bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pitfalls for the non-invasive diagnosis of wild-type transthyretin amyloid cardiomyopathy in a young adult: a case report
Authors: Chang Hao-Chih , Kuo Ling , Chung Fa-Po , Yu Wen-Chung 
Published: July 2023

Abstract

Background
Using technetium (Tc)-labelled pyrophosphate (PYP) cardiac scintigraphy, a non-invasive diagnosis of transthyretin amyloid (ATTR) cardiomyopathy can be made without histopathological confirmation. In patients suspected of ATTR cardiomyopathy, however, atypical presentations may necessitate further investigation.

Case summary
A 30-year-old man with hypertension and end-stage renal disease on peritoneal dialysis presented with progressive exertional dyspnoea. Left ventricular hypertrophy (LVH) with a maximal end-diastolic wall thickness up to 16 mm was detected on echocardiography. Speckle-tracking analysis revealed a reduced longitudinal strain of left ventricle with a relative apical sparing pattern. Although the absence of monoclonal gammopathy, a grade 3 myocardial uptake in 99mTc-PYP cardiac scintigraphy, and negative TTR gene mutation inferred the diagnosis of wild-type ATTR, the relative youth of the patient still raised concerns regarding the diagnosis. Under clinical doubt, he underwent further testing. In non-contrast cardiac magnetic resonance (CMR) with native T1 mapping, the native T1 myocardial value was within the normal range. In endomyocardial biopsy (EMB), there was no evidence of amyloid deposition, negative Congo red staining, and no immunohistochemical evidence of transthyretin expression. These results excluded the diagnosis of ATTR cardiomyopathy and prevented subsequent unnecessary treatments.

Discussion
When patients with unexplained LVH meet the non-invasive diagnostic criteria for ATTR cardiomyopathy, an EMB should be considered in selected cases. Patients presenting at an atypical age for wild-type ATTR cardiomyopathy, absence of extracardiac symptoms/signs or classic electrocardiogram features for cardiac amyloidosis should be suspected of another diagnosis and require further CMR or EMB to confirm.
Body surface potential mapping detects early disease onset in plakophilin-2-pathogenic variant carriers
Authors: Kloosterman Manon , Boonstra Machteld J , Roudijk Rob W , Bourfiss Mimount , van der Schaaf Iris , Velthuis Birgitta K , Eijsvogels Thijs M H , Kirkels Feddo P , van Dam Peter M , Loh Peter 
Published: July 2023

Abstract

Aims
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive inherited cardiac disease. Early detection of disease and risk stratification remain challenging due to heterogeneous phenotypic expression. The standard configuration of the 12 lead electrocardiogram (ECG) might be insensitive to identify subtle ECG abnormalities. We hypothesized that body surface potential mapping (BSPM) may be more sensitive to detect subtle ECG abnormalities.

Methods and results
We obtained 67 electrode BSPM in plakophilin-2 (PKP2)-pathogenic variant carriers and control subjects. Subject-specific computed tomography/magnetic resonance imaging based models of the heart/torso and electrode positions were created. Cardiac activation and recovery patterns were visualized with QRS- and STT-isopotential map series on subject-specific geometries to relate QRS-/STT-patterns to cardiac anatomy and electrode positions. To detect early signs of functional/structural heart disease, we also obtained right ventricular (RV) echocardiographic deformation imaging. Body surface potential mapping was obtained in 25 controls and 42 PKP2-pathogenic variant carriers. We identified five distinct abnormal QRS-patterns and four distinct abnormal STT-patterns in the isopotential map series of 31/42 variant carriers. Of these 31 variant carriers, 17 showed no depolarization or repolarization abnormalities in the 12 lead ECG. Of the 19 pre-clinical variant carriers, 12 had normal RV-deformation patterns, while 7/12 showed abnormal QRS- and/or STT-patterns.

Conclusion
Assessing depolarization and repolarization by BSPM may help in the quest for early detection of disease in variant carriers since abnormal QRS- and/or STT-patterns were found in variant carriers with a normal 12 lead ECG. Because electrical abnormalities were observed in subjects with normal RV-deformation patterns, we hypothesize that electrical abnormalities develop prior to functional/structural abnormalities in ARVC.
Effect of fibrosis regionality on atrial fibrillation recurrence: insights from DECAAF II
Authors: Assaf Ala , Mekhael Mario , Noujaim Charbel , Chouman Nour , Younes Hadi , Feng Han , ElHajjar Abdelhadi , Shan Botao , Kistler Peter , Kreidieh Omar , Marrouche Nassir , Donnellan Eoin 
Published: July 2023

Abstract

Aims
The amount of fibrosis in the left atrium (LA) predicts atrial fibrillation (AF) recurrence after catheter ablation (CA). We aim to identify whether regional variations in LA fibrosis affect AF recurrence.

