bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding the Implications of Glucagon-like Peptide-1 Receptor Agonists on Accelerated Facial and Skin Aging
Authors: Ridha Zainab , Fabi Sabrina Guillen , Zubar Raheel , Dayan Steven H 
Published: June 2024

Abstract

Following the advent of glucagon-like peptide-1 receptor agonists (GLP-1RAs), subsequent unintended effects such as accelerated facial aging and altered skin health have been noted. This review delves deeper into the causative underlying mechanisms and provides insights into the intricate relationship between GLP-1RAs, adipose tissue, and premature facial aging, thereby highlighting the need for a nuanced understanding of their effects on facial alterations and skin health. Studies exploring the potential effects of GLP-1RAs on facial alterations and offering insights into the possible underlying mechanisms, causes, and clinical implications were included. The accelerated facial aging and altered skin health observed in GLP-1RA patients appears to be multifactorial, involving loss of dermal and subcutaneous white adipose tissue, and altered proliferation and differentiation of adipose-derived stem cells (ADSCs), and impacts on the production and secretion of hormonal and metabolic factors. These changes compromise the structural integrity and barrier function of the skin and may lead to diminished facial muscle mass, further exacerbating the appearance of aging. The insights presented call for a paradigm shift in the clinical management of facial changes induced by GLP-1RAs, with a focus on treatment strategies aimed at targeting ADSC stimulation. These include autologous fat transfers to reintroduce cells rich in ADSCs for rejuvenation, composite fat grafting combining autologous fat with/without stromal vascular fraction, and the strategic use of soft tissue fillers for volume restoration and biostimulation. This review highlights the potential role of GLP-1RAs in modulating adipose tissue dynamics, thereby contributing to accelerated aging through metabolic, structural, and hormonal pathways.

Level of Evidence: 5
RCSB protein Data Bank: exploring protein 3D similarities via comprehensive structural alignments
Authors: Bittrich Sebastian , Segura Joan , Duarte Jose M , Burley Stephen K , Rose Yana 
Published: June 2024

Abstract

Motivation
Tools for pairwise alignments between 3D structures of proteins are of fundamental importance for structural biology and bioinformatics, enabling visual exploration of evolutionary and functional relationships. However, the absence of a user-friendly, browser-based tool for creating alignments and visualizing them at both 1D sequence and 3D structural levels makes this process unnecessarily cumbersome.

Results
We introduce a novel pairwise structure alignment tool (rcsb.org/alignment) that seamlessly integrates into the RCSB Protein Data Bank (RCSB PDB) research-focused RCSB.org web portal. Our tool and its underlying application programming interface (alignment.rcsb.org) empowers users to align several protein chains with a reference structure by providing access to established alignment algorithms (FATCAT, CE, TM-align, or Smith–Waterman 3D). The user-friendly interface simplifies parameter setup and input selection. Within seconds, our tool enables visualization of results in both sequence (1D) and structural (3D) perspectives through the RCSB PDB RCSB.org Sequence Annotations viewer and Mol* 3D viewer, respectively. Users can effortlessly compare structures deposited in the PDB archive alongside more than a million incorporated Computed Structure Models coming from the ModelArchive and AlphaFold DB. Moreover, this tool can be used to align custom structure data by providing a link/URL or uploading atomic coordinate files directly. Importantly, alignment results can be bookmarked and shared with collaborators. By bridging the gap between 1D sequence and 3D structures of proteins, our tool facilitates deeper understanding of complex evolutionary relationships among proteins through comprehensive sequence and structural analyses.

