bluuebunny/crossref_metadata_2025 huggingface dataset:
Brave New World? Care and Custody of Children at the Court for Divorce and Matrimonial Causes in Mid-Victorian England
Authors: Russell Penelope
Published: January 2024

This article considers the accessibility and impact of the mid-Victorian divorce court’s new custody powers, by tracing the children of those who petitioned the court within the first two years of the court’s establishment and contrasting this with court pleadings and orders. Focusing on the care of children by location as revealed by the census and other sources, this study then deals in more detail with individual cases to illustrate the experience of parties in divorce court processes for child custody. This study generates an original data set to find that, whereas the majority of resident female petitioners sought a custody order in the petition, only a minority ended up with an order. Three broad issues are addressed: the gendered nature of rights in respect of children on marital breakdown, the implications of legal remedies being accessed through male gatekeepers, and the exercise of discretion at the newly opened divorce court.
Comparison of 2 Fillers for Lip Injection—A Randomized-Controlled Clinical Trial Assessed by 3D Imaging
Authors: Germani Marcelo , Miranda de Souza Almeida Claudia Cristina , Muñoz-Lora Victor Ricardo Manuel
Published: January 2024

Background

Lip aging is a concern for many, and hyaluronic acid (HA) injections are a popular solution.

Objectives

This study compared 2 different HA gel technologies (OBT and NASHA) for lip augmentation in 20 volunteers.

Methods

Both groups received treatment from the same injector using the same method. Lip volume was measured with a 3D stereophotogrammetry device before, immediately after, and 30 days posttreatment. Patient satisfaction and adverse events were assessed through FACE-Q scales analysis.

Results

The NASHA group showed an immediate volume increase (P = .01), which decreased after 30 days. The OBT group did not show a significant immediate growth (P = .535) but did exhibit a significant increase after 30 days (P = .014). After 30 days, there were no significant volume differences between the groups (P = .802 and P = .999). FACE-Q analysis revealed no significant differences among groups after 30 days.

Conclusions

This study highlights that less cohesive gels may modify faster in dynamic lip areas, emphasizing the importance of selecting products based on their physicochemical and rheological properties. In the context of lip augmentation with HA, it is important not to consider immediate aesthetic changes as definitive results, as volume changes may persist and develop over time after the treatment.

Level of Evidence: 2
Improving cell type identification with Gaussian noise-augmented single-cell RNA-seq contrastive learning
Authors: Alsaggaf Ibrahim , Buchan Daniel , Wan Cen
Published: January 2024

Cell type identification is an important task for single-cell RNA-sequencing (scRNA-seq) data analysis. Many prediction methods have recently been proposed, but the predictive accuracy of difficult cell type identification tasks is still low. In this work, we proposed a novel Gaussian noise augmentation-based scRNA-seq contrastive learning method (GsRCL) to learn a type of discriminative feature representations for cell type identification tasks. A large-scale computational evaluation suggests that GsRCL successfully outperformed other state-of-the-art predictive methods on difficult cell type identification tasks, while the conventional random genes masking augmentation-based contrastive learning method also improved the accuracy of easy cell type identification tasks in general.
Prognostic impact of extramural venous invasion detected by contrast-enhanced CT colonography in colon cancer
Authors: Kato Takeharu , Tsukamoto Shunsuke , Miyake Mototaka , Kudose Yozo , Takamizawa Yasuyuki , Moritani Konosuke , Daiko Hiroyuki , Kanemitsu Yukihide
Published: January 2024

Background

The impact of computed tomography (CT)-detected extramural venous invasion on the recurrence of colon cancer is not fully understood. The aim of this study was to investigate the clinical significance of extramural venous invasion diagnosed before surgery by contrast-enhanced CT colonography using three-dimensional multiplanar reconstruction images.

Methods

Patients with colon cancer staged greater than or equal to T2 and/or stage I–III who underwent contrast-enhanced CT colonography between 2013 and 2018 at the National Cancer Center Hospital in Japan were retrospectively investigated for CT-detected extramural venous invasion. Inter-observer agreement for the detection of CT-detected extramural venous invasion was evaluated and Kaplan–Meier survival curves were plotted for recurrence-free survival using CT-TNM staging and CT-detected extramural venous invasion. Preoperative clinical variables were analysed using Cox regression for recurrence-free survival.

Results

Out of 922 eligible patients, 544 cases were analysed (50 (9.2 per cent) were diagnosed as positive for CT-detected extramural venous invasion and 494 (90.8 per cent) were diagnosed as negative for CT-detected extramural venous invasion). The inter-observer agreement for CT-detected extramural venous invasion had a κ coefficient of 0.830. The group positive for CT-detected extramural venous invasion had a median follow-up of 62.1 months, whereas the group negative for CT-detected extramural venous invasion had a median follow-up of 60.7 months. When CT-TNM stage was stratified according to CT-detected extramural venous invasion status, CT-T3 N(−)extramural venous invasion(+) had a poor prognosis compared with CT-T3 N(−)extramural venous invasion(−) and CT-stage I (5-year recurrence-free survival of 50.6 versus 89.3 and 90.1 per cent respectively; P < 0.001). In CT-stage III, the group positive for CT-detected extramural venous invasion also had a poor prognosis compared with the group negative for CT-detected extramural venous invasion (5-year recurrence-free survival of 52.0 versus 78.5 per cent respectively; P = 0.003). Multivariable analysis revealed that recurrence was associated with CT-T4 (HR 3.10, 95 per cent c.i. 1.85 to 5.20; P < 0.001) and CT-detected extramural venous invasion (HR 3.08, 95 per cent c.i. 1.90 to 5.00; P < 0.001).

