bluuebunny/crossref_metadata_2025 huggingface dataset:
Dominant‐negative chaperonin mutation ptCPN60α1S57F uncovers redundancy in chloroplast rRNA processing
Authors: Wang Chunfei , Xing Aiming , Li Yan , Wang Xingsong , Wang Xiaoqing , Xu Xiumei , An Guoyong , Hu Zhubing
Published: August 2024

The biogenesis of functional forms of chloroplast ribosomal RNAs (rRNAs) is crucial for the translation of chloroplast mRNAs into polypeptides. However, the molecular mechanisms underlying the proper processing and maturation of chloroplast rRNA species are poorly understood. Through a genetic approach, we isolated and characterized an Arabidopsis mutant, α1‐4, harboring a missense mutation in the plastid chaperonin‐60α1 gene. Using allelism tests and transgenic manipulation, we determined functional redundancy among ptCPN60 subunits. The ptCPN60α1S57F mutation caused specific defects in the formation of chloroplast rRNA species, including 23S, 5S, and 4.5S rRNAs, but not 16S rRNAs. Allelism tests suggested that the dysfunctional ptCPN60α1S57F competes with other members of the ptCPN60 family. Indeed, overexpression of the ptCPN60α1S57F protein in wild‐type plants mimicked the phenotypes observed in the α1‐4 mutant, while increasing the endogenous transcriptional levels of ptCPN60α2, β1, β2, and β3 in the α1‐4 mutant partially mitigated the abnormal fragmentation processing of chloroplast 23S, 5S, and 4.5S rRNAs. Furthermore, we demonstrated functional redundancy between ptCPN60β1 and ptCPN60β2 in chloroplast rRNA processing through double‐mutant analysis. Collectively, our data reveal a novel physiological role of ptCPN60 subunits in generating the functional rRNA species of the large 50S ribosomal subunit in Arabidopsis chloroplasts.
Contrasting demographic history and mutational load in three threatened whitebark pines (Pinus subsect. Gerardianae): implications for conservation
Authors: Kou Yi‐Xuan , Liu Mi‐Li , López‐Pujol Jordi , Zhang Qi‐Jing , Zhang Zhi‐Yong , Li Zhong‐Hu
Published: August 2024

Demographic history and mutational load are of paramount importance for the adaptation of the endangered species. However, the effects of population evolutionary history and genetic load on the adaptive potential in endangered conifers remain unclear. Here, using population transcriptome sequencing, whole chloroplast genomes and mitochondrial DNA markers, combined with niche analysis, we determined the demographic history and mutational load for three threatened whitebark pines having different endangered statuses, Pinus bungeana, P. gerardiana and P. squamata. Demographic inference indicated that severe bottlenecks occurred in all three pines at different times, coinciding with periods of major climate and geological changes; in contrast, while P. bungeana experienced a recent population expansion, P. gerardiana and P. squamata maintained small population sizes after bottlenecking. Abundant homozygous‐derived variants accumulated in the three pines, particularly in P. squamata, while the species with most heterozygous variants was P. gerardiana. Abundant moderately and few highly deleterious variants accumulated in the pine species that have experienced the most severe demographic bottlenecks (P. gerardiana and P. squamata), most likely because of purging effects. Finally, niche modeling showed that the distribution of P. bungeana might experience a significant expansion in the future, and the species' identified genetic clusters are also supported by differences in the ecological niche. The integration of genomic, demographic and niche data has allowed us to prove that the three threatened pines have contrasting patterns of demographic history and mutational load, which may have important implications in their adaptive potential and thus are also key for informing conservation planning.
The Relationship Between Social Media Usage and Responses to Hoax and Hate Speech in Padang
Authors: Lestari Yayuk , Elian Novi , Diego Diego , Anindya Annisa , Helmi Rahmadhona Fitri
Published: August 2024

The popularity of social media in Indonesia is currently on the rise, and recent trends indicate that social media usage is associated with the dissemination of various factors contributing to the development of news and information within society. Most social media users utilize their social networks to meet their news needs, even though these sources are not always accurately verifiable. Unfortunately, there is a significant amount of misinformation and hate speech found on social media,  compounded by the low media literacy rates in Indonesia, leading to rapid and widespread dissemination of information. This study aims to analyze the relationship between individual behavior in consuming media (media consumption) and their responses to hoax and hate speech on social media. The theory employed is selective exposure. The research method used is a quantitative approach utilizing correlational research methods. Sampling was conducted using a questionnaire, selecting two districts as the research sample through simple random sampling. The total number of respondents included in this study was 110, determined based on Taro Yamane's formula with a precision/tolerance error of 10%. The research findings indicate that the majority of respondents emphasize the importance of selecting information free from  negative content such as insults, hate speech, and fake news on social media platforms. Significant differences in respondent perspectives reflect variations in the assessment of accessed information, while differing opinions regarding the validity and freedom of information from certain negative elements are also evident in this study. Some respondents exhibit uncertainty regarding the objectivity and consistency between titles and content of information obtained through social media. The analysis reveals a connection between the intensity of social media usage and respondents' reactions to hoax and hate speech information. Although the relationship is relatively weak, it indicates an association between the frequency of social media usage and the way respondents respond to information containing hoaxes or hate speech.
Atmospheric Bubbling Fluidized Bed Risers: Effect of Cone Angle on Fluid Dynamics and Heat Transfer
Authors: Das Hirakh Jyoti , Mahanta Pinakeswar
Published: August 2024