Methods and results
This post hoc analysis of the DECAAF II trial includes 734 patients with persistent AF undergoing first-time CA who underwent late gadolinium enhancement magnetic resonance imaging (LGE-MRI) within 1 month prior to ablation and were randomized to MRI-guided fibrosis ablation in addition to standard pulmonary vein isolation (PVI) or standard PVI only. The LA wall was divided into seven regions: anterior, posterior, septal, lateral, right pulmonary vein (PV) antrum, left PV antrum, and left atrial appendage (LAA) ostium. Regional fibrosis percentage was defined as a region’s fibrosis prior to ablation divided by total LA fibrosis. Regional surface area percentage was defined as an area’s surface area divided by the total LA wall surface area before ablation. Patients were followed up for a year with single-lead electrocardiogram (ECG) devices. The left PV had the highest regional fibrosis percentage (29.30 ± 14.04%), followed by the lateral wall (23.23 ± 13.56%), and the posterior wall (19.80 ± 10.85%). The regional fibrosis percentage of the LAA was a significant predictor of AF recurrence post-ablation (odds ratio = 1.017, P = 0.021), and this finding was only preserved in patients receiving MRI-guided fibrosis ablation. Regional surface area percentages did not significantly affect the primary outcome.

Conclusion
We have confirmed that atrial cardiomyopathy and remodelling are not a homogenous process, with variations in different regions of the LA. Atrial fibrosis does not uniformly affect the LA, and the left PV antral region has more fibrosis than the rest of the wall. Furthermore, we identified regional fibrosis of the LAA as a significant predictor of AF recurrence post-ablation in patients receiving MRI-guided fibrosis ablation in addition to standard PVI.
The opioid tramadol blocks the cardiac sodium channel Nav1.5 in HEK293 cells
Authors: Jia Lixia , Veldkamp Marieke W , Verkerk Arie O , Tan Hanno L 
Published: July 2023

Abstract

Aims
Opioids are associated with increased risk of sudden cardiac death. This may be due to their effects on the cardiac sodium channel (Nav1.5) current. In the present study, we aim to establish whether tramadol, fentanyl, or codeine affects Nav1.5 current.

Methods and results
Using whole-cell patch-clamp methodology, we studied the effects of tramadol, fentanyl, and codeine on currents of human Nav1.5 channels stably expressed in HEK293 cells and on action potential (AP) properties of freshly isolated rabbit ventricular cardiomyocytes. In fully available Nav1.5 channels (holding potential −120 mV), tramadol exhibited inhibitory effects on Nav1.5 current in a concentration-dependent manner with an IC50 of 378.5 ± 33.2 µm. In addition, tramadol caused a hyperpolarizing shift of voltage-gated (in)activation and a delay in recovery from inactivation. These blocking effects occurred at lower concentrations in partially inactivated Nav1.5 channels: during partial fast inactivation (close-to-physiological holding potential −90 mV), IC50 of Nav1.5 block was 4.5 ± 1.1 μm, while it was 16 ± 4.8 μm during partial slow inactivation. The tramadol-induced changes on Nav1.5 properties were reflected by a reduction in AP upstroke velocity in a frequency-dependent manner. Fentanyl and codeine had no effect on Nav1.5 current, even when tested at lethal concentrations.

Conclusion
Tramadol reduces Nav1.5 currents, in particular, at close-to-physiological membrane potentials. Fentanyl and codeine have no effects on Nav1.5 current.
An approach for prioritizing candidate genes from RNA-seq using preclinical cocaine self-administration datasets as a test case
Authors: Vannan Annika , Dell’Orco Michela , Perrone-Bizzozero Nora I , Neisewander Janet L , Wilson Melissa A 
Published: July 2023

