bluuebunny/crossref_metadata_2025_split huggingface dataset:
An energy and information analysis method of logic gates based on stochastic thermodynamics
Authors: Ge Xiaohu , Ruan Muyao , Peng Xiaoxuan , Xiao Yong , Yang Yang 
Published: August 2024

Abstract
To reduce the energy consumption of logic gates in digital circuits, the size of transistors approaches the mesoscopic scale, e.g. sub-7 nanometers. However, existing energy consumption analysis methods exhibit various deviation for logic gates when the nonequilibrium information processing of mesoscopic scale transistors with ultra-low voltages is analyzed. Based on the stochastic thermodynamics theory, an information energy ratio method is proposed for the energy consumption estimation of XOR gates composed of mesoscopic scale transistors. The proposed method provides a new insight to quantify the transformation between the information capacity and energy consumption for XOR gates and extending to other logic gates. Utilizing the proposed analysis method, the supply voltage of the parity check circuit can be optimized by numerical simulations without expensive and complex practical measurements. The information energy ratio is the first analytical method to quantify the energy and information transformation of logic gates at the mesoscopic scale.
The impact of immunity on the risk of coronary artery disease: insights from a multiomics study
Authors: Bian Rutao , Li Dongyu , Xu Xuegong , Zhang Li 
Published: August 2024

Abstract

Background
Immune inflammation is intricately associated with coronary artery disease (CAD) progression, necessitating the pursuit of more efficacious therapeutic strategies. This study aimed to uncover potential therapeutic targets for CAD and myocardial infarction (MI) by elucidating the causal connection between regulatory immune-related genes (RIRGs) and these disorders.

Methodology
We performed summary data-based Mendelian randomization analysis to assess the therapeutic targets linked to expression quantitative trait loci and methylation quantitative trait loci of RIRGs in relation to CAD and MI. Independent validation cohorts and datasets from coronary artery and left ventricular heart tissue were analyzed. To strengthen causal inference, colocalization analysis and PhenoScanner phenotype scans were employed.

Results
Utilizing multiomics integration, we pinpointed EIF2B2, FCHO1, and DDT as CAD risk genes. Notably, EIF2B2 and FCHO1 displayed significant associations with MI. High EIF2B2 expression, regulated by cg16144293, heightened CAD and MI risk at rs175438. In contrast, enhanced FCHO1 expression, modulated by cg18329931, reduced CAD and MI risk at rs13382133. DDT upregulation influenced by cg11060661 and cg09664220 was associated with decreased CAD risk at rs5760120. Colocalization analysis firmly established these relationships.

Conclusion
EIF2B2, FCHO1, and DDT represent risk loci for CAD progression within RIRGs. Our identification of these genes enhances understanding of CAD pathogenesis and directs future drug development efforts.
Maternal Health Disparities in Acute Care Rehabilitation
Authors: Segraves Rebeca , Segraves Jenna , Parr Rebecca , Samel Erin , Smith-Aldrick Vivian 
Published: August 2024

Abstract
Patients with a high-risk pregnancy or who immediately give birth are often not provided access to acute care occupational and physical therapy during their hospital admission. The greatest potential for health care crises, including maternal mortality, occurs during the first 6 weeks after birth. Maternal mortality and morbidity, which continue to rise in the United States, are considered indicators of the overall population health of a country. It is estimated that over 80% of pregnancy-related deaths are preventable. The leading causes of death within the first 6 weeks after birth are hemorrhage, hypertensive disorders, and infection. Implicit biases about childbearing individuals who are perceived to be relatively young, independent, active, and healthy may unintentionally contribute to areas of substandard care that adversely impact maternal health outcomes. It is a professional and ethical imperative that health providers, including occupational and physical therapists, establish themselves as allies to patient groups at high risk for disparate treatment. The Acute Care OB Rehab Implicit Bias Self-Reflection Tool is an instrument designed for health providers to identify stereotypes that may contribute to inequitable access to rehabilitation in the hospital after birth. Including rehabilitation services for the perinatal population in the hospital setting can play a pivotal role in early detection of adverse events with activity that may directly impact the increasing maternal mortality rate in the United States.
Progressive improvement in time to diagnosis in axial spondyloarthritis through an integrated referral and education system
Authors: Chan Antoni , Rigler Kathryn , Ahmad Nadia , Lafont Tanguy 
Published: August 2024

Abstract

Objectives
To assess the delay in the diagnosis of axial SpA (axSpA) in a real-world cohort over a 16-year period and to evaluate factors associated with this delay. We implemented a service improvement project and evaluated its effectiveness in improving time to diagnosis of axSpA.