In this paper, a comparative study of fluid flow behavior and thermal characteristics of sand particles has been carried out numerically and experimentally in bubbling fluidized beds for five-cone angles of the riser wall having 0 deg, 5 deg, 10 deg, 15 deg, and 20 deg. An Eulerian model with a k–ε turbulence model is used to explore the numerical analysis, and the findings are compared to those of the experiments. For the study, the inlet air velocity is fixed at 1.5 m/s with sand particles filled up to 30 cm to maintain bubbling conditions in the risers. The results indicate that increasing the cone angle up to 10 deg while maintaining the amount of bed materials constant leads to a reduction in pressure drop. The expansion of particles along the riser is observed to decrease with the increase in the cone angle up to 10 deg. The radial solid volume fraction profile transforms to a U shape from the W-type profile as the cone angle increases up to 10 deg. Correspondingly, the solid velocity is found to have an inverted U-type and W-shaped profile for the risers. The granular temperature is also found to increase with a decrease in the solid percentage at any location. The average bed temperature, interphase, and bed-to-wall heat transfer coefficient at a location of 10 cm axial height also increase with the cone angle increase up to 10 deg. As a result, the conical riser, when designed with a greater cone angle up to 10 deg, exhibits more efficiency in terms of heat transfer characteristics. The 3D simulation results are in strong concurrence with the experimental results in all investigations.
Acoustic bright solitons propagation in bubbly liquids
Authors: Yu Jiawen , Zhang Jiangyi
Published: August 2024

We study the propagation rules of acoustic bright solitons in bubble-containing media, as well as the strong anti-interference ability of acoustic solitons; and the effects of nonlinearity, dispersion, and dissipation on the dynamic properties of acoustic solitons are also analyzed. Based on the bubble–liquid mixture model, a lossy nonlinear Schrödinger equation is obtained. The analytical expression of the enveloped bright-acoustic solitons in the bubbly liquids is derived, which can accurately capture the propagation law of the acoustic bright solitons in the physical system, even if there is viscous loss in the medium. The dissipation-induced dynamics of acoustic solitons is studied through analytical and numerical methods, and the balancing effects of nonlinearity and dispersion in the propagation of bright solitons are analyzed. Furthermore, the particle nature and dynamic stability of bright-acoustic solitons in bubble-containing media are emphasized through fully elastic collisions between solitons moving in the same and opposite directions. This process obeys the energy and momentum conservation laws. After the collision, solitons can maintain their original amplitude, speed, and shape and continue to propagate undisturbed.
Interlaboratory Study Toward Combining Gait Kinematics Data Sets of Long-Distance Runners
Authors: Fukuchi Reginaldo Kisho , Duarte Marcos , Ferber Reed
Published: August 2024

The limited sample size in gait studies has hampered progress in the field. This challenge could be addressed through multicenter studies, thereby leveraging data sets from different laboratories. This study compared 3-dimensional lower-extremity running kinematics between the Biomechanics and Motor Control Laboratory, Federal University of ABC (Brazil), and the Running Injury Clinic, University of Calgary (Canada). Three-dimensional lower-extremity kinematics from 23 male runners were collected from each laboratory using comparable instrumentation and experimental procedures. The 3-dimensional hip, knee, and ankle angles were compared within and between centers using root-mean-square deviation. Two-sample t tests Statistical Parametric Mapping tested the hypothesis that the data from both laboratories were not different. The sagittal plane hip, knee, and ankle angles were similar between laboratories, while notable differences were observed for frontal (hip and ankle) and transverse (hip and knee) plane angles. The average interlaboratory root-mean-square deviation (2.6°) was lower than the intralaboratory root-mean-square deviation (Biomechanics and Motor Control = 4.8°, Running Injury Clinic = 5.6°), with the ankle transverse angle displaying the smallest, and the knee transverse angle displaying the largest variability. This study demonstrates the potential of combining gait kinematics data from different laboratories to increase sample size, but frontal and transverse plane data should be considered with caution.
The Effect of Neurocognitive Training on Biomechanical Risk Factors Related to Anterior Cruciate Ligament Injury in Athletes: A Narrative Review
Authors: Hamoongard Majid , Letafatkar Amir , Thomas Abbey C.
Published: August 2024

Context: The best current evidence supports the effectiveness of neuromuscular training in reducing the risk of injury; however, the rate of anterior cruciate ligament (ACL) injuries is still high. Neurocognitive training (NT) has successfully improved biomechanical risk factors, but they have been considered in only a few studies. Objective: To review the literature to determine the effect of NT on biomechanical risk factors related to ACL injury in athletes. Evidence Acquisition: We searched PubMed, Google Scholar, Scopus, Science Direct, and the Physiotherapy Evidence Database from inception to August 2011. We included randomized controlled trials that used motor learning approaches and injury prevention programs to investigate kinematic and kinetic risk factors related to ACL injury. The quality of each clinical trial study was evaluated by the Physiotherapy Evidence Database scale. The eligibility criteria were checked based on the PICOS (population, intervention, comparison, outcome, and study type) framework. Evidence Synthesis: A total of 9 studies were included in the final analysis. Motor learning approaches include internal and external focus of attention, dual tasks, visual motor training, self-control feedback, differential learning, and linear and nonlinear pedagogy, combined with exercise programs. In most of the studies that used NT, a significant decrease in knee valgus; tibial abduction and external rotation; ground reaction force; and an increase in knee-, trunk-, hip-, and knee-flexion moment was observed. Conclusion: In classical NT, deviation from the ideal movement pattern especially emphasizing variability and self-discovery processes is functional in injury prevention and may mitigate biomechanical risk factors of ACL injuries in athletes. Practitioners are advised to use sport-specific cognitive tasks in combination with neuromuscular training to simulate loads of the competitive environment. This may improve ACL injury risk reduction and rehabilitation programs.
Efficacy of a Physical Activity e-Learning Course Delivered to Early Childhood Educators on Preschoolers’ Physical Activity and Sedentary Behaviors: A Cluster Randomized Controlled Trial
Authors: Bourke Matthew , Bruijns Brianne A. , Saravanamuttoo Kendall , Vanderloo Leigh M. , Tucker Patricia
Published: August 2024

