bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Accuracy of Digital Impression Techniques Based on an Integrated ADA Model
Authors: Piao Yongxu , Zhou Shuang , Zhang Rui , Gao Wenjia , Wang Mingchang , Kong Jiawen , Cai HongXin , Ma Chen , Jiang Heng Bo
Published: December 2024

Objective

The purpose of this in vitro study was to assess and compare the accuracy of three digital impression techniques based on an innovative integrated model.

Materials and Methods

The integrated model was created by incorporating crown, inlay, and long‐distance specimens from the American Dental Association (ADA) Standard No. 132. Digitized files of the model were acquired using three distinct impression techniques: intraoral scanner (IOS), extraoral scanner with negative cast (EOS_N), and extraoral scanner with positive cast (EOS_P). A coordinate measuring machine (CMM) was employed to establish the gold standard. The digital files of the model obtained via the extraoral scanner were designated the reference set for 3D fitting. Statistical analysis was performed using a one‐way analysis of variance and Tukey's posthoc test.

Results

For the crown specimen, the relative error of EOS_N for indices d1 and d2 was higher than that of IOS and EOS_P. For the inlay specimen, IOS showed the highest trueness for d3 and h2. For the long‐distance specimen, IOS exhibited superior trueness for indices l1 and l3. EOS_N displayed the lowest trueness for l2. For l4, IOS had the largest relative error. No significant differences were observed among the three groups for l5 and l6. Notable deviations were evident in the 3D fitting maps at various locations in three experimental groups.

Conclusions

The three digital impression techniques exhibited varying capacities for capturing features of the integrated ADA model. For crown preparations, IOS and EOS_P are recommended, while for inlay preparations, no technology meets the standard requirements. IOS is recommended for partial impressions, while both EOS_N and EOS_P are suited for full‐arch impressions.
‘Pasteurised’ Tilapia: Drastic Mortality of Gyrodactylus cichlidarum During the Spring 2024 Heat Wave
Authors: Miranda‐Aguirre Julio Cesar , García‐Vásquez Adriana , Salazar‐Ulloa Martha , Muñoz‐Córdova Germán , Rubio‐Godoy Miguel
Published: December 2024

During spring 2024, a heat wave induced sustained water temperatures of 34°C during a week in Veracruz, Mexico. Serendipitously, we monitored Gyrodactylus cichlidarum infecting farmed tilapia fry during this pulse warming event and recorded a drastic decline of parasite populations over the following days. We subsequently established that parasites incubated in vitro at ca. 27°C survived up to 24 h, while at ca. 30°C and 34°C, all worms died within 4–7 h. Abnormal haptor structures were observed in parasites that developed and were born at a water temperature of 34°C. Under farming conditions, no unusual fish mortality was recorded, suggesting that pulse heat treatment may be an effective method to control G. cichlidarum, a recognised tilapia pathogen.
Do Extended Reality Interventions Benefit Patients Undergoing Elective Cardiac Surgical and Interventional Procedures? A Systematic Review and Meta‐analysis
Authors: Harris Emma , Fenton Steven , Stephenson John , Ewart Fiona , Goharinezhad Salime , Lee Hyunkook , Astin Felicity
Published: December 2024

Background

Extended reality (XR) interventions have the potential to benefit patients undergoing elective cardiac surgical and interventional procedures. However, there are no systematic reviews with meta‐analyses to guide clinical care.

Aim

To critically evaluate the evidence on the effectiveness of XR interventions on patient anxiety and pain and other associated outcomes.

Design

Systematic review and meta‐analysis following the PRISMA 2020 statement.

Data Sources

A systematic search of five databases (CENTRAL, CINAHL, MEDLINE, PsycInfo, Scopus) from inception to July 2023.

Methods

Screening and data extraction was conducted independently by multiple reviewers. Stata (Version 17) was used to conduct meta‐analyses for patient anxiety and pain. Secondary patient outcomes were summarised in a synthesis. The Cochrane Risk of Bias (Version 2) tool was applied to trials and the NHLBI Study Quality Assessment tools to all other study designs.

Results

Of the 3372 records identified, 22 were included, 10 of which were eligible for inclusion in the meta‐analyses. Fifty‐seven percent of randomised trials were rated as high risk of bias. Virtual reality (VR) was the only XR technology evaluated. VR significantly reduced pre‐procedural anxiety (standardised mean difference: −1.29; 95% confidence interval − 1.96, −0.62, p < 0.001), and peri‐procedural anxiety (standardised mean difference: −0.50; 95% confidence interval − 0.83, −0.18, p < 0.003) but did not reduce pain levels, compared with usual care. VR increased pre‐procedural knowledge and postsurgical physical and pulmonary function. VR interventions may also improve emotional wellbeing, care delivery and physiological outcomes, but evidence was inconsistent.

Conclusions

XR potentially benefits cardiac patients undergoing elective invasive procedures and surgery by reducing pre‐ and peri‐procedural anxiety and increasing procedural knowledge and physical function.

