regions, the terminator at the end of the operon needs to be resistant to antitermination. So far, no studies on the mechanism of resistance to antitermination have been reported. The recently discovered conAn P-AT system is composed of two components that are encoded at the start of many conjugation operons on plasmids of Gram-positive bacteria. Here we report the identification of a conAn-resistant terminator, named TerR, in the conjugation operon of the Bacillus subtilis plasmid pLS20, re-defining the end of the conjugation operon. We investigated the various characteristics of TerR and show that its extraordinary long stem is the determining feature for resistance to antitermination. This is the first P-AT resistance mechanism to be reported.
Career Intention of Baccalaureate Student Nurses
Authors: Docherty Angie , Franklin Heather , Voss Heather , Dieckmann Nathan
Published: May 2023

AIM

This study had two aims: to determine initial career intention of nursing students and to assess whether nursing education variables predict career intentions toward public health/community health nursing.

BACKGROUND

Nursing graduates are expected to be prepared to work in community settings. However, there is uncertainty in whether students are attracted to these settings and whether nursing education is impactful in shaping career intention.

METHOD

A cross-sectional survey targeted baccalaureate and accelerated students across Oregon. Analyses utilized descriptive statistics and multiple regression.

RESULTS

Students reported most interest in acute care. Didactic and clinical learning were not related to intention to pursue a public health/community health career. The strongest predictor was career intention when starting nursing school.

CONCLUSION

Students enter nursing school with largely fixed intentions. Educators need to develop greater prenursing outreach and understanding of the drivers toward public and community health to build curricula and passion for this area of nursing.
International and Interprofessional Collaboration: An Innovative Week of Learning Across Three Professions, Three Universities, and One Ocean
Authors: Kazley Abby Swanson , Creed Joan M. , Grotenhuis Connie , Boissonneault Gilbert , Springer Hans , Alpay Laurence , Doms Rob
Published: May 2023

As the COVID-19 pandemic prevented planned international travel opportunities for students and faculty, faculty at three universities from three professions created a four-day innovative, online learning experience. Each session included presentations from each country, small-group discussions, and evaluation. The topics appealed to students regardless of profession or nationality. Daily evaluations showed attendees valued the experience. The benefits of international and interprofessional learning were evident; students gained better understanding of other professions and health care systems through sessions that expanded their thinking. International appreciation and learning can be prioritized without physical travel.
Early Empiric Antibiotic Use in Patients Hospitalized With COVID-19: A Retrospective Cohort Study*
Authors: Widere J. Christian , Davis Claire Leilani , Loomba Johanna Jean , Bell Taison D. , Enfield Kyle B. , Barros Andrew Julio ,   on behalf of the N3C Consortium
Published: May 2023

OBJECTIVE:

To investigate temporal trends and outcomes associated with early antibiotic prescribing in patients hospitalized with COVID-19.

DESIGN:

Retrospective propensity-matched cohort study using the National COVID Cohort Collaborative (N3C) database.

SETTING:

Sixty-six health systems throughout the United States that were contributing to the N3C database. Centers that had fewer than 500 admissions in their dataset were excluded.

PATIENTS:

Patients hospitalized with COVID-19 were included. Patients were defined to have early antibiotic use if they received at least 3 calendar days of intravenous antibiotics within the first 5 days of admission.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Of 322,867 qualifying first hospitalizations, 43,089 patients received early empiric antibiotics. Antibiotic use declined across all centers in the data collection period, from March 2020 (23%) to June 2022 (9.6%). Average rates of early empiric antibiotic use (EEAU) also varied significantly between centers (deviance explained 7.33% vs 20.0%, p < 0.001). Antibiotic use decreased slightly by day 2 of hospitalization and was significantly reduced by day 5. Mechanical ventilation before day 2 (odds ratio [OR] 3.57; 95% CI, 3.42–3.72), extracorporeal membrane oxygenation before day 2 (OR 2.14; 95% CI, 1.75–2.61), and early vasopressor use (OR 1.85; 95% CI, 1.78–1.93) but not region of residence was associated with EEAU. After propensity matching, EEAU was associated with an increased risk for in-hospital mortality (OR 1.27; 95% CI, 1.23–1.33), prolonged mechanical ventilation (OR 1.65; 95% CI, 1.50–1.82), late broad-spectrum antibiotic exposure (OR 3.24; 95% CI, 2.99–3.52), and late Clostridium difficile infection (OR 1.60; 95% CI, 1.37–1.87).

