bluuebunny/crossref_metadata_2025 huggingface dataset:
Leadership competencies in public health: implications for nursing leadership – a scoping review
Authors: Rojko Lucija , Kvas Andreja , Stare Janez
Published: December 2024

Purpose

Effective leadership in public health organisations is essential for achieving positive outcomes and ensuring the quality of healthcare services. This review aimed to identify the competencies that nurse leaders of organisations working in the field of public health need to perform their tasks effectively.

Design/methodology/approach

A descriptive method with a scoping review was used, searching the PubMed, ScienceDirect, and CINAHL databases. A total of 16 references were suitable for the final analysis. A summative literature analysis was conducted, identifying leadership competencies (N = 69) across various sources. The identified competencies were analysed by qualitative approach.

Findings

Competencies were categorised in 11 groups: Identifying Needs and Continuous Improvement; Strategic Planning in Line with Vision and Mission; Ensuring Professional Development; Maintaining Motivation; Delegating and Managing Tasks; Communication Skills; Building and Maintaining Relationships with Decision Makers; Problem Solving and Conflict Management; Tracking Professional Trends and Using Accurate Information; Resource Management and Human Resource Management; Organising Work.

Originality/value

The 11 groups of leadership competencies for nurses in public health organisations provide a content direction for educational activities aimed at nurse leaders and summarise the most important competencies required for effective leadership in public health organisations. Competent leadership is vital for the success and effectiveness of public health organisations in delivering quality healthcare services and addressing the evolving healthcare needs. Further research within specific field in public health is recommended to identify additional, field-specific competencies essential for effective leadership in diverse organisational settings.
A comparative analysis of deterministic and probabilistic approaches for estimating seepage flow in earth dams using a hybrid finite element method
Authors: Kheiry Milad , Kalateh Farhoud
Published: December 2024

Purpose

Computing seepage discharge in earth dams involves inherent complexities and challenges that require the use of probabilistic algorithms to accurately capture their uncertain characteristics and identify optimal solutions. This study aims to investigate the impact of uncertainty in seepage flow estimation using a novel hybrid approach, combining the analysis of Laplacian equations with the probabilistic finite element method (PFEM) and a metaheuristic algorithm.

Design/methodology/approach

To achieve this purpose, a finite element-based FORTRAN program was developed to model the problem using the Galerkin finite element method, which was validated using laboratory findings. Subsequently, Monte Carlo loops were incorporated into each model, consisting of 2000 iterations and the probability distribution function and cumulative distribution function were computed for each sub-model. A total of 138 earth dams were analysed to investigate the influence of different characteristics on seepage, including variations in dam geometry, soil permeability and water levels (both downstream and upstream). Effective seepage flow (ESF), was introduced in both deterministic and probabilistic models.

Findings

The findings indicated that the downstream slope has a more significant impact on ESF than the upstream slope, with a difference of 1.29%. Additionally, the ratio of dam height to bottom width (H/B) directly affects the ESF, resulting in a 20% increase in ESF for every 16% increase in H/B.

Originality/value

This study introduces a novel hybrid approach for estimating seepage flow in earth dams by integrating the Unlike traditional deterministic models, which often overlook the inherent .PFEM with a metaheuristic algorithman advanced uncertainties in seepage characteristics, this research effectively captures these uncertainties throughprobabilistic framework.
High Salt Exacerbates Myocardial Dysfunction In Vitro and In Vivo by Promoting SIRT1/Nrf2‐Mediated Ferroptosis
Authors: Guanji Wu , Fuqiang Liu , Fei You , Zhang Tao , Xiaolin Chen
Published: December 2024

Myocardial dysfunction is a crucial determinant of the development of heart failure in salt‐sensitive hypertension. Ferroptosis, a programmed iron‐dependent cell death, has been increasingly recognised as an important contributor to the pathophysiology of various cardiovascular diseases. This study aims to investigate the role and underlying mechanism of ferroptosis in high‐salt (HS)‐induced myocardial damage. Our results reveal that HS stimulation inhibited cell proliferation and promoted apoptosis in cardiomyocyte HL‐1 cells in a dose‐dependent manner. Ferroptotic features were observed in HS‐induced HL‐1 cells, including ferric iron accumulation, decreased glutathione levels, increased oxidative stress levels, upregulation of ferroptosis marker proteins PTGS2, 4HNE and FTH1 and downregulation of GPX4, all of which were reversed by treatment with the ferroptosis suppressor Fer‐1. Furthermore, the administration of Fer‐1 ameliorated HS‐induced ferroptosis and myocardial damage in salt‐sensitive Dahl SS rats. Additionally, we found that a HS diet suppressed the SIRT1/Nrf2 signalling pathway activation in our in vivo experiments. Activation of SIRT1/Nrf2 signalling by SIRT1 overexpression significantly attenuated ferroptosis in HS‐induced HL‐1 cells. In conclusion, our findings demonstrate that HS levels induce myocardial injury by promoting ferroptosis via the deactivation of the SIRT1/Nrf2 signalling pathway, highlighting the potential for therapeutic targeting of ferroptosis for hypertension‐related cardiovascular disorders.
Characterization of yellowfin tuna (Thunnus albacares) skin gelatin extracted by bromelain hydrolysis and ultrasound pre‐treatment
Authors: Haryati Dian , Ningrum Andriati , Witasari Lucia Dhiantika
Published: December 2024

