bluuebunny/crossref_metadata_2025 huggingface dataset:
An opportunistic pathogen under stress: how Group B Streptococcus responds to cytotoxic reactive species and conditions of metal ion imbalance to survive
Authors: Goh Kelvin G K , Desai Devika , Thapa Ruby , Prince Darren , Acharya Dhruba , Sullivan Matthew J , Ulett Glen C
Published: April 2024

Group B Streptococcus (GBS; also known as Streptococcus agalactiae) is an opportunistic bacterial pathogen that causes sepsis, meningitis, pneumonia, and skin and soft tissue infections in neonates and healthy or immunocompromised adults. GBS is well-adapted to survive in humans due to a plethora of virulence mechanisms that afford responses to support bacterial survival in dynamic host environments. These mechanisms and responses include counteraction of cell death from exposure to excess metal ions that can cause mismetallation and cytotoxicity, and strategies to combat molecules such as reactive oxygen and nitrogen species that are generated as part of innate host defence. Cytotoxicity from reactive molecules can stem from damage to proteins, DNA, and membrane lipids, potentially leading to bacterial cell death inside phagocytic cells or within extracellular spaces within the host. Deciphering the ways in which GBS responds to the stress of cytotoxic reactive molecules within the host will benefit the development of novel therapeutic and preventative strategies to manage the burden of GBS disease. This review summarizes knowledge of GBS carriage in humans and the mechanisms used by the bacteria to circumvent killing by these important elements of host immune defence: oxidative stress, nitrosative stress, and stress from metal ion intoxication/mismetallation.
AcMYB266, a key regulator of the red coloration in pineapple peel: a case of subfunctionalization in tandem duplicated genes
Authors: Zhang Wei , Wu Jing , He Junhu , Liu Chaoyang , Yi Wen , Xie Jingyao , Wu Ya , Xie Tao , Ma Jun , Zhong Ziqin , Yang Mingzhe , Chen Chengjie , Luan Aiping , He Yehua
Published: April 2024

Red fruit peel is an attractive target for pineapple breeding. Various pineapple accessions with distinct red coloration patterns exist; however, the precise molecular mechanism accounting for these differences remains unknown, which hinders the pineapple breeding process from combining high fruit quality with red peel. In this study, we characterized a transcription factor, AcMYB266, which is preferentially expressed in pineapple peel and positively regulates anthocyanin accumulation. Transgenic pineapple, Arabidopsis, and tobacco plants overexpressing AcMYB266 exhibited significant anthocyanin accumulation. Conversely, transient silencing of this gene led to decreased anthocyanin accumulation in pineapple red bracts. In-depth analysis indicated that variations of AcMYB266 sequences in the promoter instead of the protein-coding region seem to contribute to different red coloration patterns in peels of three representative pineapple varieties. In addition, we found that AcMYB266 was located in a cluster of four MYB genes exclusive to and conserved in Ananas species. Of this cluster, each was proved to regulate anthocyanin synthesis in different pineapple tissues, illustrating an interesting case of gene subfunctionalization after tandem duplication. In summary, we have characterized AcMYB266 as a key regulator of pineapple red fruit peel and identified an MYB cluster whose members were subfunctionalized to specifically regulate the red coloration of different pineapple tissues. The present study will assist in establishing a theoretical mechanism for pineapple breeding for red fruit peel and provide an interesting case for the investigation of gene subfunctionalization in plants.
Performance and emission characteristics of novel biodiesel-diesel blends: an RSM and ANN approach
Authors: Al Zubi Mohammad A , Penmetsa Ravi Varma , Kumar P Satish , Patil Pravin P , Singh Bharat , Alsubih Majed , Islam Saiful , Khan Wahaj Ahmad
Published: April 2024

In this paper, the impact of different input variables on the performance and emission features of a pongamia pinnata and rapeseed oil biodiesel with n-Butanol additive were investigated, statistically analyzed, and optimized by employing the powerful response surface methodology (RSM) based design of experiment (DOE) techniques. The vegetable oils (pongamia pinnata and rapeseed oils) were transesterified and their corresponding methyl esters were blended with diesel and n-Butanol at blend ratios 10:84:6, 10:78:12, 20:74:6 and 20:68:12. The samples were tested on a direct injection CI engine at a rated speed of 1500 rpm and standard CR of 17.5:1 at different loads. In each test, performance and emission parameters were measured. Expert machine learning (ML) methods were used to forecast these features. In addition, polynomial equations were developed for each blend using regression techniques and compared with an artificial intelligence technique. It was observed that the engine performance increased as biodiesel and additive weight percentage increased. Regardless of the loads placed on the engine and the blend ratios, the use of PPME and RSME combined with n-Butanol blends demonstrated a clear decrease in NOx compared to diesel (7.07% for P20B12 and 6.58% for R20B12). As per the trend, it is seen that the percentage reduction in CO2 emissions is greater with high percentage increase of n-Butanol in the tested sample irrespective of loads applied on the engine (2.95% more P20B12 for as compared to P20B6). For the emission characteristics, ANN demonstrated a range of 87.92% to 98.83% prediction accuracy while that of regression varies from 81.4% to 98.8% for all the samples of PPME blended biodiesel.
Jeddah strategic approaches to sustainable urban development and vision 2030 alignment
Authors: Alhubashi Haytham , Alamoudi Mohammed , Imam Ayman , Abed Ahmad , Hegazy Ibrahim
Published: April 2024

