bluuebunny/crossref_metadata_2025 huggingface dataset:
Durability of Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Booster Vaccine Protection Against Omicron Among Healthcare Workers With a Vaccine Mandate
Authors: Richterman Aaron , Behrman Amy , Brennan Patrick J , O’Donnell Judith A , Snider Christopher K , Chaiyachati Krisda H
Published: June 2022

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has spread rapidly throughout the world since being identified in South Africa in November 2021. Few studies have assessed primary series and booster vaccine effectiveness against Omicron among US healthcare workers

Methods

We conducted a test-negative case-control design to estimate BNT162b2 and mRNA1273 primary vaccination and booster effectiveness against SARS-CoV-2 infection and symptomatic coronavirus disease 2019 during an Omicron surge among employees of the University of Pennsylvania Health System. The study period was between 1 July 2021 and 5 April 2022. We defined the Delta period as 1 July to 12 December 2021 and the Omicron period as beginning 12 December 21.

Results

Our sample included 14 520 tests (2776 [19%] positive)—7422 (506 [7%] positive) during Delta and 7098 (2270 [32%] positive) during Omicron. Benchmarked against Delta, the vaccine effectiveness of 2 vaccine doses was lower during Omicron, with no significant protection against infection. Booster doses added significant protection, although they also showed reduced effectiveness during Omicron. Compared with findings in employees who had received 2 vaccine doses, 3 doses of BNT162b2 had a relative effectiveness of 50% (95% confidence interval, 42%–56%) during Omicron, relative to 78% (63%–87%) during Delta; 3 doses of mRNA1273 had a relative effectiveness of 56% (45%–65%) during Omicron, relative to 96% (82%–99%) during Delta. Restricting the sample to symptomatic tests yielded similar results to our primary analysis. After initial waning in BNT162b2 booster protection against infection, it remained largely stable for ≥16 weeks after vaccination.

Conclusions

Our findings provide a strong rationale for boosters among healthcare workers in the Omicron era.
An information theory approach to network evolution models
Authors: Farzaneh Amirmohammad , Coon Justin P
Published: June 2022

A novel Markovian network evolution model is introduced and analysed by means of information theory. It will be proved that the model, called network evolution chain, is a stationary and ergodic stochastic process. Therefore, the asymptotic equipartition property can be applied to it. The model’s entropy rate and typical sequences are also explored. Extracting particular information from the network and methods to simulate network evolution in the continuous time domain are discussed. Additionally, the Erdős–Rényi network evolution chain is introduced as a subset of our model with the additional property of its stationary distribution matching the Erdős–Rényi random graph model. The stationary distributions of nodes and graphs are calculated for this subset alongside its entropy rate. The simulation results at the end of the article back up the proved theorems and calculated values.
Combining GWAS and TWAS to identify candidate causal genes for tocochromanol levels in maize grain
Authors: Wu Di , Li Xiaowei , Tanaka Ryokei , Wood Joshua C , Tibbs-Cortes Laura E , Magallanes-Lundback Maria , Bornowski Nolan , Hamilton John P , Vaillancourt Brieanne , Diepenbrock Christine H , Li Xianran , Deason Nicholas T , Schoenbaum Gregory R , Yu Jianming , Buell C Robin , DellaPenna Dean , Gore Michael A
Published: June 2022

Tocochromanols (tocopherols and tocotrienols, collectively vitamin E) are lipid-soluble antioxidants important for both plant fitness and human health. The main dietary sources of vitamin E are seed oils that often accumulate high levels of tocopherol isoforms with lower vitamin E activity. The tocochromanol biosynthetic pathway is conserved across plant species but an integrated view of the genes and mechanisms underlying natural variation of tocochromanol levels in seed of most cereal crops remains limited. To address this issue, we utilized the high mapping resolution of the maize Ames panel of ∼1,500 inbred lines scored with 12.2 million single-nucleotide polymorphisms to generate metabolomic (mature grain tocochromanols) and transcriptomic (developing grain) data sets for genetic mapping. By combining results from genome- and transcriptome-wide association studies, we identified a total of 13 candidate causal gene loci, including 5 that had not been previously associated with maize grain tocochromanols: 4 biosynthetic genes (arodeH2 paralog, dxs1, vte5, and vte7) and a plastid S-adenosyl methionine transporter (samt1). Expression quantitative trait locus (eQTL) mapping of these 13 gene loci revealed that they are predominantly regulated by cis-eQTL. Through a joint statistical analysis, we implicated cis-acting variants as responsible for colocalized eQTL and GWAS association signals. Our multiomics approach provided increased statistical power and mapping resolution to enable a detailed characterization of the genetic and regulatory architecture underlying tocochromanol accumulation in maize grain and provided insights for ongoing biofortification efforts to breed and/or engineer vitamin E and antioxidant levels in maize and other cereals.
Pathophysiological Mechanisms Explaining the Association Between Low Skeletal Muscle Mass and Cognitive Function
Authors: Oudbier Susanne Janette , Goh Jorming , Looijaard Stéphanie Marcella Leonie Maria , Reijnierse Esmee Mariëlle , Meskers Carolus Gerardus Maria , Maier Andrea Britta
Published: June 2022

