bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bicuspid valve CT Registry of balloon expandable TAVR: BETTER TAVR Registry
Authors: Chavarria Jorge , Falcao Felipe , AlRaddadi Hatim , Aziz Amir , Dick Alexander , Chung Kevin , Sathananthan Janar , Meier David , Ali Noman , Velianou James , Natarajan Madhu , Jaffer Iqbal , Wood David , Fam Neil , Sheth Tej 
Published: August 2023

AbstractObjectivesWe evaluated determinants of stent geometry in bicuspid valves treated with balloon expandable TAVR.BackgroundThe anatomic substrate of bicuspid valves may lead to suboptimal TAVR stent expansion and geometry.MethodsA multicentre observational registry of patients who underwent post TAVR CT to determine stent area (vs nominal valve area) and stent ellipticity (maximum diameter/minimum diameter). Predictors of relative stent expansion (minimum area/average of inflow + outflow area) and stent ellipticity were evaluated in a multivariable regression model including valve calcium volume, presence of raphe calcium, sinus diameters indexed for area derived annular diameter, and performance of pre-dilation and post-dilation.ResultsThe registry enrolled 101 patients from 4 centres. Minimum stent area (vs nominal area) was 88.1% and maximum ellipticity was 1.10 with both observed near the midframe of the valve in all cases. Relative stent expansion ≥90% was observed in 64/101 patients. The only significant predictor of relative stent expansion ≥90% was performance of post-dilation (p<0.01). Relative stent expansion ≥90% was seen in 86% of patients with post dilation compared to 57% of without (p<0.001). The stent ellipticity ≥ 1.1 was observed in 47/101 patients. The significant predictors of stent ellipticity ≥1.1 was the presence of raphe calcification (p=0.02) and intercommisural diameter at 4 mm above the annular plane (p=0.004).ConclusionRelative stent expansion ≥90% was associated with the performance of post-dilation and stent ellipticity was associated with the presence of calcified raphe and sinus dimensions (Intercommisural diameter at 4 mm above the annular plane). Further studies to determine optimal deployment strategies in bicuspid valves are needed.Abstract FigureGraphical abstractPredictors of stent expansion and ellipticity from a multicenter registry of patients with bicuspid anatomy undergoing TAVR with balloon expandable valves.
Sodium-glucose Cotransporter-2 Inhibitors Stabilize Coronary Plaques in Acute Coronary Syndrome with Diabetes Mellitus
Authors: Kurozumi Atsumasa , Shishido Koki , Yamashita Takayoshi , Sato Daisuke , Uchida Syuhei , Koyama Eiji , Tamaki Yusuke , Hayashi Takahiro , Miyashita Hirokazu , Yokoyama Hiroaki , Ochiai Tomoki , Yamaguchi Masashi , Moriyama Noriaki , Tobita Kazuki , Matsumoto Takashi , Mizuno Shingo , Yamanaka Futoshi , Tanaka Yutaka , Murakami Masato , Takahashi Saeko , Saito Shigeru 
Published: August 2023