Relevance to Clinical Practice

Cardiac nurses' role can be supported by VR interventions to improve the patient experience and several aspects of patient care.

Patient or Public Contribution

Not applicable as this is a systematic review.
Psychological Distress, Antipsychotic Medications and Cardiovascular Risk Factors Among Patients With Schizophrenia
Authors: Al‐Dwaikat Tariq N. , Al‐Samouri Haya Khader , Dalky Heyam , Hamaideh Shaher H. , ALBashtawy Mohammed , Khatatbeh Haitham
Published: December 2024

Aims

This study aims to assess the correlation between antipsychotic drug use, psychological distress and cardiovascular risk factors among patients with schizophrenia.

Methods

A cross‐sectional correlational design was used to obtain data from 143 patients with schizophrenia who were conveniently selected. Data were collected by assessing selected cardiovascular risk indicators blood pressure (BP), random blood sugar (RBS), body mass index (BMI), waist‐to‐height ratio (WtHR) and waist circumference (WC). A self‐administered questionnaire was used to collect sociodemographic data, clinical history and the 18‐item Psychological Stress Index for patients with schizophrenia.

Results

The use of antipsychotics was associated with increased cardiovascular risk factors including BP, BMI and WtHR. Atypical antipsychotic medications were associated with weight gain and obesity which increase the risk of diabetes and cardiovascular diseases. Age was significantly correlated with systolic BP (r = 0.31), diastolic BP (r = 0.30) and RBS (r = 0.26). Furthermore, significant correlations were found between the duration of diagnosis with systolic (r = 0.26) and diastolic (r = 0.21) BP. None of the correlations between stress and the other study variables were significant.

Conclusion

Screening of antipsychotic side effects is needed in the early phases, and attention must be paid to the cardiovascular risk in patients with schizophrenia, particularly BP, glucose level and BMI. In addition, clinicians should be informed of this evidence to set guidelines for regular monitoring of metabolic parameters.

Reporting Method

STROBE guidelines were followed in this study.

Patient or Public Contribution

Actively involving patients in data collection, this study ensured that their voices were heard and their experiences were central to informing the research findings. In addition, involving patients in the study would enhance the relevance and applicability of the study's conclusions to real‐world contexts, promoting patient‐centered care and improved health outcomes for patients with schizophrenia.
The Role of the Simulation in Supporting Newly Graduated Nurses in Their First 5 Months of Working Transition: Findings From a Mixed‐Method Study
Authors: Mesaglio Maura , Dentice Sara , Grassetti Luca , Achil Illarj , Bernardinis Anna , Caruzzo Davide , Inserra Anna , Mansutti Irene , Mattiussi Elisa , Menegoz Sandra , Piani Tommaso , Vanzo Elena , Chiappinotto Stefania , Palese Alvisa
Published: December 2024

Aims

To understand the role of simulation in ensuring the development of the competencies expected by newly graduated register nurses (NGRNs) from the work initiation up to 5 months of transition.

Methods

Mixed‐method study design. A longitudinal phase employing the Nurse Competence Scale (NCS, from 0 to 100, excellent) to assess the perceived competencies among NGRNs (N = 151) at three time points (first day of work up to fifth month); followed by a qualitative phase involving four focus groups of preceptors (N = 16) to explore the potential role of simulation in the NGRNs' working transition. Integration was performed at findings level, using the building procedures and joint displaying the results.

Results

During the different time periods, variations emerged in the NCS scores from 64.41 out of 100 in the first day of work to 61.82 after 15 days, reaching 69.25 and 73.21 at 3 and 5 months. Nine potentialities have been identified as having simulation supporting NGRNs during their transition to independent practice. Simulation may contribute to develop competencies in some competence domains (diagnostic function, managing situation, therapeutic intervention, quality assurance and working role) while not in others (helping role and teaching–coaching).

Conclusion

Early interventions, through integration of simulation sessions into strategies offered at the unit's level may be useful to ensure an effective working transition.

Impact

Problem the study addresses: Challenges in transition from education to working settings are increasing given the difficulties of the units in providing time and support to NGRNs. Main findings: Competencies of NGRNs' are fluctuant in the five first months of work, and sub‐optimal in certain domains. Simulation may support the full development of most competencies. Impact on research: Healthcare organisations can support NGRNs to ensure smoother transitions by integrating simulations in their strategy.

Reporting Method

This study was conducted following the Good Reporting of a Mixed‐Methods Study.