Low skeletal muscle mass is associated with cognitive impairment and dementia in older adults. This review describes the possible underlying pathophysiological mechanisms: systemic inflammation, insulin metabolism, protein metabolism, and mitochondrial function. We hypothesize that the central tenet in this pathophysiology is the dysfunctional myokine secretion consequent to minimal physical activity. Myokines, such as fibronectin type III domain containing 5/irisin and cathepsin B, are released by physically active muscle and cross the blood–brain barrier. These myokines upregulate local neurotrophin expression such as brain-derived neurotrophic factor (BDNF) in the brain microenvironment. BDNF exerts anti-inflammatory effects that may be responsible for neuroprotection. Altered myokine secretion due to physical inactivity exacerbates inflammation and impairs muscle glucose metabolism, potentially affecting the transport of insulin across the blood–brain barrier. Our working model also suggests other underlying mechanisms. A negative systemic protein balance, commonly observed in older adults, contributes to low skeletal muscle mass and may also reflect deficient protein metabolism in brain tissues. As a result of age-related loss in skeletal muscle mass, decrease in the abundance of mitochondria and detriments in their function lead to a decrease in tissue oxidative capacity. Dysfunctional mitochondria in skeletal muscle and brain result in the excessive production of reactive oxygen species, which drives tissue oxidative stress and further perpetuates the dysfunction in mitochondria. Both oxidative stress and accumulation of mitochondrial DNA mutations due to aging drive cellular senescence. A targeted approach in the pathophysiology of low muscle mass and cognition could be to restore myokine balance by physical activity.
On the Rank of Hermitian Polynomials and the SOS Conjecture
Authors: Gao Yun , Ng Sui-Chung
Published: June 2022

Let $z\in \mathbb C^n$ and $\|z\|$ be its Euclidean norm. Ebenfelt proposed a conjecture regarding the possible ranks of the Hermitian polynomials in $z,\bar z$ of the form $A(z,\bar z)\|z\|^2$, known as the SOS conjecture, where SOS stands for “sums of squares”. In this article, we employ and extend the recent techniques developed for local orthogonal maps to study this conjecture and its generalizations to arbitrary signatures. We prove that for a given Hermitian form $\langle \cdot ,\cdot \rangle _\star $ on $\mathbb C^n$ of any signature with at least two nonzero eigenvalues, the ranks of the Hermitian polynomials of the form $A(z,\bar z)\|z\|^2_\star $ can only lie in certain disjoint intervals on the real line. Not only is this consistent with the SOS conjecture, but it also demonstrates that, in fact, the conjecture qualitatively holds in all signatures except the trivial ones. These intervals can be explicitly calculated in terms of $n$ and the signature of $\langle \cdot ,\cdot \rangle _\star $. In addition, the number of such intervals and their widths are of the same order as those stated in the SOS conjecture.
Nothing to see here: failed supernovae are faint or rare
Authors: Byrne R A , Fraser M
Published: June 2022

The absence of Type IIP core-collapse supernovae arising from progenitors above 17 solar masses suggests the existence of another evolutionary path by which massive stars end their lives. The direct collapse of a stellar core to a black hole without the production of a bright, explosive transient is expected to produce a long-lived, dim, red transient known as a failed supernova. Despite the detection of a number of candidates for disappearing massive stars in recent years, conclusive observational evidence for failed supernovae remains elusive. A custom-built pipeline designed for the detection of faint transients is used to re-analyse 10 yr of observations of 231 nearby galaxies from the PTF/ZTF surveys. This analysis recovers known supernovae, and yields a number of interesting transients. However, none of these are consistent with a failed supernova. Through Monte Carlo tests the recovery efficiency of our pipeline is quantified. By assuming failed supernovae occur as a Poissonian process with zero detections in the data set, 95 per cent upper limits to the rate of failed supernovae are calculated as a function of failed supernova absolute magnitude. We estimate failed supernovae to be less than 0.61, 0.33, 0.26, or 0.23 of the core-collapse SN rate for absolute magnitudes of −11, −12, −13, and −14, respectively. Finally, we show that if they exist, the Vera C. Rubin Observatory will find 1.7–3.7 failed SNe per year for an absolute bolometric luminosity of ∼6 × 1039 erg s−1 out to distances of 33–43 Mpc, depending on their assumed spectral energy distribution.
Exploring Potential for a Personalized Medicine Approach to Smoking Cessation With an American Indian Tribe
Authors: Carroll Dana Mowls , Murphy Sharon , Meier Ellen , Rhodes Kristine , Dorr Casey , Braaten Greg , Jacobson Pamala A , Frizzell Linda , Tyndale Rachel F , Hatsukami Dorothy , Hernandez Carol
Published: June 2022

Introduction

A potential precision medicine approach to smoking cessation is tailoring pharmacotherapy to a biomarker known as the nicotine metabolite ratio (NMR). Little is known about the potential impact and acceptability of this approach for American Indian (AI) persons.

Aims and Methods

Tribal-academic collaboration was formed and during 2019–2020 AI adults who smoke(N = 54) were recruited to (1) examine correlations between NMR, dependence, and smoking exposure; (2) assess the extent to which pharmacotherapy preference aligned with NMR-informed recommendations; (3) explore acceptability of NMR-informed pharmacotherapy selection. Participants provided samples for assessment of salivary NMR and urinary total nicotine equivalents (TNE) and completed a questionnaire that assessed cigarettes per day (CPD), Fagerstrom Test for Cigarette Dependence (FTCD), pharmacotherapy preference, and perceptions of NMR-informed pharmacotherapy selection.