This research article provides an in-depth look into the urban development trajectory of Jeddah, a historic port city in Saudi Arabia, which has developed into a vibrant urban center that reflects its rich past and ambitious future. The study systematically explores Jeddah’s journey through different lenses—its strategic geographical location as a maritime and pilgrimage gateway, its historical development dating back to the seventh century and its transformation influenced by diverse cultural and economic interactions. It comprehensively analyzes Jeddah’s social and economic fabric, demographic trends and the impact of these factors on the city’s urban landscape. This article examines the governance and regulatory frameworks that shape development policies in Jeddah and addresses how these frameworks are designed to meet the challenges of modern urbanization, including rapid population growth, infrastructure requirements and environmental sustainability. The research also examines the city’s response to these challenges, focusing on strategic planning, infrastructure development and sustainable urban initiatives that align with the goals of Saudi Vision 2030. This article provides an in-depth understanding of urban dynamics in Jeddah, presenting it as a case study for managing growth and modernization in rapid urban environments.
Estimation of stationary optimal transport plans
Authors: O’Connor Kevin , Nobel Andrew , McGoff Kevin
Published: April 2024

We study optimal transport for stationary stochastic processes taking values in finite spaces. In order to reflect the stationarity of the underlying processes, we restrict attention to stationary couplings, also known as joinings. The resulting optimal joining problem captures differences in the long-run average behavior of the processes of interest. We introduce estimators of both optimal joinings and the optimal joining cost, and establish consistency of the estimators under mild conditions. Furthermore, under stronger mixing assumptions we establish finite-sample error rates for the estimated optimal joining cost that extend the best known results in the iid case. We also extend the consistency and rate analysis to an entropy-penalized version of the optimal joining problem. Finally, we validate our convergence results empirically as well as demonstrate the computational advantage of the entropic problem in a simulation experiment.
A scoping review of the methodological approaches used in retrospective chart reviews to validate adverse event rates in administrative data
Authors: Connolly Anna , Kirwan Marcia , Matthews Anne
Published: April 2024

Patient safety is a key quality issue for health systems. Healthcare acquired adverse events (AEs) compromise safety and quality; therefore, their reporting and monitoring is a patient safety priority. Although administrative datasets are potentially efficient tools for monitoring rates of AEs, concerns remain over the accuracy of their data. Chart review validation studies are required to explore the potential of administrative data to inform research and health policy. This review aims to present an overview of the methodological approaches and strategies used to validate rates of AEs in administrative data through chart review. This review was conducted in line with the Joanna Briggs Institute methodological framework for scoping reviews. Through database searches, 1054 sources were identified, imported into Covidence, and screened against the inclusion criteria. Articles that validated rates of AEs in administrative data through chart review were included. Data were extracted, exported to Microsoft Excel, arranged into a charting table, and presented in a tabular and descriptive format. Fifty-six studies were included. Most sources reported on surgical AEs; however, other medical specialties were also explored. Chart reviews were used in all studies; however, few agreed on terminology for the study design. Various methodological approaches and sampling strategies were used. Some studies used the Global Trigger Tool, a two-stage chart review method, whilst others used alternative single-, two-stage, or unclear approaches. The sources used samples of flagged charts (n = 24), flagged and random charts (n = 11), and random charts (n = 21). Most studies reported poor or moderate accuracy of AE rates. Some studies reported good accuracy of AE recording which highlights the potential of using administrative data for research purposes. This review highlights the potential for administrative data to provide information on AE rates and improve patient safety and healthcare quality. Nonetheless, further work is warranted to ensure that administrative data are accurate. The variation of methodological approaches taken, and sampling techniques used demonstrate a lack of consensus on best practice; therefore, further clarity and consensus are necessary to develop a more systematic approach to chart reviewing.
Effect of different feeding strategies and dietary fiber levels on energy and protein retention in gestating sows
Authors: Wisbech Sigrid J , Nielsen Tina S , Bach Knudsen Knud E , Theil Peter K , Bruun Thomas S
Published: April 2024

The aim of the study was to investigate whether increased inclusion of sugar beet pulp (SBP) alters retention of fat, protein, and energy when backfat (BF) is restored in early- and mid-gestation. In total, 46 sows were fed one of four dietary treatments with increasing inclusion of SBP providing dietary fiber (DF) levels of 119, 152, 185, and 217 g/kg; sows were assigned to one of three feeding strategies (FS; high, medium, and low) depending on BF thickness at mating and again at day 30 for the following month. On days 0, 30, 60, and 108, body weight (BW) and BF thickness were measured and body pools of protein and fat were estimated using the deuterium oxide technique. On days 30 and 60, urine, feces, and blood samples were collected to quantify metabolites, energy, and nitrogen (N) balances. On days 15 and 45, heart rate was recorded to estimate heat energy. At farrowing, total born and weight of the litter were recorded. In early gestation, BW gain (P < 0.01) and body protein retention increased (P < 0.05) with increasing fiber inclusion, while body fat retention increased numerically by 59%. The increase in BF was greatest for sows fed the high FS, intermediate when fed the medium strategy, and negligible for sows fed the lowest FS (P < 0.001). Nitrogen intake, N loss in feces, and N balance increased linearly, whereas N loss in urine tended to decrease with increasing inclusion of fibers in early gestation. Concomitantly, fecal energy output and energy lost as methane increased linearly (P < 0.001), while energy output in urine declined linearly. Total metabolizable energy (ME) intake therefore increased from 36.5 MJ ME/d in the low fiber group to 38.5 MJ ME/d in the high fiber group (P < 0.01). Changing the ME towards more ketogenic energy was expected to favor fat retention rather than protein retention. However, due to increased intake of ME and increased N efficiency with increasing fiber inclusion, the sows gained more weight and protein with increasing fiber inclusion. In conclusion, increased feed intake improved both fat and protein retention, whereas increased DF intake increased protein retention.
Gene expression of free fatty acids-sensing G protein-coupled receptors in beef cattle
Authors: Durand Guillaume , Charrier Pierre , Bes Sébastien , Bernard Laurence , Lamothe Valérie , Gruffat Dominique , Bonnet Muriel
Published: April 2024