Abstract
RNA-sequencing (RNA-seq) technology has led to a surge of neuroscience research using animal models to probe the complex molecular mechanisms underlying brain function and behavior, including substance use disorders. However, findings from rodent studies often fail to be translated into clinical treatments. Here, we developed a novel pipeline for narrowing candidate genes from preclinical studies by translational potential and demonstrated its utility in 2 RNA-seq studies of rodent self-administration. This pipeline uses evolutionary conservation and preferential expression of genes across brain tissues to prioritize candidate genes, increasing the translational utility of RNA-seq in model organisms. Initially, we demonstrate the utility of our prioritization pipeline using an uncorrected P-value. However, we found no differentially expressed genes in either dataset after correcting for multiple testing with false discovery rate (FDR &lt; 0.05 or &lt;0.1). This is likely due to low statistical power that is common across rodent behavioral studies, and, therefore, we additionally illustrate the use of our pipeline on a third dataset with differentially expressed genes corrected for multiple testing (FDR &lt; 0.05). We also advocate for improved RNA-seq data collection, statistical testing, and metadata reporting that will bolster the field's ability to identify reliable candidate genes and improve the translational value of bioinformatics in rodent research.
The Effects of Statins on Cognitive Performance Are Mediated by Low-Density Lipoprotein, C-Reactive Protein, and Blood Glucose Concentrations
Authors: Gentreau Mélissa , Rukh Gull , Miguet Maud , Clemensson Laura E , Alsehli Ahmed M , Titova Olga E , Schiöth Helgi B 
Published: July 2023

AbstractStatins are widely used for cardiovascular disease prevention but their effects on cognition remain unclear. Statins reduce cholesterol concentration and have been suggested to provide both beneficial and detrimental effects. Our aim was to investigate the cross-sectional and longitudinal association between statin use and cognitive performance, and whether blood low-density lipoprotein, high-density lipoprotein, triglycerides, glucose, C-reactive protein, and vitamin D biomarkers mediated this association. We used participants from the UK biobank aged 40–69 without neurological and psychiatric disorders (n = 147 502 and n = 24 355, respectively). We performed linear regression to evaluate the association between statin use and cognitive performance and, mediation analysis to quantify the total, direct, indirect effects and the proportion meditated by blood biomarkers. Statin use was associated with lower cognitive performance at baseline (β = −0.40 [−0.53, −0.28], p = &lt;.0001), and this association was mediated by low-density lipoprotein (proportion mediated = 51.4%, p = .002), C-reactive protein (proportion mediated = −11%, p = .006) and blood glucose (proportion mediated = 2.6%, p = .018) concentrations. However, statin use was not associated with cognitive performance, measured 8 years later (β = −0.003 [−0.11, 0.10], p = .96). Our findings suggest that statins are associated with lower short-term cognitive performance by lowering low-density lipoprotein and raising blood glucose concentrations, and better performance by lowering C-reactive protein concentrations. In contrast, statins have no effect on long-term cognition and remain beneficial in reducing cardiovascular risk factors.
Predicting Slow Walking Speed From a Pooled Cohort Analysis: Sarcopenia Definitions, Agreement, and Prevalence in Australia and New Zealand
Authors: Zanker Jesse , Scott David , Szoeke Cassandra , Vogrin Sara , Patel Sheena , Blackwell Terri , Bird Stefanie , Kirk Ben , Center Jacqueline , Alajlouni Dima A , Gill Tiffany , Jones Graeme , Pasco Julie A , Waters Debra L , Cawthon Peggy M , Duque Gustavo 
Published: July 2023

Abstract

Background
Recent operational definitions of sarcopenia have not been replicated and compared in Australia and New Zealand (ANZ) populations. We aimed to identify sarcopenia measures that discriminate ANZ adults with slow walking speed (&lt;0.8 m/s) and determine the agreement between the Sarcopenia Definitions and Outcomes Consortium (SDOC) and revised European Working Group for Sarcopenia in Older People (EWGSOP2) operational definitions of sarcopenia.

Methods
Eight studies comprising 8 100 ANZ community-dwelling adults (mean age ± standard deviation, 62.0 ± 14.4 years) with walking speed, grip strength (GR), and lean mass data were combined. Replicating the SDOC methodology, 15 candidate variables were included in sex-stratified classification and regression tree models and receiver operating characteristic curves on a pooled cohort with complete data to identify variables and cut points discriminating slow walking speed (&lt;0.8 m/s). Agreement and prevalence estimates were compared using Cohen’s Kappa (CK).

Results
Receiver operating characteristic curves identified GR as the strongest variable for discriminating slow from normal walking speed in women (GR &lt;20.50 kg, area under curve [AUC] = 0.68) and men (GR &lt;31.05 kg, AUC = 0.64). Near-perfect agreement was found between the derived ANZ cut points and SDOC cut points (CK 0.8–1.0). Sarcopenia prevalence ranged from 1.5% (EWGSOP2) to 37.2% (SDOC) in women and 1.0% (EWGSOP2) to 9.1% (SDOC) in men, with no agreement (CK &lt;0.2) between EWGSOP2 and SDOC.