Yellowfin tuna skin waste is a potential collagen source for gelatin through hydrolysis. Enzymatic hydrolysis is eco‐friendly but expensive, necessitating efficiency improvements. Ultrasound pre‐treatment enhances efficiency via cavitation effects. This study evaluated the effects of ultrasound amplitude, pre‐treatment duration, enzyme concentration, and hydrolysis duration on yield; determined optimal conditions for ultrasound‐assisted enzymatic extraction on yield, viscosity, and gel strength; and assessed the gelatin's physicochemical and functional properties. This research consists of three stages, factor screening using one variable at a time, optimization using response surface methodology with Box‐Behnken design, and gelatin characterization. The study included three replicates. Screening identified factor ranges for optimization: 5–25 min pre‐treatment, 1%–3% enzyme concentration, and 1–5 h hydrolysis. Optimization involved 15 experimental runs, focusing on yield, viscosity, and gel strength. Optimal conditions were 25 min pre‐treatment, 1% enzyme concentration, and 2.17 h hydrolysis, yielding 64.08%, 9.29 mPa·s viscosity, and 166.28 bloom gel strength. The optimized gelatin showed emulsifying properties with EAI 50.5 m2/g and ESI 23.80 min, water‐oil holding capacities of 192% and 406%, respectively, antioxidant activity of 60.16%, and molecular weight range of 17–160 kDa. The amino acid composition was mainly glycine (29.26%) and proline (18.26%), with 76.95% digestibility. This innovative, environmentally friendly extraction method improved gelatin extraction efficiency from yellowfin tuna skin, supporting a sustainable industry.
Extraction, characterization, and hemostatic effect of collagen from the scales of Megalonibea fusca
Authors: Li Guangfeng , Guo Tengfei , Chen Huaizhong , Huang Zhihao , Chen Qunjie , Wu Chaoxi , Wang Yifei
Published: December 2024

Marine collagen is gaining more attraction than terrestrial collagen because it is free of zoonotic disease and religious constrain. In this study, we aimed to investigate and compare the physicochemical properties and functional characteristics of acid‐soluble collagen (ASC‐MF) and pepsin‐soluble collagen (PSC‐MF) extracted from scales of Megalonibea fusca. ASC‐MF and PSC‐MF were evaluated in terms of yield, collagen type, amino acid composition, thermal stability, microstructure, cytotoxicity, and other physicochemical parameters. ASC‐MF and PSC‐MF depicted 1.72 ± 0.2% and 11.72 ± 0.3% of dry weight yields, respectively, and were identified as type I collagen with an intact triple‐helical structure by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE), spectroscopic analysis, and electron microscopy. Additionally, compared with many temperate and tropical species, ASC‐MF and PSC‐MF showed higher thermal stability, with the maximum transition temperature (Tmax) of 53.50°C (ASC‐MF) and 43.16°C (PSC‐MF). CCK‐8 assay showed that ASC‐MF and PSC‐MF have no cytotoxicity in vitro. The determination of blood clotting index values showed that both ASC‐MF and PSC‐MF had good hemostatic ability. In summary, these findings show that PSC‐MF isolated from the scales of M. fusca may be a feasible alternative to terrestrial collagen sources in food and biomedical applications.
Effects of brown seaweed oligosaccharides on obesity and constipation managements
Authors: Gao Jingyu , Wu Fan , Yan Mingzhu , Wang Xuejiang , Chi Yan , Zhang Yu , Peng Yu , Li Mo , Ni Yuanying , Wen Xin
Published: December 2024

Brown seaweed oligosaccharides (BSO) have demonstrated potential as nutraceuticals with cholesterol‐lowering, anti‐obesity, and anti‐constipation properties. In this study, we initially examined how BSO impact body weight, blood lipid levels, and adipose tissue in a rat model of obesity induced by a high‐fat diet. Our findings revealed that BSO administration significantly attenuated body weight gain, ameliorated dyslipidemia, and reduced visceral adiposity. Additionally, we evaluated the prophylactic efficacy of BSO in a loperamide hydrochloride‐induced constipation mouse model by assessing defecation parameters and gastrointestinal motility. Our results indicated that BSO intervention significantly increased fecal pallet output and fecal water content, as well as improved intestinal transit. In conclusion, this study lays the foundation for a deeper understanding of how BSO may influence obesity and constipation, offering novel insights into its potential safe and efficacious clinical applications.
Association of Biomarkers Such as CA, TP, TES and ALP With Osteoarthritis Risk: A Mendelian Randomized Study
Authors: Chen Anqi , Cai Qiang
Published: December 2024

Objective

Osteoarthritis is a common joint disease caused by a variety of risk factors, and it has been found that many biochemical markers are abnormal in peripheral blood and urine of patients with OA. The aim of this study was to elucidate the causal relationship between biomarkers associated with these processes and OA using Mendelian randomization (MR) analysis.

Method

The inverse variance weighted (IVW) approach to MR was primarily used to explore causal associations between exposures and outcomes using publicly available genetic variants from large genome‐wide association studies (GWAS). That is, single nucleotide polymorphisms (SNPs) associated with 35 human blood and urine markers (363 228 healthy participants) were used as exposure, and osteoarthritis, hip osteoarthritis, and knee osteoarthritis were used as outcome variables, with the aim of exploring the causal relationship between 35 human blood and urine markers and osteoarthritis. MR‐Egger, weighted median (WM), and simple and weighted models were used as complementary methods to IVW to assess the reliability of causality. Steiger's test was used to confirm whether the causal relationship between exposure and outcome was biased by reverse causality. Sensitivity analyses used Cochran's Q statistic and funnel plots to detect heterogeneity, and the MR‐Egger intercept test and leave‐one‐out to assess horizontal multidimensionality.

