bluuebunny/crossref_metadata_2025 huggingface dataset:
Scaling of inverted PTB7-Th: PC71BM organic solar cell for large area organic photovoltaic modules
Authors: Usmani Belal , Ranjan Rahul , Gupta Raju Kumar , Garg Ashish
Published: June 2024

Performance studies of large area inverted organic photovoltaic (OPV) modules of configuration ITO/ZnO/PTB7-Th: PC71BM/MoO3/Ag are performed. At a laboratory of scale 0.06 cm2, this device configuration repeatedly demonstrates the power conversion efficiency (PCE) of ∼9%, which is within the range of PCE normally achieved for this configuration. The OPV modules with active area of 9.25 cm2 and 63 cm2 are fabricated employing spin coating techniques comprising a total area 25 cm2 (5 cm × 5 cm) and 144 cm2 (11 cm × 11 cm), respectively. The 25 cm2 module, composed of five cells connected in series show PCE of 3.256%, with short-circuit current (Jsc), open circuit voltage (Voc), and fill factor (FF), 3.210 mAcm−2, 3.20 V, and 31.719%. However, The 144 cm2 modules, composed of 10 cells connected in series show PCE 1.019, Jsc, Voc, and FF, 0.87 mAcm−2, 4.20 V, and 27.877%. The PCE dropped by 63.89% for modules of active area of 9.25 cm2 and 88.68% of modules of active area of 63 cm2. The PCE of the modules is decreased sharply due to loss in FF, and Jsc of the modules. These losses are exhibits due to quality of layer morphology, layer interfaces, and design of module. The PCE could be potentially improved up to the desired value by the further optimization of layer morphology, layer interfaces, design of module geometry, and film deposition/printing methods. The results showed that PTB7-Th: PC71BM is a splendid structure for future organic solar modules due to its high performance and compatibility with large area coatings.
Transcriptome and metabolome atlas reveals contributions of sphingosine and chlorogenic acid to cold tolerance in Citrus
Authors: Xiao Peng , Qu Jing , Wang Yue , Fang Tian , Xiao Wei , Wang Yilei , Zhang Yu , Khan Madiha , Chen Qiyu , Xu Xiaoyong , Li Chunlong , Liu Ji-Hong
Published: June 2024

Citrus is one of the most important fruit crop genera in the world, but many Citrus species are vulnerable to cold stress. Ichang papeda (Citrus ichangensis), a cold-hardy citrus species, holds great potential for identifying valuable metabolites that are critical for cold tolerance in Citrus. However, the metabolic changes and underlying mechanisms that regulate Ichang papeda cold tolerance remain largely unknown. In this study, we compared the metabolomes and transcriptomes of Ichang papeda and HB pummelo (Citrus grandis “Hirado Buntan”, a cold-sensitive species) to explore the critical metabolites and genes responsible for cold tolerance. Metabolomic analyses led to the identification of common and genotype-specific metabolites, consistent with transcriptomic alterations. Compared to HB pummelo under cold stress, Ichang papeda accumulated more sugars, flavonoids, and unsaturated fatty acids, which are well-characterized metabolites involved in stress responses. Interestingly, sphingosine and chlorogenic acid substantially accumulated only in Ichang papeda. Knockdown of CiSPT (C. ichangensis serine palmitoyltransferase) and CiHCT2 (C. ichangensis hydroxycinnamoyl-CoA: shikimate hydroxycinnamoyltransferase2), two genes involved in sphingosine and chlorogenic acid biosynthesis, dramatically decreased endogenous sphingosine and chlorogenic acid levels, respectively. This reduction in sphingosine and chlorogenic acid notably compromised the cold tolerance of Ichang papeda, whereas exogenous application of these metabolites increased plant cold tolerance. Taken together, our findings indicate that greater accumulation of a spectrum of metabolites, particularly sphingosine and chlorogenic acid, promotes cold tolerance in cold-tolerant citrus species. These findings broaden our understanding of plant metabolic alterations in response to cold stress and provide valuable targets that can be manipulated to improve Citrus cold tolerance.
LUX ARRHYTHMO links CBF pathway and jasmonic acid metabolism to regulate cold tolerance of tea plants
Authors: Wang Yanli , Tong Wei , Li Fangdong , Samarina Lidiia , Li Penghui , Yang Tianyuan , Zhang Zhaoliang , Yi Lianghui , Zhai Fei , Wang Xinchao , Xia Enhua
Published: June 2024

Cold stress declines the quality and yield of tea, yet the molecular basis underlying cold tolerance of tea plants (Camellia sinensis) remains largely unknown. Here, we identified a circadian rhythm component LUX ARRHYTHMO (LUX) that potentially regulates cold tolerance of tea plants through a genome-wide association study and transcriptomic analysis. The expression of CsLUX phased with sunrise and sunset and was strongly induced by cold stress. Genetic assays indicated that CsLUX is a positive regulator of freezing tolerance in tea plants. CsLUX was directly activated by CsCBF1 and repressed the expression level of CsLOX2, which regulates the cold tolerance of tea plants through dynamically modulating jasmonic acid content. Furthermore, we showed that the CsLUX–CsJAZ1 complex attenuated the physical interaction of CsJAZ1 with CsICE1, liberating CsICE1 with transcriptional activities to withstand cold stress. Notably, a single-nucleotide variation of C-to-A in the coding region of CsLUX was functionally validated as the potential elite haplotype for cold response, which provided valuable molecular markers for future cold resistance breeding in tea plants.
Running Fermi calculations as a superpower to gauge reality
Authors: Oliveira-Filho Edmar R , Campos-Silva Rodrigo , Hanson Andrew D
Published: June 2024