Patient or Public Contribution

Only healthcare professionals were involved.
Adenomyosis with uterine abscess formation treated by adenomyomectomy: A report of two cases
Authors: Hiratsuka Daiki , Ishizawa Chihiro , Iida Rei , Fukui Yamato , Matsuo Mitsunori , Nishida Masato , Ikemura Masako , Harada Miyuki , Wada‐Hiraike Osamu , Osuga Yutaka , Hirota Yasushi
Published: December 2024

Uterine adenomyosis is a common disease in women of reproductive age that causes dysmenorrhea, abnormal uterine bleeding, infertility, and obstetric complications. Rarely, adenomyosis can lead to abscess formation, which is refractory to antibiotics and occasionally requires surgical treatment, such as hysterectomy. However, hysterectomy should be avoided in patients who seek to preserve fertility. Herein, for the first time, we report two cases of uterine adenomyosis with abscess formation during assisted reproductive procedures that were successfully treated with adenomyomectomy, thereby preserving fertility. A history of repeated intrauterine procedures and infections was crucial in making an appropriate preoperative diagnosis. Adenomyomectomy can be an effective treatment for adenomyosis associated with abscess in patients who wish to preserve fertility.
Negative emotions, difficult conversations and leader–follower relationships
Authors: Williams Courtney E. , Thomas Jane Shumski , Gooty Janaki , Dunne Danielle D.
Published: December 2024

The world of work is replete with daily hassles that make the experience of negative emotions ubiquitous. Conversations between leaders and followers during challenging times are often characterized by negative emotions, and thus, are of central importance in modern organizations. Yet, the intersection of negative emotion, difficult conversations and leader–follower relationships is often ignored, and these topics are treated as separate areas of study. We integrate these various streams with research on asymmetrical leader negative emotion displays to identify when and how difficult conversations laden with negative emotions result in benefits to leader–follower relationships. Using a grounded theory approach, we build a theoretical model based on interviews with 21 leaders and 17 followers describing 166 difficult conversations. Our work depicts specific communication strategies that leaders use to facilitate difficult conversations. These strategies, in turn, create shared meaning and validate followers' feelings during difficult conversations, which allows for beneficial relationship‐specific outcomes to ensue. We unpack these findings in the context of the power differential between leaders and followers to advance current thinking on the intersection of negative emotions and communication in leader–follower relationships.
Not all information is from insiders: Linking information from social media and customers to newcomers' pride, learning and socialization outcomes
Authors: Chen Chong , Zhang Yihua , Wu Wen , Liu Jialin , Ni Dan , Zheng Michelle Xue , Wu Shaoxue , Zhang Mingyu , Zhang Chen
Published: December 2024

When first joining an organization, newcomers need to obtain information about relationships and tasks, as well as about the organization itself. Although many scholars have emphasized the role of information provided by organizational insiders (supervisors and coworkers) in facilitating newcomers' successful adjustment to the organization, the meaningful role of information from sources external to the organization has rarely been included in this line of research. In this study, we propose that both social media and customers can provide information about organizational performance and social image. Based on affective events theory and two fundamental social judgements of competence and warmth, we explore how positive information about organizational performance and social image from social media and customers, along with their interactive effects, affect newcomers' learning behaviours and socialization outcomes through promoting their pride in the organization. In an experiment and a four‐wave, two‐source survey, the results show that positive information from social media and customers plays a critical role in newcomer socialization. We discuss the implications for theory and practice.
Self‐Direction in Medicaid Home‐ and Community‐Based Services
Authors: Friedman Carli
Published: December 2024

Self‐direction allows people with intellectual and developmental disabilities (IDD) to control and direct their services and supports. This study's aim was to examine how states across the United States implemented self‐direction in their Medicaid Home‐ and Community‐Based Services (HCBS) 1915(c) waiver programs for people with IDD in fiscal year (FY) 2021. We found 80% of states offered self‐direction in their HCBS programs. Across the United States, the goal was to have 13% people with IDD receiving HCBS self‐direct (n = 113 692). We found, in FY 2021, 29% of services could be self‐directed and 36% of funding was projected for services eligible for self‐direction. There were vast differences in how self‐direction was implemented across states. For example, among the states that allowed self‐direction, goals for self‐direction by state ranged from 0.9% to 47.5% of people with IDD receiving HCBS. Moreover, projected spending for services eligible for self‐direction varied by state from 0.1% to 100%. We believe everyone that wants to self‐direct should have the opportunity to do so.
Training of construction robots using imitation learning and environmental rewards
Authors: Duan Kangkang , Zou Zhengbo , Yang T. Y.
Published: December 2024

Construction robots are challenging the paradigm of labor‐intensive construction tasks. Imitation learning (IL) offers a promising approach, enabling robots to mimic expert actions. However, obtaining high‐quality expert demonstrations is a major bottleneck in this process as teleoperated robot motions may not align with optimal kinematic behavior. In this paper, two innovations have been proposed. First, traditional control using controllers has been replaced with vision‐based hand gesture control for intuitive demonstration collection. Second, a novel method that integrates both demonstrations and simple environmental rewards is proposed to strike a balance between imitation and exploration. To achieve this goal, a two‐step training process is proposed. In the first step, an intuitive demonstration collection platform using virtual reality is utilized. Second, a learning algorithm is used to train a policy for construction tasks. Experimental results demonstrate that combining IL with environmental rewards can significantly accelerate the training, even with limited demonstration data.
Blame as Attention
Authors: Chislenko Eugene
Published: December 2024