CONCLUSIONS:

Although treatment of COVID-19 patients with empiric antibiotics has declined during the pandemic, the frequency of use remains high. There is significant inter-center variation in antibiotic prescribing practices and evidence of potential harm. Our findings are hypothesis-generating and future work should prospectively compare outcomes and adverse events.
Genetic Problems, Diagnosis, and Cardiovascular Manifestations of Loeys-Dietz Syndrome
Authors: Dey Subo , Cheikhali Ryan , Frishman William H. , Aronow Wilbert S.
Published: May 2023

Loeys-Dietz Syndrome (LDS) is an autosomal dominant connective tissue disorder with multisystem involvement of wide spectrum, found to be associated with transforming growth factor-β pathway. LDS is characterized by craniofacial, skeletal, cutaneous, vascular abnormalities along with aortic aneurysm and aortic dissection contributing to mortality and morbidity at a young age. Therefore, timely diagnosis and intervention in patients with LDS is vital. Several gene mutations have been described as contributing factors of LDS, causing widespread and aggressive vascular disease. Based on these gene mutations, 5 types of LDS have been described so far. Besides aortic aneurysm and dissection, some of the other cardiac manifestations of LDS involve cardiomyopathy, valvular abnormality, atrial fibrillation, patent ductus arteriosus, atrial septal defects, etc. Routine imaging of patients’ vasculatures and aggressive medical and surgical management are key factors in managing patients with LDS.
Prevalence of Mental Health Diagnoses Among Early Adolescents Before and During Foster Care
Authors: Herd Toria , Palmer Lindsey , Font Sarah
Published: May 2023

Objective:

This study aimed to characterize the rates and types of diagnosed mental health (MH) disorders among children and adolescents before and during foster care (FC) overall and by race and ethnicity.

Methods:

We used population-based linked administrative data of medical assistance (public insurance) claims records and child protective services data from a cohort of early adolescents who entered FC at 10 to 14 years old. MH diagnoses were coded according to the International Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification (ICD-9 and ICD-10) and included adjustment disorders, disruptive disorders, attention-deficit/hyperactivity disorder (ADHD), anxiety disorders, mood disorders, attachment disorders, autism, and other disorders.

Results:

Before FC entry, 41% of children and adolescents had at least 1 MH diagnosis. Attention-deficit/hyperactivity disorder (25%), mood disorders (18%), and disruptive disorders (15%) were the most common pre-entry diagnoses. Among early adolescents entering FC with no previous diagnosis, 52% were later diagnosed with adjustment disorder (accounting for 73% of all youth with a new diagnosis during FC). White early adolescents had higher rates of diagnosed MH disorders before FC, whereas racial/ethnic minority early adolescents were more likely to receive a MH diagnosis during FC. Black early adolescents were more likely than White and Hispanic early adolescents to be diagnosed with disruptive disorders and less likely to be diagnosed with anxiety or adjustment disorders during FC.

Conclusion:

Results highlight the high rates of MH needs among early adolescents before entry into FC, whether detected before or during FC. Results also illustrate disparities in pre-entry MH care between racial/ethnic minority and White early adolescents, with minority youth less likely to be receiving services before entry.
Pathway to global elimination of hepatitis B: HBV cure is just the first step
Authors: Howell Jessica , Seaman Chris , Wallace Jack , Xiao Yinzong , Scott Nick , Davies Jane , de Santis Teresa , Adda Danjuma , El-Sayed Manal , Feld Jordan J. , Gane Edward , Lacombe Karine , Lesi Olufunmilayo , Mohamed Rosmawati , Silva Marcelo , Tu Thomas , Revill Peter , Hellard Margaret E.
Published: May 2023

Hepatitis B (HBV) is a major cause of global morbidity and mortality, and the leading cause of liver cancer worldwide. Significant advances have recently been made toward the development of a finite HBV treatment that achieves permanent loss of HBsAg and HBV DNA (so-called “HBV cure”), which could provide the means to eliminate HBV as a public health threat. However, the HBV cure is just one step toward achieving WHO HBV elimination targets by 2030, and much work must be done now to prepare for the successful implementation of the HBV cure. In this review, we describe the required steps to rapidly scale-up future HBV cure equitably. We present key actions required for successful HBV cure implementation, integrated within the World Health Organization (WHO) Global Health Sector Strategy (GHSS) 2022–2030 framework. Finally, we highlight what can be done now to progress toward the 2030 HBV elimination targets using available tools to ensure that we are preparing, but not waiting, for the cure.
The Effect of Health Literacy on Health-Related Quality of Life Among Saudi Women With Chronic Diseases
Authors: ALHALAL Eman , HADIDI Bayan , SAAD Abeer Fouad , HADIDI Jahra Ali
Published: May 2023

Background

Women have unique health concerns in the context of chronic illness. Although health literacy has been linked to health-related quality of life, the pathway by which some factors mediate this relationship has not been well examined among Saudi women with chronic disease.

Purpose

This study was designed to examine the relationship between health literacy and health-related quality of life and determine the mediating roles of healthy lifestyle and patient-centered care in explaining this relationship.