Results

Our MR analysis study identified the protective effects of CA, TP, ALB, SHBG, and VITD on OA and the pathogenic effects of TES, ALP, GGT, CRP, and CHOL on OA. It suggests that the above 10 hematological and urinary markers have the potential to be important indicators for the clinical diagnosis of OA as well as for the assessment of therapeutic efficacy and disease progression.

Conclusion

This MR analysis reinforces the importance of biomarkers in the diagnosis and prediction of OA. Future studies should further investigate the mechanisms of these biomarkers and their potential as therapeutic targets for OA.
Single‐Stage Reconstruction of Large Scalp Surgical Defects With Exposed Bone Using Matriderm Flex and Full‐Thickness Skin Grafts, a Case Report
Authors: Gil‐Pallares Pedro , Almenara‐Blasco Manuel , Navarro‐Bielsa Alba , Gilaberte Yolanda
Published: December 2024

The reconstruction of full‐thickness scalp defects with exposed bone can be challenging. A single‐stage reconstruction could be the preferred option for patients with multiple comorbidities. We propose using a dermal regeneration template (Matriderm Flex) and full‐thickness skin grafts. The approach shown in this case report allows for quick healing, less donor‐site discomfort in comparison with dermatome‐harvested skin grafts, and very good aesthetic results, matching the surrounding skin thickness.
Role of the Systemic Immune‐Inflammation Index and Systemic Immune‐Response Index in the Prediction of Adverse Outcomes in Pregnant Women With Antiphospholipid Syndrome
Authors: Doğru Şükran , Ezveci Huriye , Yaman Fikriye Karanfil , Metin Ülfet Sena , Acar Ali
Published: December 2024

Problem

This study aims to evaluate the role of the systemic immune‐inflammation index (SII) and the systemic immune‐response index (SIRI) in predicting adverse perinatal outcomes (APO) in pregnant women with antiphospholipid syndrome (APS).

Methods

This is a retrospective case–control study at the tertiary center, between January 2015 and January 2023. The study included APS cases and a low‐risk control group. Pregnant women with APS (n = 52) and controls (n = 104) were compared between SII and SIRI values taken in the first trimester (1) and the last month before birth (2). It was examined whether these indexes predicted APO in cases with APS.

Results

In the APS group, SII and SIRI values taken in the first trimester (1) and in the last month before birth (2) were significantly lower than in the control group (p = 0.015, p = 0.023, p = 0.001, p = 0.001, respectively). The small for gestational age (SGA) rate was 30.8% and the stillbirth rate was 11.5% in the APS group (p = 0.017, p = 0.001). The optimum cutoff values for SGA were 584.97 (75% sensitivity, 77.8% specificity), 688.50 (62.5% sensitivity, 62.9% specificity), and 1.02 (56.3% sensitivity, 77.8% specificity) for SII 1, SII 2, and SIRI 1, respectively. The optimum cutoff value for stillbirth was 1.23 for SIRI 2 (83.3% sensitivity, 89.1% specificity, p = 0.004).

Conclusion

Pregnant women with APS had decreased blood indices in the first trimester and the last month before birth compared to the control group. In cases with APS, these indices can predict APOs like SGA and stillbirth.
Role of Decidual Natural Killer Cells in the Pathogenesis of Preeclampsia
Authors: Yue Shuang , Meng Jinlai
Published: December 2024

Preeclampsia is one of the most severe obstetric complications, yet its pathogenesis remains unclear. Decidual natural killer (dNK) cells, the most abundant immune cells at the maternal‐fetal interface, are closely associated with preeclampsia due to abnormalities in their quantity, phenotype, and function. This review summarizes the molecular mechanisms by which dNK cells regulate extravillous trophoblast (EVT) invasion, promote uterine spiral artery remodeling, and maintain immune tolerance. Furthermore, it explores how disruptions in these mechanisms and changes in the decidual microenvironment alter dNK cell properties, driving the progression of preeclampsia. Understanding the mechanisms of dNK cells and identifying potential therapeutic targets may provide new insights for clinical intervention.
Self‐management training with online intervention process for young adults with chronic conditions: Effects on self‐management, emotion regulation, and occupational balance: A randomized controlled study
Authors: Altuntaş Onur , Özkan Esma
Published: December 2024

The aim of the study was to examine the effects of online self‐management training on self‐management, emotion regulation, and occupational balance in young adults with chronic diseases. Young people participated in this cluster randomized controlled trial (n = 72; mean age, 20.80 ± 2.65 years). Eight sessions of self‐management training were applied in the study group (SG; n = 37), and one session was applied in the control group (CG; n = 35). To evaluate the training, all participants completed the Self Management‐Self Control Scale, Cognitive Emotion Regulation (CERQ), and Occupational Balance Questionnaire at the beginning and end of the training. We performed an analysis of covariance (ANCOVA). In cases where ANCOVA assumptions could not be met, the efficacy of the intervention was determined using the mixed design/split‐plot analysis of variance. Compared to the CG, SG showed a significant increase in self‐management skills. For the CERQ variable, it was observed that there was no significant difference between the study and control group mean differences after the intervention. Occupational balance remained similar between the groups. The self‐management training can have a positive impact on the development of their self‐management, particularly in chronic conditions.
Clinical relevance of immune checkpoint inhibitors for the analgesic effect of opioids: A retrospective propensity score analysis
Authors: Sumimoto Takahiro , Tanaka Ryota , Murakami Yuko , Tatsuta Ryosuke , Itoh Hiroki
Published: December 2024

Aims

This study aimed to determine the clinical relevance of the influence of coadministration of immune checkpoint inhibitors (ICIs) on the analgesic effects of opioids, focusing on the amount of change in opioid dosage.