Making Fermi calculations is a way to estimate rough but reliable numbers that enable right reasoning in science and engineering—and a skill that all scientists should practice.
Emergence of bacterial glass
Authors: Lama Hisay , Yamamoto Masahiro J , Furuta Yujiro , Shimaya Takuro , Takeuchi Kazumasa A
Published: June 2024

Densely packed, motile bacteria can adopt collective states not seen in conventional, passive materials. These states remain in many ways mysterious, and their physical characterization can aid our understanding of natural bacterial colonies and biofilms as well as materials in general. Here, we overcome challenges associated with generating uniformly growing, large, quasi-two-dimensional bacterial assemblies by a membrane-based microfluidic device and report the emergence of glassy states in two-dimensional suspension of Escherichia coli. As the number density increases by cell growth, populations of motile bacteria transition to a glassy state, where cells are packed and unable to move. This takes place in two steps, the first one suppressing only the orientational modes and the second one vitrifying the motion completely. Characterizing each phase through statistical analyses and investigations of individual motion of bacteria, we find not only characteristic features of glass such as rapid slowdown, dynamic heterogeneity, and cage effects, but also a few properties distinguished from those of thermal glass. These distinctive properties include the spontaneous formation of micro-domains of aligned cells with collective motion, the appearance of an unusual signal in the dynamic susceptibility, and the dynamic slowdown with a density dependence generally forbidden for thermal systems. Our results are expected to capture general characteristics of such active rod glass, which may serve as a physical mechanism underlying dense bacterial aggregates.
Lobbyists and Their Obligation to the Public Interest
Authors: Holyoke Thomas T
Published: June 2024

Lobbying in the United States is protected by the First Amendment's petitioning clause, so the profession cannot be suppressed, merely regulated. Since efforts to enact new regulations on the lobbying profession have largely stalled, there is a growing interest in having lobbyists regulate themselves with a canon of ethics provided by their professional associations. Many professions self-regulate, and many articulate obligations to serve the public interest. But what would it mean for lobbyists to serve the public interest? What could their ethical public service obligation be? In this article, I argue that because lobbying is protected by the Constitution, lobbyists have a reciprocal duty to serve the public interest. This creates a duality in how they view their job, as an advocate and as a guide. Following the ideas of Cassinelli, which are based on those of Rousseau, I argue that lobbyists can serve the public by engaging the people they represent, their interest group members or corporate clients, in deliberations that help them articulate their own interests and help them understand and appreciate the concerns and fears of other interests against whom they are competing to shape policy. While always vigorously lobbying for their members or clients, lobbyists also strengthen democracy and thus serve the public interest by helping those they represent empathize with others and perhaps find some common ground.
Enhancing angiogenesis in peri-implant soft tissue with bioactive silk fibroin microgroove coatings on zirconia surfaces
Authors: Wang Zhihan , Tuerxun Palati , Ng Takkun , Yan Yinuo , Zhao Ke , Jian Yutao , Jia Xiaoshi
Published: June 2024

Zirconia abutments and restorations have improved the aesthetic appeal of implant restoration, yet peri-implantitis poses a significant threat to long-term success. The soft tissue surrounding implants is a crucial biological barrier against inflammation and subsequent bone loss. Peri-implantitis, akin to periodontitis, progresses rapidly and causes extensive tissue damage. Variations in tissue structure significantly influence disease progression, particularly the lower vascular density in peri-implant connective tissue, compromising its ability to combat infection and provide essential nutrients. Blood vessels within this tissue are vital for healing, with angiogenesis playing a key role in immune defense and tissue repair. Enhancing peri-implant soft tissue angiogenesis holds promise for tissue integration and inflammation control. Microgroove surfaces have shown potential in guiding vessel growth, but using subtractive technologies to carve microgrooves on zirconia surfaces may compromise mechanical integrity. In this study, we utilized inkjet printing to prepare bioactive silk fibroin microgrooves (SFMG) coating with different sizes on zirconia surfaces. SFMG coating, particularly with 90 µm width and 10 µm depth, effectively directed human umbilical vein endothelial cells (HUVECs) along microgrooves, promoting their proliferation, migration, and tube formation. The expression of vascular endothelial growth factor A and fibroblast growth factor in HUVECs growing on SFMG coating was upregulated. Additionally, the SFMG coating activated the PI3K-AKT pathway and increased glycolytic enzyme gene expression in HUVECs. In conclusion, SFMG coating enhances HUVEC growth and angiogenesis potential by activating the PI3K-AKT pathway and glycolysis, showing promise for improving tissue integration and mitigating inflammation in zirconia abutments and restorations.
Retheorizing Intersectional Identities with the Study of Chinese LGBTQ+ Migrants
Authors: Yang Tori Shucheng , Ghaziani Amin
Published: June 2024

Intersectionality has transformed our understanding of how multiple axes of power mutually shape social inequalities. However, significant questions arise when applying the theory’s macro-level structural insights to identities on experiential, interactional, and situational levels. In this article, we retheorize intersectionality as a processual outcome. Drawing on in-depth interviews with skilled Chinese LGBTQ+ migrants in North America (n = 50), we detail three challenges that arise when individuals negotiate multiple identities across shifting interactions in national contexts: conflicts, disidentification, and indetermination. Each theme captures how individuals actively reconfigure identities while maintaining a continuous experience of mutual constitution. Instead of cohering into a unity, even one that is greater than the sum of its parts, our findings suggest that intersectionality is in an ongoing process of making, unmaking, and remaking.
Ambient Air Pollution Exposures and Child Executive Function: A US Multicohort Study
Authors: Ni Yu , Sullivan Alexis , Szpiro Adam A. , Peng James , Loftus Christine T. , Hazlehurst Marnie F. , Sherris Allison , Wallace Erin R. , Murphy Laura E. , Nguyen Ruby H. N. , Swan Shanna H. , Sathyanarayana Sheela , Barrett Emily S. , Mason W. Alex , Bush Nicole R. , Karr Catherine J. , LeWinn Kaja Z.
Published: June 2024

Background:

Executive function, which develops rapidly in childhood, enables problem-solving, focused attention, and planning. Animal models describe executive function decrements associated with ambient air pollution exposure, but epidemiologic studies are limited.