Results

Significant positive correlations were observed between NMR and FTCD (r = 0.29;p = .0383) and its abbreviated version Heaviness of Smoking Index (HIS) (r = 0.28;p =.0426). Post-hoc analyses suggest that relationships between dependence and NMR were driven by time to first cigarette. Nonsignificant, but directionally consistent, relationships were observed between NMR and CPD (r = 0.21; p =0.1436) and TNE (r = 0.24;p = .2906). Most participants preferred nicotine replacement therapy (71%) over varenicline (29%) and preference for pharmacotherapy matched NMR-based recommendations in 54% of participants. NMR-informed pharmacotherapy selection was supported by 62% of participants.

Conclusion

In a sample of AI adults who smoke, NMR was related to cigarette dependence and about one-half of participants’ pharmacotherapy preference matched their NMR-informed recommendation. There was lower acceptability of NMR-informed approach in this sample of AI adults than prior studies among white or black/African American people who smoke.

Implications

Relationships between NMR, dependence, and self-preference for pharmacotherapy suggest that NMR-informed pharmacotherapy selection may have potential for enhancing smoking quitting success in this Tribe. Lower acceptability of NMR-informed pharmacotherapy in this Tribe suggests that this approach may not be equitably utilized. Future work could include identifying community-driven solutions to mitigate precision medicine concerns.
Reducing the Joy Deficit in Sociology: A Study of Transgender Joy
Authors: Shuster Stef M , Westbrook Laurel
Published: June 2022

Joy is a crucial element of people’s everyday lives that has been understudied by sociologists. This is particularly true for scholarship about transgender people. To address what we term a joy deficit in sociology, we analyze 40 in-depth interviews with trans people in which they were asked what they find joyful about being trans. Their responses demonstrate the methodological and theoretical importance of asking about joy. Four main themes emerged from the interviews. First, interviewees easily answered the question about joy. Second, contrary to common assumptions, we found that transgender people expressed joy in being members of a marginalized group and said that they preferred being transgender. Third, embracing a marginalized identity caused the quality of their lives to improve, increasing self-confidence, body positivity, and sense of peace. Finally, being from a marginalized group facilitated meaningful connections with other people. Our findings demonstrate a vital need to address the joy deficit that exists in the sociological scholarship on transgender people specifically, and marginalized groups more generally. Bridging the sociology of knowledge and narratives, we show how accentuating joy offers nuance to understandings of the lived experiences of marginalized people that has been absent from much of sociological scholarship.
NADPH and xanthine oxidases control induction of inflammatory mediator expression by organic dust in the lung
Authors: Meganathan Velmurugan , Hamilton Cory E. , Natarajan Kartiga , Keshava Shiva , Boggaram Vijay
Published: June 2022

Exposure to organic dust in animal and agricultural farms and the ensuing lung inflammation are linked to the development of respiratory diseases. We found previously that elevated production of reactive oxygen species (ROS) by aqueous poultry organic dust extract (hereafter referred to as dust extract) mediates induction of proinflammatory mediators in airway epithelial cells. In the present study, we investigated whether ROS generated by NADPH oxidases (NOX) and xanthine oxidase (XO) controls induction of inflammatory mediators by dust extract and the underlying mechanisms in bronchial epithelial cells. Using chemical inhibitors and siRNA targeted knockdown, we found that NOX1, NOX2, NOX4, and XO‐derived ROS regulates induction of proinflammatory mediator levels. Like airway epithelial cells in vitro, NOX inhibitor VAS2870 reduced keratinocyte chemoattractant (KC), IL‐6, and TNF‐α production and 4‐hydroxynonenal (4‐HNE) staining induced by dust extract in mouse lungs. VAS2870 inhibition of proinflammatory mediators was associated with reduced NFκB and Stat3 activation indicating that NOX generated ROS activates NFκB and Stat3 to induce proinflammatory gene expression. Dust extract increased the membrane association of p47phox in airway epithelial cells indicating NOX2 activation but had no effect on NOX2 protein levels. In summary, our studies have shown that NOX and XO generated ROS control organic dust induction of proinflammatory mediators in airway epithelial cells via NFκB and Stat3 activation.
Acyl‐CoA:wax alcohol acyltransferase 2 modulates the cone visual cycle in mouse retina
Authors: Widjaja‐Adhi Made Airanthi K. , Kolesnikov Alexander V. , Vasudevan Sreelakshmi , Park Paul S.‐H. , Kefalov Vladimir J. , Golczak Marcin
Published: June 2022

The daylight and color vision of diurnal vertebrates depends on cone photoreceptors. The capability of cones to operate and respond to changes in light brightness even under high illumination is attributed to their fast rate of recovery to the ground photosensitive state. This process requires the rapid replenishing of photoisomerized visual chromophore (11‐cis‐retinal) to regenerate cone visual pigments. Recently, several gene candidates have been proposed to contribute to the cone‐specific retinoid metabolism, including acyl‐CoA wax alcohol acyltransferase 2 (AWAT2, aka MFAT). Here, we evaluated the role of AWAT2 in the regeneration of visual chromophore by the phenotypic characterization of Awat2−/− mice. The global absence of AWAT2 enzymatic activity did not affect gross retinal morphology or the rate of visual chromophore regeneration by the canonical RPE65‐dependent visual cycle. Analysis of Awat2 expression indicated the presence of the enzyme throughout the murine retina, including the retinal pigment epithelium (RPE) and Müller cells. Electrophysiological recordings revealed reduced maximal rod and cone dark‐adapted responses in AWAT2‐deficient mice compared to control mice. While rod dark adaptation was not affected by the lack of AWAT2, M‐cone dark adaptation both in isolated retina and in vivo was significantly suppressed. Altogether, these results indicate that while AWAT2 is not required for the normal operation of the canonical visual cycle, it is a functional component of the cone‐specific visual chromophore regenerative pathway.
Adaptive increases in respiratory capacity and O2 affinity of subsarcolemmal mitochondria from skeletal muscle of high‐altitude deer mice
Authors: Dawson Neal J. , Scott Graham R.
Published: June 2022