Conclusion

CT-detected extramural venous invasion was found to be an independent predictor of recurrence and could be used in combination with preoperative TNM staging to identify patients at high risk of recurrence.
Disease-linked mutations in Munc18-1 deplete synaptic Doc2
Authors: Guiberson Noah Guy Lewis , Black Luca S , Haller Jillian E , Brukner Aniv , Abramov Debra , Ahmad Saad , Xie Yan Xin , Sharma Manu , Burré Jacqueline
Published: January 2024

Heterozygous de novo mutations in the neuronal protein Munc18-1/STXBP1 cause syndromic neurological symptoms, including severe epilepsy, intellectual disability, developmental delay, ataxia and tremor, summarized as STXBP1 encephalopathies. Although haploinsufficiency is the prevailing disease mechanism, it remains unclear how the reduction in Munc18-1 levels causes synaptic dysfunction in disease as well as how haploinsufficiency alone can account for the significant heterogeneity among patients in terms of the presence, onset and severity of different symptoms.

Using biochemical and cell biological readouts on mouse brains, cultured mouse neurons and heterologous cells, we found that the synaptic Munc18-1 interactors Doc2A and Doc2B are unstable in the absence of Munc18-1 and aggregate in the presence of disease-causing Munc18-1 mutants. In haploinsufficiency-mimicking heterozygous knockout neurons, we found a reduction in Doc2A/B levels that is further aggravated by the presence of the disease-causing Munc18-1 mutation G544D as well as an impairment in Doc2A/B synaptic targeting in both genotypes. We also demonstrated that overexpression of Doc2A/B partially rescues synaptic dysfunction in heterozygous knockout neurons but not heterozygous knockout neurons expressing G544D Munc18-1.

Our data demonstrate that STXBP1 encephalopathies are not only characterized by the dysfunction of Munc18-1 but also by the dysfunction of the Munc18-1 binding partners Doc2A and Doc2B, and that this dysfunction is exacerbated by the presence of a Munc18-1 missense mutant. These findings may offer a novel explanation for the significant heterogeneity in symptoms observed among STXBP1 encephalopathy patients.
Multimodal study of multilevel pulvino-temporal connections: a new piece in the puzzle of lexical retrieval networks
Authors: Maldonado Igor Lima , Descoteaux Maxime , Rheault François , Zemmoura Ilyess , Benn Austin , Margulies Daniel , Boré Arnaud , Duffau Hugues , Mandonnet Emmanuel
Published: January 2024

Advanced methods of imaging and mapping the healthy and lesioned brain have allowed for the identification of the cortical nodes and white matter tracts supporting the dual neurofunctional organization of language networks in a dorsal phonological and a ventral semantic stream. Much less understood are the anatomical correlates of the interaction between the two streams; one hypothesis being that of a subcortically mediated interaction, through crossed cortico-striato-thalamo-cortical and cortico-thalamo-cortical loops. In this regard, the pulvinar is the thalamic subdivision that has most regularly appeared as implicated in the processing of lexical retrieval. However, descriptions of its connections with temporal (language) areas remain scarce.

Here we assess this pulvino-temporal connectivity using a combination of state-of-the-art techniques: white matter stimulation in awake surgery and postoperative diffusion MRI (n = 4), virtual dissection from the Human Connectome Project 3 and 7 T datasets (n = 172) and operative microscope-assisted post-mortem fibre dissection (n = 12).

We demonstrate the presence of four fundamental fibre contingents: (i) the anterior component (Arnold’s bundle proper) initially described by Arnold in the 19th century and destined to the anterior temporal lobe; (ii) the optic radiations-like component, which leaves the pulvinar accompanying the optical radiations and reaches the posterior basal temporal cortices; (iii) the lateral component, which crosses the temporal stem orthogonally and reaches the middle temporal gyrus; and (iv) the auditory radiations-like component, which leaves the pulvinar accompanying the auditory radiations to the superomedial aspect of the temporal operculum, just posteriorly to Heschl’s gyrus.

Each of those components might correspond to a different level of information processing involved in the lexical retrieval process of picture naming.
Regioselectivity in the sulfonium-mediated arylation reactions of 2-substituted phenols with benzothienyl sulfoxide
Authors: Wakabayashi Ryota , Fukazawa Mizuki , Kurogi Takashi , Yorimitsu Hideki
Published: January 2024

The regioselectivity in the sulfonium-mediated arylation of phenols with aryl sulfoxide is significantly influenced by the substituents at the 2 position of phenols. While most substituents tend to promote the expected C–C bond formation at the 6 position, alkyl substituents induce the minor formation of rearranged biaryls, the 1,2,3-substituted isomers.
Control of thermal and mechanical properties by double-cyclopolymerization and copolymerization of trifunctional POSS with varying organic substituents
Authors: Nakano Taishi , Imoto Hiroaki , Naka Kensuke
Published: January 2024