Many physiological functions are regulated by free fatty acids (FFA). Recently, the discovery of FFA-specific G protein-coupled receptors (FFARs) has added to the complexity of their actions at the cellular level. The study of FFAR in cattle is still in its earliest stages focusing mainly on dairy cows. In this study, we set out to map the expression of genes encoding FFARs in 6 tissues of beef cattle. We also investigated the potential effect of dietary forage nature on FFAR gene expression. To this end, 16 purebred Charolais bulls were fed a grass silage ration or a maize silage ration (n = 8/group) with a forage/concentrate ratio close to 60:40 for 196 d. The animals were then slaughtered at 485 ± 42 d and liver, spleen, ileum, rectum, perirenal adipose tissue (PRAT), and Longissimus Thoracis muscle were collected. FFAR gene expression was determined by real-time quantitative PCR. Our results showed that of the five FFARs investigated, FFAR1, FFAR2, FFAR3, and GPR84 are expressed (Ct < 30) in all six tissues, whereas FFAR4 was only expressed (Ct < 30) in PRAT, ileum, and rectum. In addition, our results showed that the nature of the forage, i.e., grass silage or maize silage, had no effect on the relative abundance of FFAR in any of the tissues studied (P value > 0.05). Taken together, these results open new perspectives for studying the physiological role of these receptors in beef cattle, particularly in nutrient partitioning during growth.
Spin polarization of photoelectrons emitted from spin-orbit coupled surface states of Pb/Ge(111)
Authors: Yaji Koichiro , Kuroda Kenta , Tsuda Shunsuke , Komori Fumio
Published: April 2024

We report that the spin vector of photoelectrons emitted from an atomic layer Pb grown on a germanium substrate [Pb/Ge(111)] can be controlled using an electric field of light. The spin polarization of photoelectrons excited by a linearly polarized light is precisely investigated by spin- and angle-resolved photoemission spectroscopy. The spin polarization of the photoelectrons observed in the mirror plane reverses between p- and s-polarized lights. Considering the dipole transition selection rule, the surface state of Pb/Ge(111) is represented by a linear combination of symmetric and asymmetric orbital components coupled with spins in mutually opposite directions. The spin direction of the photoelectrons is different from that of the initial state when the electric field vector of linearly polarized light deviates from p- or s-polarization conditions. The quantum interference in the photoexcitation process can determine the direction of the spin vector of photoelectrons.
Alpine plants exhibited deep supercooling upon exposed to episodic frost events during the growing season on the Qinghai-Tibet Plateau
Authors: Suonan Ji , Lü Wangwang , Classen Aimée T , Wang Wenying , La Ben , Lu Xuwei , Songzha Cuo , Chen Chenghao , Miao Qi , Sun Fanghui , Tsering Lhamo , Wang Shiping
Published: April 2024

Climatic warming has advanced the spring phenology of plants and disrupted the alignment of phenology with weather patterns. Such misalignments can cause problems as extreme weather events become more frequent and thus impact the survival, growth and reproduction of plants. To prevent freezing within their cells during the growing season, plants adopt a supercooling strategy. However, the weather event severity and seasonal timing may impact the plant’s recovery after a freezing event. We conducted experiments to investigate how extreme freezing events of four different severities impacted the supercooling points and senescence of two dominant alpine plant species, Potentilla saundersiana (mid-summer flowering) and Gentiana parvula (late-summer flowering) on the Qinghai-Tibet Plateau (QTP). We also explored how the phenological stage impacted P. saundersiana’s response to freezing events. We found that both species exhibited supercooling upon exposed to frost damage. However, the average supercooling point for P. saundersiana was −6.9°C and was influenced by minimum temperature, duration and phenological stage. Whereas, the average supercooling point for G. parvula was −4.8°C, and neither minimum temperature nor duration had an effect on the supercooling point. In addition, the minimum temperature treatment of −10°C caused death in both plants when held constant for 4 h. Our study provides the first experimental dataset exploring the supercooling points of alpine plants on the QTP. Given the increasing probability of alpine plants encounters frost events, these results are of great significance for understanding the growth and survival strategies of alpine plants to cope with the adverse effects of extreme climate.
Global Seasonal Activities of Respiratory Syncytial Virus Before the Coronavirus Disease 2019 Pandemic: A Systematic Review
Authors: Shan Songwei , Zhang Weixin , Gao Huizhi , Huang Pei-Yu , Du Zhanwei , Bai Yuan , Lau Yiu-Chung , Chen Dongxuan , Lau Eric H Y , Nealon Joshua , Wu Peng
Published: April 2024