Purpose: This study examined the effectiveness of an early childhood educator (ECE)-focused physical activity e-Learning course on children’s physical activity and sedentary time in childcare. Methods: A cluster randomized controlled trial was conducted in 12 childcare centers in London, Ontario, Canada. A total of 145 preschoolers and 42 ECEs participated in this study. ECEs in the intervention condition completed a 5-hour e-Learning course related to physical activity. Outcomes were preschoolers’ minutes of moderate- to vigorous-intensity physical activity, light-intensity physical activity, and sedentary time assessed using accelerometers. Results: The intervention did not have a significant effect on moderate- to vigorous-intensity physical activity (d < 0.01, P = .984), light-intensity physical activity (d = −0.17, P = .386), or sedentary time (d = 0.07, P = .717) from baseline to postintervention. There was also no significant intervention effect on moderate- to vigorous-intensity physical activity (d = 0.27, P = .260), light-intensity physical activity (d = −0.08, P = .740), or sedentary time (d = −0.15, P = .520) from baseline to follow-up. Conclusions: Providing ECEs with online training in physical activity through an e-Learning course may not be sufficient to increase physical activity levels among young children in their care. It may be essential to deliver multicomponent interventions to increase preschoolers’ engagement in physical activity in childcare.
Legitimizing and Transforming Gender Relations Within the Contemporary Equestrian Sport of Charrería in Mexico
Authors: Monterrubio Carlos , Dashper Katherine , Mendoza-Ontiveros Martha Marivel , Wadham Helen
Published: August 2024

The equestrian sport of Charrería is the national sport of Mexico. This ethnographic study illustrates ways in which Charrería helps legitimize unequal gender relations, and in some circumstances, provides opportunity to challenge and rework the wider gender order. Hegemonic masculinities are performed and reified through the gendered performances of male charros and the complementary, opposite, yet unequal, gendered performances of female escaramuzas. Yet hegemony requires constant renewal and consent, and Charrería illustrates the potential for equestrian sports events to also contribute to challenging and reworking the wider gender order and reconfiguring relations between men and women, masculinities and femininities, to be less hierarchical and oppressive.
The β-
d
-
manno
-heptoses are immune agonists across kingdoms
Authors: Tang Yue , Tian Xiaoying , Wang Min , Cui Yinglu , She Yang , Shi Zhaoxiang , Liu Jiaqi , Mao Huijin , Liu Lilu , Li Chao , Zhang Yuwei , Li Pengwei , Ma Yue , Sun Jinyuan , Du Qing , Li Jie , Wang Jun , Li De-feng , Wu Bian , Shao Feng , Chen Yihua
Published: August 2024

Bacterial small molecule metabolites such as adenosine-diphosphate-
d
-
glycero
-β-
d
-
manno
-heptose (ADP-heptose) and their derivatives act as effective innate immune agonists in mammals. We show that functional nucleotide-diphosphate-heptose biosynthetic enzymes (HBEs) are distributed widely in bacteria, archaea, eukaryotes, and viruses. We identified a conserved STT
R5
motif as a hallmark of heptose nucleotidyltransferases that can synthesize not only ADP-heptose but also cytidine-diphosphate (CDP)– and uridine-diphosphate (UDP)–heptose. Both CDP- and UDP-heptoses are agonists that trigger stronger alpha-protein kinase 1 (ALPK1)–dependent immune responses than ADP-heptose in human and mouse cells and mice. We also produced ADP-heptose in archaea and verified its innate immune agonist functions. Hence, the β-
d
-
manno
-heptoses are cross-kingdom, small-molecule, pathogen-associated molecular patterns that activate the ALPK1-dependent innate immune signaling cascade.
A new force emerges in genomics
Authors: Cohen Jon , Tsanni Abdullahi
Published: August 2024

With vision and a big personality, Christian Happi has built a world-class genomics center so Africans can help Africa
Zinc-finger CCHC-type containing protein 8 promotes RNA virus replication by suppressing the type-I interferon responses
Authors: Tu Shaoyu , Zou Jiahui , Xiong Chuhan , Dai Chao , Sun Huimin , Luo Didan , Jin Meilin , Chen Huanchun , Zhou Hongbo
Published: August 2024

Host cells have evolved an intricate regulatory network to fine tune the type-I interferon responses. However, the full picture of this regulatory network remains to be depicted. In this study, we found that knock out of zinc-finger CCHC-type containing protein 8 (ZCCHC8) impairs the replication of influenza A virus (IAV), Sendai virus (Sev), Japanese encephalitis virus (JEV), and vesicular stomatitis virus (VSV). Further investigation unveiled that ZCCHC8 suppresses the type-I interferon responses by targeting the interferon regulatory factor 3 (IRF3) signaling pathway. Mechanistically, ZCCHC8 associates with phosphorylated IRF3 and disrupts the interaction of IRF3 with the co-activator CREB-binding protein (CBP). Additionally, the direct binding of ZCCHC8 with the IFN-stimulated response element (ISRE) impairs the ISRE-binding of IRF3. Our study contributes to the comprehensive understanding for the negative regulatory network of the type-I interferon responses and provides valuable insights for the control of multiple viruses from a host-centric perspective.