Methods

A cross-sectional study was used. A random sample of 20 primary healthcare centers in Saudi Arabia was selected. A convenience sample of 300 women diagnosed with a chronic illness was recruited from these centers. Structural equation modeling was used to test the proposed relationships.

Results

Controlling for women's age and education, the hypothesized model adequately fit the data. Health literacy and its dimensions were found to positively and directly affect both patient-centered care (β = 0.614, B = 0.189, p < .001) and healthy lifestyle behaviors (β = 0.550, B = 1.211, p < .001). Furthermore, both patient-centered care (β = 0.390, B = 1.301, p < .001) and healthy lifestyle behaviors (β = 0.322, B = 0.150, p < .001) were found to positively and directly affect health-related quality of life, whereas health literacy had significant, direct (β = 0.285, B = 0.292, p < .001) and indirect (β = 0.417, B = 0.428, p < .001) effects on health-related quality of life through patient-centered care and healthy lifestyle behaviors.

Conclusions/Implications for Practice

Special consideration should be given to health literacy, patient-centered care, and healthy lifestyle behaviors to enhance health-related quality of life in women with chronic illness. Gender-specific health services and interventions are needed to improve women's health literacy.
Prognostic Factors in Alcohol-associated Liver Disease Patients Presenting With First Evidence of Ascites
Authors: Fahoum Khalid , Shen Nicole T. , Basu Elora , Lee Jihui , Kaplan Alyson , Salajegheh Annaheta , Rosenblatt Russell , Jesudian Arun , Lucero Catherine , Fortune Brett , Safford Monika , Brown Robert S.
Published: May 2023

Goals:

To identify factors associated with transplantation and death in alcohol-associated liver disease (ALD) patients presenting with first evidence of ascites.

Background:

Ascites development is a poor prognostic sign for patients with cirrhosis. Among ALD patients, the baseline factors at time of ascites development that are associated with eventual transplantation or death are currently unknown.

Study:

Adult patients with ascites in the “Evaluating Alcohol Use in Alcohol-related Liver Disease Prospective Cohort Study” (NCT03267069 clinicaltrials.gov) were identified from 2016 to 2020. Demographic, clinical, and laboratory factors at initial ascites presentation were identified as potential predictors of transplant and death as competing risks.

Results:

A total of 96 patients were identified. Median (interquartile range) follow-up time was 2.00 years (0.87 to 3.85). By last follow-up, 34/96 patients had been transplanted (35.4%) and 11/96 had died (11.4%). Prognostic factors for transplant included age per decade [hazard ratio (HR): 0.52 (95% CI, 0.33 to 0.83)], employed status [HR: 0.35 (95% CI, 0.14 to 0.90)], and sodium [HR: 0.94 (95% CI, 0.90 to 0.99)], whereas prognostic factors for death were body mass index [HR: 1.11 (95% CI, 1.00 to 1.22)], Charlson index [HR: 2.14 [95% CI, 1.13 to 4.08]), Maddrey Discriminant Function >32 (HR: 5.88 (95% CI, 1.18, 29.39)], aspartate aminotransferase [HR: 0.99 (95% CI, 0.98 to 0.997)], and a prior 12-month abstinence period [HR: 5.53 (95% CI, 1.10 to 27.83)], adjusted for age, sex, and ALD subcategory.

Conclusions:

Several factors at initial ascites presentation are associated with increased risk of transplantation or death and validation in larger cohorts will allow for improved risk stratification for ALD patients.
Nursing Home Resident, Family, and Staff Perspectives on Achieving Comfort at End of Life
Authors: Tappen Ruth M. , Sopcheck Janet
Published: May 2023

Increasing numbers of US older adults die in long-term care facilities. This qualitative study explored nursing home resident, family member, and staff perspectives and preferences regarding end-of-life care for the resident. From 67 potential participants referred by staff, 47 were found eligible and consented, including 16 residents, 10 family members, and 20 staff. A semistructured questionnaire guided the interview process and included questions such as what matters most at the end of life and whether participants would opt for any of the 8 aggressive treatments proposed for a resident at the end of life. Data were analyzed using descriptive and pattern coding for thematic interpretation. The 3 themes that emerged were centrality of comfort, what matters most at the end of life, and promoting comfort. All participant groups overwhelmingly endorsed comfort as a priority. Some participants would accept aggressive treatment to alleviate suffering and promote comfort. Residents were concerned about the well-being of their families, whereas family members emphasized the importance of their presence and that their dying relatives were not suffering. Staff sometimes filled this role on their behalf. Ancillary staff emphasized bathing, dressing, and grooming the resident to preserve the resident's dignity. The results support comfort as a priority for care at the end of life and the need for more discussion to increase mutual agreement on goals of care and what promotes comfort for the resident and family.
Predicting Uterine Rupture Risk Using Lower Uterine Segment Measurement During Pregnancy With Cesarean History: How Reliable Is It? A Review
Authors: McLeish Shian F. , Murchison Amanda B. , Smith Dora M. , Ghahremani Taylor , Johnson Isaiah M. , Magann Everett F.
Published: May 2023

Importance

Uterine rupture during labor is a calamitous event that can result in maternal/neonatal morbidity/mortality. Lower uterine segment (LUS) thickness measurement is a proposed method to determine the risk factor of uterine rupture in women undergoing trial of labor after cesarean. Does this measurement predict uterine rupture risk?