The wide variety of blame presents two difficult puzzles. Why are instances of blame categorized under so many different mental kinds, such as judgment, belief, emotion, action, intention, desire, and combinations of these? Why is “blame” used to describe both interpersonal reactions and mere causal attributions, such as blaming faulty brakes for a car crash? I introduce a new conception of blame, on which blame is attention to something as a source of badness. I argue that this view resolves both puzzles and offers an independently appealing conception of blame.
Are Credit Doors Equally Open? Gender Perspectives on Agricultural Credit Access in Sub‐Saharan Africa
Authors: Asiseh Fafanyo , Ng'ombe John N. , Quaicoe Obed , Vorsah Roger , Prah Stephen
Published: December 2024

Access to credit is vital for smallholder farmers, but gender disparities persist across the world. We study the determinants and gender disparities in agricultural credit access between female‐headed households (FHHs) and male‐headed households (MHHs) across five Sub‐Saharan African (SSA) countries: Ivory Coast, Mozambique, Nigeria, Tanzania, and Uganda. We employed the probit and Oaxaca‐Blinder probit decomposition models on a random sample of over 18,000 households. Three primary results were found. First, socioeconomic, institutional, and location‐specific factors affect agricultural credit access, with some differences observed between FHHs and MHHs. Second, both rural FHHs and MHHs are more likely to access agricultural credit than their urban counterparts. Additionally, on average, 10.36% of MHHs are more likely to access agricultural credit than FHHs across the five countries. This gap varies considerably, with Nigeria exhibiting the largest disparity (19.64%) and Ivory Coast the smallest (2.15%). Importantly, a large portion (87.55%) of the gender gap is from unexplained/unobserved sources/effects, highlighting significant structural barriers faced by FHHs. Land ownership, age, and credit perceptions contribute to widening the gender gap, while equalizing location, socioeconomic status, trust, and past borrowing could reduce it. We recommend tailored agricultural credit programs that promote gender‐inclusive and sustainable agricultural development in SSA.
Development of an ILI Service for Heavy Wall Pipelines Based on EMAT Technology
Authors: Upadhyaya Jay , Garth Clint , Kania Richard , Schartner Aaron , Hoeving Markus , Moritz Timo , Beuker Thomas , Voss Jens
Published: December 2024

Electro Magnetic Acoustic Transducer (EMAT) technology based ILI inspections have become vital for maintaining the safety of gas pipelines in order to manage crack threats. This technology has evolved over the past decade and has become widely used. As with any technology, existing EMAT services have limitations based on the physics of EMAT and the approach to the application of the technology in ILI services.

This paper will describe how TC Energy and ROSEN collaborated to develop reliable EMAT inspection services for heavy wall pipeline applications in addition to the capability of currently available technology. This technology development process involved advancements in sensor design and fabrication, incorporation of latest electronic developments to enhance magnetization as well as leveraging machine learning techniques to enable EMAT inspection of pipelines up to 16.4 mm wall thickness.

The paper will also describe the technology validation process including proof of concept, lab testing, innovative testing process on sample pipe while applying artificial defects that closely mimic natural ones, performance qualification process in line with applicable codes, pilot testing, and performance validation. The full process was executed to conform to typical industry validation requirements and to qualify under operator’s extensive technology validation program. The paper will also review preliminary results of the first pilot application and approval for broader application in pipelines.

The paper describes the collaborative efforts of the research and development teams, business line management and key account management at ROSEN as well as the technology validation, threat management, and project management teams at TC Energy. The work has culminated in five inspections completed (48″ and 36″) on the operator’s system in Canada and the USA.
Impact of Core Training on Functional Movement Screen Scores in Athletes: A Critically Appraised Topic
Authors: Niebla Camila , Carson Rebecca , Mangum L. Colby
Published: December 2024

Clinical Scenario: The Functional Movement Screen (FMS) is used to assess movement patterns and the risk of injury of active individuals. Current studies have found positive relationships with core training and injury prevention as well as lower limb stability, which can help improve FMS scores. Clinical Question: Does the implementation of a core training program have an impact on FMS scores in healthy active adults who participate in sport? Summary of Key Findings: Literature was searched for articles that included core-focused exercises and implementation of the FMS. This resulted in 25 studies being returned, only 23 of which were published in the last 10 years. Only 7 focused on the change in FMS scores after implementation of core training. Three of these studies were included in the analysis due to the specialized athlete population. All 3 studies found that using a core training program led to significantly higher FMS scores postintervention. Clinical Bottom Line: There is clear evidence that core training increases FMS scores in athletes. It is important for health care providers treating athletes to consider core training to improve functional movement patterns or FMS scores in sport-specific populations. Strength of Recommendation: Overall, there are moderate to high levels of evidence that support a grade B recommendation for core training improvements on FMS scores in athletes.
Immunopathology in human tuberculosis
Authors: Scriba Thomas J. , Maseeme Mahlatse , Young Carly , Taylor Laura , Leslie Alasdair J.
Published: December 2024