Availability and implementation
The alignment tool is part of the RCSB PDB research-focused RCSB.org web portal and available at rcsb.org/alignment. Programmatic access is available via alignment.rcsb.org. Frontend code has been published at github.com/rcsb/rcsb-pecos-app. Visualization is powered by the open-source Mol* viewer (github.com/molstar/molstar and github.com/molstar/rcsb-molstar) plus the Sequence Annotations in 3D Viewer (github.com/rcsb/rcsb-saguaro-3d).
Dual-energy computed tomography iodine quantification combined with laboratory data for predicting microvascular invasion in hepatocellular carcinoma: a two-centre study
Authors: Li Huan , Zhang Dai , Pei Jinxia , Hu Jingmei , Li Xiaohu , Liu Bin , Wang Longsheng 
Published: June 2024

Abstract

Objectives
Microvascular invasion (MVI) is a recognized biomarker associated with poorer prognosis in patients with hepatocellular carcinoma. Dual-energy computed tomography (DECT) is a highly sensitive technique that can determine the iodine concentration (IC) in tumour and provide an indirect evaluation of internal microcirculatory perfusion. This study aimed to assess whether the combination of DECT with laboratory data can improve preoperative MVI prediction.

Methods
This retrospective study enrolled 119 patients who underwent DECT liver angiography at 2 medical centres preoperatively. To compare DECT parameters and laboratory findings between MVI-negative and MVI-positive groups, Mann-Whitney U test was used. Additionally, principal component analysis (PCA) was conducted to determine fundamental components. Mann-Whitney U test was applied to determine whether the principal component (PC) scores varied across MVI groups. Finally, a general linear classifier was used to assess the classification ability of each PC score.

Results
Significant differences were noted (P &lt; .05) in alpha-fetoprotein (AFP) level, normalized arterial phase IC, and normalized portal phase IC between the MVI groups in the primary and validation datasets. The PC1-PC4 accounted for 67.9% of the variance in the primary dataset, with loadings of 24.1%, 16%, 15.4%, and 12.4%, respectively. In both primary and validation datasets, PC3 and PC4 were significantly different across MVI groups, with area under the curve values of 0.8410 and 0.8373, respectively.

Conclusions
The recombination of DECT IC and laboratory features based on varying factor loadings can well predict MVI preoperatively.

Advances in knowledge
Utilizing PCA, the amalgamation of DECT IC and laboratory features, considering diverse factor loadings, showed substantial promise in accurately classifying MVI. There have been limited endeavours to establish such a combination, offering a novel paradigm for comprehending data in related research endeavours.
Universal Targeted Haplotyping by Droplet Digital PCR Sequencing and Its Applications in Noninvasive Prenatal Testing and Pharmacogenetics Analysis
Authors: Gai Wanxia , Wang Guangya , Lam W K Jacky , Yuen Liz Y P , Jiang Peiyong , Yu Stephanie C Y , Leung Tak Y , Lau So Ling , Lo Y M Dennis , Chan K C Allen 
Published: June 2024

Abstract

Background
The analysis of haplotypes of variants is important for pharmacogenomics analysis and noninvasive prenatal testing for monogenic diseases. However, there is a lack of robust methods for targeted haplotyping.

Methods
We developed digital PCR haplotype sequencing (dHapSeq) for targeted haplotyping of variants, which is a method that compartmentalizes long DNA molecules into droplets. Within one droplet, 2 target regions are PCR amplified from one template molecule, and their amplicons are fused together. The fused products are then sequenced to determine the phase relationship of the single nucleotide polymorphism (SNP) alleles. The entire haplotype of 10s of SNPs can be deduced after the phase relationship of individual SNPs are determined in a pairwise manner. We applied dHapSeq to noninvasive prenatal testing in 4 families at risk for thalassemia and utilized it to detect NUDT15 diplotypes for predicting drug tolerance in pediatric acute lymphoblastic leukemia (72 cases and 506 controls).

Results
For SNPs within 40 kb, phase relation can be determined with 100% accuracy. In 7 trio families, the haplotyping results for 97 SNPs spanning 185 kb determined by dHapSeq were concordant with the results deduced from the genotypes of both parents and the fetus. In 4 thalassemia families, a 19.3-kb Southeast Asian deletion was successfully phased with 97 downstream SNPs, enabling noninvasive determination of fetal inheritance using relative haplotype dosage analysis. In the NUDT15 analysis, the variant status and phase of the variants were successfully determined in all cases and controls.