Aerobic energy demands have led to the evolution of complex mitochondrial reticula in highly oxidative muscles, but the extent to which metabolic challenges can be met with adaptive changes in physiology of specific mitochondrial fractions remains unresolved. We examined mitochondrial mechanisms supporting adaptive increases in aerobic performance in deer mice (Peromyscus maniculatus) adapted to the hypoxic environment at high altitude. High‐altitude and low‐altitude mice were born and raised in captivity, and exposed as adults to normoxia or hypobaric hypoxia (12 kPa O2 for 6–8 weeks). Subsarcolemmal and intermyofibrillar mitochondria were isolated from the gastrocnemius, and a comprehensive substrate titration protocol was used to examine mitochondrial physiology and O2 kinetics by high‐resolution respirometry and fluorometry. High‐altitude mice had greater yield, respiratory capacity for oxidative phosphorylation, and O2 affinity (lower P50) of subsarcolemmal mitochondria compared to low‐altitude mice across environments, but there were no species difference in these traits in intermyofibrillar mitochondria. High‐altitude mice also had greater capacities of complex II relative to complexes I + II and higher succinate dehydrogenase activities in both mitochondrial fractions. Exposure to chronic hypoxia reduced reactive oxygen species (ROS) emission in high‐altitude mice but not in low‐altitude mice. Our findings suggest that functional changes in subsarcolemmal mitochondria contribute to improving aerobic performance in hypoxia in high‐altitude deer mice. Therefore, physiological variation in specific mitochondrial fractions can help overcome the metabolic challenges of life at high altitude.
Nurses have the key to your heart
Authors: Pellegrino Kristin , Breda Karen Lucas
Published: June 2022

Independent congestive heart failure management begins with nurse and patient education and can reduce hospital readmission.
Recent advances in the diagnosis and management of tree nut and seed allergy
Authors: Labrosse Roxane , Graham François , Caubet Jean-Christoph
Published: June 2022

Purpose of review

Tree nut (TN) and seed allergies are frequent, and their prevalence appears to be on the rise. Allergic reactions associated with these foods are more frequently severe, and these allergies tend to persist into adulthood, consequently affecting quality of life. In this review, we summarize recent advances in diagnostic modalities and management strategies for TN/seed-allergic patients.

Recent findings

Clinical manifestations of TN and seed allergy range from asymptomatic sensitization to severe anaphylactic reactions. The use of emerging diagnostic tools such as component resolved diagnostics (CRD) and the basophil activation test (BAT) can help better predict clinical reactivity, the latter being currently reserved for research settings. Strict avoidance of all TN is generally not required, as most patients can tolerate select TN despite co-sensitization. Oral immunotherapy (OIT) is a promising alternative treatment instead of complete avoidance of culprit allergens, as it can safely increase the allergy threshold.

Our recent understanding of co-reactivity between various TN and seeds has shaped management opportunities, including select TN introduction and optimization of OIT, two strategies which may improve quality of life. There is a need for better minimally invasive diagnostic methods for TN and seed allergy, with CRD and BAT being promising tools.
Comparison of the Wii Balance Board System and Foam Posturography System in Assessing Postural Balance
Authors: Huang Chuan-Ching , Hung Hsiang-Hsuan , Jaw Fu-Shan , Young Yi-Ho
Published: June 2022

Objective:

Falls are a major cause of disability and mortality in the elderly. Postural balance is associated with falls and can be evaluated by posturography. However, conventional posturography is costly and requires a sufficiently large space to perform. Hence, this study developed a portable system to meet the requirement of field studies, and investigated its reliability and validity.

Design:

A custom-written software application was developed to link a computer to the Nintendo Wii balance board (WBB) and the center of pressure was acquired, which was then compared with that obtained from commercially available foam posturography (FP). Forty younger adults including 20 patients with peripheral vestibular disorders as well as 20 healthy controls, and 50 older patients with peripheral vestibular disorders were enrolled. All subjects underwent postural balance testing using the WBB system (WBSS) and FP system (FPS) in a randomized order.

Results:

For the intersystem reliability, although the WBSS obtained a significantly smaller mean sway area than the FPS, both systems revealed adequate to excellent reliability with an intraclass correlation coefficient (ICC) of 0.67 to 0.87. The WBBS showed adequate to excellent test–retest reliability (ICC: 0.53 to 0.88). For the validity, the respective cutoff sway areas were 1.03 and 3.09 cm2 under conditions C and D via the WBBS for discriminating the fallers from nonfallers.

