bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Relaxin Receptor RXFP1 Agonist AZD3427 in the Treatment of Heart Failure: A Phase 1a/b, First‐in‐Human, Randomized, Single‐Blind, Placebo‐Controlled Study
Authors: Connolly Kathleen , George Richard , Omar Sami , Matsson Elin , Åstrand Magnus , Althage Magnus , Pettersen Daniel , Mohamed Esha , Fang Kelly , Lima Joao A. C. , Kujacic Mirjana , Ödesjö Helena , Turton Michelle , Johannesson Petra , Gabrielsen Anders , Ufnal Marcin 
Published: July 2024

Background
Heart failure mortality remains high despite recent progress in pharmacological treatment. AZD3427 is a selective long‐acting analog of relaxin, a vasodilatory hormone with antifibrotic effects. We assessed the safety, pharmacokinetics, and pharmacodynamics of AZD3427 in healthy volunteers and patients with heart failure on standard‐of‐care therapy.

Methods and Results
In this first‐in‐human, phase 1a/b, randomized, single‐blind, placebo‐controlled study, healthy volunteers were randomized 6:2 to receive a single dose of AZD3427 or placebo by subcutaneous injection in 5 mixed‐ethnicity cohorts (5, 10, 30, 90, or 270 mg) and 1 Japanese‐descent cohort (270 mg), or by intravenous injection in 1 cohort (15 mg). After confirming safety and tolerability in healthy volunteers, 3 cohorts of patients with heart failure and left ventricular ejection fraction ≤40% and 3 cohorts with ejection fraction ≥41% were randomized 6:2 to receive 5 weekly doses of AZD3427 (5, 15, or 45 mg) or placebo by subcutaneous injection. In total, 56 healthy volunteers and 48 patients with heart failure were randomized. AZD3427 was well tolerated at all doses. After subcutaneous administration, AZD3427 was absorbed slowly, and exposure was approximately linear across the dose range. In patients with heart failure, AZD3427 terminal half‐life was 13 to 14 days and there were numerical increases in stroke volume and estimated glomerular filtration rate. No treatment‐emergent antidrug antibodies were detected.

Conclusions
AZD3427 had favorable safety and pharmacokinetic profiles. Hemodynamic changes in patients with heart failure were consistent with the anticipated effects of a relaxin analog. These findings support further development of AZD3427 as a novel long‐term treatment for patients with heart failure.

Registration

URL:
https://www.clinicaltrials.gov
; Unique Identifier: NCT04630067.
Midterm Outcomes of Percutaneous Intramyocardial Septal Radiofrequency Ablation for Hypertrophic Cardiomyopathy: A Single‐Center, Observational Study
Authors: Xie Xudong , Chen Siyuan , Cui Yawei , Zhou Zhenzhen , Lu Jianhua , Du Zhi , Ding Jie , Xing Kaidi , Zhang Yuesheng , Zhou Yijiang , Li Jun , Guo Xiaogang 
Published: July 2024

Background
Percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) has been reported to be safe and effective at midterm follow‐up to treat drug‐refractory hypertrophic obstructive cardiomyopathy in a single center. However, data from other centers are lacking. This retrospective cohort study aimed to investigate the efficacy and safety of PIMSRA from another independent center.

Methods and Results

PIMSRA was performed in 76 patients with hypertrophic obstructive cardiomyopathy in our center from April 2020 to June 2023. The primary outcome was the reduction of left ventricular outflow tract gradient after 6 months or more post‐PIMSRA. Secondary outcomes were periprocedural major adverse clinical events. Sixty‐one patients returned to the hospital for follow‐up 6 to 30 (median, 14) months after the procedure. At the last follow‐up of the 61 patients, the maximum septal thickness decreased from a median of 23.6 (interquartile range, 20.5–26.4) to 19.1 (interquartile range, 16.0–22.1) mm (
P
<0.001) and the left ventricular outflow tract peak gradient at rest decreased from a median of 70.0 (interquartile range, 29.1–107.5) to 20.0 (interquartile range, 10.8–48.8) mm Hg (
P
<0.001). The percentage of patients with symptoms of New York Heart Association functional class III/IV decreased from 51% to 0%. Of all 76 patients, there was no in‐hospital or 30‐day death, no right or left branch block, and no permanent pacemaker implantation. Six (8%) patients had pericardial effusion, with 1 experiencing cardiac tamponade and ventricular fibrillation, and 1 (1%) patient developed septal branch aneurysm that was treated with coil occlusion.