Phenyl- and trifluoropropyl-substituted corner-opening type cage silsesquioxane (CO-POSS) monomers capped with methacrylethoxypropyldimethylsiloxy groups at the three silanol moieties were prepared by the hydrosilylation of trisdimethylsilyl-capped heptaphenyl- and heptatrifluoropropyl-substituted trisilanols with ethylene glycol monoallyl ether and subsequent reaction with methacryloyl chloride. Reversible addition-fragmentation chain transferpolymerization was performed on these monomers, and their structures and properties were compared to those of their previously-reported isobutyl-substituted counterparts. The polymer with a phenyl group exhibited enhanced thermal and mechanical properties, whereas the polymer with a trifluoropropyl group exhibited not only water repellency but also oil repellency. In addition, trifunctional CO-POSS monomers with different organic substituents could be used for double-cyclocopolymerization, and tuning of their properties was achieved. Furthermore, the trifunctional CO-POSS monomer could be used for double-cyclocopolymerization with methyl methacrylate without cross-linking.
Lewis acid catalyzed stereospecific hydroxylation of chiral tertiary alkyl halides
Authors: Tsuchiya Naoki , Iwashita Ichikaze , Yamamoto Tetsuhiro , Akagawa Hiroki , Nishikata Takashi
Published: January 2024

Stereospecific hydroxylation of chiral tertiary alkyl halides using silver salt as Lewis acid catalyst has been developed. A series of α-hydroxy carboxamides were obtained in high yield (up to 90%) and with high enantiospecificity (es; up to 99%). The reaction proceeded in a retentive manner. Control experiments showed that the reaction proceeds via an ionic reaction and that the hydroxide source comes from both water and DMSO.
A rotaxane-based supramolecular mechanophore featuring a pyridine group in the luminophore
Authors: Mori Ryusei , Sagara Yoshimitsu
Published: January 2024

To construct a supramolecular mechanophore library, expanding the variety of emitters that can be used is significant. In this study, we demonstrate that 9-(phenylethynyl)-10-((2-pyridyl)ethynyl)anthracene can be incorporated into a rotaxane-based supramolecular mechanophore as the luminophore. The polyurethane films in which the mechanophore was covalently incorporated exhibit instantly reversible on/off switches of green fluorescence upon cycle stretching.
Normal Infant Immunologic Assessment and Uneventful Live Rotavirus Vaccination Despite Continuous Tofacitinib Exposure In Utero and During Breastfeeding
Authors: Ernest-Suarez Kenneth , Murguía-Favela Luis E , Novak Kerri L , Panaccione Remo , Constantinescu Cora , Seow Cynthia H
Published: January 2024

Background

Janus kinase (JAK) inhibitors are effective for the treatment of inflammatory bowel disease (IBD). However, this class of medications is not recommended during pregnancy or breastfeeding based on animal data suggesting teratogenesis and recent reports of transmammary transfer after maternal ingestion, raising concerns for immune system development in babies exposed to these drugs.

Methods

We present the case of a patient with IBD treated with a JAK inhibitor who decided to continue the medication throughout her pregnancy and during breastfeeding. This is the first reported case of a detailed immunologic profile in a baby exposed to tofacitinib in utero and during lactation.

Results

A 30-year-old female with ulcerative colitis with previous exposure to vedolizumab and infliximab achieved complete remission with tofacitinib therapy. The patient became pregnant after 5 months of JAK inhibitor therapy and decided to continue tofacitinib during pregnancy and while breastfeeding. The patient delivered a healthy offspring with no congenital malformations, a normal detailed immunologic profile, and subsequent safe provision of the live oral rotavirus vaccine.

Conclusions

This case highlights the importance of individualized counseling for patients of childbearing age who are candidates for JAK inhibition. Those who are pregnant or breastfeeding with refractory disease may have limited medical therapeutic options. Ongoing effective therapy for IBD resulted in complete disease remission in the mother and favorable outcomes in the infant. Further, an in-depth infant immunological assessment can lead to specific vaccination recommendations in exposed infants.
Limitations of apical sparing pattern in cardiac amyloidosis: a multicentre echocardiographic study
Authors: Cotella Juan , Randazzo Michael , Maurer Mathew S , Helmke Stephen , Scherrer-Crosbie Marielle , Soltani Marwa , Goyal Akash , Zareba Karolina , Cheng Richard , Kirkpatrick James N , Yogeswaran Vidhushei , Kitano Tetsuji , Takeuchi Masaaki , Fernandes Fábio , Hotta Viviane Tiemi , Campos Vieira Marcelo Luiz , Elissamburu Pablo , Ronderos Ricardo , Prado Aldo , Koutroumpakis Efstratios , Deswal Anita , Pursnani Amit , Sarswat Nitasha , Addetia Karima , Mor-Avi Victor , Asch Federico M , Slivnick Jeremy A , Lang Roberto M
Published: January 2024

Aims

Although impaired left ventricular (LV) global longitudinal strain (GLS) with apical sparing is a feature of cardiac amyloidosis (CA), its diagnostic accuracy has varied across studies. We aimed to determine the ability of apical sparing ratio (ASR) and most common echocardiographic parameters to differentiate patients with confirmed CA from those with clinical and/or echocardiographic suspicion of CA but with this diagnosis ruled out.