IMPORTANCE

The innate immune responses serve as the initial line of defense against invading pathogens and harmful substances. Negative regulation of the innate immune responses plays an essential role in avoiding auto-immune diseases and over-activated immune responses. Hence, the comprehensive understanding of the negative regulation network for innate immune responses could provide novel therapeutic insights for the control of viral infections and immune dysfunction. In this study, we report that ZCCHC8 negatively regulates the type-I interferon responses. We illustrate that ZCCHC8 impedes the IRF3-CBP association by interacting with phosphorylated IRF3 and competes with IRF3 for binding to ISRE. Our study demonstrates the role of ZCCHC8 in the replication of multiple RNA viruses and contributes to a deeper understanding of the negative regulation system for the type-I interferon responses.
Minimal effects after a massive intravenous terbutaline overdose in a child
Authors: Pires Kyle D , Su Mark K , Chiang William
Published: August 2024

A 22-kg female in early childhood with a history of reactive airway disease presented to a paediatric emergency department with acute shortness of breath, tachypnoea and wheezing. Despite treatment with albuterol and corticosteroids, her bronchospasm persisted, prompting the administration of terbutaline. The patient received 220 mcg (10 mcg/kg) terbutaline intravenously, followed immediately by an inadvertent supratherapeutic intravenous dose of 10 000 mcg (454.5 mcg/kg). The patient’s laboratory results obtained minutes after the medication error were notable for: potassium, 3.1 mmol/L, lactate, 2.6 mmol/L and troponin I, 0.30 ng/mL (normal <0.03 ng/mL). Over the next 48 hours, serial serum troponin values decreased. The patient was discharged home approximately 72 hours after the initial presentation and she remained well based on follow-up calls over the next several months. Given the timing and trend of troponin concentrations, we do not believe the terbutaline overdose to be responsible for the myocardial injury.
Detection of glaucoma progression on longitudinal series of en-face macular optical coherence tomography angiography images with a deep learning model
Authors: Mohammadzadeh Vahid , Liang Youwei , Moghimi Sasan , Xie Pengtao , Nishida Takashi , Mahmoudinezhad Golnoush , Eslani Medi , Walker Evan , Kamalipour Alireza , Micheletti Eleonora , Wu Jo-Hsuan , Christopher Mark , Zangwill Linda M , Javidi Tara , Weinreb Robert N
Published: August 2024

Background/aims

To design a deep learning (DL) model for the detection of glaucoma progression with a longitudinal series of macular optical coherence tomography angiography (OCTA) images.

Methods

202 eyes of 134 patients with open-angle glaucoma with ≥4 OCTA visits were followed for an average of 3.5 years. Glaucoma progression was defined as having a statistically significant negative 24-2 visual field (VF) mean deviation (MD) rate. The baseline and final macular OCTA images were aligned according to centre of fovea avascular zone automatically, by checking the highest value of correlation between the two images. A customised convolutional neural network (CNN) was designed for classification. A comparison of the CNN to logistic regression model for whole image vessel density (wiVD) loss on detection of glaucoma progression was performed. The performance of the model was defined based on the confusion matrix of the validation dataset and the area under receiver operating characteristics (AUC).

Results

The average (95% CI) baseline VF MD was −3.4 (−4.1 to −2.7) dB. 28 (14%) eyes demonstrated glaucoma progression. The AUC (95% CI) of the DL model for the detection of glaucoma progression was 0.81 (0.59 to 0.93). The sensitivity, specificity and accuracy (95% CI) of DL model were 67% (34% to 78%), 83% (42% to 97%) and 80% (52% to 95%), respectively. The AUC (95% CI) for the detection of glaucoma progression based on the logistic regression model was lower than the DL model (0.69 (0.50 to 0.88)).

Conclusion

The optimised DL model detected glaucoma progression based on longitudinal macular OCTA images showed good performance. With external validation, it could enhance detection of glaucoma progression.

Trial registration number

NCT00221897.
Central corneal thickness and the risk of primary open-angle glaucoma: a Mendelian randomisation mediation analysis
Authors: Katsimpris Andreas , Baumeister Sebastian-Edgar , Baurecht Hansjörg , Tatham Andrew J , Nolde Michael
Published: August 2024

Background

The association of central corneal thickness (CCT) with primary open-angle glaucoma (POAG) remains uncertain. Although several observational studies assessing this relationship have reported an inverse association between CCT and POAG, this could be the result of collider bias. In this study, we leveraged human genetic data to assess through Mendelian randomisation (MR) the effect of CCT on POAG risk and whether this effect is mediated by intraocular pressure (IOP) changes.

Methods

We used 24 single-nucleotide polymorphisms (SNPs) associated with CCT (p value<5×10
−8
) from a genome-wide association study (GWAS) (N=17 803) provided by the International Glaucoma Genetics Consortium and 53 SNPs associated with IOP (p value<5×10
−8
) from a GWAS of the UK Biobank (UKBB) (N=97 653). We related these instruments to POAG using a GWAS meta-analysis of 8283 POAG cases and 753 827 controls from UKBB and FinnGen.