Methods
A cohort of axSpA patients newly diagnosed between January 2008 and December 2023 were studied. Surveys were carried out in 2013, 2017, 2019 and 2023 to assess time to diagnosis, which was divided into four periods from onset of inflammatory back pain to year of axSpA diagnosis. The time to diagnosis over the study period was analysed using a statistical process control chart.

Results
Over the study period, 988 referrals were received and 366 (37%) had axSpA. There was a progressive increase in the number of females with axSpA. The mean time to diagnosis significantly decreased from 9.8 years (s.d. 1.2) in 2008 to 1.0 years (s.d. 1.0) in 2023. The greatest delay was from the onset of back pain to first seeing their general practitioners (GPs; mean 3.2 years). There was a significant improvement in the mean time to diagnosis across the time periods through the service improvement interventions.

Conclusion
Structural and organizational change in triage, referral and clinic pathways has led to earlier recognition of axSpA. This is further enhanced through an integrated education program and awareness campaign for the public, GPs and healthcare professionals, including physiotherapists. With continuous quality improvement cycles, we achieved our aim of reducing the mean time to diagnosis to 1 year.
Balancing functions of antifouling, nitric oxide release and vascular cell selectivity for enhanced endothelialization of assembled multilayers
Authors: Zhang Sulei , Sun Jun , Guo Shuaihang , Wang Yichen , Zhang Yuheng , Lei Jiao , Liu Xiaoli , Chen Hong 
Published: August 2024

Abstract
Surface endothelialization is a promising way to improve the hemocompatibility of biomaterials. However, current surface endothelialization strategies have limitations. For example, various surface functions are not well balanced, leading to undesirable results, especially when multiple functional components are introduced. In this work, a multifunctional surface was constructed by balancing the functions of antifouling, nitric oxide (NO) release and endothelial cell promotion via layer-by-layer (LBL) self-assembly. Poly(sodium p-styrenesulfonate-co-oligo(ethylene glycol) methacrylate) (negatively charged) and polyethyleneimine (positively charged) were deposited on silicon substrates to construct multilayers by LBL self-assembly. Then, organic selenium, which has a NO-releasing function, and the cell-adhesive peptide Gly-Arg-Glu-Asp-Val-Tyr, which selectively promotes endothelial cells, were introduced on the assembled multilayers. Poly(oligo(ethylene glycol) methacrylate) is a hydrophilic component for antifouling properties, and poly(sodium p-styrenesulfonate) is a heparin analog that provides negative charges. By modulating the contents of poly(oligo(ethylene glycol) methacrylate) and poly(sodium p-styrenesulfonate) in the copolymers, the NO release rates catalyzed by the modified surfaces were regulated. Moreover, the behaviors of endothelial cells and smooth muscle cells on modified surfaces were well controlled. The optimized surface strongly promoted endothelial cells and inhibited smooth muscle cells to achieve endothelialization effectively.
Rapid fabrication of biomimetic PLGA microsphere incorporated with natural porcine dermal aECM for bone regeneration
Authors: Zhou Xiaosong , Guo Min , Wang Zongliang , Wang Yu , Zhang Peibiao 
Published: August 2024

Abstract
Bioactive microspheres coated with acellular extracellular matrix (aECM) have received extensive attention in bone tissue engineering. In this work, biomimetic microspheres with different aECM ratios, uniform size and controllable size were prepared easily by blending natural porcine dermal aECM and poly (lactic-co-glycolic acid) (PLGA) using electrohydrodynamic spraying and solidification actuated by solvent extraction method. In this work, the appropriate polymer concentration and preparation voltage were investigated, and the surface morphology of the microspheres was observed by scanning electron microscope. Sirius red was used to visualize aECM exposure on the surface of the microspheres. The in vitro and in vivo experiments were carried out to evaluate the bioactivity and osteogenic properties of the microspheres. The results showed that the morphology and size of PLGA microspheres had little influence on the aECM blending. In vitro experiments showed that the higher the content of aECM, the better the cell adhesion performance. In vivo, rat calvarial defect models were observed and characterized at 4 and 8 weeks postoperatively, and the values of BV/TV of 50aECM/PLGA were 47.57 ± 1.14% and 72.92 ± 2.19%, respectively. The results showed that the skull healing effect was better in aECM-containing microspheres. In conclusion, aECM/PLGA composite microspheres can increase cell adhesion performance through the addition of aECM. Moreover, in vivo experiments have proved that aECM/PLGA microspheres are beneficial to bone repair, which means the aECM/PLGA microspheres are a promising bone tissue engineering material.
Constructing a highly efficient multifunctional carbon quantum dot platform for the treatment of infectious wounds
Authors: Zhang Hangzhen , Bai Jiafan , Chen Xiangli , Wang Linyu , Peng Wenzhen , Zhao Yuancong , Weng Jie , Zhi Wei , Wang Jianxin , Zhang Kai , Zhang Xingdong 
Published: August 2024