Methods:

We examined associations between early childhood air pollution exposure and school-aged executive function in 1235 children from three US pregnancy cohorts in the ECHO-PATHWAYS Consortium. We derived point-based residential exposures to ambient particulate matter ≤2.5 µm in aerodynamic diameter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) at ages 0–4 years from spatiotemporal models with a 2-week resolution. We assessed executive function across three domains, cognitive flexibility, working memory, and inhibitory control, using performance-based measures and calculated a composite score quantifying overall performance. We fitted linear regressions to assess air pollution and child executive function associations, adjusting for sociodemographic characteristics, maternal mental health, and health behaviors, and examined modification by child sex, maternal education, and neighborhood educational opportunity.

Results:

In the overall sample, we found hypothesized inverse associations in crude but not adjusted models. Modified associations between NO2 exposure and working memory by neighborhood education opportunity were present (P
interaction = 0.05), with inverse associations more pronounced in the “high” and “very high” categories. Associations of interest did not differ by child sex or maternal education.

Conclusion:

This work contributes to the evolving science regarding early-life environmental exposures and child development. There remains a need for continued exploration in future research endeavors, to elucidate the complex interplay between natural environment and social determinants influencing child neurodevelopment.
Aortic Stiffness Is Associated With Higher Nighttime Ambulatory Blood Pressure in Middle-Aged and Older Adults
Authors: Carlini Nicholas A. , Stump Olivia E. , Lumadue Elizabeth J. , Harber Matthew P. , Fleenor Bradley S.
Published: June 2024

Purpose:

The objective of this study was to determine the relationship between aortic stiffening and brachial and central ambulatory blood pressure (AMBP) in a nonclinical sample of middle-aged and older adults (MA/O). We hypothesized aortic stiffness would be positively associated with 24-hr, daytime, and nighttime brachial and central AMBP.

Methods:

Fifty-one participants aged ≥50 yr (21 males and 30 females, mean age 63.4 ± 9.0 yr) with a body mass index <35 kg/m2 who also had a resting brachial blood pressure (BP) <160/100 mmHg with or without BP medications were recruited for this cross-sectional analysis. All participants underwent measures of aortic stiffness (carotid-femoral pulse wave velocity [cfPWV]) and 24-hr AMBP monitoring. Bivariate correlations assessed the relationship between cfPWV, brachial, and central AMBP. Partial correlations were used to independently adjust for traditional cardiovascular disease (CVD) risk factors including age, sex, waist circumference, glucose, and augmentation index normalized to heart rate 75 bpm, a surrogate measure of arterial stiffness, and in a multivariable combined model.

Results:

Nighttime brachial systolic BP (r = 0.31) and central systolic BP (r = 0.30) were correlated with cfPWV in the multivariable combined model (P≤ .05). Nighttime brachial pulse pressure and central pulse pressure were correlated with cfPWV after independently adjusting for all CVD risk factors (P≤ .05, all) but not when combined in the multivariable model (P> .05).

Conclusions:

Higher nighttime brachial and central AMBP with older age are related, in part, to greater aortic stiffening. Therefore, interventions to lower or prevent aortic stiffening may also lower nighttime BP in MA/O adults to lower CVD risk.
Effectiveness and safety of glecaprevir/pibrentasvir for 8 weeks in the treatment of patients with acute hepatitis C: A single-arm retrospective study
Authors: Pol Stanislas , Thompson Alexander J. , Collins Michelle , Venier Elisa , Cotte Laurent , Laguno Centeno Montserrat , Mera Jorge , Reiberger Thomas , Burroughs Margaret , Semizarov Dimitri G. , Iacob Alexandru M. , Welhaven Anne , Fredrick Linda M. , Doyle Joseph S.
Published: June 2024

Background and Aims:

No direct-acting antiviral is currently approved for acute HCV infection, delaying treatment. We investigated the effectiveness and safety of 8-week glecaprevir/pibrentasvir (G/P) in patients with acute HCV infection.

Approach and Results:

This noninterventional, single-arm, retrospective chart review was designed to enroll adults/adolescents with acute HCV infection. Analyses were conducted on a full analysis set (FAS; all enrolled) and modified FAS (FAS excluding nonvirologic failures). The primary end point (modified FAS) was sustained virologic response at posttreatment week 12 (SVR12) with superiority to 92.6% threshold determined by historic chronic HCV G/P SVR12 rates. Secondary end points (FAS) included SVR12, on-treatment virologic failure, posttreatment relapse, and reinfection. Adverse events and safety laboratory values were assessed.