Results

MR analysis suggested a positive association between CCT and POAG (OR of POAG per 50 µm increase in CCT: 1.38; 95% CI: 1.18 to 1.61; p value<0.01). MR mediation analysis showed that 28.4% of the total effect of CCT on POAG risk was mediated through changes in IOP. The primary results were consistent with estimates of pleiotropy-robust MR methods.

Conclusion

Contrary to most observational studies, our results showed that a higher CCT is associated with an increased risk of POAG.
Impact of aspirin dose according to race in secondary prevention of atherosclerotic cardiovascular disease: a secondary analysis of the ADAPTABLE randomised controlled trial
Authors: Marquis-Gravel Guillaume , Mulder Hillary , Wruck Lisa M , Benziger Catherine P , Effron Mark B , Farrehi Peter M , Girotra Saket , Gupta Kamal , Kripalani Sunil , Muñoz Daniel , Polonsky Tamar S , Whittle Jeff , Harrington Robert , Rothman Russell , Hernandez Adrian F , Jones WS
Published: August 2024

Objectives

To evaluate whether the effectiveness and safety of low (81 mg daily) versus high-dose (325 mg daily) aspirin is consistent across races among patients with established atherosclerotic cardiovascular disease (ASCVD).

Design

A secondary analysis of the randomised controlled trial ADAPTABLE was performed.

Setting

The study was conducted in 40 centres and one health plan participating in the National Patient-Centred Clinical Research Network (PCORnet) in the USA.

Participants

Among 15 076 participants with established ASCVD, 14 096 had self-reported race available and were included in the analysis. Participants were divided according to self-reported race as Black (n=1311, 9.3%), White (n=11 990, 85.1%) or other race (n=795, 5.6%).

Interventions

Participants were randomised to open-label daily aspirin doses of 81 mg versus 325 mg in a 1:1 ratio for a median of 26.2 months.

Primary and secondary outcomes measures

The primary effectiveness endpoint was a composite of death from any cause, hospitalisation for myocardial infarction or hospitalisation for stroke. The primary safety endpoint was hospitalisation for bleeding requiring blood product transfusion.

Results

Estimated cumulative incidence of the primary effectiveness endpoint at median follow-up with the 81 mg and the 325 mg daily doses were 6.70% and 7.12% in White participants (adjusted HR: 1.00 [95% CI: 0.88 to 1.15]); 12.27% and 10.69% in Black participants (adjusted HR: 1.40 [95% CI: 1.02 to 1.93]); and 6.88% and 7.69% in other participants (adjusted HR: 0.86 [95% CI: 0.54 to 1.39]) (p-interaction=0.12), respectively. There was no significant interaction between self-reported race and assigned aspirin dose regarding the secondary effectiveness and the primary safety endpoints.

Conclusion

Race is not an effect modifier on the impact of aspirin dosing on effectiveness and safety in patients with established ASCVD. In clinical practice, treatment decisions regarding aspirin dose in secondary prevention of ASCVD should not be influenced by race.

Trial registration number

NCT02697916.
Pharmacist-led primary care interventions to promote medicines optimisation and reduce overprescribing: a systematic review of UK studies and initiatives
Authors: Chambers Duncan , Preston Louise , Clowes Mark , Cantrell Anna J , Goyder Elizabeth C
Published: August 2024

Objectives

To systematically review and synthesise evidence on the effectiveness and implementation barriers/facilitators of pharmacist-led interventions to promote medicines optimisation and reduce overprescribing in UK primary care.

Design

Systematic review.

Setting

UK primary care.

Methods

We searched MEDLINE, Embase, CINAHL PsycINFO and The Cochrane Library for UK-based studies published between January 2013 and February 2023. Targeted searches for grey literature were conducted in May 2023. Quantitative and qualitative studies (including conference abstracts and grey literature) that addressed a relevant intervention and reported a primary outcome related to changes in prescribing were eligible for inclusion. Quality of included studies was assessed using the Multiple Methods Appraisal Tool. We performed a narrative synthesis, grouping studies by publication status, setting and type of data reported (effectiveness or implementation).

Results

We included 14 peer-reviewed journal articles and 11 conference abstracts, together with 4 case study reports. The journal articles reported 10 different interventions, 5 delivered in general practice, 4 in care homes and 1 in community pharmacy. The quality of evidence was higher in general practice than in care home settings. It was consistently reported that the intervention improved outcomes related to prescribing, although the limited number of studies and wide range of outcomes reported made it difficult to estimate the size of any effect. Implementation was strongly influenced by relationships between pharmacists and other health and care professionals, especially general practitioners. Implementation in care homes appeared to be more complex than in general practice because of differences in systems and ‘culture’ between health and social care.

Conclusions

Pharmacist-led interventions have been reported to reduce overprescribing in primary care settings in the UK but a shortage of high-quality evidence means that more rigorous studies using high-quality designs are needed. More research is also needed in community pharmacy settings; to assess intervention effects on patient outcomes other than prescribing and to investigate how reducing overprescribing can impact health inequalities.