Varied seasonal patterns of respiratory syncytial virus (RSV) have been reported worldwide. We conducted a systematic review on articles identified in PubMed reporting RSV seasonality based on data collected before 1 January 2020. RSV seasonal patterns were examined by geographic location, calendar month, analytic method, and meteorological factors including temperature and absolute humidity. Correlation and regression analyses were conducted to explore the relationship between RSV seasonality and study methods and characteristics of study locations. RSV seasons were reported in 209 articles published in 1973–2023 for 317 locations in 77 countries. Regular RSV seasons were similarly reported in countries in temperate regions, with highly variable seasons identified in subtropical and tropical countries. Longer durations of RSV seasons were associated with a higher daily average mean temperature and daily average mean absolute humidity. The global seasonal patterns of RSV provided important information for optimizing interventions against RSV infection.
Entropy-based detection of Twitter echo chambers
Authors: Pratelli Manuel , Saracco Fabio , Petrocchi Marinella
Published: April 2024

Echo chambers, i.e. clusters of users exposed to news and opinions in line with their previous beliefs, were observed in many online debates on social platforms. We propose a completely unbiased entropy-based method for detecting echo chambers. The method is completely agnostic to the nature of the data. In the Italian Twitter debate about the Covid-19 vaccination, we find a limited presence of users in echo chambers (about 0.35% of all users). Nevertheless, their impact on the formation of a common discourse is strong, as users in echo chambers are responsible for nearly a third of the retweets in the original dataset. Moreover, in the case study observed, echo chambers appear to be a receptacle for disinformative content.
Inspiratory Muscle Training in Patients Living With Chronic Kidney Disease and Receiving Hemodialysis: Meta-Analysis of Randomized Controlled Trials
Authors: Brüggemann Ana Karla Vieira , Schardong Jociane , Righi Natiele Camponogara , Plentz Rodrigo Della Méa
Published: April 2024

Objective

People living with chronic kidney disease (CKD) and receiving hemodialysis (HD) have impaired respiratory muscle strength and endurance. The objective of this study was to systematically review the effects of inspiratory muscle training (IMT) on respiratory muscle strength, functional capacity, lung function, quality of life, endothelial function, and oxidative stress in people living with CKD and receiving HD.

Methods

An electronic search was conducted from inception to June 2023. Randomized controlled trials that evaluated the effects of IMT on respiratory muscle strength, functional capacity, lung function, endothelial function, quality of life, or oxidative stress in adults living with CKD and receiving HD, compared with control, placebo IMT, or conventional physical therapy, were included.

Results

Eight studies were included, totaling 246 people. The meta-analysis showed that IMT increased the maximum inspiratory pressure (MIP) by 22.53 cm H2O, the maximum expiratory pressure (MEP) by 19.54 cm H2O, and the distance covered in the 6-minute walk test by 77.63 m. Changes in lung function and quality of life were not observed. It was not possible to quantitatively analyze data on endothelial function and oxidative stress.

Conclusion

IMT improves MIP, MEP, and functional capacity in people living with CKD and receiving HD. IMT did not demonstrate significant results for lung function and quality of life. Effects on endothelial function and oxidative capacity remain uncertain.

Impact

Inspiratory muscle training improves MIP, MEP, and functional capacity in people living with CKD and receiving HD, compared with conventional physical therapy or controls or placebo intervention. Increases in functional capacity in this population are extremely important because of the relationship with the survival of these people.
Physician estimate of inflammation vs global assessment in explaining variations in swollen joint counts in rheumatoid arthritis patients
Authors: Schmukler Juan , Li Tengfei , Pincus Theodore
Published: April 2024

Objective

To analyse patients with RA for inflammatory activity by physician estimate of global assessment (DOCGL) vs an estimate of inflammatory activity (DOCINF) to explain variation in the swollen joint count (SJC).

Methods

Patients with RA were studied at routine care visits. Patients completed a multidimensional health assessment questionnaire (MDHAQ) and the physician completed a 28-joint count for swollen (SJC), tender (TJC) and deformed (DJC) joints and a RheuMetric checklist with a 0–10 DOCGL visual numeric scale (VNS) and 0–10 VNS estimates of inflammation (DOCINF), damage (DOCDAM) and patient distress (DOCSTR). The disease activity score in 28 joints with ESR (DAS28-ESR), Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) were calculated. Individual scores and RA indices were compared according to Spearman correlation coefficients and regression analyses.

Results

A total of 104 unselected patients were included, with a median age and disease duration of 54.5 and 5 years, respectively. The median DAS28-ESR was 2.9 (Q1–Q3: 2.0–3.7), indicating low activity. DOCINF was correlated significantly with DOCGL (ρ = 0.775). Both DOCGL and DOCINF were correlated significantly with most other measures; correlations with DOCGL were generally higher than with DOCINF other than for SJC. In regression analyses, DOCINF was more explanatory of variation in SJC than DOCGL and other DAS28-ESR components.