Abstract
Antibiotic resistance poses a huge threat to public health, which has increased the difficulty and transmission of disease treatment, as well as the burden and cost of medical institutions. In response to the current problems and challenges in inflammation control and treatment of bacterial infected wounds, inspired by antibacterial mechanisms based on active elements such as N, S, Cu and tannic acid (TA), a highly efficient multifunctional carbon quantum dot platform was proposed in this study and constructed through their special assembly in a solvothermal reaction system for the treatment of infected wounds. By introducing active elements such as N, S and Cu, this carbon quantum dot platform is endowed with antibacterial properties, while also achieving good angiogenesis promoting performance through the use of ion Cu. Meanwhile, the good antioxidant activity of TA (one of the precursors used) enables this platform to have better immunomodulatory performance in vivo. The research results on the treatment of bacterial infection models indicate that the multifunctional carbon quantum dots obtained can accelerate the healing of infected wounds by inhibiting bacterial infection, regulating immunoreaction, accelerating collagen deposition and promoting angiogenesis. This multifunctional carbon quantum dot platform shows good clinical application prospects in treating bacterial infected wounds. Additionally, the fluorescence characteristics of such carbon dots can be expected to realize visual therapy in the future.
Serine protease inhibitor E2 protects against cartilage tissue destruction and inflammation in osteoarthritis by targeting NF-κB signalling
Authors: Wang Linzhu , Chen Shuangshuang , Zhang Huizhen , Wei Guozhao , Ma Fenghua , Zhang Mingxiu , Zhang Boyang , Yang Sen , Cheng Hongyi , Yang Ruonan , Wang Ruifeng , Liu Mengyuan , Song Yang , Li Xuelian , E Xiaoqiang 
Published: August 2024

Abstract

Objective
OA is a chronic disease characterized by cartilage degeneration and inflammation, with no approved disease-modifying drugs. This study aimed to identify pathogenic genes and elucidate their mechanism in OA.

Methods
We systematically identified pathogenic genes combined sing-cell and bulk transcriptome profiles of cartilage tissues in OA. Adenovirus carrying the serpin peptidase inhibitor clade E member 2 (serpinE2) or exogenous serpinE2 was injected into monosodium iodoacetate (MIA)-induced OA-model rats. Histological analysis, immunohistochemistry and Alcian blue staining were performed. In vitro, immunofluorescence, quantitative real-time PCR (RT-qPCR), ELISA and western blot assays were performed.

Results
serpinE2 exhibited elevated expression and hypomethylation, showing a positive association with collagen pathway activities in patients with OA. Silencing serpinE2 aggravated MIA-induced knee cartilage degeneration in OA-model rats. Conversely, the intra-articular injection of exogenous serpinE2 ameliorated articular cartilage degeneration, reduced pain-related behavioural responses and relieve synovitis in MIA-induced OA-model rats. Exogenous serpinE2 not only attenuated the elevation of NLRP3, IL-1β and caspase1 expression levels but also restored the reduction in cell viability induced by lipopolysaccharide (LPS) in chondrocytes. Mechanistically, we found that exogenous serpinE2 inhibited LPS-induced reactive oxygen species (ROS) release and NF-κB signalling activation.

Conclusions
serpinE2 plays a protective role in cartilage and synovium tissues, suggesting that serpinE2 gene transfer or molecules that upregulate serpinE2 expression could be therapeutic candidates for OA.
The use of intravenous methylprednisolone in giant cell arteritis: a population-based study
Authors: Henningson Hampus , Hammar Björn , Mohammad Aladdin J 
Published: August 2024

Abstract

Objectives
To determine clinical characteristics, outcome and occurrence of comorbidities in patients with biopsy-confirmed giant cell arteritis (GCA) treated with intravenous methylprednisolone (IVMP) vs those receiving oral glucocorticoids (OGC) only.

Methods
A retrospective study included patients with GCA diagnosed from 2004 through 2019. Clinical and laboratory characteristics, and cumulative GC dose were compared in patients receiving IVMP vs OGCs. Changes in visual acuity (VA), occurrence of comorbidities after GCA diagnosis, and mortality were analysed.