Conclusions
The dHapSeq represents a robust and scalable haplotyping approach with numerous clinical and research applications.
Genetic variants associated with cardiorespiratory symptoms of long COVID. The GINA-COVID study
Authors: Polo-Alonso S , Camps-Vilaro A , Degano I R , Marti-Lluch R , Pinsach-Abuin M , Selga E , Puigdecanet E , Pedrerol-Alvarez M , Puigmule M , Perez A , Subirana I , Elosua R , Brugada R , Ramos R , Marrugat J 
Published: June 2024

Abstract

Introduction
SARS-CoV-2 infection can cause persistent symptoms, which are known as long COVID (LC). The WHO defines this condition as the presence of any symptom after the viral infection that persist for at least 3 months. Its incidence is estimated to be between 10% and 70% of all COVID cases, and include a wide range of symptoms. Some of them are related with the cardiorespiratory (CR) systems. The identification of the genetic variants related to the CR symptoms of LC could enhance the prevention of these symptoms after the viral infection.

Purpose
To evaluate the association between genetic variants and CR symptoms of LC.

Methods
We conducted a case-control study that involved 2,422 patients infected with SARS-CoV-2 from Catalan primary care and hospitals. Follow-up for a minimum of 1 year was performed, spontaneously declared symptoms and duration were recorded. Then, we considered LC CR cases the occurrence at least one of the following CR symptoms (dyspnea, polypnea, fatigue, chest pain, heart palpitations or cough) 3 months or more after infection (WHO definition). Controls were COVID-19 participants without any CR symptom in that period. Individuals were genotyped by the Axiom Spanish Biobank Array, with 757,836 markers that include rare and low-frequency Spanish variants. Genome-wide association study was performed by fitting a logistic regression adjusting for age, sex and the first 10 principal components. P-value significance threshold was established at 5x10-8.

Results
Following the quality control process for genotyping, a total of 2,147 participants were considered, with cases comprising 41.43% of the sample. Cases and controls characteristics are shown in Table 1. Cases were younger, predominantly female, and of American descent compared to controls. The prevalence of smoking, hypertension and history of coronary artery disease was lower in cases than in controls, as well as the risk of coronary artery disease. Upon genotyping, no significant associations between LC CR symptoms and genetic variants were obtained in the association study (Figure 1).

Conclusions
LC cases with CR symptoms exhibit a more favourable cardiovascular risk profile compared to controls. Nevertheless, there is no significant association observed between genetic variants and the CR symptoms of LC.
Screening for arrhythmogenic heart disease in school age children-a pilot study
Authors: Bagkaki A , Parthenakis F , Chlouverakis G , Anastasakis A , Papagiannis I , Germanakis I 
Published: June 2024

Abstract

Introduction
There is a relative lack of data regarding efficacy of cardiovascular (CV) screening programs including ECG when applied in young children, for early detection of unrecognized genetic conditions associated with high risk for sudden cardiac death (SCD).

Purpose
We evaluated the performance of a CV screening program, including 12-lead ECG recording, when applied in selected populations of Mediterranean children.

Methods
A CV screening program for primary schools, approved by Ministry of Health, was applied in a sample of primary schools of a Mediterranean island, in geographical isolated areas with reported increased SCD incidence. Participation was voluntary following parental consent. After completion of a standardized history questionnaire by parents, children underwent clinical evaluation and 12-lead ECG recording, at local health stations. A stepwise referral pattern was established, including pediatric cardiology evaluation and molecular DNA confirmatory testing, whenever the possibility of inherited arrhythmogenic CV disease was increased.