Conclusions

Variation in SJC is explained more by a 0–10 DOCINF VNS than the traditional DOCGL or any other measure in RA patients seen in routine care. DOCINF on a RheuMetric checklist can provide informative quantitative scores concerning inflammatory activity in RA patients monitored over long periods.
A Changing Nursing Landscape
Authors: Kirton Carl A.
Published: April 2024

These are complicated times for the world and for nursing.
Understanding the ‘Dancing Nurses of TikTok’
Authors: Christianson Jacqueline , Calonder Sarah , Leiberg Jessica , Riggs Virginia
Published: April 2024

Judgment by nursing leaders is the wrong response.
Microaggressions in Nursing
Authors: Frazer Christine , Lopez Lois , Graham-Perel Ashley , Ochs Jessica , Pool Natalie , Land Denise , Sailsman Sonique
Published: April 2024

How to address these behaviors to promote health equity and inclusion
Nurses Honoring Fallen Nurses
Authors: Girgenti Constance , Pieroni Sheri , Raldiris Tonya
Published: April 2024

Nurse honor guards are groups of volunteer nurses that attend fellow nurses' funerals or memorial services and conduct a brief ceremony to recognize the nurse's dedication to the profession. These ceremonies incorporate elements of nursing's history, including the wearing of traditional nursing uniforms. Nurse honor guards highlight that nurses not only tend to the well-being of their patients but also share a collective responsibility to support and care for one another. This article describes what nurse honor guards do and discusses the authors' experiences participating in them.
Screening for serious mental illness in a correctional setting
Authors: Kohl Stephanie A. , Tovar Elizabeth G.
Published: April 2024

Background:

Serious mental illness (SMI) is more common among adults in correctional settings than in the general population. No standard exists for SMI screening across correctional settings; SMI therefore often goes undetected in these facilities. Placing individuals with unidentified SMI who are incarcerated in general population cells increases their risk for self-harming behaviors, suicide, and for being victims or perpetrators of exploitation and violence.

Methods:

This article describes a quantitative, descriptive study conducted to evaluate the use of the Brief Jail Mental Health Screen (BJMHS) tool to screen for possible SMI among individuals in a jail setting.

Results:

A total of 89 individuals who were incarcerated in one jail setting were screened either with the facility's internally developed standard medical questionnaire (SMQ) or with the BJMHS. Findings showed that 28% screened positive for possible SMI using the BJMHS as compared with only 3% using the SMQ.

Conclusion:

The BJMHS flagged a higher number of possible instances of SMI than the jail's SMQ, potentially signifying its screening superiority. Identification of SMI leads to better care for individuals who are incarcerated, and it increases safety for the individual with SMI, the greater jail population, and jail staff. Findings from this study were shared with system leadership, which has replaced other screening tools with the BJMHS in at least 250 correctional facilities throughout the US.
Safety and Efficacy of Vocacapsaicin for Management of Postsurgical Pain: A Randomized Clinical Trial
Authors: Shafer Steven L. , Teichman Sam L. , Gottlieb Ira J. , Singla Neil , Minkowitz Harold S. , Leiman David , Vaughn Benjamin , Donovan John F.
Published: April 2024

Background

Nonopioid management of postsurgical pain remains a major unmet need. Few studies have evaluated transient receptor potential vanilloid subfamily member 1 agonists for analgesia after surgery. This study examines intraoperative vocacapsaicin, a novel prodrug of the transient receptor potential vanilloid subfamily member 1 agonist capsaicin, in a validated model of postsurgical pain.

Methods

This was a triple-blinded, randomized, placebo-controlled, dose-ranging trial in patients undergoing bunionectomy. Patients were randomized 1:1:1:1 to surgical site administration of 14 ml of placebo or one of three vocacapsaicin concentrations: 0.30, 0.15, or 0.05 mg/ml. The prespecified primary endpoint was the area-under-the-curve of the numerical rating scale pain score at rest through 96 h for the 0.30 mg/ml group. Prespecified ordered, secondary endpoints for the 0.30 mg/ml group included the percentage of patients who did not require opioids from 0 to 96 h, total opioid consumption through 96 h, and the area-under-the-curve of the numerical rating scale pain score for the first week.

Results

The 147 patients were randomized. During the first 96 h, vocacapsaicin (0.30 mg/ml) reduced pain at rest by 33% versus placebo (primary endpoint, 95% CI [10%, 52%], effect size [Cohen’s d] = 0.61, P = 0.005). Of patients receiving vocacapsaicin (0.30 mg/ml), 26% did not require postoperative opioids for analgesia (P = 0.025) versus 5% of patients receiving placebo. Vocacapsaicin (0.30 mg/ml) reduced opioid consumption over the first 96 h by 50% versus placebo (95% CI [26%, 67%], effect size = 0.76, P = 0.002). Vocacapsaicin (0.30 mg/ml) reduced pain over the first week by 37% versus placebo (95% CI [12%, 57%], effect size = 0.62, P = 0.004). The treatment effect persisted for at least 2 weeks. All study endpoints showed an administered concentration-versus-response relationship. Vocacapsaicin was well tolerated with no differences between groups in any safety parameter.

Conclusions

A single, local administration of vocacapsaicin during surgery reduced pain and opioid consumption for at least 96 h after surgery compared to control.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Exploring the Impact of Age, Frailty, and Multimorbidity on the Effect of ICU Interventions: A Systematic Review of Randomized Controlled Trials
Authors: Perrella Andrew , Geen Olivia , Ahuja Manan , Scott Stephanie , Kaushik Ramya , Ferrante Lauren E. , Brummel Nathan E. , Muscedere John , Rochwerg Bram
Published: April 2024

OBJECTIVES:

To date, age, frailty, and multimorbidity have been used primarily to inform prognosis in older adults. It remains uncertain, however, whether these patient factors may also predict response to critical care interventions or treatment outcomes.