Conclusion:

The WBBS yielded adequate to excellent reliability and validity for accessing postural balance, and had good performance in discriminating the fallers from nonfallers. The WBBS has advantages over the commercial FPS of low cost, easy portability, programmability, and may be better-suited to mass detection and research programs. Most importantly, this WBBS can be performed outside the hospital for testing postural balance, especially in the elderly.
Bridging the Racial Divide
Authors: Dockery Tajuane H.
Published: June 2022

Recent civil unrest has proven that positive role models are essential to help bridge the nation's racial divide. Nurses are primed to be among these role models as trusted and respected healthcare professionals. Nursing's code of ethics defines nurses' moral obligations to respect all people and advocate for justice. Christian nurses face a higher calling: to love one's neighbors as themselves. This article explores the application of a Christian worldview of Fawcett's metaparadigm of nursing as a foundation for nurses to extend the love of Christ and promote racial healing.
Enhancing the Cultural Competence of Baccalaureate Nursing Students Through Short-term Study Abroad Programs
Authors: Nourse Somer Rae
Published: June 2022

The purpose of this study was to examine the experiences of baccalaureate nursing students on a short-term study abroad program to Peru and the effect on baccalaureate nursing student cultural competence. A qualitative descriptive study was conducted using student pretravel and posttravel journals. The major themes of advocacy, ethnocentric shift, and cultural competence emerged after the study abroad program. Results of this study will be used to inform and improve future study abroad programs to prepare students for a career caring for diverse clients.
Blood Pressure Screening in Faith Communities
Authors: Sailors Ronnette , Saint Debra , Ayer Nicole
Published: June 2022

There is a direct relationship between elevated blood pressure and cardiovascular disease, so screening for elevated blood pressure is an essential nursing activity. This quality improvement project involving faith community nurses (FCNs) in 24 congregations and other sites tracked readings of blood pressures taken, referrals made, and education sessions provided during a 21-month period. Surveys revealed the project increased participants' awareness about screenings, FCN services, and evidence-based protocols, in addition to identifying high-risk congregants for care and treatment.
Embedding Financial Services in Frequented, Trusted Settings: Building on Families' Pre-existing Economic Mobility Efforts
Authors: Alexander Savannah P. , Kim Inhye (Cellina) , Hatcher Cyndie , Suh Hyun Soo , Ha Yoonsook , Marcil Lucy E.
Published: June 2022

Objective:

The aim of this study was to understand parents'/guardians' experiences and aspirations around economic mobility and their impact on the acceptability and use of financial services embedded in frequented, trusted settings such as schools and pediatric clinics.

Method:

We recruited 18 English-speaking guardians with at least 1 child enrolled in a school for low-income families and eligible for Internal Revenue Service-sponsored free tax preparation. Each participant completed a semistructured interview before tax filing; a subset completed follow-up interviews. We used grounded theory analysis.

Results:

We developed the following theoretical model based on our key thematic findings to describe the acceptability and use of financial services within the context of guardians' lived experiences and pre-existing efforts to build economic mobility: Families experience multilevel barriers to economic mobility. Despite these barriers, guardians are proactively working to build economic mobility by empowering the next generation with knowledge, skills, and assets and resiliently pursuing economic goals. As a result, guardians will accept empowering, nonjudgmental, expert, and trustworthy financial services that contribute to their existing efforts. To move from acceptance to use, financial services must be effectively publicized, accessible, and supportive.

Conclusion:

Financial services may be more acceptable and used if they are embedded in trusted organizations and have expert, supportive staff with lived experience who empower guardians to work toward their economic goals, accessible platforms, and effective publicity. These characteristics may facilitate uptake and economic mobility. Trusted organizations serving young families can partner with financial services to test these findings and help families build economic mobility.
Sacubitril/Valsartan Improves Sexual Function and Fibrosis of the Clitoral and Vaginal Tissues in Female Spontaneously Hypertensive Rats
Authors: Zhuang Chenchen , Yi Guozi , Wang Wenjuan , Sun Runmin , Qi Miaomiao , Yu Jing
Published: June 2022

Female sexual dysfunction is common in hypertension. The effects of sacubitril/valsartan (SAC/VAL) as a potential therapy for hypertension and heart failure have not been studied in relation to sexual function and genital fibrosis in female spontaneously hypertensive rats (SHRs). Thirty female SHRs were administered VAL, SAC/VAL, or saline. Ten normotensive female Wistar–Kyoto (WKY) rats were included in the control group. We assessed estrous cyclicity and sexual behavior in the female rats. In addition, the morphology of clitoral and vaginal tissues was evaluated by histological analyses. Western blotting and enzyme-linked immunosorbent assays were used to assess the levels of fibrotic markers in vaginal and clitoral tissues. Furthermore, the protein levels of phosphatase and tensin homolog deleted from chromosome 10 (PTEN), phosphoinositide-3-kinase (PI3K), and AKT expression were measured by Western blotting. SAC/VAL treatment improved hypertension-induced sexual dysfunction, exhibited as a prolonged estrus phase, increased receptivity and proceptive events, and decreased aggressive events, compared with those of VAL treatment and control SHRs without treatments. In addition, SAC/VAL-treated SHRs had lower levels of fibrotic markers, estradiol, and estrogen receptor α/β than the levels of VAL-treated SHRs or SHRs without treatment. Moreover, SAC/VAL decreased p-PTEN expression and increased p-PI3K and p-AKT expression at the protein level compared with those in VAL treatment alone. VAL and SAC/VAL treatments have significantly increased sexual receptivity and proceptivity, decreased aggressiveness, and improved the fibrosis of vaginal and clitoral tissues in female SHRs. However, SAC/VAL treatment shows more effective results compared with VAL treatment, which may be related to the PTEN/PI3K/AKT pathway.
Ameliorative Role of Fluconazole Against Abdominal Aortic Constriction–Induced Cardiac Hypertrophy in Rats
Authors: Shoieb Sherif M. , Alammari Ahmad H. , Levasseur Jody , Silver Heidi , Dyck Jason R. B. , El-Kadi Ayman O. S.
Published: June 2022