ABSTRACTBackgroundSodium-glucose cotransporter-2 inhibitors (SGLT2i) are widely used in cardiology and are effective in treating acute coronary syndrome (ACS). Their effects on unstable plaque in ACS patients remains unclear. This study aimed to examine the effectiveness of SGLT2i in coronary plaque phenotypes based on optical coherence tomography (OCT) images and the prognosis of ACS with type 2 diabetes mellitus (T2DM).MethodsThis retrospective study included 109 patients in the total cohort and 29 patients in the OCT cohort. Based on SGLT2i administration after ACS, the total cohort was categorized into non-SGLT2i (n = 69) and SGLT2i (n = 40) groups. The OCT cohort had 15 and 14 patients in non-SGLT2i and SGLT2i groups, respectively. OCT images of unstable plaque were analyzed in non-stented lesions during ACS catheterization and at 6-month follow-ups. The total cohort was assessed after 1 year for major adverse cardiovascular events (MACE), including all-cause mortality, revascularization, cerebrovascular disease, and heart failure hospitalization.ResultsSGLT2i improved unstable lesions with a significantly thicker fibrous cap (48 ± 15 μm vs. 26 ± 24 μm, p = 0.005), reduced lipid arc (-29 ± 12° vs. -18 ± 14°, p = 0.028), and higher % decrease in total lipid arc (-35 ± 13% vs. -19 ± 18%, p = 0.01) as well as a lower MACE incidence (Log rank p = 0.023, HR 4.72 [1.08, 20.63]) and revascularization rate (adjusted HR 6.77 [1.08, 42.52]) compared to the non-SGLT2i group.ConclusionsSGLT2i stabilizes atherosclerosis and improves ACS prognosis in patients with T2DM.Clinical PerspectiveWhat is new?We analyzed serial OCT images both baseline and follow-up in patients with ACS and T2DM undergoing PCI, and evaluated how effect SGLT2i had on unstable plaques.ACS patients with SGLT2i administration showed coronary atherosclerotic lesions to be stabilized on follow-up.What are the clinical implications?SGLT2i can stabilize unstable plaques by controlling the inflammatory cascade on patients with T2DM.SGLT2i administration will be one option to improve their prognosis in patients with ACS and T2DM undergoing PCI.
Computed tomography-derived normative values and z-scores of right ventricular outflow tract structures in the pediatric population
Authors: Soszyn Natalie , Schweigert Justin , Franco Salvador R. , Morgan Gareth J. , Mitchell Max , Zablah Jenny E. 
Published: August 2023

AbstractBackgroundRecent advances in available percutaneous device technology require accurate measurements and quantification of relationships between right ventricular outflow tract (RVOT) structures in children with and without congenital heart disease to determine device suitability. To date, no population study has described normal reference ranges of these measurements by computed tomography (CT). We aimed to establish normative values for four CT-derived measurements between RVOT structures from a heterogeneous population without heart disease and develop z-scores useful for clinical practice.MethodsPatients without heart disease who underwent cardiac CT between April 2014 and February 2021 at Children’s Hospital Colorado were included. Distance between the right ventricular (RV) apex to pulmonary valve (PV), PV to pulmonary trunk bifurcation, and bifurcation to the right and left pulmonary artery were measured. Previously validated models were used to normalize the measurements and calculate Z-scores. Each measurement was plotted against BSA and Z-scores distributions were used as reference lines.ResultsThree-hundred sixty-four healthy patients with a mean age of 8.8 years (range 1–21), 58% male, and BSA of 1 m2(range 0.4–2.1) were analyzed. The Haycock formula was used to present data as predicted values for a given BSA and within equations relating each measurement to BSA. Predicted values and Z-score boundaries for all measurements are presented.ConclusionWe report CT-derived normative data for four measurements between RVOT structures from a heterogenous cohort of healthy children. Knowledge of this normative data will be useful in both determining device fit and customising future devices to accommodate the diverse pediatric size range.Clinical PerspectiveRecent advances in advanced percutaneous technology require accurate measurements and quantification of relationships between RVOT structures to determine patient selection and device suitability. The availability of a robust range of normal reference values can provide valuable information for current device selection and future development of customized devices for the RVOT tailored to accommodate the broad size, anatomic and physiologic heterogenicity seen in the pediatric population. We report CT-derived normative data for four measurements between cardio-pulmonary structures from a heterogenous cohort of healthy children and young adults. This data may be useful in planning surgical or catheter-guided interventions in the management of children with congenital heart disease.
Oxidative stress biomarkers in hypothyroid, non thyroid illness and euthyroid dogs
Authors: Mohanambal K , Satish Kumar K , Nagaraj P , Usha Rani M , Ravi Kumar Y 
Published: August 2023