Mycobacterium tuberculosis
(
M.tb
) is a bacterial pathogen that has evolved in humans, and its interactions with the host are complex and best studied in humans. Myriad immune pathways are involved in infection control, granuloma formation, and progression to tuberculosis (TB) disease. Inflammatory cells, such as macrophages, neutrophils, conventional and unconventional T cells, B cells, NK cells, and innate lymphoid cells, interact via cytokines, cell-cell communication, and eicosanoid signaling to contain or eliminate infection but can alternatively mediate pathological changes required for pathogen transmission. Clinical manifestations include pulmonary and extrapulmonary TB, as well as post-TB lung disease. Risk factors for TB progression, in turn, largely relate to immune status and, apart from traditional chemotherapy, interventions primarily target immune mechanisms, highlighting the critical role of immunopathology in TB. Maintaining a balance between effector mechanisms to achieve protective immunity and avoid detrimental inflammation is central to the immunopathogenesis of TB. Many research gaps remain and deserve prioritization to improve our understanding of human TB immunopathogenesis.
Crystal structure of the human LAG-3–HLA-DR1–peptide complex
Authors: Petersen Jan , Llerena Carmen , Golzarroshan Bagher , Faoro Camilla , Triebel Frederic , Rossjohn Jamie
Published: December 2024

T cell activity is governed by T cell receptor (TCR) signaling and constrained by immune checkpoint molecules, including programmed cell death protein 1 (PD-1), cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), and lymphocyte activation gene 3 (LAG-3). The basis for how LAG-3 binds to human leukocyte antigen class II molecules (HLA-II) remains unknown. Here, we present the 3.4-angstrom crystal structure of a LAG-3–peptide–HLA-II complex and probe the energetics of the complex interface. Coincident with the HLA-II binding site of the ancestrally related, monomeric CD4 receptor, the LAG-3 homodimer laterally engages two HLA-II molecules via distal D1 domain surfaces, imposing a 38° angular offset. The LAG-3–HLA-II interface is discontinuous and lacks involvement of the D1 extra loop, a binding site for anti–LAG-3 therapeutic monoclonal antibodies. Upon HLA-II binding, intrinsically mobile loops of the LAG-3 molecule become ordered, with contact residues highly conserved across HLA-DR, DQ, and DP allomorphs. Our data provide a structural foundation for development of immunomodulatory approaches targeting LAG-3.
PWWP domain-containing protein Crf4-3 specifically modulates fungal azole susceptibility by regulating sterol C-14 demethylase ERG11
Authors: Yu Pengju , Ye Shuting , Zhou Mi , Zhang Long , Zhang Zhongchi , Sun Xianyun , Li Shaojie , Hu Chengcheng
Published: December 2024

The widespread use of azole antifungals in agriculture and clinical settings has led to serious drug resistance. Overexpression of the azole drug target 14α-demethylase ERG11 (CYP51) is the most common fungal resistance mechanism. However, the presence of additional regulatory proteins in the transcriptional response of
erg11
is not yet fully elucidated. In this study, leveraging the identified key promoter region of
erg11
that controls its response to azoles in
Neurospora crassa
, we pinpointed a protein, Crf4-3, which harbors a PWWP domain and exerts a positive regulatory influence on azole resistance, as determined by DNA pulldown assays. The removal of Crf4-3 results in heightened sensitivity to azoles while remaining unaffected by other stressors tested. Additionally, the deletion leads to the abolition of transcriptional responses of genes such as
erg11
and
erg6
to ketoconazole. Interestingly, the basal expression of
erg1
,
erg11
,
erg25
, and
erg3A
is also affected by the deletion of
crf4-3
, indicating its role in sterol homeostasis. Crf4-3 homologs are broadly distributed across the
Pezizomycotina
fungi. The gene deletion for its homologous protein in
Aspergillus fumigatus
also significantly improves sensitivity to azoles such as voriconazole, primarily through the attenuation of the transcriptional response of
erg11
. Our data, for the first time, identified Crf4-3 as a novel regulatory protein in the azole stress response of filamentous fungi, offering fresh insights into the mechanisms of azole resistance.

IMPORTANCE

Transcriptional control of pivotal genes, such as
erg11
, stands as the primary driver of azole resistance. Although considerable effort has been dedicated to identifying transcription factors involved, our knowledge regarding the use of transcriptional regulation strategies to combat azole resistance is currently limited. In this study, we reveal that a PWWP domain-containing protein Crf4-3, which is conserved in
Pezizomycotina
fungi, modulates fungal azole sensitivity by transcriptionally regulating sterol biosynthetic genes, including
erg11
. These results also broaden the understanding of fungal PWWP domain-containing proteins regarding their roles in regulating resistance against azole antifungals. Considering research on small molecules targeting the PWWP domain in humans, Crf4-3 homolog emerges as a promising target for designing fungal-specific drugs to combat azole resistance.
Reducing unplanned extubation in the neonatal intensive care unit: a quality improvement project
Authors: Tyrer Samantha , Bhatia Risha , Kidman Anna , Fitzgerald Riannah , Roberts Calum T
Published: December 2024

Background and aim

Unplanned extubation (UE) is an adverse event that can occur for neonates that are intubated and mechanically ventilated. UE is recognised as an important quality measure in the neonatal intensive care unit (NICU) due to the negative impact these events may have on the neonate. We aimed to use quality improvement (QI) methodology to reduce the rate of UE to the global standard of <1/100 ventilation days.