Results
A total of 419 patients (69% female) were included. In total, 111 patients were initially treated with IVMP, 104 (94%) of whom showed visual manifestations at onset and 308 received OGCs only. Ninety patients (21.5%) exhibited visual involvement at onset, verified by an ophthalmologist. Compared with OGC, patients receiving IVMP exhibited lower inflammatory response at presentation. There was a tendency for improvement in VA with the use of IVMP, but the results were not statistically significant (OR 1.19, 95% CI 0.35–4.01). Patients treated with IVMP had a higher risk of newly diagnosed diabetes mellitus within a year of GCA diagnosis (OR 2.59, 95% CI 1.19–5.63). This risk remained elevated after adjusting for cumulative OGC dose at three months (adjusted OR 3.30, 95% CI 1.29–8.43). There was no difference in survival between treatment groups.

Conclusions
Our study found no evidence supporting any benefit of using IVMP in improving VA or survival. IVMP may increase diabetes risk within a year of GCA diagnosis. Further studies are needed to evaluate the value of IVMP in GCA.
What Lies Beneath: Critical Contexts in Medical Education Research
Authors: Colbert-Getz Jorie M. , Ryan Michael S. , Ortega Pilar 
Published: August 2024

Abstract
Medical education is a complex field involving interacting contexts of settings, individuals, and institutional culture. Understanding how contexts interact is important for the applicability of research findings. In this article, the authors describe contexts highlighted in this year’s Research in Medical Education articles related to being and belonging, the definition of medical education, assessment and feedback, and learning and climate. The authors summarize the various contexts and examine implications for the medical education research community.
Incidence of liver complications with hemochromatosis-associated HFE p.C282Y homozygosity: The role of central adiposity
Authors: Lucas Mitchell R. , Pilling Luke C. , Atkins Janice L. , Melzer David 
Published: August 2024

Background and Aims:
The HFE p.C282Y+/+ (homozygous) genotype and central adiposity both increase liver disease and diabetes risks, but the combined effects are unclear. We estimated waist-to-hip ratio (WHR) associations with incident clinical outcomes in routine care in p.C282Y+/+ participants in the UK Biobank community cohort.

Approach and Results:
Baseline WHR data available in 1297 male and 1602 female p.C282Y+/+ with 13.3-year mean follow-up for diagnoses. Spline regressions and Cox proportional hazard models were adjusted for age and genetic principal components. Cumulative incidence was from age 40 to 80 years. In p.C282Y+/+ males, there were positive linear WHR relationships for hospital inpatient–diagnosed liver fibrosis/cirrhosis (p = 2.4 × 10−5), liver cancer (p = 0.007), non-alcoholic fatty liver disease (p = 7.7 × 10−11), and type 2 diabetes (p = 5.1 × 10−16). The hazard ratio for high WHR in p.C282Y+/+ males (≥0.96; 33.9%) was 4.13 for liver fibrosis/cirrhosis (95% CI: 2.04–8.39, p = 8.4 × 10−5 vs. normal WHR); cumulative age 80 incidence 15.0% (95% CI: 9.8%–22.6%) versus 3.9% (95% CI: 1.9%–7.6%); for liver cancer, cumulative incidence was 9.2% (95% CI: 5.7%–14.6%) versus 3.6% (95% CI: 1.9%–6.6%). Hemochromatosis was diagnosed in 23 (96%) of the 24 high WHR p.C282Y+/+ males with incident fibrosis/cirrhosis. High WHR (≥0.85; 30.0%) p.C282Y+/+ females had raised hazards for liver fibrosis/cirrhosis (hazard ratio = 9.17, 95% CI: 2.51–33.50, p = 3.8 × 10−7) and Non-alcoholic fatty liver disease (hazard ratio = 5.17, 95% CI: 2.48–10.78, p = 1.2 × 10−5). Fibrosis/cirrhosis associations were similar in the subset with additional primary care diagnoses.

Conclusions:
In p.C282Y+/+ males and females, increasing WHR is associated with substantially higher risks of liver complications. Interventions to reduce central adiposity to improve these outcomes should be tested.
A Novel Symptomatic Lecithin-Cholesterol Acyltransferase Gene Mutation With Corneal Amyloidosis
Authors: Abu Dail Yaser , Flockerzi Elias , Flockerzi Fidelis , Matthaei Mario , Cursiefen Claus , Seitz Berthold 
Published: August 2024

Purpose:
To present ocular clinical, histological, systemic, and genetic findings of a patient with familial lecithin-cholesterol acyltransferase (LCAT) deficiency caused by a novel genetic variant of the LCAT gene associated with secondary corneal amyloidosis.

