bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in nucleic acid-targeted therapies for cardiovascular disease prevention
Authors: Makhmudova Umidakhon , Steinhagen-Thiessen Elisabeth , Volpe Massimo , Landmesser Ulf 
Published: July 2024

Abstract
Nucleic acid-based therapies are being rapidly developed for prevention and management of cardiovascular diseases (CVD). Remarkable advancements have been achieved in the delivery, safety, and effectiveness of these therapeutics in the past decade. These therapies can also modulate therapeutic targets that cannot be sufficiently addressed using traditional drugs or antibodies. Among the nucleic acid-targeted therapeutics under development for CVD prevention are RNA-targeted approaches, including antisense oligonucleotides (ASO), small interfering RNAs (siRNA), and novel genome editing techniques.
Genetic studies have identified potential therapeutic targets that are suggested to play a causative role in development and progression of CVD. RNA- and DNA-targeted therapeutics can be particularly well delivered to the liver, where atherogenic lipoproteins and angiotensinogen (AGT) are produced. Current targets in lipid metabolism include proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein A (ApoA), apolipoprotein C3 (ApoC3), angiopoietin-like 3 (ANGPTL3). Several large-scale clinical development programs for nucleic acid-targeted therapies in cardiovascular prevention are under way, which may also be attractive from a therapy adherence point of view, given the long action of these therapeutics. In addition to genome editing, the concept of gene transfer is presently under assessment in preclinical and clinical investigations as a potential approach for addressing low-density lipoprotein receptor deficiency. Furthermore, ongoing research is exploring the use of RNA-targeted therapies to treat arterial hypertension by reducing hepatic angiotensinogen (AGT) production.
This review summarizes the rapid translation of siRNA and ASO therapeutics as well as gene editing into clinical studies to treat dyslipidemia and arterial hypertension for CVD prevention. It also outlines potential innovative therapeutic options that are likely relevant to the future of cardiovascular medicine.
ImmRNA: a database of RNAs associated with tumor immunity
Authors: Shen Fangfang , Li Zelian , Wu Pengfei , Wang Jinpeng 
Published: July 2024

Abstract
The relationship between different ribonucleic acids (RNAs) and tumor immunity has been widely investigated. However, a systematic description of tumor immune-related RNAs in different tumors is still lacking. We collected the relationship of tumor immune-related RNAs from the published literature and presented them in a user-friendly interface, “ImmRNA” (http://www.immrna.cn/), to provide a resource to study immune-RNA-cancer regulatory relations. The ImmRNA contains 49 996 curated entries. Each entry includes gene symbols, gene types, target genes, downstream effects, functions, immune cells, and other information. By rearranging and reanalyzing the data, our dataset contains the following key points: (i) providing the links between RNAs and the immune in cancers, (ii) displaying the downstream effects and functions of RNAs, (iii) listing immune cells and immune pathways related to RNA function, (iv) showing the relationship between RNAs and prognostic outcomes, and (v) exhibiting the experimental methods described in the article. ImmRNA provides a valuable resource for understanding the functions of tumor immune-related RNAs.
Database URL: http://www.immrna.cn/
Influence of examiner calibration on clinical and MRI diagnosis of temporomandibular joint disc displacement: a systematic review and meta-analysis
Authors: Maracci Lucas Machado , Savegnago Gleica Dal Ongaro , Antoniazzi Raquel Pippi , Marquezan Mariana , Silva Tatiana Bernardon , Liedke Gabriela Salatino 
Published: July 2024

Abstract

Objectives
This study aimed to verify the accuracy of clinical protocols for the diagnosis of disc displacement (DD) compared with MRI, considering examiners’ calibration.

Methods
PubMed, Cochrane (Central), Scopus, Web of Science, LILACS, Embase, Science Direct, Google Scholar, and DANS EASY Archive databases were searched. Two reviewers independently screened and selected the studies. A meta-analysis was conducted using the R Statistical software. Results are shown using sensitivity and specificity, and 95% confidence intervals.

Results
Of the 20 studies included in the systematic review, only three were classified as low risk of bias. Seventeen studies were included in the meta-analysis. Compared to MRI, clinical protocols showed overall sensitivity and specificity of 0.75 (0.63-0.83) and 0.73 (0.59-0.84) for DD diagnosis, respectively. For DD with reduction, sensitivity was 0.64 (0.48-0.77) and specificity was 0.72 (0.48-0.87). For DD without reduction, sensitivity was 0.58 (0.39-0.74) and specificity 0.93 (0.83-0.97). Only 8 studies reported examiner calibration when performing clinical and/or MRI evaluation; nevertheless, calibration showed a tendency to improve the diagnosis of DD.