Methods and results

We identified 544 patients with confirmed CA and 200 controls (CTRLs) as defined above (CTRL patients). Measurements from transthoracic echocardiograms were performed using artificial intelligence software (Us2.AI, Singapore) and audited by an experienced echocardiographer. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance and optimal cut-offs for the differentiation of CA patients from CTRL patients. Additionally, a group of 174 healthy subjects (healthy CTRL) was included to provide insight on how patients and healthy CTRLs differed echocardiographically. LV GLS was more impaired (−13.9 ± 4.6% vs. −15.9 ± 2.7%, P < 0.0005), and ASR was higher (2.4 ± 1.2 vs. 1.7 ± 0.9, P < 0.0005) in the CA group vs. CTRL patients. Relative wall thickness and ASR were the most accurate parameters for differentiating CA from CTRL patients [area under the curve (AUC): 0.77 and 0.74, respectively]. However, even with the optimal cut-off of 1.67, ASR was only 72% sensitive and 66% specific for CA, indicating the presence of apical sparing in 32% of CTRL patients and even in 6% healthy subjects.

Conclusion

Apical sparing did not prove to be a CA-specific biomarker for accurate identification of CA, when compared with clinically similar CTRLs with no CA.
Deep learning for automatic volumetric segmentation of left ventricular myocardium and ischaemic scar from multi-slice late gadolinium enhancement cardiovascular magnetic resonance
Authors: Jani Vivek P , Ostovaneh Mohammad , Chamera Elzbieta , Kato Yoko , Lima Joao A C , Ambale-Venkatesh Bharath
Published: January 2024

Aims

This study details application of deep learning for automatic volumetric segmentation of left ventricular (LV) myocardium and scar and automated quantification of myocardial ischaemic scar burden from late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR).

Methods and results

We included 501 images and manual segmentations of short-axis LGE-CMR from over 20 multinational sites, from which 377 studies were used for training and 124 studies from unique participants for internal validation. A third test set of 52 images was used for external evaluation. Three models, U-Net, Cascaded U-Net, and U-Net++, were trained with a novel adaptive weighted categorical cross-entropy loss function. Model performance was evaluated using concordance correlation coefficients (CCCs) for LV mass and per cent myocardial scar burden. Cascaded U-Net was found to be the best model for the quantification of LV mass and scar percentage. The model exhibited a mean difference of −5 ± 23 g for LV mass, −0.4 ± 11.2 g for scar mass, and −0.8 ± 7% for per cent scar. CCC were 0.87, 0.77, and 0.78 for LV mass, scar mass, and per cent scar burden, respectively, in the internal validation set and 0.75, 0.71, and 0.69, respectively, in the external test set. For segmental scar mass, CCC was 0.74 for apical scar, 0.91 for mid-ventricular scar, and 0.73 for basal scar, demonstrating moderate to strong agreement.

Conclusion

We successfully trained a convolutional neural network for volumetric segmentation and analysis of LV scar burden from LGE-CMR images in a large, multinational cohort of participants with ischaemic scar.
Reconsidering the developmental origins of adult disease paradigm
Authors: Wells Jonathan C K , Desoye Gernot , Leon David A
Published: January 2024

In uncomplicated pregnancies, birthweight is inversely associated with adult non-communicable disease (NCD) risk. One proposed mechanism is maternal malnutrition during pregnancy. Another explanation is that shared genes link birthweight with NCDs. Both hypotheses are supported, but evolutionary perspectives address only the environmental pathway. We propose that genetic and environmental associations of birthweight with NCD risk reflect coordinated regulatory systems between mother and foetus, that evolved to reduce risks of obstructed labour. First, the foetus must tailor its growth to maternal metabolic signals, as it cannot predict the size of the birth canal from its own genome. Second, we predict that maternal alleles that promote placental nutrient supply have been selected to constrain foetal growth and gestation length when fetally expressed. Conversely, maternal alleles that increase birth canal size have been selected to promote foetal growth and gestation when fetally expressed. Evidence supports these hypotheses. These regulatory mechanisms may have undergone powerful selection as hominin neonates evolved larger size and encephalisation, since every mother is at risk of gestating a baby excessively for her pelvis. Our perspective can explain the inverse association of birthweight with NCD risk across most of the birthweight range: any constraint of birthweight, through plastic or genetic mechanisms, may reduce the capacity for homeostasis and increase NCD susceptibility. However, maternal obesity and diabetes can overwhelm this coordination system, challenging vaginal delivery while increasing offspring NCD risk. We argue that selection on viable vaginal delivery played an over-arching role in shaping the association of birthweight with NCD risk.
Genetic inhibition of angiopoietin-like protein-3, lipids, and cardiometabolic risk
Authors: Gobeil Émilie , Bourgault Jérôme , Mitchell Patricia L , Houessou Ursula , Gagnon Eloi , Girard Arnaud , Paulin Audrey , Manikpurage Hasanga D , Côté Valérie , Couture Christian , Marceau Simon , Bossé Yohan , Thériault Sébastien , Mathieu Patrick , Vohl Marie-Claude , Tchernof André , Arsenault Benoit J
Published: January 2024

Background and Aims

RNA-based, antibody-based, and genome editing-based therapies are currently under investigation to determine if the inhibition of angiopoietin-like protein-3 (ANGPTL3) could reduce lipoprotein-lipid levels and atherosclerotic cardiovascular disease (ASCVD) risk. Mendelian randomisation (MR) was used to determine whether genetic variations influencing ANGPTL3 liver gene expression, blood levels, and protein structure could causally influence triglyceride and apolipoprotein B (apoB) levels as well as coronary artery disease (CAD), ischaemic stroke (IS), and other cardiometabolic diseases.