Objectives

This review examines current evidence to determine if a thin LUS ultrasound diagnosis during pregnancy with prior cesarean delivery(s) can reliably predict uterine rupture risk while attempting vaginal birth after cesarean (VBAC).

Evidence Acquisition

Electronic databases (PubMed and CINAHL) were searched with one limitation of abstracts in English. Search terms used were “lower uterine segment” AND “risk(s)” AND “rupture” OR “dehiscence.

Results

After reviewing 164 identified articles, 15 were used in this review. Of the studies including LUS thickness measurement, notable differences were found: gestational age at time of measurement, full thickness measurement versus myometrial thickness, number of sonographers involved, ultrasound technique (transabdominal vs transvaginal), and blinding. Other factors influencing LUS thickness include fetal weight, amniotic fluid volume, and gestational age. The most recent systematic review and meta-analysis suggests that an LUS > 3.65 mm should be safe for a VBAC, 2–3.65 mm is probably safe, and <2 mm identifies a patient at higher risk for uterine rupture/dehiscence.

Conclusions

Study heterogeneity, absence of an agreed upon thickness threshold, poor correlation between ultrasound and MRI measurements, or physical cesarean measurements currently make VBAC uterine rupture risk prediction uncertain.

Relevance

Our aim is to analyze existing literature to determine if evidence supports LUS measurement in women undergoing VBAC after cesarean to determine risk of uterine rupture.

Target Audience

Obstetricians and gynecologist, family physicians

Learning Objectives

After completing this learning activity, the participant should be able to identify the differences and how they occur between studies evaluating the thinness of the LUS in women undergoing a trial of labor after cesarean delivery; compare the accuracy of LUS measurement between ultrasound, MRI, and physical measurement at cesarean delivery; and describe the factors that influence the thinness of the LUS.
Mixed Ovarian Neoplasms With Gastrointestinal-type Mucinous and Mullerian Epithelial Components
Authors: Chui Michael Herman , Ellenson Lora H.
Published: May 2023

Primary mucinous ovarian neoplasms, gastrointestinal-type (GI-type), are composed of mucin-producing tumor cells resembling intestinal goblet cells or gastric foveolar epithelium. In contrast to seromucinous tumors, which exhibit endocervical-type mucinous differentiation and are thought to be derived from endometriosis, the cell/tissue-of-origin of most GI-type mucinous ovarian tumors is unknown. We identified 8 GI-type mucinous ovarian tumors (cystadenomas, n=4; borderline tumor/carcinoma, n=4) with spatially distinct areas that showed morphologic features of Mullerian-type epithelial differentiation (ciliated cells or endometrioid-type glands). Immunohistochemistry for cell lineage markers and Alcian blue (pH 2.5)/Periodic Acid-Schiff staining were performed. Morphologically distinct components were isolated by microdissection, from which extracted DNA was analyzed by targeted next-generation sequencing. In all cases, immunohistochemistry demonstrated mucin-producing cells to be positive for at least one GI marker (CK20 or CDX2), while areas with morphologic features of Mullerian differentiation were positive for PAX8, ER and/or PR, and lacked expression of CK20 and CDX2; CK7 was strongly and diffusely positive in all tumor cells. Tumor cells with a gastric-type phenotype produced neutral mucin, while acidic mucin was present within intestinal-type goblet cells. Targeted sequencing revealed ARID1A mutations in all mixed borderline tumors/carcinomas (n=4); other recurrent genetic alterations included KRAS (n=2) and TP53 mutations (n=2). Shared mutations were present in paired Mullerian and GI-type mucinous tumor components in 4 mixed borderline tumors/carcinomas, with more shared mutations between components than private mutations specific to each component. All mixed borderline tumors/carcinomas were associated with endometriosis (n=3) or Mullerian inclusion cysts (n=1); mutation or loss of ARID1A expression was seen in these putative precursor lesions in 2 cases. Hence, ovarian neoplasms composed of clonally related GI-type mucinous and Mullerian-type epithelial components harbor ARID1A mutations and are frequently associated with endometriosis. The existence of a Mullerian stem/progenitor cell with the capacity to differentiate toward cell lineages within the GI-tract may be involved in the pathogenesis of at least a subset of GI-type mucinous ovarian neoplasms.