PROSPERO registration number

CRD42023396366.
Comparing mechanochemical endovenous ablation using Flebogrif with endovenous laser ablation in the treatment of primary great saphenous vein incompetence: protocol for a multicentre, open-label, non-inferiority, observer-blinded, randomised controlled trial (REBORN trial)
Authors: Oud Sharon , Alozai Tamana , Schreve Michiel A , Mooij Michael C , van Vlijmen Clarissa J , Ünlü Çağdaş
Published: August 2024

Introduction

Endovenous laser ablation (EVLA) is associated with an excellent outcome in the treatment of great saphenous vein (GSV) incompetence. However, the use of thermal ablation requires tumescent anaesthesia and is associated with a risk of thermal damage. Mechanochemical endovenous ablation (MOCA) is a non-thermal ablation (NTA) alternative, which combines mechanical endothelial damage with the infusion of a sclerosant liquid or foam. Tumescent anaesthesia is not required. Preliminary experiences with MOCA using the Clarivein device show less intraprocedural and postprocedural pain and a faster clinical improvement compared with EVLA. Flebogrif (Balton, Poland) is a relatively new MOCA device. To determine the role of MOCA using Flebogrif, a well-designed, randomised controlled clinical trial of sufficient sample size and follow-up time is required. In this article, we provide the study protocol for the REBORN trial, aiming to demonstrate that MOCA using Flebogrif is not inferior to EVLA for the outcome of anatomical success in the treatment of GSV incompetence.

Methods and analysis

This multicentre, open-label, non-inferiority, observer-blinded, randomised controlled trial randomises patients who are diagnosed with GSV incompetence and aged 18–80 years between Flebogrif and EVLA. 310 patients in 3 participating centres (Northwest Clinics Alkmaar, Skin and Vein Clinic Oosterwal Alkmaar and Red Cross Hospital Beverwijk) will be included. The primary outcome is anatomical success at 12 months. Secondary outcomes are intraprocedural pain, operation time, technical success, postprocedural pain, safety, anatomical success during other follow-up moments, complications, clinical success, aesthetic result, disease-specific quality of life, reinterventions, anterior accessory saphenous vein reflux and neovascularisation. Patients will be followed up at 1 week, 1, 6, 12, 24 and 60 month(s) after treatment.

Ethics and dissemination

The institutional review board (Medical Ethical Review Committee of the Vrije Universiteit Medical Center) approved this study on 17 May 2021 under case number 2020.0740. Written informed consent is obtained by the coordinating investigator from all participants prior to study enrolment. After completion of the trial, the results will be submitted to an international scientific journal for peer-reviewed publication.

Trial registration number

Overzicht van Medisch-wetenschappelijk Onderzoek in Nederland, NL-OMON25145, previously NL9527; Centrale Commissie Mensgebonden Onderzoek, NL74491.029.20.
Phase-resolved MRI for measurement of pulmonary perfusion and ventilation defects in comparison with dynamic contrast-enhanced MRI and129Xe MRI
Authors: Ouyang Tao , Tang Yichen , Zhang Chen , Yang Qi
Published: August 2024

Introduction

This meta-analysis aims to evaluate the agreement and correlation between phase-resolved functional lung MRI (PREFUL MRI) and dynamic contrast-enhanced (DCE) MRI in evaluating perfusion defect percentage (QDP), as well as the agreement between PREFUL MRI and129Xe MRI in assessing ventilation defect percentage (VDP).

Method

A systematic search was conducted in the Medline, Embase and Cochrane Library databases to identify relevant studies comparing QDP and VDP measured by DCE MRI and129Xe MRI compared with PREFUL MRI. Meta-analytical techniques were applied to calculate the pooled weighted bias, limits of agreement (LOA) and correlation coefficient. The publication bias was assessed using Egger’s regression test, while heterogeneity was assessed using Cochran’s Q test and Higgins I2statistic.

Results

A total of 399 subjects from 10 studies were enrolled. The mean difference and LOA were −2.31% (−8.01% to 3.40%) for QDP and 0.34% (−4.94% to 5.62%) for VDP. The pooled correlations (95% CI) were 0.65 (0.55 to 0.73) for QDP and 0.72 (0.61 to 0.80) for VDP. Furthermore, both QDP and VDP showed a negative correlation with forced expiratory volume in 1 s (FEV1). The pooled correlation between QDP and FEV1was −0.51 (−0.74 to −0.18), as well as between VDP and FEV1was −0.60 (−0.73 to −0.44).

Conclusions

PREFUL MRI is a promising imaging for the assessment of lung function, as it demonstrates satisfactory deviations and LOA when compared with DEC MRI and129Xe MRI.

PROSPERO registration number

CRD42023430847.
Systematic development of an injury and illness prevention programme for athletes with a physical impairment: the TIPAS study
Authors: Luijten Sietske C M , Nauta Joske , Janssen Thomas , Holla Jasmijn , Jenniskens Simone C N , Verhagen Evert
Published: August 2024

Background/aim

The participation of individuals with physical impairment in sports has numerous benefits, yet there is also the risk of sustaining sport-related injuries or illnesses. Therefore, prevention programmes of these problems are needed to ensure that individuals can maintain a healthy, active lifestyle. Currently, very few prevention interventions are accessible for these athletes. Therefore, the article aims to describe the development process of the Tailored Injury Prevention in Adapted Sports intervention, an online tailored injury and illness prevention intervention for athletes with a physical impairment.

Methods

The development was guided by the Knowledge Transfer Scheme (KTS).