Overall, 202 adults were enrolled; in the modified FAS, 150/151 (99.3%; 95% CI: 96.3–99.9) achieved SVR12, demonstrating superiority to efficacy threshold. In the FAS, the SVR12 rate was 74.3% and the on-treatment virologic failure rate was 0%. Relapse and reinfection rates after the final treatment visit (FAS) were 0.5% and 3%, respectively; 39 patients had missing SVR12 data. No on-treatment alanine aminotransferase elevations > 3 × upper limit of normal with total bilirubin > 2 × upper limit of normal were reported. All 53 patients with alanine aminotransferase Grade ≥ 2 at baseline improved to Grade 0/1 on treatment. No adverse eventss of hepatic decompensation/failure or leading to G/P discontinuation occurred. Two patients had serious adverse events unrelated to G/P.

Conclusions:

Eight-week G/P therapy was effective and well-tolerated in patients with acute HCV infection. Data support further investigation of G/P in acute HCV to shorten care cascades, reduce transmission, and support HCV elimination.
Bintrafusp alfa and chemotherapy as first-line treatment in biliary tract cancer: A randomized phase 2/3 trial
Authors: Oh Do-Youn , Ikeda Masafumi , Lee Choong-kun , Rojas Carlos , Hsu Chih-Hung , Kim Jin Won , Shen Lin , Furuse Junji , Park Joon Oh , Borad Mitesh , de Braud Filippo , Bridgewater John , Lee Sunyoung S. , Moehler Markus , Audhuy Francois , Osada Motonobu , Sato Masashi , Yoo Changhoon
Published: June 2024

Background and Aims:

We compared the safety and efficacy of bintrafusp alfa (BA) in combination with gemcitabine+cisplatin (GemCis), to those of GemCis alone, in patients with biliary tract cancer.

Approach and Results:

This randomized, double-blind, placebo-controlled, adaptive design phase 2/3 trial (NCT04066491) included adults who are treatment-naive with locally advanced/metastatic biliary tract cancer. Patients (N = 297) were randomized to receive an IV infusion of BA (2400 mg once/3 wk) plus GemCis (gemcitabine 1000 mg/m2+cisplatin 25 mg/m2 on days 1 and 8/3 wk; 8 cycles) (BA group, n = 148) or placebo+GemCis (placebo group, n = 149). The primary end point was overall survival (OS). For adaptation analysis (phase 2-phase 3; data cutoff: May 20, 2021), efficacy was assessed in the first 150 patients who were antibiotic-naive when 80 progression-free survival events had occurred and ≥ 19 weeks of follow-up had been completed (BA, n = 73; placebo, n = 77). Median OS (95% CI) for the BA (11.5 mo [9.3–not estimable]) and placebo (11.5 mo [10.0–not estimable]) groups was comparable (hazard ration 1.23 [95% CI 0.66–2.28]; p = 0.7394); OS data maturity was 27.2% (41 events/151 patients). The most common grade ≥3 treatment-related adverse event was anemia (BA, 26.0%; placebo, 22.8%). Bleeding adverse events were reported more frequently in the BA group (28.8%) versus the placebo group (7.4%). Deaths within 60 days of the first dose were reported in 7.5% and 1.3% of patients in the BA and placebo groups, respectively.

Conclusions:

BA+GemCis did not provide a clinically meaningful benefit compared with GemCis alone as first-line treatment for biliary tract cancer, and the study was discontinued early (terminated: August 20, 2021).
Gender-based Disparity in Performing Aortic Valve Surgery in the United State Before Availability of Percutaneous Valve Implantation
Authors: Movahed Mohammad Reza , Soltani Moghadam Arman , Hashemzadeh Mehrnoosh , Hashemzadeh Mehrtash
Published: June 2024

Background:

Aortic valve surgery has been performed increasingly in high-risk patients. The goal of this study was to evaluate this trend based on gender in the United States before the availability of percutaneous aortic valve replacement.

Method:

The Nationwide Inpatient Sample database was utilized to calculate the age-adjusted utilization rate for aortic valve surgery from 1988 to 2011 in the United States using International Classification of Diseases, Ninth Revision coding for aortic valve surgery.

Results:

A total population of 258,506 patients who underwent aortic valve between 1988 and 2011 were available for our study over the age of 20. We found that the age-adjusted rate of aortic valve surgery gradually increased from 1988 until 2009 and stabilized thereafter with a persistently higher rate for men. For men, age-adjusted rate in 1988 was 13.3 per 100,000 versus 27.0 in year in the year 2011 per 100,000. For women, the age-adjusted rate in 1988 was 6.07 per 100,000 versus 11.4 in year 2011 per 100,000.

Conclusions:

Aortic valve surgery utilization has stabilized in recent years in both genders in the United States. However, this rate has been persistently more than double in men. The cause of this higher utilization in males needs further investigation.
Neuroanatomical evidence and a mouse calcitonin gene–related peptide model in line with human functional magnetic resonance imaging data support the involvement of peptidergic Edinger–Westphal nucleus in migraine
Authors: Al-Omari Ammar , Gaszner Balázs , Zelena Dóra , Gecse Kinga , Berta Gergely , Biró-Sütő Tünde , Szocsics Péter , Maglóczky Zsófia , Gombás Péter , Pintér Erika , Juhász Gabriella , Kormos Viktória
Published: June 2024