DATA SOURCES:

We conducted a systematic search of top general medicine and critical care journals for randomized controlled trials (RCTs) examining critical care interventions published between January 1, 2011, and December 31, 2021.

STUDY SELECTION:

We included RCTs of critical care interventions that examined any one of three subgroups—age, frailty, or multimorbidity. We excluded cluster RCTs, studies that did not report interventions in an ICU, and studies that did not report data examining subgroups of age, frailty, or multimorbidity.

DATA EXTRACTION:

We collected study characteristics (single vs. multicountry enrollment, single vs. multicenter enrollment, funding, sample size, intervention, comparator, primary outcome and secondary outcomes, length of follow-up), study population (inclusion and exclusion criteria, average age in intervention and comparator groups), and subgroup data. We used the Instrument for assessing the Credibility of Effect Modification Analyses instrument to evaluate the credibility of subgroup findings.

DATA SYNTHESIS:

Of 2037 unique citations, we included 48 RCTs comprising 50,779 total participants. Seven (14.6%) RCTs found evidence of statistically significant effect modification based on age, whereas none of the multimorbidity or frailty subgroups found evidence of statistically significant subgroup effect. Subgroup credibility ranged from very low to moderate.

CONCLUSIONS:

Most critical care RCTs do not examine for subgroup effects by frailty or multimorbidity. Although age is more commonly considered, the cut-point is variable, and relative effect modification is rare. Although interventional effects are likely similar across age groups, shared decision-making based on individual patient preferences must remain a priority. RCTs focused specifically on critically ill older adults or those living with frailty and/or multimorbidity are crucial to further address this research question.
Differences between brachial and aortic blood pressure in adolescence and their implications for diagnosis of hypertension
Authors: Hughes Alun D. , Davey Smith George , Howe Laura D. , Lawlor Deborah , Jones Siana , Park Chloe M. , Chaturvedi Nish
Published: April 2024

Objectives:

Blood pressure (BP) is the leading global cause of mortality, and its prevalence is increasing in children and adolescents. Aortic BP is lower than brachial BP in adults. We aimed to assess the extent of this difference and its impact on the diagnosis of hypertension among adolescents.

Methods:

We used data from 3850 participants from a UK cohort of births in the early 1990s in the Southwest of England, who attended their ∼17-year follow-up and had valid measures of brachial and aortic BP at that clinic [mean (SD) age 17.8 (0.4) years, 66% female individuals]. Data are presented as mean differences [95% prediction intervals] for both sexes.

Results:

Aortic systolic BP (SBP) was lower than brachial SBP [male, −22.3 (−31.2, −13.3) mmHg; female, −17.8 (−25.5, −10.0) mmHg]. Differences between aortic and brachial diastolic BP (DBP) were minimal. Based on brachial BP measurements, 101 male individuals (6%) and 22 female individuals (1%) were classified as hypertensive. In contrast, only nine male individuals (<1%) and 14 female individuals (<1%) met the criteria for hypertension based on aortic BP, and the predictive value of brachial BP for aortic hypertension was poor (positive-predictive value = 13.8%). Participants with aortic hypertension had a higher left ventricular mass index than those with brachial hypertension.

Conclusion:

Brachial BP substantially overestimates aortic BP in adolescents because of marked aortic-to-brachial pulse pressure amplification. The use of brachial BP measurement may result in an overdiagnosis of hypertension during screening in adolescence.
Regulatory T cells and bioenergetics of peripheral blood mononuclear cells linked to pediatric obesity
Authors: Rose Shannon , Landes Reid D. , Vyas Kanan K. , Delhey Leanna , Blossom Sarah
Published: April 2024

Background:

Obesity-associated inflammation drives the development of insulin resistance and type 2 diabetes. We sought to identify associations of circulating regulatory T cells (Treg) with the degree of obesity (eg, body mass index Z-score [BMIz]), insulin resistance (homeostatic model of insulin resistance [HOMA-IR]), and glycemic control (HbA1c) in children and adolescents. We further sought to examine associations among bioenergetics of peripheral blood mononuclear cells (PBMCs) and CD4 T cells and BMIz, HOMA-IR, and HbA1c.

Methods:

A total of 65 children and adolescents between the ages 5 and 17 years were studied. HbA1c and fasting levels of plasma glucose and insulin were measured. We quantified circulating Tregs (CD3+CD4+CD25+CD127-FoxP3+) by flow cytometry, and measured mitochondrial respiration (oxygen consumption rate [OCR]) and glycolysis (extracellular acidification rate [ECAR]) in PBMCs and isolated CD4 T cells by Seahorse extracellular flux analysis.

Results:

Tregs (% CD4) are negatively associated with BMIz but positively associated with HOMA-IR. In PBMCs, OCR/ECAR (a ratio of mitochondrial respiration to glycolysis) is positively associated with BMIz but negatively associated with HbA1c.

Conclusions:

In children, Tregs decrease as body mass index increases; however, the metabolic stress and inflammation associated with insulin resistance may induce a compensatory increase in Tregs. The degree of obesity is also associated with a shift away from glycolysis in PBMCs but as HbA1c declines, metabolism shifts back toward glycolysis. Comprehensive metabolic assessment of the immune system is needed to better understand the implications immune cell metabolic alterations in the progression from a healthy insulin-sensitive state toward glucose intolerance in children.