AbstractThere are only a few numbers of published reports available on oxidative stress parameters in hypothyroidism and many of which are in the field of human medicine. Studies on hypothyroidism in dogs lack an assessment of oxidative stress and some are vague and inconclusive. So, the current study was formulated primarily to address variations in chief antioxidant parameters in dogs with hypothyroidism, non-thyroid illness and euthyroidism. Secondly, magnitude of oxidative stress was measured in hypothyroid dogs prior to and during the course of levothyroxine therapy, which were compared statistically. Evaluation of thyroid profile (TT4, fT4 and cTSH) was carried out prior to the assessment of oxidative stress biomarkers such as, serum malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH) and catalase. A total of 45 dogs were employed in the study, that includes 19 dogs with hypothyroidism, 11 dogs with non-thyroid illness and 15 dogs with euthyroidism. These dogs were brought either to the dermatological unit or the immunization unit. Dogs were divided into three groups: group 1 represented hypothyroidism (low fT4 or low TT4 and high cTSH); group 2 represented non-thyroid disease (low or normal TT4 and low cTSH i.e., inconclusive levels of thyroid hormones); and group 3 represented dogs with normal thyroid levels (euthyroid dogs). Descriptive statistics and normality plots were carried out using SPSS software version 21. Assuming that the variances were unequal, P values were calculated and compared by one-way ANOVA, post hoc multiple comparison analysis using the Games-Howell test. The mean thyroid hormone levels of hypothyroid dogs before (Day 0) and after (Day 60) treatment was significantly different (P<0.05). Hypothyroid dogs (group 1) displayed significantly lower mean fT4 levels (0.56±0.07) and higher mean cTSH levels (8.14±1.17) when compared to other groups. The mean values of serum biochemical parameters showed significant differences among groups (P<0.01). Various biomarkers showed a significant alteration viz., there was a significant reduction in catalase, SOD, GSH and increase in MDA in hypothyroid dogs when compared with euthyroid dogs. However, following therapy for 60 days, catalase, SOD and GSH levels elevated and MDA level reduced significantly and reached nearly to that of euthyroid dogs. Further, there was no significant difference between NTI and euthyroid dogs which demonstrated the antioxidant defence against oxidative stress in hypothyroid dogs. As an outcome, antioxidant measures and serum biochemical tests can be employed as a diagnostic tool to rule out oxidative stress in hypothyroid dogs.
KAT6Amutations in Arboleda-Tham syndrome drive epigenetic regulation of posteriorHOXCcluster
Authors: Singh Meghna , Spendlove Sarah , Wei Angela , Bondhus Leroy , Nava Aileen , N. de L. Vitorino Francisca , Amano Seth , Lee Jacob , Echeverria Gesenia , Gomez Dianne , Garcia Benjamin A. , Arboleda Valerie A. 
Published: August 2023

ABSTRACTArboleda-Tham Syndrome (ARTHS) is a rare genetic disorder caused by heterozygous,de novotruncating mutations inLysine(K) acetyltransferase 6A(KAT6A). ARTHS is clinically heterogeneous and characterized by several common features including intellectual disability, developmental and speech delay, hypotonia and affects multiple organ systems.KAT6Ais highly expressed in early development and plays a key role in cell-type specific differentiation. KAT6A is the enzymatic core of a histone-acetylation protein complex, however the direct histone targets and gene regulatory effects remain unknown. In this study, we use ARTHS patient (n=8) and control (n=14) dermal fibroblasts and perform comprehensive profiling of the epigenome and transcriptome caused byKAT6Amutations. We identified differential chromatin accessibility within the promoter or gene body of 23%(14/60) of genes that were differentially expressed between ARTHS and controls. Within fibroblasts, we show a distinct set of genes from the posteriorHOXCgene cluster (HOXC10,HOXC11,HOXC-AS3, HOXC-AS2, HOTAIR) that are overexpressed in ARTHS and are transcription factors critical for early development body segment patterning. The genomic loci harboring HOXC genes are epigenetically regulated with increased chromatin accessibility, high levels of H3K23ac, and increased gene-body DNA methylation compared to controls, all of which are consistent with transcriptomic overexpression. Finally, we used unbiased proteomic mass spectrometry and identified two new histone post-translational modifications (PTMs) that are disrupted in ARTHS: H2A and H3K56 acetylation. Our multi-omics assays have identified novel histone and gene regulatory roles ofKAT6Ain a large group of ARTHS patients harboring diverse pathogenic mutations. This work provides insight into the role of KAT6A on the epigenomic regulation in somatic cell types.
EpiVar Browser: advanced exploration of epigenomics data under controlled access
Authors: Lougheed David R , Liu Hanshi , Aracena Katherine A , Grégoire Romain , Pacis Alain , Pastinen Tomi , Barreiro Luis B , Joly Yann , Bujold David , Bourque Guillaume 
Published: August 2023