Conclusions
Grip strength is the primary discriminating characteristic for slow walking speed in ANZ women and men, consistent with findings from the SDOC. Sarcopenia Definitions and Outcomes Consortium and EWGSOP2 definitions showed no agreement suggesting these proposed definitions measure different characteristics and identify people with sarcopenia differently.
Racial disparities in inpatient palliative care consultation among frail older patients undergoing high-risk elective surgical procedures in the United States: a cross-sectional study of the national inpatient sample
Authors: Kim Kyung Mi , Muench Ulrike , Maki John E , Yefimova Maria , Oh Anna , Jopling Jeffrey K , Rinaldo Francesca , Shah Nirav R , Giannitrapani Karleen Frances , Williams Michelle Y , Lorenz Karl A 
Published: July 2023

Abstract
Surgical interventions are common among seriously ill older patients, with nearly one-third of older Americans facing surgery in their last year of life. Despite the potential benefits of palliative care among older surgical patients undergoing high-risk surgical procedures, palliative care in this population is underutilized and little is known about potential disparities by race/ethnicity and how frailty my affect such disparities. The aim of this study was to examine disparities in palliative care consultations by race/ethnicity and assess whether patients’ frailty moderated this association. Drawing on a retrospective cross-sectional study of inpatient surgical episodes using the National Inpatient Sample of the Healthcare Cost and Utilization Project from 2005 to 2019, we found that frail Black patients received palliative care consultations least often, with the largest between-group adjusted difference represented by Black–Asian/Pacific Islander frail patients of 1.6 percentage points, controlling for sociodemographic, comorbidities, hospital characteristics, procedure type, and year. No racial/ethnic difference in the receipt of palliative care consultations was observed among nonfrail patients. These findings suggest that, in order to improve racial/ethnic disparities in frail older patients undergoing high-risk surgical procedures, palliative care consultations should be included as the standard of care in clinical care guidelines.
Myofibrillar myopathy hallmarks associated with ZAK deficiency
Authors: Stonadge Amy , Genzor Aitana V , Russell Alex , Hamed Mohamed F , Romero Norma , Evans Gareth , Pownall Mary Elizabeth , Bekker-Jensen Simon , Blanco Gonzalo 
Published: July 2023

Abstract
The ZAK gene encodes two functionally distinct kinases, ZAKα and ZAKβ. Homozygous loss of function mutations affecting both isoforms causes a congenital muscle disease. ZAKβ is the only isoform expressed in skeletal muscle and is activated by muscle contraction and cellular compression. The ZAKβ substrates in skeletal muscle or the mechanism whereby ZAKβ senses mechanical stress remains to be determined. To gain insights into the pathogenic mechanism, we exploited ZAK-deficient cell lines, zebrafish, mice and a human biopsy. ZAK-deficient mice and zebrafish show a mild phenotype. In mice, comparative histopathology data from regeneration, overloading, ageing and sex conditions indicate that while age and activity are drivers of the pathology, ZAKβ appears to have a marginal role in myoblast fusion in vitro or muscle regeneration in vivo. The presence of SYNPO2, BAG3 and Filamin C (FLNC) in a phosphoproteomics assay and extended analyses suggested a role for ZAKβ in the turnover of FLNC. Immunofluorescence analysis of muscle sections from mice and a human biopsy showed evidence of FLNC and BAG3 accumulations as well as other myofibrillar myopathy markers. Moreover, endogenous overloading of skeletal muscle exacerbated the presence of fibres with FLNC accumulations in mice, indicating that ZAKβ signalling is necessary for an adaptive turnover of FLNC that allows for the normal physiological response to sustained mechanical stress. We suggest that accumulation of mislocalized FLNC and BAG3 in highly immunoreactive fibres contributes to the pathogenic mechanism of ZAK deficiency.
DNA methylation mediated by RdDM pathway and demethylation affects furanone accumulation through regulation of QUINONE OXIDOREDUCTASE in strawberry
Authors: Li Yunduan , Shi Yanna , Li Yichen , Lu Jiao , Sun Yunfan , Zhang Yuanyuan , Chen Wenbo , Yang Xiaofang , Grierson Donald , Lang Zhaobo , Jiang Guihua , Chen Kunsong 
Published: July 2023