Methods

A 12-month retrospective audit on mechanically ventilated neonates in our NICU identified a mean UE rate of 1.78/100 ventilation days. A clinical guideline focusing on best practice was introduced with key interventions identified by a review of the literature as those which were thought to reduce UE rates. The key interventions in the clinical guideline were introduced sequentially. UE rates were analysed monthly using control charts and the reported cause of each UE event was analysed. Three 12-month periods were included: preintroduction of QI interventions (period 1), during introduction of QI interventions (period 2), and after introduction of QI interventions (period 3).

Results

The introduced interventions reduced the mean rate of UE from 1.78/100 ventilation days in period 1 to 0.8/100 ventilation days in period 3 of the QI project.

Conclusions

The key interventions introduced in this QI project were successful in reducing rates of UE by 55%, allowing achievement of the global standard of <1/100 ventilation days.
Genetic variation in circadian regulator geneBMAL1in psychiatric, psychological and cardiometabolic traits: a trans-ancestry UK Biobank study
Authors: Daudali Hamza , Anderson Jana , Bailey Mark E S , Fradera Alexander , Niedzwiedz Claire L , Lyall Donald , Lyall Laura M M , Strawbridge Rona J
Published: December 2024

Background

The link between cardiometabolic disease and mental illness has been well established but remains incompletely explained. One hypothesis suggests that circadian rhythm dysregulation links cardiometabolic disease and mental illnesses.BMAL1is a circadian rhythm regulatory gene. Human genetic studies have implicatedBMAL1in depression, schizophrenia, bipolar disorder as well as body mass index, blood pressure and lipid levels.

Objective

We investigated theBMAL1locus genetic variants for associations with both cardiometabolic and mental illness.

Methods

Genetic and phenotypic data from UK Biobank (~500 000 participants) of White British, African-Caribbean, South Asian, white European and Multiple ancestries were used. Regression analyses using Plink 1.09 was used to identify significant associations, with Bonferroni multiple testing correction. Multiple ancestry meta-analyses using METAL software was used to investigate trans-ancestry consistency in genetic effects.

Findings

We identified associations for body mass index, anhedonia, diastolic and systolic blood pressure, waist-hip ratio, major depressive disorder, neuroticism and risk-taking. Meta-analyses indicated that there are ancestry-wide and ancestry-specific effects on cardiometabolic, mental illness and related traits.

Conclusions

Our results suggest that the associations for mental illness (and related traits) and those for cardiometabolic traits are distinct rather than shared and that these associations were consistent across ancestry groups.

Clinical implications

Further investigation into the tissue-specific roles ofBMAL1is required to fully understand the clinical impact of these findings.
Comparison of the effect of medium-chain fatty acids and long-chain fatty acids on postprandial appetite and lipemia: a randomised crossover trial
Authors: Jadallah Ruaa , Hammad Shatha S
Published: December 2024

Background

Postprandial lipemia (PPL) has been recognised as a cardiovascular disease risk factor. Appetite and PPL can be influenced by the length of saturated fatty acids (FAs). Thus, this study aims to investigate if different FA chain lengths have different impacts on appetite and PPL in healthy volunteers.

Methods

This is a randomised crossover single-blinded intervention study of 20 healthy adults. Coconut oil and palm oil were consumed in the form of biscuits. Blood serum samples were withdrawn after an overnight fast and 1, 2, 4 and 6 hours after eating the test meals and examined for blood lipid profile (total cholesterol (TC), high-density lipoprotein (HDL) and triglycerides (TG)), while Friedewald’s equation was used to calculate low-density lipoprotein (LDL). Visual analogue scales were used by participants to rate their appetites, and an ad libitum meal was weighed to determine the energy intake.

Results

The net area under the curve of TG and TC following the coconut oil were significantly lower than following the palm oil (Pvalue ≤0.05). In the mean of the change in TC, LDL and HDL from the baseline, a significant difference was found after 6 hours of eating the biscuits (Pvalue ≤0.05). The perceptions of hunger and fullness did not significantly differ between the two types of FAs. Also, the energy and macronutrient intakes were not significantly different after the two types of oil, neither at the ad libitum meal nor on the day following the treatments.

Conclusion

The selection of FA chain length may influence PPL, and thus cardiovascular disease risk in a way that is functionally significant. However, this study detected no influence of FA chain length on appetite up to 40 hours post-treatment.

Trial registration number

NCT05539742.
Vitamin D and/or calcium to prevent fractures and falls: protocol for a systematic review and meta-analysis
Authors: Massé Olivier , Mercurio Claudia Mei , Dupuis Sébastien , Arruda Alexandra , Desforges Katherine , Dugré Nicolas , Dallaire Gabriel , Williamson David
Published: December 2024

Background

Previous systematic reviews on fracture and fall prevention have generally shown no efficacy with calcium or vitamin D alone and conflicting findings with that of vitamin D combined with calcium. Despite these findings, increases in vitamin D and calcium prescriptions have been reported in many countries, as many clinicians, guidelines and regulatory agencies still largely recommend universal supplementation to adults.