Conclusion
The sensitivity and specificity of clinical protocols in the diagnosis of DD are slightly below the recommended values, as well as the studies lack calibration of clinical and MRI examiners. Examiner calibration seems to improve the diagnosis of DD.
Reoperative extended arch repair for acute type A aortic dissection after previous cardiac surgery: insights from a relatively young redo series
Authors: Zhang Yixiao , Wang Yulin , Liu Fangyu , Chen Qiyi , Shao Kejie , Lai Hao , Wang Chunsheng , Ji Qiang 
Published: July 2024

Abstract

OBJECTIVES
To evaluate the impact of previous cardiac surgery (PCS) on clinical outcomes after reoperative extended arch repair for acute type A aortic dissection.

METHODS
This study included 37 acute type A aortic dissection patients with PCS (PCS group) and 992 without PCS (no-PCS group). Propensity score-matching yielded a subgroup of 36 pairs (1:1). In-hospital outcomes and mid-term survival were compared between the 2 groups.

RESULTS
The PCS group was older (56.7 ± 14.2 vs 52.2 ± 12.6 years, P = 0.036) and underwent a longer cardiopulmonary bypass (median, 212 vs 183 min, P &lt; 0.001) compared with the no-PCS group. Operative death occurred in 88 (8.6%) patients, exhibiting no significant difference between groups (13.5% vs 8.4%, P = 0.237). Major postoperative morbidity was observed in 431 (41.9%) patients, also showing no difference between groups (45.9% vs 41.7%, P = 0.615). Moreover, the multivariable logistic regression analysis revealed that PCS was not significantly associated with operative mortality (adjusted odds ratio 2.58, 95% confidence interval 0.91–7.29, P = 0.075) or major morbidity (adjusted odds ratio 1.92, 95% confidence interval 0.88–4.18, P = 0.101). The 3-year cumulative survival rates were 71.1% for the PCS group and 83.9% for the no-PCS group (log-rank P = 0.071). Additionally, Cox regression indicated that PCS was not significantly associated with midterm mortality (adjusted hazard ratio 1.40, 95% confidence interval 0.44–4.41, P = 0.566). After matching, no significant differences were found between groups in terms of operative mortality (P &gt; 0.999), major morbidity (P &gt; 0.999) and midterm survival (P = 0.564).

CONCLUSIONS
No significant differences were found between acute type A aortic dissection patients with PCS and those without PCS regarding in-hospital outcomes and midterm survival after extended arch repair.
Predicting fragility fractures based on frailty and bone mineral density among rural community-dwelling older adults
Authors: Lee Jeongmin , Kim Jinyoung , Jeong Chaiho , Ha Jeonghoon , Lim Yejee , Baek Ki-Hyun 
Published: July 2024

Abstract

Objective
We aim to investigate the association between bone mineral density (BMD) measurement and fragility fractures and assess the predictive value of combining BMD measurement and frailty for fracture risk assessment.

Methods
This retrospective cohort study analyzed data from 5126 rural Koreans in the Chungju Metabolic Disease Cohort study. Frailty was defined using Fried's frailty phenotype. Fractures were assessed via structured medical interviews. Adjusted odds ratios (ORs) were calculated considering age, sex, body mass index, behavior, BMD, handgrip strength, medications, and comorbidities.

Results
The study cohort consisted of 5126 participants comprising 1955 (38.1%) males and 3171 (61.9%) females. Osteoporosis significantly increased the fracture risk across all types, except vertebral fracture, with adjusted OR (95% CI) of 1.89 (1.23-3.47) for any fracture, 2.05 (1.37-2.98) for hip fracture, 2.18 (1.06-4.50) for other fracture, and 1.71 (1.03-3.63) for major osteoporotic fracture (MOF). Frail individuals exhibited significantly increased risk for any fracture (OR 2.12; 95% CI, 1.21-3.71), vertebral fracture (2.48; 1.84-3.61), hip fracture (2.52; 1.09-3.21), other fracture (2.82; 1.19-8.53), and MOF (1.87; 1.01-3.47). The combination of frailty and BMD further increased the risks, with frail individuals demonstrating elevated ORs across BMD categories. In subgroup analyses, men showed a significant association between frailty with osteoporosis in hip fracture and MOF. Frail women with osteoporosis exhibited the highest risks for all fractures, particularly vertebral (OR 5.12; 95% CI, 2.07-9.68) and MOF (OR 5.19; 95% CI, 2.07-6.61). Age-specific analysis revealed that individuals aged 70 and older exhibited markedly higher fracture risks compared with those under 70. The combination of frailty and low BMD further elevated the fracture risk. Frailty was applied with BMD and demonstrated superior risk prediction for MOF compared with that with either score alone (area under the curve 0.825; P = .000).