Abstract
Recently, increasing evidence suggests that DNA methylation plays a crucial role in fruit ripening. However, the role of DNA methylation in regulating specific traits, such as flavor, remains unclear. Here, we report a role of DNA methylation in affecting furanone biosynthesis in strawberry. Strawberry quinone oxidoreductase (FaQR) is a key enzyme in furanone biosynthesis. There are four FaQR homologs in strawberry cultivar ‘Yuexin’, and one of them, FaQR3, contributes ~50% of FaQR transcripts, indicating a major role of FaQR3 in furanone biosynthesis. Through characterization of levels of DNA methylation and FaQR3 transcript and furanone contents during fruit ripening and after the application of DNA methylation inhibitor, we found that the DNA methylation level of the FaQR3 promoter was negatively correlated with FaQR3 expression and furanone accumulation, suggesting that DNA methylation may be involved in furanone biosynthesis through adjusting FaQR3 expression, and responded to different temperatures consistently. In addition, transient expression of a gene in the RNA-directed DNA methylation (RdDM) pathway, FaAGO4, and enrichment analysis of the 24-nucleotide siRNAs suggested that DNA methylation in the FaQR3 promoter is mediated by the RdDM pathway. Transient RNA interference (RNAi) of FaDML indicated that the demethylation pathway may be involved in regulating furanone accumulation. These findings provide new insights into the role of DNA methylation and demethylation in affecting flavor quality in strawberry during fruit ripening.
Alcohol intake including wine drinking is associated with decreased platelet reactivity in a large population sample
Authors: Pashek Robin E , Nkambule Bongani B , Chan Melissa V , Thibord Florian , Lachapelle Amber R , Cunha Jason , Chen Ming-Huei , Johnson Andrew D 
Published: July 2023

Abstract

Background
Alcohol consumption is linked to decreased platelet function. Whether this link is dependent on sex or type of beverage remains unclear.

Methods
Cross-sectional data were obtained from the Framingham Heart Study (N = 3427). Alcohol consumption was assessed by using standardized medical history and Harvard semi-quantitative food frequency questionnaires. Five bioassays measured 120 platelet reactivity traits across agonists in whole-blood and platelet-rich plasma samples. Linear mixed-effects models adjusted for age, sex and aspirin use, hypertension, body mass index, cholesterol, high-density lipoprotein, triglycerides, smoking and diabetes evaluated associations between platelet reactivity and alcohol consumption. Beta effects, the regression coefficients that estimate the amount of change in each unit of the predictor variable whereas all other predictor variables remain fixed, for heavy alcohol consumption were compared with effects of aspirin use.

Results
Alcohol consumption was associated with decreased platelet reactivity, with more associations among wine and liquor compared with beer. Many platelet–alcohol associations in the full sample (86%, P &lt; 0.01) had larger effect sizes in females. Lower light transmission aggregometry adenosine diphosphate (1.82 µM) maximum aggregation (P = 2.6E-3, 95% CI = –0.07, –0.02, β = –0.042) and area under the curve (P = 7.7E-3, 95% CI = –0.07, –0.01, β = –0.039) were associated with white wine consumption; however, red wine had no associations with platelet reactivity. The effect of aspirin use was on average 11.3 (±4.0) times greater than that of heavy drinking in our full sample.

Conclusions
We confirm associations between alcohol consumption and decreased platelet reactivity. Effects appeared larger for liquor and wine intake and in our female cohort. Red wine consumption is not associated with lower platelet function, contrasting with prior population studies. Although we report an inhibitory relationship between alcohol intake and platelet function, these effects appear much smaller than that of aspirin use.
Geometric Morphometric Assessment of Toe Shape in Forest and Urban Lizards Following Hurricane Disturbances
Authors: Michaud R , Hagey T J , De León L F , Revell L J , Avilés-Rodríguez K J 
Published: July 2023

SynopsisEvidence suggests that hurricanes can influence the evolution of organisms, with phenotypic traits involved in adhesion, such as the toepads of arboreal lizards, being particularly susceptible to natural selection imposed by hurricanes. To investigate this idea, we quantified trait variation before and after Hurricanes Irma and Maria (2017) in forest and urban populations of the Puerto Rican lizard Anolis cristatellus. We found that the hurricanes affected toe morphology differently between forest and urban sites. In particular, toepads of the forefeet were longer and narrower in forest, but wider in urban populations, compared to pre-hurricane measures. Toepads of the hind feet were larger in area following the hurricanes. Fore and rear toes increased in length following the hurricane. There were no changes in the number of lamellae scales or lamellae spacing, but lamellae 6–11 of the forefeet shifted proximally following the hurricane. We also measured clinging performance and toe shape. We found that toepad area and toe lengths were stronger predictors of adhesive forces than toepad shape. Our results highlight an interaction between urbanization and hurricanes, demonstrating the importance to consider how urban species will respond to extreme weather events. Additionally, our different results for fore and rear feet highlight the importance of evaluating both of these traits when measuring the morphological response to hurricanes in arboreal lizards.