Methods and analysis

We will conduct a systematic review of randomised controlled trials on the efficacy of vitamin D and/or calcium in fracture and fall prevention. A systematic search will be performed in Medline, Embase, CENTRAL, International Clinical Trials Registry Platform and Clinicaltrials.gov (1 January 2024). We will also hand search abstracts published in relevant congress and journals (2021–2023) and the reference lists of included trials. We will consider any trial involving the pharmacological administration of calcium alone, vitamin D alone or vitamin D combined with calcium against placebo or no treatment in adults. The primary outcome will be the number of participants with fractures at any site. The secondary outcomes will be the number of participants with hip fractures, non-vertebral fractures, vertebral fractures and falls, and the rate of falls. Two reviewers will independently screen and include the trials, extract the data and assess the risk of bias using the second version of the Cochrane risk-of-bias tool. We plan to pool outcomes to conduct random-effects meta-analyses and to appraise the certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Many prespecified subgroup and sensitivity analyses will be performed to explore the potential heterogeneity and to test the robustness of our findings.

Ethics and dissemination

This systematic review does not require research ethics approval. The results will be disseminated in peer-reviewed journals and help inform clinicians, guidelines and regulatory agencies.

PROSPERO registration number

CRD42023483915
Employing artificial intelligence for optimising antibiotic dosages in sepsis on intensive care unit: a study protocol for a prospective observational study (KI.SEP)
Authors: Marko Britta , Palmowski Lars , Nowak Hartmuth , Witowski Andrea , Koos Björn , Rump Katharina , Bergmann Lars , Bandow Julia , Eisenacher Martin , Günther Patrick , Adamzik Michael , Sitek Barbara , Rahmel Tim
Published: December 2024

Introduction

In sepsis treatment, achieving and maintaining effective antibiotic therapy is crucial. However, optimal antibiotic dosing faces challenges due to significant variability among patients with sepsis. Therapeutic drug monitoring (TDM), the current gold standard, lacks initial dosage adjustments and global availability. Even with daily TDM, antibiotic serum concentrations (ASCs) often deviate from the therapeutic range. This study addresses these challenges by developing machine learning (ML)-based ASC prediction models capable of handling variable data input and encompassing diverse clinical, laboratory, microbiological and proteomic parameters without the need for daily TDM.

Methods

This prospective observational study is conducted in a German university hospital intensive care unit. Eligible sepsis patients receive continuous antibiotic therapy with piperacillin/tazobactam (n=100) or meropenem (n=100) within 24 hours. Exclusion criteria include refusal, pregnancy, lactation and severe anaemia (haemoglobin <8 g/dL). Blood samples for TDM are collected from patients, along with clinical and laboratory parameters on days 1–8 and day 30 or on discharge. ML models predicting ASC between day 1 and day 8 serve as primary and key secondary endpoints. We will use the collected data to develop multifaceted ML-based algorithms aimed at optimising antibiotic dosing in sepsis. Our two-way approach involves creating two distinct algorithms: the first focuses on predictive accuracy and generalisability using routine clinical parameters, while the second leverages an extended dataset including a plethora of factors currently insufficiently explored and not available in standard clinical practice but may help to enhance precision. Ultimately, these models are envisioned for integration into clinical decision support systems within patient data management systems, facilitating automated, personalised treatment recommendations for sepsis.

Ethics and dissemination

The study received approval from the Ethics Committee of the Medical Faculty of Ruhr-University Bochum (No. 23-7905). Findings will be disseminated through open-access publication in a peer-reviewed journal and social media channels.

Trial registration number

DRKS00032970.
tREatment of trIaNgular FibrOcaRtilage ComplEx Ruptures (REINFORCER): protocol for randomised, controlled, blinded, efficacy trial of triangular fibrocartilage complex tears
Authors: Kaivorinne Antti , Räisänen Mikko Petteri , Karjalainen Teemu , Jokihaara Jarkko , Gvozdenovic Robert , Wilcke Maria , Reito Aleksi , Anttila Turkka , Pönkkö Annele , Lauridsen Carsten , Tanskanen Tuukka , Mattila Ville M
Published: December 2024

Introduction

Triangular fibrocartilage complex (TFCC) tear is often considered to be the cause of ulnar wrist pain. The primary treatment typically involves non-operative methods; however, in cases of persistent symptoms, operative intervention has been proposed as a viable option. Depending on the tear’s morphology, treatment may involve debridement (central or radial tear) or repair (peripheral tear). Efficacy of operative treatment has not been studied in a randomised controlled trial.