Trial registration:

This observational study was registered at the ClinicalTrials.gov (NCT03960333, https://clinicaltrials.gov/study/NCT03960333?term=NCT03960333&rank=1).
The effect of coenzyme Q10 intake on metabolic profiles in women candidates for in-vitro fertilization: a randomised trial
Authors: Ahmadi Asouri Sahar , Asemi Reza , Aghadavod Esmat , Jamilian Mehri
Published: April 2024

Objective:

Infertility and the pathogenesis of polycystic ovarian syndrome (PCOS) are both influenced by insulin resistance and dyslipidemia. Presumably, adding coenzyme Q10 (CoQ10) to these patients’ diets will be beneficial. Therefore, this study aimed to examine the effects of CoQ10 supplementation on metabolic profiles in women candidates for in-vitro fertilization (IVF).

Trial design and methods:

For this randomized, double-blinded, parallel, placebo-controlled clinical experiment, 40 PCOS-positive infertile women who were IVF candidates were included. They ranged in age from 18 to 40. The 20 participants in the two intervention groups received either CoQ10 or a placebo for 8 weeks. The expression of glucose transporter 1 (GLUT-1), peroxisome proliferator-activated receptor gamma (PPAR-γ), low-density lipoprotein receptor (LDLR), as well as metabolic profiles such as insulin metabolism and lipid profiles were evaluated. Quantitative RT-PCR determined the expression of GLUT-1, PPAR-γ, and LDLR on peripheral blood mononuclear cells. Lipid profiles and fasting glucose were assessed using enzymatic kits, and insulin was determined using Elisa kit.

Results:

In comparison to the placebo, CoQ10 supplementation significantly reduced blood insulin levels (−0.3±1.0 vs. 0.5±0.7, P=0.01) and insulin resistance (−0.1±0.2 vs. 0.1±0.2, P=0.01), and increased PPAR-γ expression (P=0.01). In infertile PCOS patients’ candidates for IVF, CoQ10 supplementation showed no appreciable impact on other metabolic profiles. Also, CoQ10 supplementation revealed no significant impact on GLUT-1 (P=0.30), or LDLR (P=0.27) expression. Within-group changes in insulin levels (P=0.01) and insulin resistance (P=0.01) showed a significant elevation in the placebo group. When we adjusted the analysis for baseline BMI, baseline values of variables, and age, our findings were not affected.

Conclusions:

Eight weeks of CoQ10 supplementation demonstrated positive benefits on PPAR-γ expression, insulin resistance, and serum insulin in infertile PCOS women candidates for IVF.
Endometrial Cancer in a Family With RAD51D Gene Mutation
Authors: Gilmore Brittany , Logan Linda , McKinnon Wendy , Everett Elise , Bryant Bronwyn H.
Published: April 2024

RAD51 complex plays an important role in homologous recombination deficiency and germline mutations have a well-documented association with breast and tubo-ovarian carcinoma, as well as serous-type endometrial carcinoma. We report a family of French Canadian ancestry with a germline mutation in RAD51D and two sisters presenting with endometrial carcinoma, endometrioid-type. The risk factors for endometrial adenocarcinoma, endometrioid-type are discussed in the context of the RAD51-associated carcinomas described to date.
Human Papillomavirus–Associated Multiphenotypic Carcinoma: First Description of a Vulval Case
Authors: Currie Charlotte C. , Leaning Darren , McCluggage W. Glenn , Spoor Emma
Published: April 2024

Human papillomavirus (HPV)–associated multiphenotypic sinonasal carcinoma is a rare and recently described epithelial neoplasm exhibiting myoepithelial differentiation and morphological overlap with salivary gland neoplasms, especially adenoid cystic carcinoma; it is commonly associated with HPV, especially type 33. It has mainly been reported in the nasal cavity and paranasal sinuses with a single case reported in the breast. Herein, we report the first vulval example in a 47-year-old patient who presented with a large craggy mass in the region of the Bartholin gland. The histologic features were of a high-grade carcinoma composed of basaloid cells arranged in sheets and nests, with occasional ductal formations, surrounded by densely hyalinised basement membrane-type material. There was diffuse block-type immunoreactivity with p16 and HPV genotyping revealed high-risk HPV type 16. In reporting this case, we highlight the propensity for “salivary gland-type” neoplasms to arise in the vulva, especially in the Bartholin gland, and stress that pathologists should consider salivary-type neoplasms when faced with a morphologically unusual vulval tumor.
Brief Report: Group-Based Trajectory Modeling to Determine Long-Term HIV Viral Load Trends Among Children With HIV in Kenya
Authors: Neary Jillian , Njuguna Irene , Wagner Anjuli D. , Richardson Barbra A. , Chebet Daisy , Langat Agnes , Ngugi Evelyn , Benki-Nugent Sarah , Moraa Hellen , Hawes Stephen E. , Overbaugh Julie , Slyker Jennifer A. , Lehman Dara A. , Wamalwa Dalton , John-Stewart Grace
Published: April 2024

Background:

Identifying determinants of longitudinal HIV viral load (VL) trajectories using group-based trajectory modeling (GBTM) can inform clinical strategies and mechanisms of nonadherence among children.

Methods:

Children under 12 months old who were newly diagnosed with HIV were enrolled in the Optimizing Pediatric HIV therapy cohort (NCT00428116) from 2007 to 2010. Children initiated antiretroviral therapy at enrollment, and VL was assessed every 3 months for 24 months post–antiretroviral therapy and every 6 months thereafter up to 8 years old. VL trajectory groups were defined using GBTM. Fisher's exact and Kruskal–Wallis tests were used to determine the correlates of each trajectory group compared with the sustained-low VL group.