Conclusions
PIMSRA allows for the reduction in the left ventricular outflow tract gradient and enhances symptomatic improvement, with a limited incidence of adverse events and complications among patients with hypertrophic obstructive cardiomyopathy.
Immediate effect of quadri-pulse stimulation on human brain microstructures and functions
Authors: Kimura Ikko , Hayashi Masamichi J. , Amano Kaoru 
Published: July 2024

Abstract
It remains unclear whether repetitive stimulation of a single brain area immediately alters brain microstructure. Thus, we investigated the immediate changes in human brain microstructures following repetitive extrinsic excitation of the left primary motor cortex (M1) through quadri-pulse stimulation (QPS). Sixteen right-handed healthy adults underwent excitatory (QPS5) and inhibitory (QPS50) QPS. Diffusion magnetic resonance imaging (MRI) and resting-state functional MRI were conducted before and after QPS to detect microstructural and functional changes, respectively. No significant alterations in microstructural indices after QPS5 or QPS50 were observed in the cerebral cortex. The functional connectivity (FC) between the bilateral M1 was significantly decreased after QPS5, while it was not significantly modulated after QPS50. Microstructural changes exhibited no significant correlation with this FC change in any region after QPS5 or QPS50. Although no significant FC change was observed following QPS50, these results may suggest that repetitive stimulation of a single brain area can be insufficient to induce immediate microstructural alterations. This would be supported by demonstrating the lack of microstructural changes after QPS together with changes in cortical excitability of the stimulated region.
Bibliometric Insight Into Thyroid Cancer Research: A Comprehensive Review and Future Directions
Authors: Wu Christopher , Swann Sellers , Holland Michelle , Kasmirski Julia A. , Gibson Quince-Xhosa D. , Fazendin Jessica , Chen Herbert , Gillis Andrea 
Published: July 2024

Introduction In the past 3 decades, thyroid cancer research has surged, becoming the leading topic in clinical thyroidology. Despite this, there’s a lack of data identifying key articles, authors, and journals. This study aims to provide insights for authors, physicians, and research labs by highlighting the most influential journals, authors, and research topics in thyroid cancer. Methods A comprehensive search was conducted using the Scopus database, employing the medical subject heading (MeSH) terms “Thyroid” and “Cancer” in the titles, abstracts, or keywords of articles. The search was limited to English articles in academic medicine journals published between January 1993 and December 2021. Results The search yielded 21 472 articles across 3076 journals, authored by 13 974 senior authors. The number of journals publishing on thyroid cancer expanded from 29 in 1993 to 733 in 2021, marking an average annual growth of 14%. Article output on the topic increased from 54 in the initial year to 1580 by 2021, with an annual growth rate of 16%. A thematic analysis revealed 369 articles mentioning “BRAF” since 2004, 479 articles on “ultrasound” techniques, 325 on “ablation” methods, and 453 articles focusing on “genetics” in thyroid cancer. The Journal of Clinical Endocrinology and Metabolism emerged as the most prolific, publishing 1017 articles over the 29-year period. Conclusion This study guides resource allocation towards impactful journals for thyroid cancer researchers, helps identify key contributors for collaboration or mentorship, and provides a framework for similar analyses in other fields.
US State and Territorial Indigenous Consultation Laws: A Potential Strategy to Improve the Social Determinants of Health
Authors: Riley Lorinda , Hulama Kristina , Tapu Ian , Weightmann Anna , Louis-Perkins Tehani , Kajiwara Carly , Maldanado Kamaile , Ravida Meldrick 
Published: July 2024