Conclusions
Combining frailty with BMD provides a more accurate fracture risk assessment for individuals over 50 years.
Longer school schedules, childcare and the quality of mothers’ employment
Authors: Berthelon Matias , Kruger Diana , Lauer Catalina , Tiberti Luca , Zamora Carlos 
Published: July 2024

Summary
Better employment quality can improve personal well-being, social cohesion, and inclusive growth and development. Yet good quality jobs – associated with greater well-being – are less accessible to women than men. While it is understood that policies balancing family and work lead to greater female labour participation, this paper investigates whether one such policy – increased childcare – improves the quality of jobs where mothers are employed. The context we analyse is a nationwide school reform in Chile that extended school schedules for primary school-aged children, providing childcare services. We combine administrative data of the phase-in of the policy with panel data of individual mothers’ employment outcomes and socio-economic characteristics. We estimate a fixed-effects model that controls for mothers’ unobserved heterogeneity and identifies the effect of the policy from plausibly exogenous temporal and spatial variations in access to schools with long schedules and exogenous exposure to the policy. We find a positive effect of childcare on several measures of employment quality and gender gaps within the couple. Our evidence suggests that the mechanism driving the impact is the implicit subsidy to the cost of childcare, affecting the opportunity cost of mothers’ time. In addition, we find heterogeneous results by mothers’ education level. Access to childcare through longer primary school schedules can increase household welfare and can play a role in reducing income and gender inequalities.
Extracellular Vesicle MicroRNAs as Predictive Biomarkers in Postoperative Delirium After Spine Surgery: Preliminary Study
Authors: Cho Young-Eun , Kim Jeongmin , Vorn Rany , Cho Hyeonmi , Baek Wonhee , Park Hyunki , Yun Sijung , Kim Hyung-Suk , Cashion Ann K , Gill Jessica , Koo Bon-Nyeo , Lee Hyangkyu 
Published: July 2024

Abstract
Postoperative delirium (POD) can cause poor patient outcomes in older adults who undergo surgery. In this study, we tested plasma extracellular vesicle (EV) miRNAs obtained before the delirium event to find predictive POD biomarkers after spine surgery. We recruited patients who are more than 70 years old and have undergone spine surgery. Finally, POD patients (n = 31) were included, with no-POD patients matched in age, sex, medical history, and type of surgery (n = 31). Peripheral blood was collected from patients in the operating room after the operation was completed. EVs were isolated from plasma, and the 798 miRNA expression level from EVs was measured using a NanoString platform. Sixty-two patients were included in the study; all were Korean, 67.7% were females, and the median age was 75 years. Preoperative medical history was not statistically different between no-POD and POD patients except for hypertension and the American Society of Anesthesiologists physical status. From the miRNA profiling, we identified 142 significantly differentially expressed miRNAs in POD patients compared with no-POD patients, which are associated with psychological/neurological disorders. The top 10 differentially expressed miRNAs including miR-548ar-5p and miR-627-5p were all upregulated in POD patients and the results were validated using qRT-PCR from the independent sets of samples (n = 96). We demonstrated the potential of plasma EV-miRNAs as predictive biomarkers to identify the risk group of POD after spine surgery. It also provides opportunities for future studies investigating the role of EV-miRNAs in delirium pathology.
Growth Differentiation Factor 15 as a Biomarker of Cardiovascular Risk in Chronic Musculoskeletal Pain
Authors: León-González Rocío , Ortolá Rosario , Carballo-Casla Adrián , Sotos-Prieto Mercedes , Buño-Soto Antonio , Rodríguez-Sánchez Isabel , Pastor-Barriuso Roberto , Rodríguez-Artalejo Fernando , García-Esquinas Esther 
Published: July 2024

Abstract

Background
It is unknown whether growth differentiation factor 15 (GDF-15) is associated with chronic musculoskeletal pain (CMP) and whether or not its association with incident cardiovascular disease (CVD) changes according to CMP status.