The urocortin 1 (UCN1)–expressing centrally projecting Edinger–Westphal (EWcp) nucleus is influenced by circadian rhythms, hormones, stress, and pain, all known migraine triggers. Our study investigated EWcp's potential involvement in migraine. Using RNAscope in situ hybridization and immunostaining, we examined the expression of calcitonin gene–related peptide (CGRP) receptor components in both mouse and human EWcp and dorsal raphe nucleus (DRN). Tracing study examined connection between EWcp and the spinal trigeminal nucleus (STN). The intraperitoneal CGRP injection model of migraine was applied and validated by light–dark box, and von Frey assays in mice, in situ hybridization combined with immunostaining, were used to assess the functional–morphological changes. The functional connectivity matrix of EW was examined using functional magnetic resonance imaging in control humans and interictal migraineurs. We proved the expression of CGRP receptor components in both murine and human DRN and EWcp. We identified a direct urocortinergic projection from EWcp to the STN. Photophobic behavior, periorbital hyperalgesia, increased c-fos gene–encoded protein immunoreactivity in the lateral periaqueductal gray matter and trigeminal ganglia, and phosphorylated c-AMP–responsive element binding protein in the STN supported the efficacy of CGRP-induced migraine-like state. Calcitonin gene–related peptide administration also increased c-fos gene–encoded protein expression, Ucn1 mRNA, and peptide content in EWcp/UCN1 neurons while reducing serotonin and tryptophan hydroxylase-2 levels in the DRN. Targeted ablation of EWcp/UCN1 neurons induced hyperalgesia. A positive functional connectivity between EW and STN as well as DRN has been identified by functional magnetic resonance imaging. The presented data strongly suggest the regulatory role of EWcp/UCN1 neurons in migraine through the STN and DRN with high translational value.
Illness perceptions and blood pressure control among hypertensive Filipino Americans: A cross-sectional study
Authors: dela Cruz Felicitas A. , Yu Chong Ho (Alex) , Lao Brigette T.
Published: June 2024

Background:

Among Asian Americans, Filipino Americans (FAs)—who constitute the fourth largest US immigrant group and who fill in health care workforce shortages—experience high prevalence but low control rates of high blood pressure (HBP). Research reveals that patients' illness perceptions, their common-sense model (CSM) of the illness, influence treatment behaviors, and management outcomes. However, scarce information exists about FAs' perceptions about HBP.

Purpose:

To address this gap, we conducted a cross-sectional study to (a) identify the illness perceptions of hypertensive FAs, (b) classify these perceptions into clusters, and (c) determine the association between illness perceptions and BP control.

Methodology:

The responses of 248 FAs with HBP to the Brief Illness Perception Questionnaire were analyzed using JMP Pro version 17 to discover their CSMs or illness perceptions. We used iterative K means cluster analysis to classify variations in CSMs and analysis of means chart to determine the association of illness perceptions and BP control.

Results:

Hypertensive FAs expressed threatening (negative) views of HBP through their emotional perceptions of the illness and its chronic time line, whereas their positive views centered on their cognitive beliefs about understanding HBP and its controllability. Based on the biomedical model of HBP, the overall illness perceptions or CSMs encompassed three clusters. Generally, threatening illness perceptions were associated with stage 2 HBP.

Conclusions/Implications:

The findings underscore the need for nurse practitioners to elicit, listen, discern, and understand the illness perceptions or CSMs of hypertensive FAs to improve BP treatment and control with scientifically and culturally tailored interventions.
Reimagining the Future of Clinical Nursing Education: A Cohort Partnership Model
Authors: Buron Bill , Abbott Eng Cassy , Eagleton Alison
Published: June 2024

Background:

As the demand for registered nurses increases, innovative methods for stabilizing, improving, and ensuring the longevity of quality clinical nursing education should be considered. Traditionally, full-time nursing faculty teach nursing students in clinical settings.

Problem:

Considering the impending nurse educator crisis, characterized by increasing demands on a dwindling nursing faculty, traditional approaches to clinical nursing education are no longer feasible.

Approach:

A new clinical cohort model (CCM), developed from an academic/health system partnership, is proposed as an innovative approach to future clinical nursing education.

Outcomes:

CCM implementation resulted in a significant reduction in the cost of educating nursing students. The health care system noted a 100% postgraduation 2-year retention rate among cohort students. Nursing students overwhelmingly expressed satisfaction, comfort, and new opportunities through participation in the CCM.

Conclusions:

This new CCM has significant benefits for schools of nursing, health care systems, and nursing students.
Implementing a Pediatric Escape Room Simulation to Improve Student Learning
Authors: Stanek Rachel J. , Montgomery Kathleen E. , Anibas Melissa
Published: June 2024

Background:

Escape room simulations are an innovative teaching methodology that may be useful in addressing pediatric-specific content and clinical placement limitations of generalist nursing programs.

Problem:

This project studied if a pediatric escape room simulation improved students’ knowledge and confidence in pediatric nursing to support the development of the pediatric nursing workforce.

Approach:

A pediatric escape room simulation was developed for a large Midwestern university’s prelicensure nursing program. Students completed surveys to assess knowledge and confidence in pediatric nursing. Simulation quality was assessed using the Simulation Learning Effectiveness Inventory.

Outcomes:

Students’ (N = 37) knowledge and confidence in pediatric nursing concepts significantly increased after the simulation. Students responded positively to the simulation and recommended it be included in the undergraduate curriculum.

Conclusions:

The pediatric escape room simulation offers a promising alternative for students to gain pediatric-specific knowledge and confidence for prelicensure nursing programs in the context of limited pediatric clinical placements.
Risk Factors for Adverse Outcomes in Kidney Transplants From Donors After Circulatory Death With Normothermic Regional Perfusion: A Systematic Analysis
Authors: Savoye Emilie , Martin-Lefèvre Laurent , Dantal Jacques , Dorez Didier , Gaudez François , Drouin Sarah , Riou Bruno , Strecker Guillaume , Thierry Antoine , Legeai Camille , Bronchard Régis , Kerbaul François , Antoine Corinne ,   the Controlled Donation After the Circulatory Determination of Death National Steering Committee
Published: June 2024

Background.