Methods

RNA sequencing of 246 explanted liver samples and genome-wide genotyping was performed to identify single-nucleotide polymorphisms (SNPs) associated with liver expression of ANGPTL3. Genome-wide summary statistics of plasma protein levels of ANGPTL3 from the deCODE study (n = 35 359) were used. A total of 647 carriers of ANGPTL3 protein-truncating variants (PTVs) associated with lower plasma triglyceride levels were identified in the UK Biobank. Two-sample MR using SNPs that influence ANGPTL3 liver expression or ANGPTL3 plasma protein levels as exposure and cardiometabolic diseases as outcomes was performed (CAD, IS, heart failure, non-alcoholic fatty liver disease, acute pancreatitis, and type 2 diabetes). The impact of rare PTVs influencing plasma triglyceride levels on apoB levels and CAD was also investigated in the UK Biobank.

Results

In two-sample MR studies, common genetic variants influencing ANGPTL3 hepatic or blood expression levels of ANGPTL3 had a very strong effect on plasma triglyceride levels, a more modest effect on low-density lipoprotein cholesterol, a weaker effect on apoB levels, and no effect on CAD or other cardiometabolic diseases. In the UK Biobank, the carriers of rare ANGPTL3 PTVs providing lifelong reductions in median plasma triglyceride levels [−0.37 (interquartile range 0.41) mmol/L] had slightly lower apoB levels (−0.06 ± 0.32 g/L) and similar CAD event rates compared with non-carriers (10.2% vs. 10.9% in carriers vs. non-carriers, P = .60).

Conclusions

PTVs influencing ANGPTL3 protein structure as well as common genetic variants influencing ANGPTL3 hepatic expression and/or blood protein levels exhibit a strong effect on circulating plasma triglyceride levels, a weak effect on circulating apoB levels, and no effect on ASCVD. Near-complete inhibition of ANGPTL3 function in patients with very elevated apoB levels may be required to reduce ASCVD risk.
Mitral transcatheter edge-to-edge repair vs. isolated mitral surgery for severe mitral regurgitation: a French nationwide study
Authors: Deharo Pierre , Obadia Jean Francois , Guerin Patrice , Cuisset Thomas , Avierinos Jean Francois , Habib Gilbert , Torras Olivier , Bisson Arnaud , Vigny Pascal , Etienne Christophe Saint , Semaan Carl , Guglieri Mickael , Dumonteil Nicolas , Collart Frederic , Gilard Martine , Modine Thomas , Donal Erwan , Iung Bernard , Fauchier Laurent
Published: January 2024

Background and Aims

Mitral valve surgery and, more recently, mitral transcatheter edge-to-edge repair (TEER) are the two treatments of severe mitral regurgitation in eligible patients. Clinical comparison of both therapies remains limited by the number of patients analysed. The objective of this study was to analyse the outcomes of mitral TEER vs. isolated mitral valve surgery at a nationwide level in France.

Methods

Based on the French administrative hospital discharge database, the study collected information for all consecutive patients treated for mitral regurgitation with isolated TEER or isolated mitral valve surgery between 2012 and 2022. Propensity score matching was used for the analysis of outcomes.

Results

A total of 57 030 patients were found in the database. After matching on baseline characteristics, 2160 patients were analysed in each arm. At 3-year follow-up, TEER was associated with significantly lower incidence of cardiovascular death (hazard ratio 0.685, 95% confidence interval 0.563–0.832; P = .0001), pacemaker implantation, and stroke. Non-cardiovascular death (hazard ratio 1.562, 95% confidence interval 1.238–1.971; P = .0002), recurrent pulmonary oedema, and cardiac arrest were more frequent after TEER. No significant differences between the two groups were observed regarding all-cause death (hazard ratio 0.967, 95% confidence interval 0.835–1.118; P = .65), endocarditis, major bleeding, atrial fibrillation, and myocardial infarction.

Conclusions

Our results suggest that TEER for severe mitral regurgitation was associated with lower cardiovascular mortality than mitral surgery at long-term follow-up. Pacemaker implantation and stroke were less frequently observed after TEER.
Obesity and cardiovascular health
Authors: Welsh Aimee , Hammad Muhammad , Piña Ileana L , Kulinski Jacquelyn
Published: January 2024

Obesity has risen to epidemic levels worldwide over the past few decades and has become a huge global health burden owing to its direct contribution to the development of some of the most prevalent chronic diseases including diabetes, hypertension, hyperlipidaemia, and other cardiovascular diseases. Obesity is a disease of positive energy balance resulting from complex interactions between abnormal neurohumoral responses and an individual’s socioeconomic, environmental, behavioural, and genetic factors leading to a state of chronic inflammation. Understanding the complex nature of the disease is crucial in determining the best approach to combat its rising numbers. Despite recent advancements in pharmacological therapy for the treatment of obesity, reversing weight gain and maintaining weight loss is challenging due to the relapsing nature of the disease. Prevention, therefore, remains the key which needs to start in utero and continued throughout life. This review summarizes the role obesity plays in the pathophysiology of various cardiovascular diseases both by directly affecting endothelial and myocyte function and indirectly by enhancing major cardiovascular risk factors like diabetes, hypertension, and hyperlipidaemia. We highlight the importance of a holistic approach needed to prevent and treat this debilitating disease. Particularly, we analyse the effects of plant-based diet, regular exercise, and non-exercise activity thermogenesis on obesity and overall cardiorespiratory fitness. Moreover, we discuss the significance of individualizing obesity management with a multimodal approach including lifestyle modifications, pharmacotherapy, and bariatric surgery to tackle this chronic disease.
Influence of repeated plaque visualization on cardiovascular risk reduction after 3 years: a randomized controlled trial
Authors: Whitmore Kristyn , Zhou Zhen , Ryan Jacqueline D M , Magnussen Costan G , Carrington Melinda J , Marwick Thomas H
Published: January 2024

Aims

Helping people to understand their cardiovascular (CV) risk can influence the choices they make for risk reduction, including medication adherence and lifestyle modification. This study sought whether repeated visualization of coronary artery calcium (CAC) images was effective in sustaining long-term risk control in primary prevention, independent of a risk reduction programme.