Results

In the first step, a cohort study and a qualitative study were conducted to define the problem statement. In the second step, a systematic review was performed in order to learn from theory. Steps 3 and 4 involved an iterative process involving collaboration with diverse expert groups. This included defining athletes’ needs and creating a health problem blueprint, after which the intervention content was created. To ensure accuracy and completeness, a feedback loop was incorporated. In the final phase of this step, we refined the language used within the intervention together with athletes. Finally, an effect and process evaluation will take place in the last step of the KTS.

Conclusions

Through a five-step approach of the KTS, we developed an online injury and illness prevention intervention for athletes with a physical impairment. This intervention provides direct, timely feedback based on their current health status. Furthermore, it takes the sport and the physical impairment of the athletes into account with regard to the given prevention advices.
Hang up your cleats and hope for the best? A cross-sectional study of five health domains in retired elite female rugby players
Authors: Thornton Jane S , Hewitt Chloe , Khan Karim , Speechley Mark , Ambrose Ashley , Reilly Kristen , Mountjoy Margo Lynn , Gouttebarge Vincent , Crossley Kay
Published: August 2024

Objectives

To investigate retired elite female rugby players’ health outcomes (and their relationships) in five key areas (musculoskeletal, cognitive, mental, reproductive/endocrinological and cardiovascular) and how those compare with the general population.

Methods

Female rugby players aged ≥18 years old and retired from elite competition ≥2 years were recruited via email or social media to complete a 179-item online questionnaire and neurocognitive assessment. Data from general population controls (matched for age and sex) were obtained where available.

Results

159 participants responded (average age 43 (±5) years). 156 (98%) reported a hip/groin, knee, foot/ankle or lower back injury during their career, of which 104 (67%) reported ongoing pain. Participants reported worse hip and knee outcomes compared with the general population (p<0.0001). 146 (92%) reported sustaining one or more concussions. History of concussion was associated with lower-than-average scores on neurocognitive assessment. Compared with general population data, retired female rugby players reported less anxiety (OR=0.079 (95% CI 0.03 to 0.19)), depression (OR=0.67 (95% CI 0.57 to 0.78)) and distress (OR=0.17 (95% CI 0.15 to 0.19)). Amenorrhoea rates were higher compared with matched controls, and the age at menopause was younger. The prevalence of hypertension was higher. The rugby players perceived that their health decreased in retirement and cited a lack of physical activity as a main contributor.

Conclusion

Our findings point to the potential value of screening and monitoring, and identifying preventative measures during sporting careers to promote health and long-term quality of life for athletes.
Management of bicuspid aortic valve disease in the transcatheter aortic valve implantation era
Authors: Jahangiri Marjan , Prendergast Bernard
Published: August 2024

In an era of rapidly expanding use of transcatheter aortic valve implantation (TAVI), the management of patients with bicuspid aortic valve (BAV) disease is far less well established than in those with trileaflet anatomy. Results of isolated surgical aortic valve replacement are excellent in suitable patients, and surgery also allows treatment of concomitant pathology of the aortic root and ascending aorta that is frequently encountered in this cohort. Conversely, TAVI provides an excellent alternative in older patients who may be unsuitable for surgery, although outcomes in BAV disease have only been reported in relatively small non-randomised series. Here, we discuss the pertinent literature on this topic and outline contemporary interventional treatment options in this challenging setting.
Impact of initiation of targeted therapy on the use of psoriatic arthritis-related treatments and healthcare consumption: a cohort study of 9793 patients from the French health insurance database (SNDS)
Authors: Pina Vegas Laura , Iggui Siham , Sbidian Emilie , Claudepierre Pascal
Published: August 2024

Objectives

To assess the potential impact of targeted therapies for psoriatic arthritis (PsA) on symptomatic treatments (non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, opioid analgesics), methotrexate and mood disorder treatments and on hospitalisation and sick leave.

Methods

Using the French health insurance database, this nationwide cohort study included adults with PsA who were new users (not in the year before the index date) of targeted therapies for ≥9 months during 2015–2021. Main endpoints were difference in proportion of users of associated treatments, hospitalisations and sick leaves between 3 and 9 months after and 6 months before targeted therapy initiation. Logistic regression models adjusted for sex, age, psoriasis, inflammatory bowel disease and Charlson Comorbidity Index compared the impact of biologics initiation (tumour necrosis factor inhibitor (TNFi)/interleukin 17 inhibitor (IL17i)/IL12/23i) on associated treatment discontinuation.

Results

Among 9793 patients initiating targeted therapy for PsA (mean age: 51±13 years, 47% men), 62% initiated TNFi, 14% IL17i, 10% IL12/23i, 1% Janus kinase inhibitor, 12% phosphodiesterase-4 inhibitor. After treatment initiation, the proportion of treatment users was significantly reduced for NSAIDs (−15%), opioid analgesics (−9%), prednisone (−9%), methotrexate (−15%) and mood disorder treatments (−2%), along with decreased hospitalisations (−12%) and sick leaves (−4%). TNFi had a greater sparing effect on NSAIDs and prednisone use than IL17i (ORa=1.04, 95% CI=1.01 to 1.07; 1.04, 1.02 to 1.06) and IL12/23i (1.07, 1.04 to 1.10; 1.06, 1.04 to 1.09). Odds of methotrexate discontinuation was reduced with TNFi versus IL17i (0.96, 0.94 to 0.98) and IL12/23i (0.94, 0.92 to 0.97).