This study examined 1071 adult primary kidney transplants from the French-controlled donation after the circulatory determination of death (cDCD) program, which uses normothermic regional perfusion (NRP), and involves short cold ischemia times (CIT) and constrained asystole times differing by donor age.

Methods.

Logistic regression identified risk factors for primary nonfunction (PNF), delayed graft function (DGF), and graft failure.

Results.

Risk factors for PNF included donor hypertension, admission for ischemic vascular stroke, and HLA DR mismatches. Risk factors for DGF included functional warm ischemia time >40 min, dialysis >2 y, recipient body mass index of 30 kg/m2 or higher, recipient diabetes, and CIT >10 h. Risk factors for 1-y graft failure included donor hypertension, donor lung recovery, ostial calcification, recipient cardiovascular comorbidities, and HLA DR mismatches. A high donor estimated glomerular filtration rate protected against DGF and graft failure at 1-y. After adjustment restricted to recipient and graft factors and donor age, the risks of PNF, DGF, and graft failure increased with donor age up to 65 y and then remained stable.

Conclusions.

The study suggests that cDCD kidney transplants are highly successful, but also that its outcomes are influenced by lung recovery, poor HLA DR matching, and warm ischemia times differing with donor age. Our study identified several risk factors for kidney transplantation failure after cDCD with systematic use of NRP and some of them seem as modifiable variables associated with cDCD transplant outcome.
An optimized and robust workflow for quantifying the canonical histone ubiquitination marks H2AK119ub and H2BK120ub by LC-MS/MS
Authors: Lopes Mariana , Lund Peder J. , Garcia Benjamin A.
Published: June 2024

The eukaryotic genome is packaged around histone proteins, which are subject to a myriad of post-translational modifications. By controlling DNA accessibility and the recruitment of protein complexes that mediate chromatin-related processes, these modifications constitute a key mechanism of epigenetic regulation. Since mass spectrometry can easily distinguish between these different modifications, it has become an essential technique in deciphering the histone code. Although robust LC-MS/MS methods are available to analyze modifications on the histone N-terminal tails, routine methods for characterizing ubiquitin marks on histone C-terminal regions, especially H2AK119ub, are less robust. Here we report the development of a simple workflow for the detection and improved quantification of the canonical histone ubiquitination marks H2AK119ub and H2BK120ub. The method entails a fully tryptic digestion of acid-extracted histones followed by derivatization with heavy or light propionic anhydride. A pooled sample is then spiked into oppositely labeled single samples as a reference channel for relative quantification, and data is acquired using PRM-based nanoLC-MS/MS. We validated our approach with synthetic peptides as well as treatments known to modulate the levels of H2AK119ub and H2BK120ub. This new method complements existing histone workflows, largely focused on the lysine-rich N-terminal regions, by extending modification analysis to other sequence contexts.
Nitazoxanide ameliorates OVA-induced airway inflammation in asthmatic mice via p38-MAPK/NFkB and AMPK/STAT3 pathways
Authors: Huang Zhuyun , Zhang Yanwen , Sun Yudi , Wang Qian , Men Zhonglan , Chu Fuao , Sun Shuangyong
Published: June 2024

Nitazoxanide has an anti-inflammatory effect, we clarified the ameliorative effect of nitazoxanide on asthmatic airway inflammation by conducting in vitro and in vivo experiments. In vitro, we assessed the effect of nitazoxanide on cytokine production by lipopolysaccharide-stimulated RAW 264.7 cells, as well as the diastolic effect of nitazoxanide on isolated rat airways. Nitazoxanide was found to have a diastolic effect on isolated tracheal spasms caused by spasmogenic substances, and to inhibit IL-6 and IL-1β production by RAW 264.7 cells. Meanwhile, nitazoxanide can inhibit the proliferation and migration of human bronchial smooth muscle cells (HBSMCs). In vivo, an ovalbumin (OVA)-induced asthma model was established in mice, and the airway resistance was measured by Whole Body Plethysmography (WBP) after inhalation of acetylcholine in mice, and the levels of IL-4, IL-6, IL-12, and IL-17 were detected in bronchoalveolar lavage fluid (BALF) of mice by ELISA and the inflammatory cells were counted. H&E staining was used to observe the changes in lung histopathology, and the expression of NFkB, MAPK, AMPK, and STAT3 in lung tissues was quantified using Western-blot. Nitazoxanide reduced inflammatory cell infiltration and goblet cell proliferation in the lungs of asthmatic mice. Moreover, the expression of IL-4, IL-5, and IL-6 in BALF was down-regulated in asthmatic mice. In addition, nitazoxanide could inhibit the expression of NFkB, MAPK, STAT 3 proteins and ascend the expression of AMPK in lung tissues. In conclusion, nitazoxanide could diastole airway smooth muscle and ameliorate OVA-induced airway inflammation in asthmatic mice via NFkB/MAPK and AMPK/STAT3 pathways.
Loss-of-function mutations in the dystonia gene THAP1 impair proteasome function by inhibiting PSMB5 expression
Authors: Ramage Dylan E. , Grant Drew W. , Timms Richard T.
Published: June 2024