Methods and results

Asymptomatic, statin-naïve participants, 40–70 years, with a family history of premature coronary artery disease and a CAC score from 1–400 were randomized to a nurse-led CV risk reduction programme or standard care with bi-annual reviews. Only the intervention group (220 of 449 participants) visualized their CAC image (with repeat exposure in the first 3 months) and were initiated on statin therapy. The primary outcome was change in Framingham Risk Score (FRS) at 36 months, and the impact of CAC image recall on CV risk was assessed. The reduction in FRS (difference in differences (DID) −3.4% [95% CI: −4.4% to −2.4%], P ≤ 0.001 and low density lipoprotein cholesterol −1.2 mmol/L [95% CI: −1.4 to −1.0], P ≤ 0.001) over 36 months was greater in the intervention than the control group. Within the intervention group, sustained recall of CAC images at 24 months was associated with lower systolic blood pressure (DID −4.3 mmHg [95% CI: −7.7 to −0.9], P = 0.01) and waist circumference (DID −2.0 cm [95% CI: −3.9 to −0.1], P = 0.03) at 36 months compared to unsustained recall.

Conclusion

A nurse-led programme, combining personalized patient visualization of CAC imaging with statin therapy, is beneficial for improving CV risk. Recalling the presentation of CAC images through repeated visual exposure may influence risk reduction.

Registration

Australia New Zealand Clinical Trials Registry: ACTRN12614001294640

Lay summary

This trial sought to determine whether visualization of coronary artery calcium (CAC) images influences behaviour change and cardiovascular risk reduction within a structured nurse-led programme vs. standard care. Intervention participants visualized their personalized CAC images within the first three months and commenced statin therapy. Control participants were blinded to their CAC images and were not provided statin therapy. Intervention participants had a greater absolute reduction in the Framingham Risk Score (difference in differences −3.4% [95% CI: −4.4% to −2.4%], P ≤ 0.001) compared to controls. Those with sustained recollection of their CAC images within the intervention group also had greater reductions in systolic blood pressure and waist circumference.
Prevalence and clinical significance of low QRS voltages in healthy individuals, athletes, and patients with cardiomyopathy: implications for sports pre-participation cardiovascular screening
Authors: Pelliccia Antonio , Drezner Jonathan A , Zorzi Alessandro , Corrado Domenico
Published: January 2024

Low QRS voltages (LQRSV), defined as a QRS amplitude from peak to nadir < 0.5 mV in all limb leads, are an emerging diagnostic finding on the electrocardiogram (ECG). In healthy individuals and athletes, LQRSV are rare (2.2–4% of elite athletes, 0.5% of recreational athletes, and 0.3% of sedentary individuals). LQRSV athletes commonly show ventricular arrhythmias (VAs) on exercise, and up to 40% of those with LQRSV and VAs have late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR). The prevalence of LQRSV in arrhythmogenic cardiomyopathy ranges from 17–40%, predicts left ventricular (LV) involvement, and is correlated with more extensive LGE replacement on CMR. In hypertrophic cardiomyopathy (HCM), LQRSV ranges from 0.7–11%. LQRSV-HCM patients have more segments with LGE, despite relatively smaller LV mass, suggesting a more advanced clinical stage and a worse prognosis. In dilated cardiomyopathy (DCM), LQRSV range from 6–7%, but may be higher (36%) in certain genetic forms of DCM. On a follow-up, LQRSV are independently associated with incident cardiac events, such as sudden death, sustained ventricular arrhythmia, or appropriate internal cardioverter defibrillator discharge. In cardiac amyloid, LQRSV range from 34–66% and demonstrate a negative prognostic value, with worse clinical outcomes regardless of underlying biologic, genetic, and clinical variables. In conclusion, LQRSV deserve careful consideration for exclusion of arrhythmogenic substrates in healthy individuals, athletes, and patients. While additional research is needed, it is reasonable that LQRSV should trigger clinical investigation to exclude underlying diseases at risk of life-threatening arrhythmias.
Beyond early LDL cholesterol lowering to prevent coronary atherosclerosis in familial hypercholesterolaemia
Authors: Ibrahim Shirin , Reeskamp Laurens F , de Goeij Jim N , Hovingh G Kees , Planken R Nils , Bax Willem A , Min James K , Earls James P , Knaapen Paul , Wiegman Albert , Stroes Erik S G , Nurmohamed Nick S
Published: January 2024

Aims

Familial hypercholesterolaemia (FH) patients are subjected to a high lifetime exposure to low density lipoprotein cholesterol (LDL-C), despite use of lipid-lowering therapy (LLT). This study aimed to quantify the extent of subclinical atherosclerosis and to evaluate the association between lifetime cumulative LDL-C exposure and coronary atherosclerosis in young FH patients.