Objectives: The United Nations (UN) has articulated the right to self-determination as a human right for Indigenous people; however, US states and territories have been slow to operationalize this aspect of the UN Declaration on the Rights of Indigenous Peoples. Indigenous consultation laws require all federal executive agencies to consult with tribal nations before implementing policies that have a “tribal implication,” and these form the cornerstone of US efforts to implement the UN Declaration on the Rights of Indigenous Peoples. Despite these federal efforts, less is known about the degree to which state and territorial laws require consultation with Indigenous communities. Methods: We reviewed all Indigenous consultation laws identified through a search of 50 US states, the District of Columbia, and 5 territories to provide a holistic picture of how jurisdictions have regulated Indigenous consultation efforts. Results: Of the 56 states, 49 (87.5%) had at least 1 Indigenous consultation law; the remaining 7 jurisdictions had none. States engaged in Indigenous consultation in various ways, generally falling into 1 of 3 categories: (1) centralized consultation facilitated through an agency or department, (2) indirect consultation through a designated commission, and (3) fragmented Indigenous consultation through discrete laws. Important gaps were identified, including the lack of a definition for Indigenous consultation, the absence of an appeal process, and the need to train state officials on existing policies. Conclusions: The results provide a baseline on the degree to which US states and territories consult with Indigenous communities and can be used to identify gaps in US compliance with UN human rights mandates.
Assessing Decision Fatigue in General Practitioners’ Prescribing Decisions Using the Australian BEACH Data Set
Authors: Maier Mona , Powell Daniel , Harrison Christopher , Gordon Julie , Murchie Peter , Allan Julia L. 
Published: July 2024

Background General practitioners (GPs) make numerous care decisions throughout their workdays. Extended periods of decision making can result in decision fatigue, a gradual shift toward decisions that are less cognitively effortful. This study examines whether observed patterns in GPs’ prescribing decisions are consistent with the decision fatigue phenomenon. We hypothesized that the likelihood of prescribing frequently overprescribed medications (antibiotics, benzodiazepines, opioids; less effortful to prescribe) will increase and the likelihood of prescribing frequently underprescribed medications (statins, osteoporosis medications; more effortful to prescribe) will decrease over the workday. Methods This study used nationally representative primary care data on GP-patient encounters from the Bettering the Evaluation and Care of Health program from Australia. The association between prescribing decisions and order of patient encounters over a GP’s workday was assessed with generalized linear mixed models accounting for clustering and adjusting for patient, provider, and encounter characteristics. Results Among 262,456 encounters recorded by 2,909 GPs, the odds of prescribing antibiotics significantly increased by 8.7% with 15 additional patient encounters (odds ratio [OR] = 1.087; confidence interval [CI] = 1.059–1.116). The odds of prescribing decreased significantly with 15 additional patient encounters by 6.3% for benzodiazepines (OR = 0.937; CI = 0.893–0.983), 21.9% for statins (OR = 0.791; CI = 0.753–0.831), and 25.0% for osteoporosis medications (OR = 0.750; CI = 0.690–0.814). No significant effects were observed for opioids. All findings were replicated in confirmatory analyses except the effect of benzodiazepines. Conclusions GPs were increasingly likely to prescribe antibiotics and were less likely to prescribe statins and osteoporosis medications as the workday wore on, which was consistent with decision fatigue. There was no convincing evidence of decision fatigue effects in the prescribing of opioids or benzodiazepines. These findings establish decision fatigue as a promising target for optimizing prescribing behavior. Highlights We found that as general practitioners progress through their workday, they become more likely to prescribe antibiotics that are reportedly overprescribed and less likely to prescribe statins and osteoporosis medications that are reportedly underprescribed. This change in decision making over time is consistent with the decision fatigue phenomenon. Decision fatigue occurs when we make many decisions without taking a rest break. As we make those decisions, we become gradually more likely to make decisions that are less difficult. The findings of this study show that decision fatigue is a possible target for improving guideline-compliant prescribing of pharmacologic medications.
Implementing constraint-induced movement therapy into practice in sub-acute stroke: Experiences and perceptions of stroke survivors and therapists
Authors: Jarvis Kathryn A , Edelstyn Nicola MJ , Hunter Susan M 
Published: July 2024