The 26S proteasome is a multi-catalytic protease that serves as the endpoint for protein degradation via the ubiquitin-proteasome system. Proteasome function requires the concerted activity of 33 distinct gene products, but how the expression of proteasome subunits is regulated in mammalian cells remains poorly understood. Leveraging coessentiality data from the DepMap project, here we characterize an essential role for the dystonia geneTHAP1in maintaining the basal expression ofPSMB5. PSMB5 insufficiency resulting from loss of THAP1 leads to defects in proteasome assembly, impaired proteostasis and cell death. Exploiting the fact that the toxicity associated with loss of THAP1 can be rescued upon exogenous expression of PSMB5, we define the transcriptional targets of THAP1 through RNA-seq analysis and perform a deep mutational scan to systematically assess the function of thousands of single amino acid THAP1 variants. Altogether, these data identify THAP1 as a critical regulator of proteasome function and suggest that aberrant proteostasis may contribute to the pathogenesis of THAP1 dystonia.
Development of a Time-Resolved Fluorescence Resonance Energy Transfer ultra-high throughput screening assay for targeting SYK and FCER1G interaction
Authors: Du Yuhong , Wang Dongxue , Katis Vittorio L. , Zoeller Elizabeth L. , Qui Min , Levey Allan I. , Gileadi Opher ,   Emory-SAGE-SGC TREAT-AD Center, Fu Haian
Published: June 2024

The spleen tyrosine kinase (SYK) and high affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) interaction has a major role in the normal innate and adaptive immune responses, but dysregulation of this interaction is implicated in several human diseases, including autoimmune disorders, hematological malignancies, and Alzheimer’s Disease. Development of small molecule chemical probes could aid in studying this pathway both in normal and aberrant contexts. Herein, we describe the miniaturization of a time-resolved fluorescence resonance energy transfer (TR-FRET) assay to measure the interaction between SYK and FCER1G in a 1536-well ultrahigh throughput screening (uHTS) format. The assay utilizes the His-SH2 domains of SYK, which are indirectly labeled with anti-His-terbium to serve as TR-FRET donor and a FITC-conjugated phosphorylated ITAM domain peptide of FCER1G to serve as acceptor. We have optimized the assay into 384-well HTS format and further miniaturized the assay into a 1536-well uHTS format. Robust assay performance has been achieved with a Z’ factor > 0.8 and signal-to-background (S/B) ratio > 15. The utilization of this uHTS TR-FRET assay for compound screening has been validated by a pilot screening of 2,036 FDA-approved and bioactive compounds library. Several primary hits have been identified from the pilot uHTS. One compound, hematoxylin, was confirmed to disrupt the SYK/FECR1G interaction in an orthogonal protein–protein interaction assay. Thus, our optimized and miniaturized uHTS assay could be applied to future scaling up of a screening campaign to identify small molecule inhibitors targeting the SYK and FCER1G interaction.
Mutual information for detecting multi-class biomarkers when integrating multiple bulk or single-cell transcriptomic studies
Authors: Zou Jian , Li Zheqi , Carleton Neil , Oesterreich Steffi , Lee Adrian V. , Tseng George C.
Published: June 2024

Motivation

Biomarker detection plays a pivotal role in biomedical research. Integrating omics studies from multiple cohorts can enhance statistical power, accuracy and robustness of the detection results. However, existing methods for horizontally combining omics studies are mostly designed for two-class scenarios (e.g., cases versus controls) and are not directly applicable for studies with multi-class design (e.g., samples from multiple disease subtypes, treatments, tissues, or cell types).

Results

We propose a statistical framework, namely Mutual Information Concordance Analysis (MICA), to detect biomarkers with concordant multi-class expression pattern across multiple omics studies from an information theoretic perspective. Our approach first detects biomarkers with con-cordant multi-class patterns across partial or all of the omics studies using a global test by mutual information. A post hoc analysis is then performed for each detected biomarkers and identify studies with concordant pattern. Extensive simulations demonstrate improved accuracy and successful false discovery rate control of MICA compared to an existing MCC method. The method is then applied to two practical scenarios: four tissues of mouse metabolism-related transcriptomic studies, and three sources of estrogen treatment expression profiles. Detected biomarkers by MICA show intriguing biological insights and functional annotations. Additionally, we implemented MICA for single-cell RNA-Seq data for tumor progression biomarkers, highlighting critical roles of ribosomal function in the tumor microenvironment of triple-negative breast cancer and underscoring the potential of MICA for detecting novel therapeutic targets.

Availability

https://github.com/jianzou75/MICA
Dynamic changes in structure and function of brain mural cells around chronically implanted microelectrodes
Authors: Wellman Steven M. , Forrest Adam M. , Douglas Madeline M. , Subbaraman Ashwat , Zhang Guangfeng , Kozai Takashi D.Y.
Published: June 2024

1.0

Integration of neural interfaces with minimal tissue disruption in the brain is ideal to develop robust tools that can address essential neuroscience questions and combat neurological disorders. However, implantation of intracortical devices provokes severe tissue inflammation within the brain, which requires a high metabolic demand to support a complex series of cellular events mediating tissue degeneration and wound healing. Pericytes, peri-vascular cells involved in blood-brain barrier maintenance, vascular permeability, waste clearance, and angiogenesis, have recently been implicated as potential perpetuators of neurodegeneration in brain injury and disease. While the intimate relationship between pericytes and the cortical microvasculature have been explored in other disease states, their behavior following microelectrode implantation, which is responsible for direct blood vessel disruption and dysfunction, is currently unknown. Using two-photon microscopy we observed dynamic changes in the structure and function of pericytes during implantation of a microelectrode array over a 4-week implantation period. Pericytes respond to electrode insertion through transient increases in intracellular calcium and underlying constriction of capillary vessels. Within days following the initial insertion, we observed an influx of new, proliferating pericytes which contribute to new blood vessel formation. Additionally, we discovered a potentially novel population of reactive immune cells in close proximity to the electrode-tissue interface actively engaging in encapsulation of the microelectrode array. Finally, we determined that intracellular pericyte calcium can be modulated by intracortical microstimulation in an amplitude- and frequency-dependent manner. This study provides a new perspective on the complex biological sequelae occurring the electrode-tissue interface and will foster new avenues of potential research consideration and lead to development of more advanced therapeutic interventions towards improving the biocompatibility of neural electrode technology.
Improving the Reliability and Accuracy of Population Receptive Field Measures Using a Logarithmically Warped Stimulus
Authors: Chang Kelly , Fine Ione , Boynton Geoffrey M.
Published: June 2024