Methods
In total, 1 957 randomly selected adults aged ≥65 years without prior CVD were followed up between 2015 and 2023. CMP was classified according to its intensity, frequency, and interference with daily activities. The association between GDF-15 levels and CMP was assessed using linear models with progressive inclusion of potential confounders, whereas the association between GDF-15 and CVD risk was evaluated with Cox proportional hazard models with similar adjustment and interaction terms between GDF-15 and CMP. The incremental predictive performance of GDF-15 over standard predictors was evaluated using discrimination and risk reclassification metrics.

Results
GDF-15 concentrations were 6.90% (95% confidence interval [CI]: 2.56; 11.25) higher in individuals with CMP, and up to 8.89% (4.07; 15.71) and 15.79% (8.43; 23.16) higher in those with ≥3 CMP locations and interfering pain. These increased levels were influenced by a higher prevalence of cardiometabolic risk factors, functional impairments, depressive symptoms, and greater levels of inflammation in individuals with CMP. In fully adjusted models, a twofold increase in GDF-15 was associated with a 1.49 increased risk (95% CI: 1.08; 2.05) of a CVD event in individuals with CMP, but not among those without CMP (1.02 [0.77; 1.35]); p-interaction 0.041. Adding GDF-15 to models including the Framingham Risk Score improved predictive performance among individuals with CMP.

Conclusions
We provide evidence that GDF-15 could serve as a biomarker to assess CMP, as well as to predict CVD incidence in individuals with CMP.
Physical Frailty and the Risk of Degenerative Valvular Heart Disease
Authors: Guo Xinli , Li Ziang , Long Tianxin , Cheng Sijing , Yang Cheng , Jiang Chenqing , Ma Haowen , Gao Ruixin , Song Changpeng , Huang Xiaohong , Wu Yongjian 
Published: July 2024

Abstract

Background and Objectives
The relationship between physical frailty, age-related conditions, and the incidence of degenerative valvular heart disease (VHD) remains unclear. This study aimed to investigate the potential association between physical frailty and the development of degenerative VHD.

Research Design and Methods
Participants from the UK Biobank who were initially free of VHD and heart failure were categorized into 3 groups based on the frailty phenotype: non-frailty, pre-frailty, and frailty. The frailty phenotype was determined by evaluating the following 5 components: weight loss, exhaustion, reduced physical activity, slow gait speed, and low grip strength. The incidence of degenerative VHD, including mitral valve regurgitation (MR), aortic valve regurgitation (AR), and aortic valve stenosis (AS), was assessed using hospital admission or death registries.

Results
Among the 331 642 participants, 11 885 (3.6%) exhibited frailty and 143 379 (43.2%) were categorized as pre-frailty. During a median follow-up of 13.8 years, there were 3 684 MR, 1 205 AR, and 3 166 AS events. Compared to non-frailty participants, those with pre-frailty and frailty showed significantly increased risks for MR (hazard ratio [HR], HRpre-frailty:1.19, 95% confidence interval [CI]: 1.11–1.28; HRfrailty: 1.50, 95% CI: 1.30–1.74), AR (HRpre-frailty:1.19, 95% CI: 1.05–1.34; HRfrailty: 1.58, 95% CI: 1.22–2.04), and AS (HRpre-frailty:1.19, 95% CI: 1.11–1.29; HRfrailty: 1.74, 95% CI: 1.51–2.00). Among the 5 components, slow gait speed showed the strongest association with the risk of various types of VHD (HRMR: 1.50, 95% CI: 1.34–1.65; HRAR: 1.50, 95% CI: 1.24–1.80; HRAS: 1.46, 95% CI: 1.32–1.62), followed by exhaustion, low grip strength, and weight loss.

Discussion and Implications
Pre-frailty and frailty were associated with a higher risk of all 3 types of degenerative VHD. Early detection and intervention for pre-frailty and frailty in middle-aged and older individuals may assist in preventing or delaying the onset of degenerative VHD.
Scaling of the geomagnetic secular variation timescale
Authors: Tsang Yue-Kin , Jones Chris A 
Published: July 2024