Methods and results

Familial hypercholesterolaemia patients, divided into a subgroup of early treated (LLT initiated <25 years) and late treated (LLT initiated ≥25 years) patients, and an age- and sex-matched unaffected control group, underwent coronary CT angiography (CCTA) with artificial intelligence-guided analysis. Ninety genetically diagnosed FH patients and 45 unaffected volunteers (mean age 41 ± 3 years, 51 (38%) female) were included. Familial hypercholesterolaemia patients had higher cumulative LDL-C exposure (181 ± 54 vs. 105 ± 33 mmol/L ∗ years) and higher prevalence of coronary plaque compared with controls (46 [51%] vs. 10 [22%], OR 3.66 [95%CI 1.62–8.27]). Every 75 mmol/L ∗ years cumulative exposure to LDL-C was associated with a doubling in per cent atheroma volume (total plaque volume divided by total vessel volume). Early treated patients had a modestly lower cumulative LDL-C exposure compared with late treated FH patients (167 ± 41 vs. 194 ± 61 mmol/L ∗ years; P = 0.045), without significant difference in coronary atherosclerosis. Familial hypercholesterolaemia patients with above-median cumulative LDL-C exposure had significantly higher plaque prevalence (OR 3.62 [95%CI 1.62–8.27]; P = 0.001), compared with patients with below-median exposure.

Conclusion

Lifetime exposure to LDL-C determines coronary plaque burden in FH, underlining the need of early as well as potent treatment initiation. Periodic CCTA may offer a unique opportunity to monitor coronary atherosclerosis and personalize treatment in FH.
Examining potential Long COVID effects through utilization of healthcare resources: a retrospective, population-based, matched cohort study comparing individuals with and without prior SARS-CoV-2 infection
Authors: Castriotta Luigi , Onder Graziano , Rosolen Valentina , Beorchia Yvonne , Fanizza Caterina , Bellini Benedetta , Floridia Marco , Giuliano Marina , Silenzi Andrea , Pricci Flavia , Grisetti Tiziana , Grassi Tiziana , Tiple Dorina , Villa Marika , Profili Francesco , Francesconi Paolo , Barbone Fabio , Bisceglia Lucia , Brusaferro Silvio
Published: January 2024

Background

A significant proportion of individuals reports persistent clinical manifestations following SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) acute infection. Nevertheless, knowledge of the burden of this condition—often referred to as ‘Long COVID’—on the health care system remains limited. This study aimed to evaluate healthcare utilization potentially related to Long COVID.

Methods

Population-based, retrospective, multi-center cohort study that analyzed hospital admissions and utilization of outpatient visits and diagnostic tests between adults aged 40 years and older recovered from SARS-CoV-2 infection occurred between February 2020 and December 2021 and matched unexposed individuals during a 6-month observation period. Healthcare utilization was analyzed by considering the setting of care for acute SARS-CoV-2 infection [non-hospitalized, hospitalized and intensive care unit (ICU)-admitted] as a proxy for the severity of acute infection and epidemic phases characterized by different SARS-CoV-2 variants. Data were retrieved from regional health administrative databases of three Italian Regions.

Results

The final cohort consisted of 307 994 previously SARS-CoV-2 infected matched with 307 994 uninfected individuals. Among exposed individuals, 92.2% were not hospitalized during the acute infection, 7.3% were hospitalized in a non-ICU ward and 0.5% were admitted to ICU. Individuals previously infected with SARS-CoV-2 (vs. unexposed), especially those hospitalized or admitted to ICU, reported higher utilization of outpatient visits (range of pooled Incidence Rate Ratios across phases; non-hospitalized: 1.11–1.33, hospitalized: 1.93–2.19, ICU-admitted: 3.01–3.40), diagnostic tests (non-hospitalized: 1.35–1.84, hospitalized: 2.86–3.43, ICU-admitted: 4.72–7.03) and hospitalizations (non-hospitalized: 1.00–1.52, hospitalized: 1.87–2.36, ICU-admitted: 4.69–5.38).

Conclusions

This study found that SARS-CoV-2 infection was associated with increased use of health care in the 6 months following infection, and association was mainly driven by acute infection severity.
Capitalism and the French Revolution
Authors: Sonenscher Michael
Published: January 2024

The aim of this article is to raise, and begin to answer, a question about the relationship between the French Revolution and capitalism. Discussion of the relationship between the two subjects began somewhat later in the nineteenth century than is usually assumed and owed quite a lot to the thought of one of Jean Jaurès’ contemporaries, the Italian Marxist Antonio Labriola. As will be shown, the connection that Labriola made between capitalism and the French Revolution was based on a number of distinctive concepts of capitalism, the French Revolution and history itself. One of the implications of this article is to suggest that without these concepts the French Revolution could begin to look quite different.
Multienvironment genomic prediction in tetraploid potato
Authors: Wilson Stefan , Zheng Chaozhi , Maliepaard Chris , Mulder Han A , Visser Richard G F , van Eeuwijk Fred
Published: January 2024