Results
929 primary school children, (462 male, 467 female), median age 8,5 (range 5,5 -11,5 yrs) have been evaluated during eight years (2014-22). 52 children (5,6%) had an indication for further diagnostic or lifestyle modification for CV risk factors, including ECG abnormalities (n=16, 1.7%), abnormal heart auscultation (n=21, 2.2%), hypertension (n=10, 1%) and positive 1st degree family history of SCD (n= 5, 0.5%).
ECG abnormalities included WPW (n=1, 0.1%), VES (n=4, 0.4%), probable LVH (n=2), abnormal QRS axis (n=7 ) and QTc prolongation (n=2, 0.2%) both boys, with QTc 475 and QTc 490. Children with ECG abnormalities underwent further evaluation including ambulatory ECG monitoring and regular follow up. Family ECG screening was positive in one child with prolonged QTc (490ms, wide T wave), regarding his father (QTc=460) and one sister (QTc=490). Further molecular DNA testing was negative in the first child, while it revealed a novel KCNH2 heterozygous mutation (NP_000229.1:p.Ser606Tyr) in child and affected family members in the second case. In silico analysis using Polyphen-2 and SIFT suggested that the Ser606Tyr mutation might be harmful, and the family was advised to receive b-blocker prophylactic treatment.

Conclusions
A stepwise approach from ECG population screening to molecular diagnostics can detect and genetically characterize subclinical cases of inherited CV disease, associated with arrhythmogenic SCD also in pediatrics. Larger scale studies are needed to define the cost-effectiveness of a structured CV disease screening including ECG in school age children.
Comparison of peripheral muscle strength, functional capacity and activities of daily living in frail and non-frail adult individuals with congenital heart disease
Authors: Topcuoglu C , Vardar Yagli N , Ertugrul I , Aykan H , Karagoz T , Saglam M 
Published: June 2024

Abstract

Background/Introduction
Frailty is associated with a higher incidence of cardiovascular disease and risks of all-cause mortality, leading to a reduction in life expectancy. Cardiorespiratory fitness and peripheral muscle strength are shown to be the strongest predictors of the level of frailty and the potential for frailty to decrease over time.

Purpose
The aim of this study was to compare peripheral muscle strength, functional capacity and activities of daily living in frail and non-frail adult individuals with congenital heart disease (ACHD).

Methods
A cross-sectional study design was used. A total of 36 individuals with ACHD, 14 frail (24.50±10.14 years) and 22 non-frail (24.68±6.24 years) were included in the study. Frailty; according to the Fried criteria, which consist of parameters as muscle strength weakness, involuntary weight loss, decreased physical activity, decreased mobility, and fatigue. Peripheral muscle strength was assessed using a digital dynamometer, functional capacity using the Six Minute Walk Test (6MWT) and activities of daily living using the Glittre Activities of Daily Living Test.

Results
Knee extensor muscle strength (p=0.011), shoulder abduction muscle strength (p=0.012) and 6MWT distance (p=0.007) in frail individuals with ACHD was lower than non-frail individuals. Glittre Activities of Daily Living Test duration was higher in frail individuals with ACHD than in non-frail individuals (p=0.023).

Conclusion(s)
Upper and lower peripheral muscle strength, functional capacity and activities of daily living were impaired in individuals with frail ACHD. Early assessment of frailty in individuals with ACHD and implementation of individualized exercise training programs in frail individuals may be useful in reducing the impact associated with frailty.
Cognitive impairment is associated with lower physical function in patients with heart failure
Authors: Klompstra L , Papageorgiou J M , Jaarsma T , Stromberg A 
Published: June 2024

Abstract

Introduction
Cognitive impairment is a common and serious comorbidity in patients with heart failure (HF) and its prevalence follows the severity of the condition. Preventing deterioration in patients with heart failure is key to improve outcomes. Cognitive impairment might be correlated to physical function.

Purpose
To assess cognitive impairment in patients with HF and exploring its potential association with physical function.

Methods
Data was collected in 246 patients with HF (mean age 68±10, 28% female). Cognition was measured with the Montreal Cognitive Assessment (MoCA). Physical function was measured with an activity monitor – Actigraph (minutes/day spent in sedentary time, light physical activity and moderate to vigorous physical activity (MVPA) as well as steps daily), exercise capacity (6-minute walk test), self-selected walking speed (gait speed for 10 meters in seconds) and the dynamic balance/mobility (Sit-to-stand test: number in 30 seconds). Difference in physical function between patients who have mild to moderate cognitive impairment (MoCA cut off value 26) were compared to patients who had no to light cognitive impairment (MoCA Cut off value ³27) with Mann-Whitney U tests.