Introduction: Constraint-induced movement therapy has been shown to be effective in a sub-group of sub-acute stroke survivors but has not been widely implemented in the United Kingdom. This study explored therapist and stroke survivor perceptions and experiences of constraint-induced movement therapy and explored the non-agreement (incongruence) and agreement (congruence) of these perspectives. Method: Consenting occupational therapists ( n = 3) and physiotherapist ( n = 5) participated in a focus group discussion. Four-stroke survivors undertook pre- and post-constraint-induced movement therapy interviews. Stroke survivor participants selected and undertook an evidence-based constraint-induced movement therapy protocol. Focus groups and interview audio recordings were independently analysed thematically. Therapist and stroke survivor views were subsequently synthesised using meta-ethnographic principles. Findings: Four over-arching themes were identified: motivation and determination to participate in constraint-induced movement therapy; who benefits; which protocol; making constraint-induced movement therapy feasible. The final over-arching theme comprised five sub-themes: fatigue and sleep; pain; transport; need for support; training, support and mentorship for therapists. Stroke survivors and therapists held contrasting views on three themes. Conclusion: Participating stroke survivors successfully undertook a self-selected, evidence-based constraint-induced movement therapy protocol. The identified enablers and barriers should inform future constraint-induced movement therapy protocol development. The contrasting views held by therapists and stroke survivors reinforce the need for collaborative communication and opportunity for choice during constraint-induced movement therapy.
Factors Influencing Novice and Beginner Nurses’ Intention to Report Medication Errors and Near Misses
Authors: Braiki Raouaa , Douville Frédéric , Gagnon Marie-Pierre 
Published: July 2024

Introduction Novice and beginner nurses make more medical errors than senior nurses. However, there is significant underreporting of medication errors and near misses among novice and beginner nurses. Objective To identify the factors that influence the intention of novice and beginner nurses to report medication errors and near misses. Methods A cross-sectional exploratory study was carried out among third-year nursing students in a Quebec university (n = 143). Data was collected through a self-reported questionnaire based on the adapted Theory of Planned Behavior. Simple descriptive analyses and a series of contingency analyses were performed using Chi-2 or Fisher exact tests. Correction of multiple tests was done using Bonferroni test. Results All theoretical constructs were significantly associated with intention. Sociodemographic factors (age, sex, experience and education program) were also associated with intention. Discussion and conclusion Further studies are needed to identify the determinants of intention to report medication errors and near misses among novice and beginner nurses. More attention is required in nursing practice and education to act on these factors, thus encouraging novice and beginner nurses to report medication errors and near misses.
Aerodynamic performance and flow optimization of axial fan based on the neural network and genetic algorithm
Authors: Sun Tianyi , Wu Xiaoming , Mao Kejun , Wang Zhengdao , Yang Hui , Wei Yikun 
Published: July 2024

The blades of an axial fan are optimized using artificial neural networks and genetic algorithms in this paper. In first, a parametric axial fan blade model is established with constraints imposed on several parameters. The chord length, maximum camber, maximum camber position, blade thickness, and airfoil stagger angle are considered as an optimization parameter of axial fan. The static pressure efficiency and static pressure of axial fan are regarded as the optimization objectives. An optimization calculation of an axial fan blade is carried out based on the combination of artificial neural network and genetic algorithm. The objective aim of optimization is to improve the static pressure efficiency, the static pressure of axial fan and to reduce the flow loss of axial fan. Numerical results of axial fan demonstrate that the pressure distribution gradient and turbulent kinetic energy contour maps of the optimized axial fan are effectively suppressed within the impeller region compared with that of original axial fan. Furthermore, the internal flow stability of the optimized axial fan also is significantly improved by studying the pressure fluctuation and the Fast Fourier Transform (FFT) of pressure fluctuation. Experimental results of axial fan aerodynamic performance further demonstrate that the static pressure of the optimized axial fan rises as much as 90.93 Pa and the improved static pressure efficiency is effectively improved as much as 7.43% at the design flow rates compared with that of the original axial fan. The application of optimized axial flow fans is of great significance in energy-saving of energy equipment.
Daprodustat reduces skeletal muscle ischemia-reperfusion injury in mice
Authors: Wu Weiqiang , Zhang Yongfa , Zhang Ying , Zhang Jiuyun , Li Renbin , Ke Tie 
Published: July 2024