SUMMARY
The ratio of the magnetic power spectrum and the secular variation spectrum measured at the Earth’s surface provides a timescale $\tau _{\rm sv}(l)$ as a function of spherical harmonic degree l. $\tau _{\rm sv}$ is often assumed to be representative of timescales related to the dynamo inside the outer core and its scaling with l is debated. To assess the validity of this surmise and to study the time variation of the geomagnetic field $\dot{\boldsymbol {B}}$ inside the outer core, we introduce a magnetic timescale spectrum $\tau (l,r)$ that is valid for all radius r above the inner core and reduces to the usual $\tau _{\rm sv}$ at and above the core–mantle boundary (CMB). We study $\tau$ in a numerical geodynamo model. At the CMB, we find that $\tau \sim l^{-1}$ is valid at both the large and small scales, in agreement with previous numerical studies on $\tau _{\rm sv}$. Just below the CMB, the scaling undergoes a sharp transition at small l. Consequently, in the interior of the outer core, $\tau$ exhibits different scaling at the large and small scales, specifically, the scaling of $\tau$ becomes shallower than $l^{-1}$ at small l. We find that this transition at the large scales stems from the fact that the horizontal components of the magnetic field evolve faster than the radial component in the interior. In contrast, the magnetic field at the CMB must match onto a potential field, hence the dynamics of the radial and horizontal magnetic fields are tied together. The upshot is $\tau _{\rm sv}$ becomes unreliable in estimating timescales inside the outer core. Another question concerning $\tau$ is whether an argument based on the frozen-flux hypothesis can be used to explain its scaling. To investigate this, we analyse the induction equation in the spectral space. We find that away from both boundaries, the magnetic diffusion term is negligible in the power spectrum of $\dot{\boldsymbol {B}}$. However, $\dot{\boldsymbol {B}}$ is controlled by the radial derivative in the induction term, thus invalidating the frozen-flux argument. Near the CMB, magnetic diffusion starts to affect $\dot{\boldsymbol {B}}$ rendering the frozen-flux hypothesis inapplicable. We also examine the effects of different velocity boundary conditions and find that the above results apply for both no-slip and stress-free conditions at the CMB.
Enhancing computational efficiency in 3-D seismic modelling with half-precision floating-point numbers based on the curvilinear grid finite-difference method
Authors: Wan Jialiang , Wang Wenqiang , Zhang Zhenguo 
Published: July 2024

SUMMARY
Large-scale and high-resolution seismic modelling are very significant to simulating seismic waves, evaluating earthquake hazards and advancing exploration seismology. However, achieving high-resolution seismic modelling requires substantial computing and storage resources, resulting in a considerable computational cost. To enhance computational efficiency and performance, recent heterogeneous computing platforms, such as Nvidia Graphics Processing Units (GPUs), natively support half-precision floating-point numbers (FP16). FP16 operations can provide faster calculation speed, lower storage requirements and greater performance enhancement over single-precision floating-point numbers (FP32), thus providing significant benefits for seismic modelling. Nevertheless, the inherent limitation of fewer 16-bit representations in FP16 may lead to severe numerical overflow, underflow and floating-point errors during computation. In this study, to ensure stable wave equation solutions and minimize the floating-point errors, we use a scaling strategy to adjust the computation of FP16 arithmetic operations. For optimal GPU floating-point performance, we implement a 2-way single instruction multiple data (SIMD) within the floating-point units (FPUs) of CUDA cores. Moreover, we implement an earthquake simulation solver for FP16 operations based on curvilinear grid finite-difference method (CGFDM) and perform several earthquake simulations. Comparing the results of wavefield data with the standard CGFDM using FP32, the errors introduced by FP16 are minimal, demonstrating excellent consistency with the FP32 results. Performance analysis indicates that FP16 seismic modelling exhibits a remarkable improvement in computational efficiency, achieving a speedup of approximately 1.75 and reducing memory usage by half compared to the FP32 version.
Creation Is Not Like a Box of Chocolates: Why Is the First Judgment Recognizing Copyrightability of AI-Generated Content Wrong?
Authors: Wang Qian 
Published: July 2024

Abstract
The judgment of the Beijing Internet Court recognizing copyrightability of AI-generated images is flawed for three reasons. First, the judgment treats generative AI as a tool of creation akin to a brush, camera or Photoshop. But generative AI is not a passive means for the author to implement the act of creation that directly produce works; instead, it is actively involved in the decision-making process of the substance of the resulting content. Second, the judgment attaches much importance to the creative nature of the text prompts and other inputs of the user of generative AI, while it fails to make the analysis within the framework of the idea/expression dichotomy. Different generative AI systems, and even the same generative AI, may generate completely different images based on exactly the same ‘user’s inputs’. This fact shows that ‘user’s inputs’ are an unprotectable idea in relation to the outcome of the AI production, because a single creative and original idea may lead to a large number of expressions. Third, while acknowledging that the relationship between generative AI and its users is akin to the relationship between the commissioned party and the commissioner during the creation of a painting, the judgment wrongly attributes user’s authorship of AI-generated content to AI’s lack of free will and legal personality.