Methods

This study used data from patients who used opioids during anticancer therapy at the Oita University Hospital between September 2014 and October 2023. The primary outcome measure was the amount of change in morphine mg equivalent opioid dose during the period of anticancer therapy. Propensity score matching was performed to reduce confounding effects.

Results

The study enrolled 235 patients; 101 received ICI and 134 received no ICI. Before propensity score matching, there were significant differences between the ICI and non‐ICI groups in lines of anticancer therapy, type of primary cancer, body mass index, maximum opioid dose and the amount of change in opioid dose. Following propensity score matching, 73 patients each were included in the ICI and non‐ICI groups. Analysis of the propensity score‐matched cohort showed a significant increase in the median amount of change in opioid dose in ICI group vs non‐ICI group (22.5 vs. 15.0 morphine mg equivalents, interquartile range; 0.0, 40.0 vs. 0.0, 30.0, P = .044). Multiple regression analysis identified ICI administration and body mass index as significant independent factors associated with the amount of change in opioid dose (P = .014 and .027, respectively).

Conclusions

ICI administration significantly increased opioid dosage regardless of patient background. Our findings would provide valuable insight into future pain management strategies.
Can Natural Supporters Be Fostered to Support Adults With Intellectual Disabilities to Become Local Volunteers or to Join Mainstream Leisure Groups in Irish Rural Towns and Villages?
Authors: Boland Geraldine , Potter Anne‐Marie , de Paor Eilin , Guerin Suzanne
Published: December 2024

Background/Aims

This study explored supporting the social inclusion of adults with intellectual disabilities living in rural areas, by engaging natural supporters (other than family members and paid staff).

Methods

This qualitative study involved educating and preparing six local connectors—each a member of mainstream volunteering and/or leisure clubs to support six people with intellectual disabilities to join. Qualitative interviews were used to explore the experiences of local connectors.

Findings

Six clusters of meaning were identifiable from content analysis including the support provided by local connectors, communication/interaction and supports for continued attendance. Rural local connectors had strong local knowledge and connections that facilitated those with disabilities to make local acquaintances.

Conclusions/Implications

As part of a structured programme, natural supporters can be engaged to support people with intellectual disabilities to become known and make connections in their rural neighbourhoods. Implications for practice include sourcing social roles as close as possible to home for rural dwellers and the importance of flexible transport. The characteristics of local connectors and the club ethos/culture that facilitates social inclusion are identified. Policy recommendations include that local authorities offering funding to local clubs develop guidelines and education for members, with a view to embedding diverse membership as a guiding principle.
Spinal Cord Stimulation for Prolonged Disorders of Consciousness: A Study on Scalp Electroencephalography
Authors: Sun Jian , Yan Jiuqi , Zhao Liang , Wei Xiang , Qiu Chang , Dong Wenwen , Luo Bei , Zhang Wenbin
Published: December 2024

Background

Patients with disorders of consciousness (DOC) undergoing spinal cord stimulation (SCS) for arousal treatment require an assessment of their conscious state before and after the procedure. This is typically evaluated using behavioral scales (CRS‐R), but this method can be influenced by the subjectivity of the physician. Event‐related potentials (ERP) and EEG power spectrum are associated with the recovery of consciousness. This study aims to explore the electrophysiological and behavioral evidence of consciousness recovery in DOC patients after spinal cord stimulation (SCS) and to investigate the role of scalp EEG as a guide for preoperative assessment related to the surgery.

Methods

For the 27 recruited patients, the CRS‐R scale assessment and ERP P300 evaluation were completed before the surgery. At 3 months post‐surgery, all 27 patients underwent the same assessments as preoperatively, and at 6 months post‐surgery, the same evaluations were repeated for the 15 patients who could still be followed up. Between May 2023 and November 2023, resting‐state EEG was collected from 13 patients using a 19‐channel setup, with additional resting‐state EEG recordings taken at 3 months and 6 months after the surgery. The EEG data were processed using EEGLAB to obtain P300‐related metrics and EEG power spectrum. Changes in the CRS‐R scale, ERP, and EEG power spectrum before and after the surgery were compared.

Results

The Behavioral Scale (CRS‐R) showed significant improvement at 3 months and 6 months post‐surgery compared to preoperative assessments, with statistical significance (p < 0.001). The resting‐state EEG power in the 5–9 Hz frequency band demonstrated statistically significant improvements at the P3 and O1 electrodes; however, this statistical result do not survive FDR correction. In the 9–13 Hz and 20–35 Hz frequency bands, the power spectrum showed statistically significant improvements across most electrodes of the brain, and these results survive FDR correction (p < 0.05). The mean amplitude, peak, and latency of P300 at the Pz electrode showed significant improvements at 3 months and 6 months post‐surgery compared to preoperative values, with statistical significance (p < 0.05).