Results:

Five VL trajectory groups were identified among 89 children with 522 VL visits from 6 to 24 months: sustained-low (63% of children), sustained-very-high (16%), sustained-high (9%), low-to-high (7%), and high-with-periods-of-low (6%). Children in the sustained-high group were more frequently on a first-line protease inhibitor (PI)-based regimen (63% vs 38%; P = 0.03) and had younger caregivers (median: 22 vs 28 years; P = 0.02). Among 54 children with 560 VL visits followed from 48 to 96 months, 5 trajectory groups were identified: sustained-low (74%), mid-range (4%), periods-of-low (7%), high-to-low (7%), and sustained-high (7%). Those in the high-to-low group had younger caregivers (21 vs 29 years; P = 0.01).

Conclusions:

GBTM identified unique VL patterns among children with unsuppressed VL. Caregiver and regimen-related characteristics were associated with patterns of nonsuppression. Younger caregivers may benefit from tailored counseling to help them support child antiretroviral therapy adherence. Palatable regimens are necessary for viral suppression among children with HIV.
Non-apoptotic role of EGL-1 in exopher production and neuronal health inCaenorhabditis elegans
Authors: Wu Zheng , Cardona Eric A. , Pierce Jonathan T.
Published: April 2024

While traditionally studied for their pro-apoptotic functions, recent research suggests BH3-only proteins also have non-apoptotic roles. Here, we find that EGL-1, the BH3-only protein inCaenorhabditis elegans, promotes the cell-autonomous production of exophers in adult neurons. Exophers are large, micron-scale vesicles that are ejected from the cell and contain cellular components such as mitochondria. EGL-1 facilitates exopher production potentially through regulation of mitochondrial dynamics. Moreover, an endogenous, low level of EGL-1 expression appears to benefit dendritic health. Our findings provide insights into the mechanistic role of BH3-only protein in mitochondrial dynamics, downstream exopher production, and ultimately neuronal health.

Significance statement

BH3-only proteins were known for their function in inducing cell death. Their presence in healthy adult neurons, however, suggests additional roles. Our study focused on the BH3-only protein EGL-1 in the nematodeCaenorhabditis elegans, where its apoptotic role was discovered. We reveal a new role in cell-autonomously promoting exopher production – a process where neurons extrude large vesicles containing potentially harmful cell contents. EGL-1 appears to promote this by regulating mitochondrial dynamics. We also report that low levels of EGL-1 benefit neuronal health and function. These findings expand our understanding of BH3-only proteins, mitochondrial dynamics, and exopher production in neurons and provide insights for neurodegenerative diseases.
A factorial randomised controlled trial to examine the potential effect of a text-message based intervention on reducing adolescent susceptibility to e-cigarette use: A study protocol
Authors: Barnes Courtney , Turon Heidi , McCrabb Sam , Mantach Stephanie , Janssen Lisa , Duffy Megan , Groombridge Daniel , Hodder Rebecca Kate , Meharg David , Robinson Elly , Bialek Caitlin , Wallace Seaneen , Leigh Lucy , Wolfenden Luke
Published: April 2024

Introduction

Adolescent e-cigarette use, globally and within Australia, has increased in recent years. In response, public health agencies have called for the development of education and communication programmes targeting adolescents. Despite such recommendations, few rigorous evaluations of such interventions currently exist. The main objective of this study is to examine the potential effect of a text-message intervention targeting parents and adolescents on adolescent susceptibility to e-cigarette use (e.g. intentions towards using e-cigarettes). Secondary objectives are to: (1) examine the effect of the intervention on adolescent e-cigarette and combustible tobacco use; and (2) examine the acceptability of the intervention.

Methods and analysis

A randomised controlled trial employing a 2x2 factorial design will be conducted with parent-adolescent dyads (aged 12-15 years). Dyads will be randomly allocated to one of four arms: Arm 1 - a text-message intervention delivered to adolescents only; Arm 2 – a text- message intervention delivered to the parents of adolescents only; Arm 3 – a text-message intervention delivered to both the parents and adolescents; and Arm 4 - an information only control, consisting of an e-cigarette factsheet provided to parents only. Participant recruitment commenced in April 2023 with the aim to recruit 120 parent-adolescent dyads. Data collection to assess study outcomes will occur at baseline, 6-, 12- and 24-months post the commencement of the intervention. The primary endpoint will be 6-month follow-up. The primary outcome will be adolescent susceptibility to e-cigarette use, assessed using validated items. Analyses of trial outcomes will be undertaken under an intention-to-treat framework, with all participants included in the analysis in the group they were allocated.

Ethics and dissemination

Ethics approval has been obtained from the University of Newcastle Human Research Ethics Committee (H-2022-0340). Findings will be disseminated in peer-reviewed journals and at conferences.

Trial registration

Prospectively registered with Australia New Zealand Clinical Trials Registry (ACTRN12623000079640).

STRENGTHS AND LIMITATIONS

This study will employ a rigorous factorial randomised controlled trial design to test the effectiveness of a text-message based intervention;

This study will contribute to the limited existing evidence base, with no randomised controlled trials aiming to prevent adolescent e-cigarette use currently published yet several underway;

Selection bias may occur if adolescents who are highly susceptible to e-cigarette use refuse to participate in the study.