Cytochrome P450 1B1 (CYP1B1) is known to be involved in the pathogenesis of several cardiovascular diseases, including cardiac hypertrophy and heart failure, through the formation of cardiotoxic metabolites named as mid-chain hydroxyeicosatetraenoic acids (HETEs). Recently, we have demonstrated that fluconazole decreases the level of mid-chain HETEs in human liver microsomes, inhibits human recombinant CYP1B1 activity, and protects against angiotensin II–induced cellular hypertrophy in H9c2 cells. Therefore, the overall purpose of this study was to elucidate the potential cardioprotective effect of fluconazole against cardiac hypertrophy induced by abdominal aortic constriction (AAC) in rats. Male Sprague–Dawley rats were randomly assigned into 4 groups such as sham control rats, fluconazole-treated (20 mg/kg daily for 4 weeks, intraperitoneal) sham rats, AAC rats, and fluconazole-treated (20 mg/kg) AAC rats. Baseline and 5 weeks post-AAC echocardiography were performed. Gene and protein expressions were measured using real-time PCR and Western blot analysis, respectively. The level of mid-chain HETEs was determined using liquid chromatography–mass spectrometry. Echocardiography results showed that fluconazole significantly prevented AAC-induced left ventricular hypertrophy because it ameliorated the AAC-mediated increase in left ventricular mass and wall measurements. In addition, fluconazole significantly prevented the AAC-mediated increase of hypertrophic markers. The antihypertrophic effect of fluconazole was associated with a significant inhibition of CYP1B1, CYP2C23, and 12-LOX and a reduction in the formation rate of mid-chain HETEs. This study demonstrates that fluconazole protects against left ventricular hypertrophy, and it highlights the potential repurposing of fluconazole as a mid-chain HETEs forming enzymes' inhibitor for the protection against cardiac hypertrophy.
Headaches in Traumatic Brain Injury: Improvement Over Time, Associations With Quality of Life, and Impact of Migraine-Type Headaches
Authors: Flynn Spencer , Moore Brian , van der Merwe Andre J. , Moses Anita , Lo Jessica , Shahim Pashtun , Chan Leighton
Published: June 2022

Objective:

To describe headache characteristics over time in patients with traumatic brain injury (TBI).

Setting:

Patients enrolled and followed at the National Institutes of Health Clinical Center between 2011 and 2020.

Participants:

There were 147 patients with TBI, with 74 mild TBI (mTBI), 49 moderate (modTBI), 24 severe (sTBI), and 20 individuals without brain injury (IWBIs).

Design:

Regular surveys of headache characteristics in patients with TBI were conducted. Patients were enrolled as early as 30 days post-injury and followed up to 5 years, for 419 total visits and 80 patients with multiple return visits.

Main Measures:

Surveys of headache characteristics, including headache severity, were measured on a 0- to 10-point Likert scale and headache frequency quantified as headaches per month. Patients with migraine-type headaches (n = 39) were identified by a clinician-administered tool. Functional outcomes were measured using the Glasgow Outcome Scale-Extended (GOS-E) and quality of life by the Satisfaction with Life Scale (SWLS) and the 36-item Short Form Survey (SF-36).

Results:

At their initial visit, patients with TBI had more severe and frequent headaches than IWBIs (median 5 vs 2.5, P < .001; median 2 vs 0.2, P < .001), as did patients with mTBI compared with modTBI/sTBI (all P ≤ .01). Migraines were associated with lower SWLS and SF-36 scores. Migraines and young age were associated with higher headache severity and frequency across time points. Longitudinally, time post-injury correlated with improvement in headache severity and frequency without differences by injury severity. However, time post-injury did not correlate with improvement in headache characteristics in a patient subgroup with moderate/severe headaches.

Conclusion:

Our findings suggest that patients with mild, moderate, or severe TBI see improvement in headaches over time. However, patients should be counseled that improvement is modest and seen more in patients with milder headache symptoms. Patients with migraine headaches in particular are at risk for worse headache characteristics with greater impact on quality of life.
IMPACT OF PENETRATION AND IMAGE ANALYSIS IN OPTICAL COHERENCE TOMOGRAPHY ON THE MEASUREMENT OF CHOROIDAL VASCULARITY PARAMETERS
Authors: Chen Sisi , Zheng Gu , Yu Xiangle , Jiang Yanfeng , Lin Zhiyang , Lin Guangqing , Chen Wen , Shen Meixiao , Lu Fan
Published: June 2022

Purpose:

To investigate the impact of penetration and image analysis in different optical coherence tomography (OCT) instruments on the measurement of choroidal vascularity parameters.

Methods:

Twenty-three healthy volunteers were imaged using two swept-source OCTs and one spectral-domain OCT. A fully automatic segmentation method based on ResNet-UNet and Niblack local threshold binarization was performed to quantify the relevant choroidal vascular parameters, including choroidal vascularity index, total choroidal volume, and luminal volume. The intraclass correlation coefficient (ICC) and coefficient of repeatability (COR) were used to analyze the repeatability and consistency of automatic and manual segmentation, respectively.

Results:

Both swept-source OCT devices showed good consistency of luminal volume and total choroidal volume measurements (all ICC value >0.98 with COR% < 8.53%) based on manual segmentation, whereas the consistency of the spectral-domain OCT was lower (ICC value <0.60 with COR% > 40%), which was greatly improved after using the automatic algorithm (ICC value >0.99 with COR% < 4%). The repeatability of choroidal vascularity index obtained from different OCT images using manual or automatic segmentation showed good agreement (all ICC values >0.85), whereas the choroidal vascularity index measurement from the spectral-domain OCT was larger than the other two swept-source OCT devices (ICC value <0.65).