Conclusion

Our study shows that SCS can effectively improve the consciousness states of patients with DOC. After surgery, there were positive changes in the EEG power spectrum of the patients, transitioning from type “B” to better types “C” and “D.” The average amplitude, peak, and latency of P300 also demonstrated significant improvements postoperatively. We believe that the “ABCD” model and ERP assessment applied during the preoperative evaluation can effectively enhance the success rate of SCS surgery in promoting awakening.
Evolving Impact of COVID‐19 on Intestinal Transplant Recipients: A Single‐Center Experience
Authors: Powers Colin , Corrente Brielle , Joyce Jennifer , Stein William , Polydor Shelly , Gunabushanam Vikraman , Khanna Ajai , Silveira Fernanda P. , Cruz Ruy J.
Published: December 2024

Background

There has been significant concern about coronavirus disease 2019 (COVID‐19) among transplant recipients, particularly those who are highly immunosuppressed. Several studies have analyzed the impact of COVID‐19 on different solid organ transplant patients. However, few isolated case reports of COVID‐19 in intestinal and multivisceral transplant (ITx and MVTx) recipients are available in the literature. We report the first single‐center study evaluating the clinical course and outcome of COVID‐19 in ITx/MVTx recipients.

Methods

Adult patients (age ≥ 18 years) with confirmed cases of COVID‐19 between February 2020 and February 2024 were included in this study.

Results

Twelve of the 67 (17.9%) ITx/MVTx recipients followed at our center had COVID‐19. Seven patients (58%) were female, and the median age at diagnosis was 47 years (range: 31–68 years). The average time from transplantation to COVID‐19 was 89 months (range: 14–215 months). Nine patients (75%) required hospitalization; three of them were admitted to the intensive care unit (ICU) and required ventilator support. One patient had COVID‐19 on two different occasions. Treatment modalities consisted of monoclonal antibody treatment (n = 5), of antiviral therapy (n = 4), and steroid monotherapy (n = 1). Three patients received combination therapy. Three patients (25%) developed irreversible respiratory failure and died after prolonged ventilator use.

Conclusions

Our data suggested a possible increase in the incidence of COVID‐19 in ITx and MVTx recipients with an unchanged mortality rate despite the use of vaccines and new therapeutic modalities. Further multicenter studies are needed to analyze the real impact of COVID‐19 on this unique population.
Mechanical Circulatory Support for Right Ventricular Primary Graft Dysfunction After Heart Transplant: A Review
Authors: Hart Einar A. , Braithwaite S. A. , Hermens J. A. J. , Kraaijeveld A. O. , Ramjankhan F. , van Laake L. W. , Oerlemans M. I. F. J. , Szymanski M. K.
Published: December 2024

Primary graft dysfunction (PGD) is the most common cause of early mortality following heart transplantation. Although PGD can affect both ventricles, isolated right ventricular dysfunction (RV‐PGD) is observed in nearly half of PGD patients. RV‐PGD requires specific medical management to support the preload, afterload, and function of the failing RV; however, the use of mechanical circulatory support of the RV (RV‐MCS) might be required when optimal medical therapy is insufficient in preventing forward failure and retrograde venous congestion. While RV‐MCS options provide the opportunity to prevent or to recover from circulatory shock states, MCS is associated with a significant risk of complications. As a result of recent developments in short‐term mechanical support devices, less invasive, percutaneous options for RV‐MCS are available. In this review, we discuss the available devices, their advantages and disadvantages, and reported outcomes in RV‐PGD.
A Five‐Year Prospective, Randomized, Open‐Label Study of Standard‐Dose Versus Low‐Dose Prolonged‐Release Tacrolimus With or Without Angiotensin‐Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Post Kidney Transplantation
Authors: Campbell Patricia M. , Cantarovich Marcelo , Gangji Azim , Houde Isabelle , Jevnikar Anthony M. , Monroy‐Cuadros Felix‐Mauricio , Nickerson Peter W. , Pâquet Michel R. , Prasad G. V. Ramesh , Senécal Lynne , Wolff Jean‐Luc , Schwartz Jason J. , Rush David N.
Published: December 2024

Introduction

Novel approaches to improve long‐term outcomes in kidney transplant recipients are required. Here, we present the 5‐year data from a multicenter, prospective, Phase 3b trial evaluating treatment outcomes with standard (STD) or low (LOW) dose prolonged‐release tacrolimus (TAC) combined with ACEi/ARB or other antihypertensive therapy (OAHT) in Canadian kidney transplant recipients.

Methods

Adult de novo kidney transplant recipients were randomized 2 × 2 to STD or LOW dose TAC and ACEi/ARB or OAHT. Patients had received a first or second transplant from a living or deceased donor and had ≥ 1 human leukocyte antigen mismatch with their donor.

Results

There were 281 patients from 13 sites across Canada. Overall patient survival was 95.7% and was comparable between groups. Graft survival at study end was 89.7% in the LOW+OAHT group and 94.4%–97.1% in the other groups and BPAR, and Class II de novo donor‐specific antibodies (dnDSA) were higher in the LOW+OAHT group than in the other groups. However, these differences were not statistically significant. Graft function, blood pressure (BP), and proteinuria were similar between the groups; however, between 2 and 5 years there was a 2‐fold or greater increase in the use of ACEi/ARB in patients randomized initially to OAHT, mostly because of hypertension and proteinuria. There were no unexpected safety findings.