AbstractMotivationHuman epigenomic data has been generated by large consortia for thousands of cell types to be used as a reference map of normal and disease chromatin states. Since epigenetic data contains potentially identifiable information, similarly to genetic data, most raw files generated by these consortia are stored in controlled-access databases. It is important to protect identifiable information, but this should not hinder secure sharing of these valuable datasets.ResultsGuided by theFramework for responsible sharing of genomic and health-related datafrom the Global Alliance for Genomics and Health (GA4GH), we have developed a tool to facilitate the exploration of epigenomics datasets’ aggregate results, while filtering out identifiable information. Specifically, the EpiVar Browser allows a user to navigate an epigenetic dataset from a cohort of individuals and enables direct exploration of genotype-chromatin phenotype relationships. Because the information about individual genotypes is not accessible and aggregated in the output that is made available, no identifiable data is released, yet the interface allows for dynamic genotype - epigenome interrogation. This approach has the potential to accelerate analyses that would otherwise require a lengthy multi-step approval process and provides a generalisable strategy to facilitate responsible access to sensitive epigenomics data.Availability and implementationOnline portal instance:https://computationalgenomics.ca/tools/epivarSource code:https://github.com/c3g/epivar-browser
Evaluating the transmission risk of amyloid beta peptide via ingestion
Authors: Raine Joshua , Tolwinski Nicholas , Gruber Jan , Mathuru Ajay S. 
Published: August 2023

AbstractBackgroundRecent reports suggest that amyloid beta (Aβ) peptides can exhibit prion-like pathogenic properties. Transmission of Aβ peptide and the development of associated pathologies after surgeries with contaminated instruments and intravenous or intracerebral inoculations have now been reported across fish, rodents, primates, and humans. This raises a worrying prospect of Aβ peptides also having other characteristics typical of prions, such as evasion of the digestive process. We asked if such transmission of Aβ aggregates via ingestion was possible.MethodsWe made use of a transgenicDrosophila melanogasterline expressing human Aβ peptide prone to aggregation. Fly larvae were fed to adult zebrafish under two feeding schemes. The first was a short-term, high-intensity scheme over 48 hours to determine transmission and retention in the gut. The second, long-term scheme specifically examined retention and accumulation in the brain. The gut and brain tissues were examined by histology, western blotting, and mass spectrometric analyses.ResultsNone of the analyses could detect Aβ aggregates in the guts of zebrafish following ingestion, despite being easily detectable in the feed. Additionally, there was no detectable accumulation of Aβ in the brain tissue or development of associated pathologies after prolonged feeding.ConclusionsWhile human Aβ aggregates do not appear to be readily transmissible by ingestion across species, two prospects remain open. First, this mode of transmission, if occurring, may stay below a detectable threshold and may take much longer to manifest. A second possibility is that the human Aβ peptide may not be able to trigger self-propagation or aggregation in other species. Either possibility requires further investigation, taking into account the possibility of such transmission from agricultural species used in the food industry.
A semi-automated method for quantifying optokinetic reflex tracking acuity
Authors: Kiraly James K. , Harris Scott C. , Al-Khindi Timour , Dunn Felice A. , Kolodkin Alex 
Published: August 2023