Conclusion:

For healthy youngsters, the penetration of OCT plays a role in the measurement precision for choroidal vascularity parameters, and automatic segmentation can improve the ability of choroidal boundary identification with deficient penetration, suggesting these factors need to be considered in clinical work.
DETECTION AND LOCALIZATION OF RETINAL BREAKS IN ULTRAWIDEFIELD FUNDUS PHOTOGRAPHY USING a YOLO v3 ARCHITECTURE-BASED DEEP LEARNING MODEL
Authors: Oh Richul , Oh Baek-Lok , Lee Eun Kyoung , Park Un Chul , Yu Hyeong Gon , Yoon Chang Ki
Published: June 2022

Purpose:

We aimed to develop a deep learning model for detecting and localizing retinal breaks in ultrawidefield fundus (UWF) images.

Methods:

We retrospectively enrolled treatment-naive patients diagnosed with retinal break or rhegmatogenous retinal detachment and who had UWF images. The YOLO v3 architecture backbone was used to develop the model, using transfer learning. The performance of the model was evaluated using per-image classification and per-object detection.

Results:

Overall, 4,505 UWF images from 940 patients were used in the current study. Among them, 306 UWF images from 84 patients were included in the test set. In per-object detection, the average precision for the object detection model considering every retinal break was 0.840. With the best threshold, the overall precision, recall, and F1 score were 0.6800, 0.9189, and 0.7816, respectively. In the per-image classification, the model showed an area under the receiver operating characteristic curve of 0.957 within the test set. The overall accuracy, sensitivity, and specificity in the test data set were 0.9085, 0.8966, and 0.9158, respectively.

Conclusion:

The UWF image-based deep learning model evaluated in the current study performed well in diagnosing and locating retinal breaks.
FDA Emergency Use Authorization-Approved Novel Coronavirus Disease 2019, Pressure-Regulated, Mechanical Ventilator Splitter That Enables Differential Compliance Multiplexing
Authors: Paulsen Michael J. , Zhu Yuanjia , Park Matthew H. , Imbrie-Moore Annabel M. , Baker Sam , Walter Edmonston David , Dawson Tyler , Ly Evan , Martin Bell Shannon , Tran Nick A. , Jung Jinsuh , Cedarleaf-Pavy Jordan , Sridhar K. R. , Venkataraman Venkat , Woo Y. Joseph
Published: June 2022

Infection with the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may cause viral pneumonia and acute respiratory distress syndrome (ARDS). Treatment of ARDS often requires mechanical ventilation and may take weeks for resolution. In areas with a large outbreaks, there may be shortages of ventilators available. While rudimentary methods for ventilator splitting have been described, given the range of independent ventilatory settings required for each patient, this solution is suboptimal. Here, we describe a device that can split a ventilator among up to four patients while allowing for individualized settings. The device has been validated in vitro and in vivo.
Development and validation of a nomogram for predicting the likelihood of metastasis in prostate cancer patients undergoing Ga-68 PSMA PET/CT due to biochemical recurrence
Authors: Coskun Nazim , Kartal M. Oguz , Erdogan A. Sinem , Ozdemir Elif
Published: June 2022

Objective

To develop a nomogram based on commonly used clinical data for predicting the likelihood of metastasis in gallium-68 prostate-specific membrane antigen PET/computed tomography (Ga-68 PSMA PET/CT) scans of prostate cancer patients with confirmed biochemical recurrence (BCR).

Methods

One-hundred thirty-five (n = 135) patients who underwent Ga-68 PSMA PET/CT due to BCR were included in the study. Predictors of metastasis in Ga-68 PSMA PET/CT were determined with multivariable logistic regression analysis. Coefficients derived from the regression model were used to develop a prediction nomogram. The performance of the prediction model was evaluated with receiver operating characteristic analysis. Internal validation was performed with 50 bootstrap resamples, and the nomogram’s clinical benefit was assessed with decision curve analysis.

Results

Multivariable logistic regression analysis revealed that ISUP group, prostate-specific antigen (PSA) before PET and PSA doubling time were independent predictors of metastasis in Ga-68 PSMA PET/CT. A prediction nomogram was developed according to this model [the area under curve: 0.866; 95% confidence interval (CI), 0.788–0.944]. The best cutoff value of the nomogram-derived likelihood for predicting metastasis was 60%, with a bootstrap-corrected accuracy of 78.8%. An online version of the nomogram was implemented on pro-gram.nzm.co (https://pro-gram.nzm.co).

Conclusion

The proposed nomogram provides a practical approach for predicting the likelihood of imaging-based metastasis according to Ga-68 PSMA PET/CT in patients with BCR, with results ≥60% being the most accurate cutoff for referring patients to Ga-68 PSMA PET/CT. If validated in a larger cohort, this tool can serve as a guide for the appropriate use of Ga-68 PSMA PET/CT.
Mycophenolate Mofetil Use Is Associated With Reduced Incidence of Food Allergy in Liver Transplanted Children
Authors: Haflidadottir Svanhildur , Østensen Anniken Bjørnstad , Matthews Iren Lindbak , Line Pål-Dag , Almaas Runar
Published: June 2022

Objectives:

The incidence of food allergy in children following liver transplantation is high, and the pathogenesis is still not known. We aimed to identify risk factors for development of food allergies in liver transplant children.