Purpose The purpose of the present work was to assess the specific effects and underlying mechanisms of Daprodustat (GSK1278863) on skeletal muscle injury induced by ischemia reperfusion (I/R). Methods C57BL/6 mice were randomized into the skeletal muscle I/R injury (I/R), Daprodustat (GSK1278863) pretreatment and I/R (I/R + GSK) and sham operation (Sham) groups. The skeletal muscle I/R injury model was established by placing an orthodontic rubber band at the left hip joint for 3 h and releasing it for 3 h. H&E staining, wet weight/dry weight ratio assessment, TUNEL assay, ELISA, qRT-PCR and immunoblot were utilized to assess the effects of Daprodustat. Results Daprodustat pretreatment significantly ameliorated apoptosis in skeletal muscle cells, reduced oxidative damage and suppressed inflammatory cytokines. Mechanistically, Daprodustat positively affected NF-κB signaling activation. Conclusion These data demonstrated that Daprodustat may provide a potential clinical approach for preventing or treating skeletal muscle injury induced by I/R.
“What you Say Matters”: Review of Clinical Outcome of Advanced Medical Directives Between Cancer and Non-cancer Patients in a Chinese Culture Society
Authors: Chan Ka Po , Chung Wai Kei , Hsu Dany Young , Kong Shun Yin , Tin Winnie , Chan Chun Hung , Hwang Elaine , Chan Oi Man , Chui Ruby , Cheng Hon Wai Benjamin 
Published: July 2024

Introduction Advance medical directives (AMD) are statements made by individuals indicating the life-sustaining treatment that they would refuse in the future when they lost their mental capacity for medical decisions. While the proposal for the AMD legislation is ongoing locally in Hong Kong SAR, there are limited reviews on the clinical outcomes associated with it. Objective To provide a comprehensive review on clinical outcomes of signed AMD. Methodology Retrospective, multi-center study, which includes AMD signed within five cluster hospitals. Records of signed AMD from 1st JAN 2020 to 31st DEC 2022 were retrieved from a central registry. Clinical information of each patient was obtained from the electronic patient record. Result 456 patients with documented AMD were included in the study. 91.6% of AMD were signed by palliative care (PC) team. Majority (74.6%) of the patients were accompanied by family members or friends when AMD were signed. The concordance rate between the AMD and the medical care received was 89.5%. No patient revoked their AMD. Cancer and non-cancer patients showed similar rates of AMD concordance, frequency of Accident & Emergency Department (AED) visits or acute ward admissions, duration of hospital stays in the 30 days before death, and prevalence of receiving invasive or intensive treatments. Conclusion Our study demonstrated that PC team currently plays a pivotal role in AMD completion, and AMD remains important in ensuring patients’ care preferences are executed across different medical conditions. With the upcoming AMD legislation in Hong Kong SAR, adequate promotion and education should be launched.
Do Palatoplasty Procedures Resolve Hypernasality as Effectively as Pharyngoplasty Procedures in Patients with 22q11.2 Deletion Syndrome?
Authors: Williams Jessica L. , Perry Jamie L. , Singh Davinder J. , Sitzman Thomas J. 
Published: July 2024

Objective Compare the effectiveness of palatoplasty and pharyngoplasty procedures at resolving hypernasality in patients with 22q11.2 deletion syndrome (22q). Design Retrospective cohort study. Setting Metropolitan children's hospital. Patients Fourteen patients with 22q presenting for management of velopharyngeal insufficiency. Interventions Palatoplasty or pharyngoplasty procedure. Main Outcome Measure Resolution of hypernasality 12 months postoperatively. Results Both procedure groups had a mean preoperative velopharyngeal gap of 6.2 mm during phonation. No patient who underwent palatoplasty achieved resolution of hypernasality; 1/7 patients had worse hypernasality, 4/7 had no change, and 2/7 had improved hypernasality. In contrast, hypernasality was resolved in 6/7 patients in the pharyngoplasty group, which was significantly ( P = .03) higher than the palatoplasty group. Conclusions In patients with 22q, palatoplasty procedures may be less effective than pharyngoplasty procedures at resolving hypernasality. This may be due to underlying anatomic or physiologic differences, such as increased pharyngeal depth and hypodynamic muscles.