Methods and analysis

This is a prospective, randomised, controlled, blinded multicentre trial, with two randomisation stratums. The first stratum includes central or radial TFCC tears, while the second stratum comprises peripheral TFCC tears. Each stratum consists of two parallel 1:1 arms, comparing the efficacy of (1) debridement of central or radial tear with placebo surgery and (2) repair of peripheral tear with physiotherapy. Participants are recruited from secondary and tertiary referral hospitals in Denmark, Finland and Sweden.

Primary outcome is the Patient-Rated Wrist Evaluation (PRWE) at 1 year. Secondary outcomes include subjective and objective outcome measures at 6 months, 1, 2, 5 and 10 years follow-ups.

Ethics and dissemination

The trial was approved by the Pirkanmaa Hospital District Institutional Review Board in March 2020. All participants will be asked to give a written informed consent. The results of the trial will be disseminated as published articles in peer-reviewed journals.

Trial registration number

NCT04576169.
Knee osteotomy combined with meniscal allograft transplantation versus knee osteotomy alone in patients with unicompartmental knee osteoarthritis: a prospective double-blind randomised controlled trial protocol
Authors: Zanasi Lorenzo , Boffa Angelo , De Marziani Luca , Lisignoli Gina , Belvedere Claudio , Miceli Marco , Zaffagnini Stefano , Filardo Giuseppe , Di Martino Alessandro
Published: December 2024

Introduction

Knee osteotomy combined with meniscal allograft transplantation (MAT) showed promising results to treat unicompartmental knee osteoarthritis (OA) secondary to meniscal deficiency and knee malalignment. However, there is still no high-level evidence to demonstrate whether the combination of these two treatments is superior to osteotomy alone.

Methods and analysis

52 patients with unicompartmental knee OA Kellgren-Lawrence grade ≤3 secondary to meniscal deficiency and knee malalignment (aged 20–60 years) are randomised to undergo knee osteotomy associated with MAT or knee osteotomy alone in a 1:1 ratio. The primary outcome is the International Knee Documentation Committee (IKDC) subjective score at 12 months. The secondary outcomes are the IKDC subjective score at 1, 3 and 6 months, the Western Ontario and McMaster Universities Osteoarthritis Index score, the Knee Injury and Osteoarthritis Outcome Score, the Visual Analogue Scale, the EuroQol Visual Analogue Scale, the Tegner Activity Level Scale, objective parameters (transpatellar circumference, suprapatellar circumference and range of motion), patient expectation on treatment efficacy and patient satisfaction at 1, 3, 6 and 12 months. Radiographs are performed at baseline and at 1-, 6- and 12-month follow-ups and magnetic resonance evaluations at baseline and at 12 months. Biomechanical assessment is performed through gait analysis before surgery and at 12 months, investigating motion data, biomechanical parameters and muscle activation through electromyography. In addition, to detect early joint environment changes and potential MAT effects in protecting the articular surface providing a better knee homeostasis, biological markers of cartilage turnover and inflammation obtained from synovial fluid, serum and urine are evaluated at baseline and at 24 hours, 1-, 3-, 6- and 12-month follow-ups.

Ethics and dissemination

The study protocol has been approved by Emilia Romagna’s Ethics Committee (CE-AVEC), Bologna, Italy. Written informed consent is obtained from all participants. Findings of this study will be disseminated through peer-reviewed publications and conference presentations.

Protocol version

March 2023.

Trial registration number

NCT05840887.
Cost-effectiveness of percutaneous mitral repair for patients with severe secondary mitral regurgitation: an updated evaluation using a modelling approach based on COAPT final data after 5-year follow-up
Authors: Connock Martin , Auguste Peter , Obadia Jean-François , Armoiry Xavier
Published: December 2024

Objectives

To evaluate the cost-effectiveness of percutaneous repair (PR) for secondary mitral regurgitation.

Design

An economic evaluation using a time-varying Markov model comprising three states to assess the cost and effectiveness of PR added to guideline-directed medical treatment (GDMT) compared with GDMT alone. Clinical outcomes considered within the model were overall survival and heart failure (HF) hospitalisations (HFH), and the incremental cost-effectiveness ratio (ICER) was calculated. Cost data were derived from a literature search. Sensitivity analyses were undertaken.

Setting

The French healthcare system perspective assuming a lifetime horizon.

Participants

Published data at 5 years obtained from patients enrolled in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation study.

Results

In our base case, we chose cubic spline models to extrapolate overall survival, and we used log-logistic models to estimate cumulative HFH. After discounting, the model generated life-years of 3.843 years and 3.055 years for PR+GDMT and GDMT, respectively. Discounted total quality-adjusted life-year (QALY) values were 2.572 and 1.945 for PR+GDMT and GDMT, respectively (incremental 0.627 QALY). Discounted total costs were €42 709 and €20 732 for the intervention and the control groups, respectively (incremental €21,977), resulting in an ICER of €35,068/QALY. At a threshold of €50 000 per QALY, PR had a 0.85 probability of being cost-effective.

Conclusion

Updated trial data have enabled investigators to provide a more reliable estimation of the ICER, which suggests that PR has good value for money compared with GDMT alone.