The population receptive field method, which measures the region in visual space that elicits a BOLD signal in a voxel in retinotopic cortex, is a powerful tool for investigating the functional organization of human visual cortex with fMRI (Dumoulin & Wandell, 2008). However, recent work has shown that population receptive field (pRF) estimates for early retinotopic visual areas can be biased and unreliable, especially for voxels representing the fovea. Here, we show that a ‘log-bar’ stimulus that is logarithmically warped along the eccentricity dimension produces more reliable estimates of pRF size and location than the traditional moving bar stimulus. The log-bar stimulus was better able to identify pRFs near the foveal representation, and pRFs were smaller in size, consistent with simulation estimates of receptive field sizes in the fovea.
Aerial litter mimicry: a novel form of floral deception mediated by a monoterpene synthase
Authors: Liu Ming-Fai , Chen Junhao , Goodrich Katherine R. , Chiu Sung Kay , Pang Chun-Chiu , Scharaschkin Tanya , Saunders Richard M. K.
Published: June 2024

Floral mimics deceive their pollinators by developing visual and olfactory resemblance to their models. Our knowledge on the diversity of models is expanding rapidly. We report a system in which the flowers exhibit phenotypes similar to aerial litter and deceives an aerial litter specialist beetle to achieve pollination.

We assessed the floral phenology and the effective pollinators of an Australian understorey treelet,Meiogyne heteropetala(Annonaceae). The similarities of morphology, colour and odour between the flowers and co-occurring aerial litter were investigated. The terpene synthase involved in floral scent emission was identified by expression patterns and product profile. The behavioural responses of the pollinator to various odours were assessed using bioassays.

The erotylid beetleLoberus sharpiis the most likely effective pollinator ofM. heteropetala, and its eggs were found on the petals ofM. heteropetala.Loberus sharpiwas exclusively found in aerial litter andM. heteropetalaflowers. The morphology and spectral reflectance of the flowers overlap with aerial litter. The floral scent was dominated by monoterpenes, especially 1,8-cineole. The cineole synthase MhCINS was the only highly expressed floral terpene synthase and possessed a highly similar product profile to the floral scent composition. NMDS showed that the volatile composition ofM. heteropetalaflowers is distinct from other congeners and highly similar to aerial litter, indicating advergence to aerial litter. Visual and odour resemblance, coupled with the deposition of eggs on the flowers, provides evidence that the beetles were deceived into pollinating the flowers. Behavioural experiments showed that the pollinator was attracted to both aerial litter andM. heteropetalaflowers. The beetles were also attracted to 1,8-cineole and synthetic mixes of floral odour and MhCINS products. The beetles were unable to distinguish floral scent from MhCINS products, nor from 1,8-cineole, suggesting MhCINS alone sufficed to attract the pollinator olfactorily. The beetles, however, preferred aerial litter over flowers. The beetles likely categorised the flower as a general, but not the most preferred brood substrate.

Synthesis.This study reports the first case of floral mimicry of aerial litter and characterises the biochemical process responsible for olfactory mimicry.
Large-scale genotyping and meta-analysis ofPIEZO1short tandem repeat alleles suggest a modest association with malaria susceptibility
Authors: Leffler Ellen M. , Band Gavin , Jeffreys Anna E. , Rowlands Kate , Hubbart Christina , Bojang Kalifa A. , Conway David J. , Jallow Muminatou , Sisay-Joof Fatoumatta , D’Alessandro Umberto , Ndila Carolyne M. , Macharia Alexander W. , Marsh Kevin , Williams Thomas N. , Kachala David , Molyneux Malcolm , Nyirongo Vysaul , Taylor Terrie E. , Rockett Kirk A. , Kwiatkowski Dominic P.
Published: June 2024

PIEZO1 forms a mechanosensitive ion channel involved in regulating calcium levels in red blood cells. E756del, a deletion allele within a short tandem repeat (STR) inPIEZO1, is common in many African populations and has been proposed to be associated with protection from malarial disease, but epidemiological evidence has been inconsistent. Here, we use Illumina sequencing of amplicons covering thePIEZO1STR to genotype 5,558 severe malaria cases and 8,174 population controls from The Gambia, Kenya, and Malawi. We estimate a modest effect for E756del and meta-analysis with two published studies, for a total of 8,224 cases and 10,103 controls, reveals a consistent protective effect (OR=0.93, 95% CI 0.88-0.99). By comprehensively genotyping the STR, we identify additional, less common alleles, with two (Q745del and E756ins) showing consistent, but also modest, risk effects across studies. Although allele frequency differentiation between African and non-African populations could be consistent with a selective effect, we show that it is not exceptional compared with STR variants genome wide. Thus, our results support a protective effect of E756del against risk of malaria but with a much smaller effect size than initially reported.