Conclusion

Patients randomized to LOW TAC with renin‐angiotensin system (RAS) blockade had similar outcomes at 5 years as patients treated with STD TAC with or without RAS blockade, whereas those randomized to LOW TAC without RAS blockade showed a non‐significant trend towards more rejections and dnDSA

Trial Registration:

ClinicalTrials.gov identifier: NCT00933231
A phase I, randomized, placebo‐controlled trial to evaluate the pharmacokinetics, safety, and tolerability of nirsevimab in healthy Chinese adults
Authors: Mao Xiaomeng , Hua Xiaohan , Wu Chengyi , Ge Xiaoyun , Zhang Jie , Wu Xiaojie , Kubiak Robert J. , Wählby Hamrén Ulrika , Villafana Tonya , Christou Georgios , Green Jannine , Takas Therese , Jin Yuwen
Published: December 2024

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) in infants worldwide. Nirsevimab, an extended half‐life monoclonal antibody against RSV, is approved in China for the prevention of RSV lower respiratory tract disease in infants; however, global nirsevimab trials did not enroll Chinese infants. To inform the investigation of nirsevimab for the prevention of RSV LRTI in Chinese infants, this Phase I, randomized, placebo‐controlled trial evaluated the pharmacokinetics (PK) and safety of nirsevimab in healthy Chinese adults. Participants were randomized 3:1 to a single 300 mg intramuscular dose of nirsevimab or placebo and were followed through 150 days post‐dose. Serum nirsevimab concentrations were measured and PK parameters of maximum serum concentration (Cmax), time to maximum concentration (tmax), and area under the concentration‐time curve from time 0 to Day 150 (AUC0–150) were estimated. Treatment emergent adverse events (AEs), clinical laboratory data, and vital signs were evaluated. Overall, 24 participants were randomized to nirsevimab (n = 18) or placebo (n = 6). Nirsevimab geometric mean (coefficient of variation [%CV]) Cmax was 46.9 (21.7) μg/mL, median (range) tmax was 7.0 (4.9, 29.9) days, and geometric mean (%CV) AUC0–150 was 4210.6 (13.6) μg·day/mL. Treatment‐emergent AEs (all Grade 1 or Grade 2 in severity) were reported in 5/18 (27.8%) nirsevimab recipients and 2/6 (33.3%) placebo recipients. No serious AEs, new onset chronic disease, or deaths were reported. Overall, safety and PK outcomes were consistent with those observed in healthy adults in the USA, with no new safety concerns.
The Evaluation of Right Ventricular Synchrony by Two‐Dimensional Speckle Tracking Echocardiography in Connective Tissue Disease‐Associated Pulmonary Arterial Hypertension
Authors: Ma Hong , Wu HongPing , Sun XiaoXuan , Wang Qiang , Zheng YaGuo
Published: December 2024

Objectives

Numerous studies have demonstrated impaired right ventricular (RV) synchronicity in pulmonary arterial hypertension (PAH). However, few studies have focused on connective tissue disease (CTD)‐associated PAH. This study evaluates RV dyssynchrony and its prognostic value in CTD‐associated PAH.

Methods

One hundred thirteen CTD patients and 32 healthy controls were consecutively recruited. The patients were further divided into two groups: the CTD‐nonPAH group (sPAP ˂ 36 mmHg, n = 60) and the CTD‐PAH group (sPAP ≥ 36 mm Hg, n = 53). RV dyssynchrony was evaluated by determining the standard deviation of the heart rate–corrected intervals from QRS onset to peak strain for the four segments (RV‐SD4) using 2D speckle‐tracking echocardiography (2D‐STE). All patients were followed up, and the primary endpoint was clinical worsening.

Results

Compared to the health control, the CTD patients exhibited obviously prolonged RV‐SD4 (13.3 ± 6.8 ms vs. 41.2 ± 36.5 ms, p < 0.001). Among 113 CTD patients, the CTD‐PAH patients had longer RV‐SD4 than the CTD‐nonPAH patients (20.8 ± 9.9 ms vs. 64.3 ± 41.6 ms, p < 0.001). RV‐SD4 was moderately positively correlated with RV longitudinal strain (r = 0.632, p < 0.001), sPAP (r = 0.644, p < 0.001), and were negatively correlated with TAPSE (r = –0.547, p < 0.001), and FAC (r = –0.611, p < 0.001). In the follow‐up, 23 patients experienced clinical worsening. The ROC analysis suggested that RV‐SD4 level >60.6 ms predicted clinical worsening with 91.3% sensitivity and 66.7% specificity (AUC = 0.891, p < 0.001). Multivariate Cox analysis showed that TAPSE (HR = 0.739; 95% CI 0.623–0.878; p = 0.001) and RV‐SD4 (HR = 6.148; 95% CI 1.718–22.000; p = 0.005) were independent predictive parameters of clinical worsening.

Conclusion

CTD patients exhibit impaired RV synchronicity, which is linked to RV function and pulmonary artery pressure. RV dyssynchrony could predict clinical worsening in CTD‐PAH.
Scalp high‐frequency oscillation spatial distribution is consistent over consecutive nights, while rates vary with antiseizure medication changes
Authors: Karatza Panagiota , Cserpan Dorottya , Moser Katharina , Lo Biundo Santo Pietro , Sarnthein Johannes , Ramantani Georgia
Published: December 2024

Objective

This study aimed to investigate two key aspects of scalp high‐frequency oscillations (HFOs) in pediatric focal lesional epilepsy: (1) the stability of scalp HFO spatial distribution across consecutive nights, and (2) the variation in scalp HFO rates in response to changes in antiseizure medication (ASM).

Methods

We analyzed 81 whole‐night scalp electroencephalography (EEG) recordings from 20 children with focal lesional epilepsy. We used a previously validated automated HFO detector to assess scalp HFO rates (80–250 Hz) during non–rapid eye movement (NREM) sleep. The spatial distribution of HFO rates across consecutive nights was evaluated using Hamming similarity, and changes in ASM were classified as increased, decreased, or stable.