Methods:
Case report.

Results:
A 74-year-old woman presented with decreased visual acuity (VA), sensitivity to light, and progressive whitening of both corneas for approximately 20 years. The patient had undergone penetrating keratoplasty (PKP) on the right eye 6 years ago. Ophthalmologic examination revealed decreased VA in both eyes (OD: 0.05, OS: 0.3), and even further reduced glare VA (OD: 0.05, OS: 0.1), diffuse whitish corneal opacity involving the total thickness of the corneal stroma without crystalline deposits, and a marked peripheral diffuse arcus. Systemic examination revealed severely reduced plasma high-density lipoprotein cholesterol levels, target cells in blood smear, and chronic normochromic anemia. Clinically, LCAT deficiency was the most likely diagnosis. Further genetic analysis confirmed the diagnosis. The patient is homozygous for the novel variant c.943T>C (p.Trp315Arg) in the LCAT gene. Histologic examination of the cornea removed during the first keratoplasty revealed amyloid deposits. The cornea removed at the second keratoplasty had small vacuoles in the anterior stroma, indicating recurrence of lipid deposition.

Conclusions:
LCAT deficiency is a rare genetic disorder that can cause corneal opacities because of lipid deposition in the cornea. Systemic manifestations may help in the differential diagnosis to other diseases associated with severe high-density lipoprotein cholesterol reduction. Genetic analysis is employed to confirm the diagnosis. Some mutations in the LCAT gene seem to be associated with secondary corneal amyloidosis. Further investigation of this association is warranted. A recurrence of corneal opacity after PKP seems to occur mainly in the anterior corneal stroma.
Corneal Sensitivity and Neuropathy in Patients With Ocular Graft-Versus-Host Disease
Authors: Surico Pier Luigi , Yavuz Saricay Leyla , Singh Rohan Bir , Kahale Francesca , Romano Francesco , Dana Reza 
Published: August 2024

Purpose:
To assess corneal sensitivity changes in patients with ocular graft-versus-host disease using a non-contact and Cochet–Bonnet esthesiometer. In addition, we evaluate the association between corneal sensitivity and subbasal nerve changes and epitheliopathy in these patients.

Methods:
In this retrospective study, the clinical data and images were evaluated for 36 patients (19 female, 17 male) who fulfilled the inclusion criteria. The analyzed data included demographic and ocular surface parameters, including best-corrected visual acuity, corneal sensitivity with non-contact (mbar) and Cochet–Bonnet (cm) esthesiometer, corneal fluorescein staining (CFS) and symptoms scores, tear volume (Schirmer-I test, mm/5′), and subbasal nerve density (μm/mm2; assessed with in vivo confocal microscopy).

Results:
The mean age of the study cohort was 59.9 ± 10.5 years. The mean corneal sensitivity assessed by Cochet–Bonnet and non-contact esthesiometer was 5.9 ± 0.3 cm and 7.3 ± 2.0 mbar, respectively. The ocular surface parameters included a corneal fluorescein staining (CFS) score, as per the National Eye Institute grading scheme, of 6.9 ± 3.5, and a Schirmer-I test result of 7.5 ± 6.2 mm/5 minutes.. Total corneal subbasal nerve density was inversely associated with CFS scores (r = −0.74; P < 0.001). Moreover, similar correlations between CFS scores and main trunk (r = −0.62; P < 0.001) and branch (r = −0.59; P < 0.001) nerve densities were observed. A significant correlation was found between reduced corneal sensitivity and higher CFS scores (r = 0.66; P < 0.001). Higher pressures were correlated with lower total (r = −0.83; P < 0.001), main trunk (r = −0.62; P < 0.001), and branch (r = −0.72; P < 0.001) nerve densities. The univariate analysis showed that corneal sensitivity loss (assessed with non-contact esthesiometer) was correlated with advanced age of the patients (P = 0.049) and inversely associated with total (P < 0.001), main trunk (P < 0.001), and branch (P < 0.001) nerve densities. In addition, sensitivity loss was inversely associated with punctal occlusion (cauterization (P = 0.001) or plug placement (P < 0.001). The multivariate analysis adjusted for age and punctal occlusion confirmed the associations in the univariate analysis.

Conclusions:
In this study, we observed that corneal sensitivity loss was associated with reduced main trunk, branch, and total nerve density in patients with ocular graft-versus-host disease. In addition, a significant correlation was observed between reduced corneal nerve density, corneal sensitivity, and severity of epitheliopathy.