Multienvironment genomic prediction was applied to tetraploid potato using 147 potato varieties, tested for 2 years, in 3 locations representative of 3 distinct regions in Europe. Different prediction scenarios were investigated to help breeders predict genotypic performance in the regions from one year to the next, for genotypes that were tested this year (scenario 1), as well as new genotypes (scenario 3). In scenario 2, we predicted new genotypes for any one of the 6 trials, using all the information that is available. The choice of prediction model required assessment of the variance–covariance matrix in a mixed model that takes into account heterogeneity of genetic variances and correlations. This was done for each analyzed trait (tuber weight, tuber length, and dry matter) where examples of both limited and higher degrees of heterogeneity was observed. This explains why dry matter did not need complex multienvironment modeling to combine environments and increase prediction ability, while prediction in tuber weight, improved only when models were flexible enough to capture the heterogeneous variances and covariances between environments. We also found that the prediction abilities in a target trial condition decreased, if trials with a low genetic correlation to the target were included when training the model. Genomic prediction in tetraploid potato can work once there is clarity about the prediction scenario, a suitable training set is created, and a multienvironment prediction model is chosen based on the patterns of G×E indicated by the genetic variances and covariances.
Expression and potential regulatory functions of Drosophila octopamine receptors in the female reproductive tract
Authors: Rohrbach Ethan W , Knapp Elizabeth M , Deshpande Sonali A , Krantz David E
Published: January 2024

Aminergic signaling is known to play a critical role in regulating female reproductive processes in both mammals and insects. In Drosophila, the ortholog of noradrenaline, octopamine, is required for ovulation as well as several other female reproductive processes. Two octopamine receptors have already been shown to be expressed in the Drosophila reproductive tract and to be required for egg-laying: OAMB and Octβ2R. The Drosophila genome contains 4 additional octopamine receptors—Octα2R, Octβ1R, Octβ3R, and Oct-TyrR—but their cellular patterns of expression in the reproductive tract and potential contribution(s) to egg-laying are not known. In addition, the mechanisms by which OAMB and Octβ2R regulate reproduction are incompletely understood. Using a panel of MiMIC Gal4 lines, we show that Octα2R, Octβ1R, Octβ3R, and Oct-TyrR receptors are not detectable in either epithelium or muscle but are clearly expressed in neurons within the female fly reproductive tract. Optogenetic activation of neurons that express at least 3 types of octopamine receptors stimulates contractions in the lateral oviduct. We also find that octopamine stimulates calcium transients in the sperm storage organs and that its effects in spermathecal, secretory cells, can be blocked by knock-down of OAMB. These data extend our understanding of the pathways by which octopamine regulates egg-laying in Drosophila and raise the possibility that multiple octopamine receptor subtypes could play a role in this process.
Bayesian tomography using polynomial chaos expansion and deep generative networks
Authors: Meles Giovanni Angelo , Amaya Macarena , Levy Shiran , Marelli Stefano , Linde Niklas
Published: January 2024

Implementations of Markov chain Monte Carlo (MCMC) methods need to confront two fundamental challenges: accurate representation of prior information and efficient evaluation of likelihood functions. The definition and sampling of the prior distribution can often be facilitated by standard dimensionality-reduction techniques such as Principal Component Analysis (PCA). Additionally, PCA-based decompositions can enable the implementation of accurate surrogate models, for instance, based on polynomial chaos expansion (PCE). However, intricate geological priors with sharp contrasts may demand advanced dimensionality-reduction techniques, such as deep generative models (DGMs). Although suitable for prior sampling, these DGMs pose challenges for surrogate modelling. In this contribution, we present a MCMC strategy that combines the high reconstruction performance of a DGM in the form of a variational autoencoder with the accuracy of PCA–PCE surrogate modelling. Additionally, we introduce a physics-informed PCA decomposition to improve accuracy and reduce the computational burden associated with surrogate modelling. Our methodology is exemplified in the context of Bayesian ground-penetrating radar traveltime tomography using channelized subsurface structures, providing accurate reconstructions and significant speed-ups, particularly when the computation of the full-physics forward model is costly.
Ascent of volatile-rich felsic magma in dykes: a numerical model applied to deep-sourced porphyry intrusions
Authors: Abdullin R , Melnik O , Rust A , Blundy J , Lgotina E , Golovin S
Published: January 2024

Dyke propagation is a mechanism for more rapid ascent of felsic magmas through the crust than is possible via diapirs or percolative flow. As it ascends, the magma undergoes complex physical and chemical transformations induced by decompression and cooling. These processes dramatically change the magma density and viscosity, which in turn affect magma ascent rate and the depth at which the dyke arrests. We present a mathematical model of dyke propagation for silicic magmas taking into account the presence of multiple volatile species (H2O and CO2), bubble growth, heat advection and loss, crystallization and latent heat release. We consider conditions for dykes associated with porphyry ore deposits, which may represent an end-member in rapid ascent of felsic magmas from depth. In particular, we simulate the propagation of dykes launched from a deep (900 MPa), volatile-saturated magma source, testing the effects of the magma H2O/CO2 content, temperature and mass on its ascent rate and final emplacement depth. The model predicts short ascent times (hours to days), with a large increase in viscosity at shallow depth, leading to stagnation and solidification of the dyke. Higher initial water content, higher temperature and larger mass of the magma in the dyke promote faster propagation and shallower arrest. Volatile loss from ascending magma remains limited until the stagnation depth, providing a potential mechanism for transfer of deep volatiles to hypabyssal blind intrusions associated with porphyry ore deposits. Our findings are applicable to the problem of silicic magma ascent through the crust more generally.