Methods:

One hundred seven children and adolescents who underwent liver transplantation from 1999 to 2019 were included. Data were retrospectively collected from medical records and included total and specific immunoglobulin E (IgE), eosinophil cationic protein, and eosinophil count 12 months after transplantation and at yearly follow-up (median follow-up).

Results:

Twenty-four/107 (22%) patients reported clinical food reactions. Median time from transplantation to debut of food allergy was 1.6 [interquartile range (IQR): 0.6–3.3] years. Mycophenolate mofetil (MMF) was discontinued in 24 out of 78 patients (31%) due to side effects. Children treated with MMF in addition to tacrolimus 1 year after transplantation reported less food allergy (12.5% vs 37.8%, P = 0.003) and sensitization to food allergens one year after transplantation (8.9% vs 17.8%, P = 0.02) than those not receiving MMF. Tacrolimus trough levels did not differ between the patients treated with MMF and those who were not. Treatment with MMF 2 years after transplantation was associated with less food allergy (P = 0.001) and food sensitization (P = 0.002), also when adjusted for age at transplantation (P = 0.006 and P = 0.03, respectively) or for use of basilixmab (P = 0.015 and P = 0.018, respectively). Basiliximab was also associated with less food allergies.

Conclusions:

Use of MMF 1 and 2 years after transplantation was associated with less food allergy and sensitization against food allergens. The effect of MMF was not due to reduced trough levels of tacrolimus.
Effectiveness of International Hospice and Palliative Care Training for Health Care Professionals in Countries of the Western Pacific Region
Authors: Na Hyunjoo , Lee Gyungjoo , Hwang Hye-lyung , Kim Sujeong , Yong Jinsun
Published: June 2022

As hospice and palliative care is a holistic service grounded in spirituality, training in spiritual care is essential. This study aimed to describe an international workforce training program for hospice and palliative care that emphasized spiritual care and evaluate the effectiveness of the training implementation. A quasi-experimental study was conducted with 28 health care professionals from 4 countries in the Western Pacific Region, who attended the international workforce trainings on hospice and palliative care. Data were collected before and after the trainings using a self-reported survey questionnaire. The participants' palliative care knowledge, spiritual well-being, perceived stress, and compassion competency were analyzed to evaluate the training program. Whereas the participants' knowledge of hospice and palliative care (P < .001) and compassion competency increased (P = .004), their perceived stress decreased post training (P = .002). This study provided an extensive description of an international workforce training program of hospice and palliative care for potential replication of the training in other regions of the world. Because training in hospice and palliative care positively influenced health care professionals' spiritual care competency, future training and studies should consider spiritual care factors, along with intellectual aspects.
“I Didn't Want My Baby to Pass, But I Didn't Want Him Suffering Either”
Authors: Broden Elizabeth G. , Hinds Pamela S. , Werner-Lin Allison V. , Curley Martha A. Q. ,   for the RESTORE Study Investigators
Published: June 2022

Little is known about how nursing care at the end of a child's life impacts long-term parental bereavement. We aimed to explain, contextualize, and examine comparisons between quantitative trends in children's end-of-life care and parents' qualitative perceptions. We used a mixed methods design, combining quantitative data from the RESTORE clinical trial with qualitative interviews with bereaved parents. Patients who died during RESTORE were included in quantitative analyses. A subset of their parents was interviewed 7 to 11 years later. The quantitative analyses included 104 children. Eight parents were interviewed; 4 had a child die after cancer, and 4 had a child die after a complex chronic illness. Quantitatively, patients' pain and sedation scores were generally comfortable. Children died with multiple invasive devices in place. Parents' descriptions of their child's comfort and critical care requirements differed by illness trajectory (cancer, complex chronic illness). Parents' memories of their child's suffering aligned with peaks in clinical scores, rather than averages. Invasive devices and equipment altered parents' ability to make meaningful final memories with the dying child. Pediatric intensive care clinicians may need to broaden how they attend to dying children's pain and corresponding parental distress, as parents' memories of their dying child's suffering persist for years.
Challenges in Palliative Care Nursing at a University Hospital
Authors: Zeilinger Elisabeth L. , Gabal Ablah , Adamidis Feroniki , Popov Petar , Jaeger Karin , Hufgard-Leitner Miriam , Brettner Robert , Titzer Harald , Masel Eva Katharina , Unseld Matthias
Published: June 2022

We examined the perception of palliative care nurses regarding challenges, coping strategies, resources, and needs when working in a university hospital in Austria. A qualitative descriptive design was applied, using semistructured interviews with 8 female and 2 male nurses. All interviews were recorded as digital audio and transcribed verbatim. We used thematic analysis and MAXQDA. In our analysis, 6 themes emerged: Four themes related to challenges: (a) lack of a supporting structural framework, (b) conflict in interdisciplinary work, (c) conflict with caregivers, and (d) dealing with death in a highly specialized university environment. One theme related to (e) individual solutions and coping strategies, and 1 theme comprised (f) needs and suggestions for improvements. Taking care of the family of a dying person, handling threatening situation, and working with inexperienced physicians were among the most important challenges reported by nurses. A supportive team, professional counseling, and training related to communication skills and to culturally specific needs of families are perceived to be necessary to provide high-quality palliative care. Addressing the needs of nurses can substantially improve their working condition and has an impact not only on the nurses themselves but also on the quality of patient care.