Conclusions

Targeted therapy initiation for PsA reduced the use of associated treatment and healthcare, with TNFi having a slightly greater effect than IL17i and IL12/23i, except for methotrexate discontinuation.
Plasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts
Authors: Sand Jannie Marie Bülow , Jessen Henrik , Leeming Diana Julie , Yu Sheeline , Lee Chris J , Hu Buqu , Sun Ying , Adams Taylor , Pivarnik Taylor , Liu Angela , Woo Samuel , McGovern John R , Fiorini Vitória , Saber Tina , Higuero-Sevilla Jean Paul , Gulati Mridu , Kaminski Naftali , Damsky William , Shaw Albert C , Mohanty Subhasis , Goobie Gillian , Zhang Yingze , Herzog Erica Lyndrup , Ryu Changwan
Published: August 2024

Introduction

The pathogenesis of sarcoidosis involves tissue remodelling mediated by the accumulation of abnormal extracellular matrix, which is partly the result of an imbalance in collagen synthesis, cross-linking and degradation. During this process, collagen fragments or neoepitopes, are released into the circulation. The significance of these circulating collagen neoepitopes in sarcoidosis remains unknown.

Methods

We employed plasma samples from patients with sarcoidosis enrolled in A Case Control Etiologic Study of Sarcoidosis (ACCESS) and Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS), and healthy control patients recruited from the Yale community. Plasma concentrations of type III and VI collagen degradation (C3M and C6M) and formation (PRO-C3 and PRO-C6) were quantified via neoepitope-specific competitive ELISA, and statistical associations were sought with clinical phenotypes.

Results

Relative to healthy controls, the plasma of both sarcoidosis cohorts was enriched for C3M and C6M, irrespective of corticosteroid use and disease duration. While circulating collagen neoepitopes were independent of Scadding stage, there was a significant association between multiorgan disease and PRO-C3, PRO-C6 and C3M in the ACCESS cohort; PRO-C3 and C6M displayed this property in GRADS. These findings were unrelated to plasma levels of interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10 and IL-13. Moreover, PRO-C3 was associated with dermatological disease in both cohorts.

Discussion

In two well-characterised sarcoidosis cohorts, we discovered that the plasma is enriched for neoepitopes of collagen degradation (C3M and C6M). In multiorgan disease, there was an association with circulating neoepitopes of type III formation (PRO-C3), perhaps mediated by dermatological sarcoidosis. Further investigation in this arena has the potential to foster new insights into the pathogenic mechanisms of this complex disease.
Establishing validated RT-qPCR workflow for the analysis of oligodendrocyte gene expression in the developing murine brain
Authors: Smith Samantha , Swan Emma R. , Furber Kendra L.
Published: August 2024

Myelination is essential for the proper conduction of impulses across neuronal networks. Mature, myelinating glia differentiate from progenitor cells through distinct stages that correspond to oligodendrocyte-specific gene expression markers. Reverse transcription quantiatative PCR (RT-qPCR) is a common technique used to quantify gene expression across cell development; however, a lack of standardization and transparency in methodology may lead to irreproducible data. Here, we have designed and validated RT-qPCR assays for oligodendrocyte genes and reference genes in the developing C57BL6/J mouse brain that align with the MIQE guidelines, including quality controls for primer specificity, temperature dependence, and efficiency. A panel of eight commonly used reference genes was ranked using a series of reference gene stability methods that consistently identified Gapdh, Sdha, Hmbs, Hprt1, and Pgk1 as the top candidates for normalization across brain regions. In the cerebrum, myelin genes peaked in expression at postnatal day 21, which corresponds to the peak of developmental myelination. The gene expression patterns from the brain homogenate were in agreement with previously reported RNA-seq and microarray profiles from oligodendrocyte lineage cells. The validated RT-qPCR assays begin to build a framework for future investigation into the molecular mechanisms that regulate myelination in mouse models of brain development, aging, and disease.
Crustal melting recorded by dykes along the gold-bearing Melanson Brook Fault, northern New Brunswick Appalachians
Authors: Bustard Aaron L. , Lentz David R. , Walker James A. , McFarlane Christopher R.M.
Published: August 2024

Dykes intruding along the Melanson Brook Fault record two magmatic episodes in northern New Brunswick. Dykes at the South Gold Zone of the Elmtree gold deposit are aphanitic and magnesian–calcic, whereas those at Ellis Brook (2.5 km to the west) are ilmenite-series and weakly peraluminous with hornblende– and plagioclase–porphyritic phases. Elevated 147Sm/144Nd generated by partial melting, titanium depletion, absence of rare earth element fractionation, and trondhjemite-like compositions indicate that the South Gold Zone dykes were sourced from low-volume fluid-fluxed melting of gabbroic crust. An Sm–Nd-depleted model mantle age of 1.1 Ga for the Ellis Brook dykes suggests that they were sourced from melting of Ganderian crustal rocks rather than the sinking Acadian slab. 143Nd/144Nd evolution curves for the South Gold Zone dykes intersect that of the Ellis Brook dykes at 432 and 427 Ma. This suggests that the magma from which the South Gold Zone dykes crystallized was extracted from a similar source area as the magma that generated the Ellis Brook dykes. Evidence of fluid exsolution in the Ellis Brook dykes indicates that they could be a potential source for reduced intrusion-related gold mineralization. The Ellis Brook dykes yielded a U–Pb zircon age of 391 ± 5 Ma, which is consistent with the timing of oceanic slab break-off at the end of the Acadian orogenic cycle. Extraction of South Gold Zone magma occurred up to 40 Myr earlier, likely during the Salinic orogenic cycle.