ABSTRACTThe study of murine behavioral responses to visual stimuli is a key component of understanding mammalian visual circuitry. One notable response is the optokinetic reflex (OKR), a highly conserved innate behavior necessary for image stabilization on the retina. The OKR provides a robust readout of image tracking ability and has been extensively studied to understand the logic of visual system circuitry and function in mice from different genetic backgrounds. The OKR consists of two phases: a slow tracking phase as the eye follows a stimulus to the edge of the visual plane, and a compensatory fast phase saccade that maintains the image within the visual field. Assessment of the OKR has previously relied on counting individual compensatory eye saccades to estimate tracking speed. To obtain a more direct quantification of tracking ability, we have developed a novel, semi-automated analysis program that allows for rapid and reproducible quantification of unidirectional tracking gains, in addition to being adaptable to any video-oculography equipment. Our analysis program allows for the selection of slow tracking phases, modeling of the vertical and horizontal eye vectors, quantification of eye movement relative to the stimulus, and organization of resultant data into a usable spreadsheet for statistical and graphical comparisons. This quantitative and streamlined analysis pipeline provides a faster and more direct measurement of OKR responses, thereby facilitating further study of visual behavior responses.SUMMARYWe describe here a semi-automated quantitative analysis method that directly measures eye tracking resulting from murine visual system responses to two-dimensional image motion. A Python-based user interface and analysis algorithm allows for higher throughput and more quantitative measurements of eye tracking parameters than previous methods.
Differential functional reorganization of ventral and dorsal visual pathways following childhood hemispherectomy
Authors: Ayzenberg Vladislav , Granovetter Michael C. , Robert Sophia , Patterson Christina , Behrmann Marlene 
Published: August 2023

AbstractHemispherectomy is a surgical procedure in which an entire hemisphere of a patient’s brain is resected or functionally disconnected to manage seizures in individuals with drug-resistant epilepsy. Despite the extensive loss of input from both ventral and dorsal visual pathways of one hemisphere, pediatric patients who have undergone hemispherectomy show a remarkably high degree of perceptual function across many domains. In the current study, we sought to understand the extent to which functions of the ventral and dorsal visual pathways reorganize to the contralateral hemisphere following childhood hemispherectomy. To this end, we collected fMRI data from an equal number of left and right hemispherectomy patients who completed tasks that typically elicit lateralized responses from the ventral or the dorsal pathway, namely, word (left ventral), face (right ventral), tool (left dorsal), and global form (right dorsal) perception. Overall, there was greater evidence of functional reorganization in the ventral pathway than in the dorsal pathway. Importantly, because ventral and dorsal reorganization was tested in the very same patients, these results cannot be explained by idiosyncratic factors such as disease etiology, age at the time of surgery, or age at testing. These findings suggest that because the dorsal pathway may mature earlier, it may have a shorter developmental window of plasticity than the ventral pathway and, hence, be less malleable.
A special role for anterior cingulate cortex, but not orbitofrontal cortex or basolateral amygdala, in choices involving information
Authors: González Valeria V. , Ashikyan Sonya A. , Zhang Yifan , Rickard Anne , Yassine Ibrahim , Romero-Sosa Juan Luis , Blaisdell Aaron P. , Izquierdo Alicia 
Published: August 2023

AbstractSubjects often are willing to pay a cost for information. In a procedure that promotes paradoxical choices, animals choose between a richer option followed by a cue that is rewarded 50% of the time (No-info)vsa leaner option followed by one of two cues that signal certain outcomes: one always rewarded (100%), and the other never rewarded, 0% (Info). Since decisions involve comparing the subjective value of options after integrating all their features, preference for information may rely on cortico-amygdalar circuitry. To test this, male and female rats were prepared with bilateral inhibitory DREADDs in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), basolateral amygdala (BLA), or null virus (control). We inhibited these regions after stable preference was acquired. We found that inhibition of ACC destabilized choice preference in female rats without affecting latency to choose or response rate to cues. A logistic regression fit revealed that the previous choice strongly predicted preference in control animals, but not in female rats following ACC inhibition. The results reveal a causal, sex-dependent role for ACC in decisions involving information.