Results

For each patient, we analyzed 3 ± 1 whole‐night scalp EEG recordings, with a mean duration of 650 ± 215 min per recording. The distribution of HFO remained stable across consecutive nights, with a Hamming similarity of 88% ± 6%. Four patients had at least one ASM dosage decrease, nine patients had both ASM dosage decreases and increases, two patients had only ASM dosage increases, and five patients had no changes in ASM during the study period. A decrease in ASM dosage was associated with increased HFO rates (from .16 ± .32 to .22 ± .36 HFO/min; p = .03), whereas an increase in ASM dosage led to decreased HFO rates (from .32 ± .54 HFO/min to .22 ± .38 HFO/min; p = .005) when comparing the last night to the first.

Significance

The spatial distribution of scalp HFOs remained consistent across multiple nights, whereas fluctuations in HFO rates correlated with changes in ASM dosage. These findings suggest that scalp HFOs may not only help identify epileptogenic brain tissue but also monitor treatment response.
A Socioecological Approach to Support the Transition to Adult Care for Youth With Medical Complexity: Family Perspectives and Recommendations
Authors: Li Lin , Carter Nancy , Gorter Jan Willem , Till Linda , White Marcy , Strachan Patricia H.
Published: December 2024

Introduction

The transition from paediatric to adult health care (i.e., ‘health care transition’) poses many challenges for youth with medical complexity (YMC) and their families. YMC need specific approaches to supporting transition, tailored to individual youth and family contexts. In this study, we examine the contextual factors influencing families' transition experiences and describe their recommendations for improving the experience.

Methods

We conducted a qualitative explanatory case study in Ontario, Canada. We completed 21 interviews with 17 participants (11 mothers, 2 fathers, 2 YMC, 2 siblings) from 11 families of YMC. Six YMC (55%) were under 18 years of age (pre‐transfer) and five (45%) were aged 18 years and older (post‐transfer). Analytic approaches included reflexive thematic analysis and directed content analysis.

Findings

Participants described how the interplay of personal and environmental factors impacted their transition experiences. Recommendations for health care providers focused on providing instrumental and psychological support, advocacy and care continuity. Families expressed a need for better access to information and support from primary care providers. System‐level recommendations included streamlining transition processes, improving adult health care services and expanding community supports. A socioecological model is presented to guide health care providers and decision makers in assessing and tackling the challenges faced by YMC and their families during transition.

Conclusion

Findings highlight the complexity and scope of issues surrounding the transition to adult care for YMC in Ontario, with evidence of major gaps in services across multiple sectors and settings. Ongoing efforts are needed to move evidence into practice and advocate for more equitable and responsive care for YMC during the transition and beyond.

Patient or Public Contribution

The research team included two parent co‐researchers with lived experience, who contributed to protocol refinement, funding acquisition, recruitment, findings interpretation and ongoing knowledge translation efforts.
Ceramics as alternative solutions for the geological disposal of high‐level radioactive waste: Andra's R&D program
Authors: Debelle Aurélien , Besnard Clémence , Miot Stéphanie , Perret Emilie , Couillaud Samuel , Ganster Patrick , Rossignol Fabrice , German Guillaume , Reine Bénédicte , Pasteau Antoine , Bourbon Xavier , Perrochon Olivier , Bumbieler Frédéric
Published: December 2024

The concept of a safe geological disposal facility designed to manage radioactive waste is on the basis of the multibarrier system comprising both the host rock and various engineered barriers. The robustness of the latter depends directly on the building materials used. With specific regard to high‐level waste, Andra's Cigéo project includes, among others, two barriers, i.e., the disposal container and the microtunnel liner. A scenario was built and shows that safety requirements are satisfied using of low carbon steel for these two components. However, to further increase safety margins and simplify the operation of the facility, Andra decided to study other materials less prone to corrosion. Consequently, Andra launched an R&D program to assess the technical feasibility of a high‐level waste container and a microtunnel liner made from ceramics, with the technical characteristics needed to meet safety requirements. This document describes the current situation for these activities and suggests ways this objective can be met.
FOXP3 Transcriptionally Activates Fatty Acid Scavenger Receptor CD36 in Tumour‐Induced Treg Cells
Authors: Dhar Subhanki , Sarkar Tania , Bose Sayantan , Pati Subhadip , Chakraborty Dwaipayan , Roy Dia , Panda Abir K. , Guin Aharna , Mukherjee Sumon , Jana Kuladip , Sarkar Diptendra K. , Sa Gaurisankar
Published: December 2024

The host immune system is adapted in a variety of ways by tumour microenvironment and growing tumour interacts to promote immune escape. One of these adaptations is manipulating the metabolic processes of cells in the tumour microenvironment. The growing tumour aggressively utilise glucose, its primary energy source available in tumour site, and produce lactate by Warburg effect. In such a hostile environment, tumour‐infiltrating immune cells are unable to survive metabolically. Tumour‐infiltrating CD4+ Treg cells, on the other hand, adapted to an alternative energy‐generating system, switching from the highly‐competitive glucose to the fatty‐acid metabolic pathway, by down‐regulating glucose‐metabolising genes and up‐regulating fatty‐acid metabolising genes. Tregs with high‐levels of the fatty acid scavenger receptor CD36, a key component of the fatty‐acid metabolic pathway, aided this metabolic shift. Treg cell formation was hampered when the fatty‐acid metabolic pathway was disrupted, showing that it is necessary for Treg cell development. FOXP3, the Treg lineage‐specific transcription factor, regulates fatty‐acid metabolism by inducing CD36 transcription. A high‐fat diet enhanced Treg development while suppressing anti‐tumour immunity, whereas a low‐fat diet suppressed Treg development. The altered metabolism of tumour‐infiltrating Treg cells enables their rapid generation and survival in the hostile tumour microenvironment, aiding cancer progression. Fascinatingly, mice fed with a low‐fat diet showed a positive prognosis with chemotherapy than mice fed with a high‐fat diet. Thus, a maximum efficacy of chemotherapy might be achieved by altering diet composition during chemotherapy, providing a promising indication for future cancer treatment.
Don't Downsize This! Social Reactions to Mass Dismissals on Twitter
Authors: Bassanini Andrea , Caroli Eve , Ferreira Bruno Chaves , Reberioux Antoine
Published: December 2024