Results
A total of 246 patients with HF were evaluated, 171 patients (70%) had mild cognitive impairment and 3 patients (1%) had moderate cognitive impairment. Patients with mild or moderate cognitive impairment, were older (mean 69 vs. 63 years old, p-value&lt;.001) and with diverse comorbidities, as they suffered more often from COPD (18% vs 7%, p-value=0.015) and stroke (15% vs. 6%, p-value 0.028) compared to patients with no to light cognitive impairment. Patients with mild or moderate cognitive impairment spent more time sedentary (median 562 vs. 530 min/day, p-value=0.029), less time in MVPA (median 10 vs. 21 min/day, p-value=0.003) compared to patients with no to light cognitive impairment and walked less steps a day (median 3884 vs. 5206, p-value=0.002). No differences were found in spent time in light physical activity (206 vs 226 min/day p-value=0.65). Patients with mild or moderate cognitive impairment walked a lower number of meters on the 6MWT (median 438 vs. 528 meters, p-value=&lt;.001), were slower on gait speed (median 6 vs. 5 seconds, p-value&lt;.001) and on the sit-to-stand test (median 11 vs. 9 times, p-value&lt;.001) compared to patients with no to light cognitive impairment.

Conclusion
71% of patients with heart failure had mild or moderate cognitive impairment, which was negative associated with physical function. Screening for cognitive impairment together with physical function may decrease adverse events by identifying those who need tailored care.
Is GRACE 2.0 a better predictor of post-MI mortality than GRACE in patients with known diabetes compared to those without?
Authors: Soman B , Chrysostomou P , Chatterjee T , De Silva R , Sathyapalan T , Chattopadhyay S 
Published: June 2024

Abstract

Purpose
To explore whether there is any difference in the predictive ability of GRACE 2.0 in determining post-MI mortality at 6 months after discharge in patients with and without diabetes.

Methods
A large dataset of patients admitted to a medium sized district general hospital in UK collected over 6 years for submission to the Myocardial Infarction National Audit Project (MINAP) was analysed. This is a validated dataset with high case ascertainment. GRACE and GRACE 2.0 scores and probabilities for death at 6 months were computed using web-based calculators. Diabetes status was recorded from the patient’s history, drug chart and individual case note review. The mortality data was obtained from hospital and general practice records. The patients were censored at the last recorded contact with a health professional after discharge. GRACE 2.0 model discrimination was assessed by comparing the area under the receiver operating curve (AUC) in patients with and without diabetes using the DeLong method. GRACE 2.0 model calibration was assessed graphically by comparing the observed % and the mean predicted % of mortality in each decile of the GRACE score.

Results
2838 patients were entered into the database over the 6-year period. Complete data was available for 2784 patients. 783 patients had known diabetes. Death within 6 months of admission occurred in 242 patients (89(11.4%) with and 153(7.6%) without diabetes). GRACE was worse at predicting mortality in patients with (AUC 0.746, 95% CI 0.714 to 0.776) than without (AUC 0.814 95% CI 0.796 to 0.831) diabetes (δAUC 0.0679, p=0.0323). GRACE 2.0 had similar results (AUC 0.753 95% CI 0.721 to 0.783 with diabetes and AUC 0.817 95% CI 0.799 to 0.833 without diabetes; δAUC 0.0634, p=0.0450) (Fig 1 Upper panel). Predictive efficacy of GRACE 2.0 for mortality was similar to GRACE in both patients with and without diabetes. Calibration curves show that the mortality predicted by GRACE 2.0 was consistently higher than the observed mortality especially in diabetic patients suggesting that the it overestimated risk in this group (Fig 1 Lower panel).

Conclusion
GRACE 2.0 is worse in predicting mortality in patients with diabetes than in those without. There is no difference in the predictive ability of GRACE 2.0 versus GRACE in patients with diabetes. GRACE 2.0 seems it overestimates risk in both groups.