We study social reactions on Twitter to job destructions. We use information on large‐scale restructuring events announced in the United Kingdom from 2013 to 2018. We match it with data on the number and sentiments of the tweets involving the company name posted around the time of the announcement. We show that job destruction announcements elicit numerous, strongly negative reactions, four times larger than the positive reactions to job creation announcements. We also show that these negative reactions are associated with significant losses in the market value of the downsizing firms, pointing to costs that add to standard dismissal costs.
Introducing a New Corpus of Definitive M&A Agreements, 2000–2020
Authors: Adelson Peter , Jennejohn Matthew , Nyarko Julian , Talley Eric
Published: December 2024

Contract design and architecture is an important topic within economics, finance, and law. However, attempts to study it are significantly constrained by the limited availability of public, high quality data. In this paper, we introduce a new corpus of 7929 Definitive Merger Agreements submitted to the SEC between 2000 and 2020 involving a transaction in excess of $100 million. Through a combination of machine learning and human evaluation, we associate these agreements with other metadata, such as deal size, industry classification, and advising law firms. In addition, we identify and make available the text of individual clauses contained in these agreements. In a final step, we provide an illustration of how these data can be used to generate novel insights into M&A contract design and drafting practices.
Rocksitter Flies (Lauxaniidae: Cestrotus) are Key‐Pollinators of Ceropegia pulchellior—A Threatened and Localised South African Endemic With Foetid‐Scented Flowers
Authors: Heiduk Annemarie , Gaimari Stephen , Whittington Andrew , Johnson Steven D. , Shuttleworth Adam
Published: December 2024

Short‐tongued saprophilous flies are a diverse but under‐appreciated group of pollinators, which are particularly important for flowers in the subtribe Stapeliinae (Apocynaceae‐Asclepiadoideae‐Ceropegieae). This clade of plants is characterised by repeated shifts between tubular kettle‐trap and open non‐trap flowers and chemical mimicry (of decomposing substrates or dying insects) to attract specific fly pollinators. The biology of most Stapeliinae, particularly those with non‐trap flowers, remains poorly studied, hampering our understanding of the mechanisms driving diversification in this plant group. We examined the pollination biology and floral traits of Ceropegia pulchellior, a South African endemic with non‐trap flowers confined to Natal Group Sandstone on the Durban escarpment. Observations showed that flowers are visited exclusively by flies which forage on small amounts of nectar in the corona cavities. Flowers were pollinated primarily by lauxaniid flies in the genus Cestrotus, although several muscid fly species also contribute. Pollinator exclusion experiments confirmed that the plants depend on these flies for reproduction. Reproductive success was low (fruit set never exceeding 8% of flowers). Pollen transfer efficiency was relatively high but variable across the flowering period. GC–MS analysis of floral scent revealed that the foetid odour is dominated by aliphatic acids and p‐cresol with small amounts of indole, supporting the assumption that C. pulchellior mimics decaying substrates to selectively attract detritus‐feeding (saprophagous) flies as pollinators. Analysis of spectral reflectance of flowers indicates that flower colours, when viewed by the fly pollinators, are not chromatically distinct from the habitat background, suggesting that flowers rely on olfactory rather than visual signals to attract pollinators. This study contributes to the growing awareness of the complexity of pollination systems in the Stapeliinae, in terms of the wide diversity of fly taxa involved, the intricate pollen transfer mechanisms, and the unusual floral scent chemistry associated with mimicry of oviposition substrates and food sources.
Shade Modulation Ability of Direct vs. Direct–Indirect Prepless Composite Veneers
Authors: Altamimi Yazeed , Fahl Newton , Rocha Mateus G. , Oliveira Dayane , Neiva Gisele F. , Maia Rodrigo R.
Published: December 2024

Objective

Assess the shade modulation ability of direct–indirect prepless composite veneer using distinct composite resins and cement shades by instrumental and visual assessments.

Materials and Methods

A total of 270 samples of direct and direct–indirect composite veneers were fabricated using three composite resins (3M Filtek Supreme Ultra A1B, Tokuyama Omnichroma, Transcend Universal) over a 3D designed mold in 10 × 10 mm cuboid shape with three depth cuts on the surface (0.3, 0.5, and 0.7 mm) to stimulate the veneer preparation and bonded using Ivoclar Variolink Esthetic LC neutral and light cement shades over a standard C4 shade substrate. Measurements were gathered through instrumental assessment by spectrophotometry and through visual assessment by four dental professionals. Color differences (ΔE00) were calculated according to the CIEDE2000 formula. Statistical analysis was conducted using three‐way ANOVA followed by the Tukey test.

Results

The ΔE values were influenced by the technique (p < 0.001), thickness (p < 0.001), and type of composite resin (p < 0.001). Cement shades were not statistically significant in the final shade of the direct–indirect technique (p = 0.168). There was no mismatch in the visual assessment between the direct–indirect samples compared to the direct samples.

Conclusion

There is a difference in the final shade between the direct and direct–indirect techniques in the instrumental but not in the visual evaluation. The two cement shades used did not influence the final shade of the composite veneers.