bluuebunny/crossref_metadata_2025_split huggingface dataset:
Poly-p-dioxanone Thread Leads to Fat Metabolism Around the Thread in Pig Subcutaneous Back Fat
Authors: Su Diya , Niu Huanyun , Wang Shiwei , Wang Jieqing 
Published: January 2024

Abstract

Background
When poly-p-dioxanone (PDO) thread is implanted subcutaneously, in addition to collagen hyperplasia, it can also cause denaturation of surrounding adipocytes and reduce the thickness of the fat layer. Hitherto, no studies have thoroughly investigated the effects of PDO thread on adipose tissue.

Objectives
In this study, the effect of PDO thread on adipose tissue was investigated in an animal model.

Methods
In the current study, PDO thread was implanted into subcutaneous adipose tissue of the back in a miniature pig. Implantation site tissue and control site tissue were taken 12 weeks after implantation for hematoxylin and eosin (H&E) staining and transcriptome sequencing. Gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed to investigate the differential gene expression between PDO thread implantation and control site tissue.

Results
An obvious decrease in the number, fusion, and denaturation of adipocytes can be seen by H&E staining. Sequencing analysis results showed that many of the genes identified, which were downregulated after PDO thread implantation, were involved in functions and pathways related to lipid metabolism, such as fatty acid metabolism, fatty acid degradation, and lipid cell lipolysis regulation. Some genes related to fatty acid metabolism were significantly downregulated in the PDO tissue at 12 weeks compared to the control tissue.

Conclusions
Our results showed PDO thread implantation can cause a decrease in the number of adipocytes, as well as a significant alteration of the expression levels of some genes involved in lipid metabolism-related pathways. PDO thread might play an important role in promoting lipolysis.

Level of Evidence: 5
Ocrelizumab associates with reduced cerebrospinal fluid B and CD20dim CD4+ T cells in primary progressive multiple sclerosis
Authors: van Puijfelik Fabiënne , Blok Katelijn M , Klein Kranenbarg Romy A M , Rip Jasper , de Beukelaar Janet , Wierenga-Wolf Annet F , Wokke Beatrijs , van Luijn Marvin M , Smolders Joost 
Published: January 2024

Abstract
The anti-CD20 monoclonal antibody ocrelizumab reduces disability progression in primary progressive multiple sclerosis. CD20 is a prototypical B-cell marker; however, subpopulations of CD4+ and CD8+ T cells in peripheral blood and cerebrospinal fluid also express low levels of CD20 (CD20dim). Therefore, direct targeting and depletion of these CD20dim T-cell subpopulations may contribute to the therapeutic effect of ocrelizumab. The aim of this observational cohort study was to compare CD20+ B-cell and CD20dim T-cell distributions between peripheral blood and cerebrospinal fluid of ocrelizumab-treated or ocrelizumab-untreated people with primary progressive multiple sclerosis. Ocrelizumab treatment was associated with depletion of circulating B cells and CD20dim CD4+ and CD20dim CD8+ T cells (P &lt; 0.0001, P = 0.0016 and P = 0.0008, respectively) but, in cerebrospinal fluid, only with lower proportions of B cells and CD20dim memory CD4+ T cells (P &lt; 0.0001 and P = 0.0043, respectively). The proportional prevalence of cerebrospinal fluid CD20dim memory CD8+ T cells was not significantly reduced (P = 0.1333). Only in cerebrospinal fluid, the proportions of CD20dim cells within CD4+ and not CD8+ T cells positive for CCR5, CCR6 and CXCR3 were reduced in ocrelizumab-treated participants. The proportion of CD20dim CD4+ T cells and abundance of CD4+ relative to CD8+ T cells in cerebrospinal fluid correlated positively with age (R = 0.6799, P = 0.0150) and Age-Related Multiple Sclerosis Severity score (R = 0.8087, P = 0.0014), respectively. We conclude that, in contrast to cerebrospinal fluid CD20dim CD8+ T cells, B cells and CD20dim CD4+ T cells are reduced in cerebrospinal fluid of people with primary progressive multiple sclerosis with an ocrelizumab-associated depletion of circulating B cells and CD20dim T cells. Therefore, these cells are likely to contribute to the therapeutic effects of ocrelizumab in people with primary progressive multiple sclerosis.
Synthesis of dioxapropellanes using Mn(III)-based oxidative tandem cyclization of tetracarbonyl compounds with diarylethenes
Authors: Shibuya Keisuke , Chikamatsu Ayaka , Hisano Kazuki , Nishino Hiroshi 
Published: January 2024

Abstract
The Mn(III)-based oxidation of tetracarbonyl compounds with 1,1-diarylethenes formed dioxapropellanes. The use of methylenebis(3-hydroxycyclohex-2-en-1-one)s as a tetracarbonyl compound led to the production of 3,4,5,6,7,9-hexahydro-8H-4a,9a-(epoxyethano)xanthene-1,8(2H)-diones in good yields. Although the reaction competed with self-cyclization to form 3,5,6,7-tetrahydro-4H-spiro[benzofuran-2,1′-cyclohexane]-2′,4,6′-triones, it could be controlled by adding the co-solvent formic acid at room temperature. The reactions of alkyl- and aryl-substituted methylenebis(3-hydroxycyclohex-2-en-1-one)s resulted in the corresponding dioxapropellanes as a diastereomixture. The formation of diastereomers is explained by the steric hindrance of the intermediate carbocations during tandem cyclization. The reactions using 2-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-en-1-yl)butane-1,4-diones and 2,2′-methylenebis(3-hydroxycyclopent-2-en-1-one)s also produced the corresponding dioxapropellanes. The structure determination of the products and the reaction pathway for the formation of dioxapropellanes are discussed.
Task learning is subserved by a domain-general brain network
Authors: Yeon Jiwon , Larson Alina Sue , Rahnev Dobromir , D’Esposito Mark 
Published: January 2024

Abstract
One of the most important human faculties is the ability to acquire not just new memories but the capacity to perform entirely new tasks. However, little is known about the brain mechanisms underlying the learning of novel tasks. Specifically, it is unclear to what extent learning of different tasks depends on domain-general and/or domain-specific brain mechanisms. Here human subjects (n = 45) learned to perform 6 new tasks while undergoing functional MRI. The different tasks required the engagement of perceptual, motor, and various cognitive processes related to attention, expectation, speed-accuracy tradeoff, and metacognition. We found that a bilateral frontoparietal network was more active during the initial compared with the later stages of task learning, and that this effect was stronger for task variants requiring more new learning. Critically, the same frontoparietal network was engaged by all 6 tasks, demonstrating its domain generality. Finally, although task learning decreased the overall activity in the frontoparietal network, it increased the connectivity strength between the different nodes of that network. These results demonstrate the existence of a domain-general brain network whose activity and connectivity reflect learning for a variety of new tasks, and thus may underlie the human capacity for acquiring new abilities.
Synthesis and optical properties of chiral dinaphthofuran possessing two methyl groups in the bay region
Authors: Sakai Misato , Wakabayashi Sae , Hasegawa Koki , Imayoshi Ayumi , Imai Yoshitane , Sasamori Takahiro , Tsubaki Kazunori 
Published: January 2024

Abstract
8,8′-dimethyl-1,1′-bi-2-naphthol (7) was synthesized by oxidative dimerization of 8-methyl-2-naphthol (6). Camphorsulfonyl chloride was used as a chiral-resolving agent, followed by the synthesis of chiral dimethyl dinaphthofuran 3 by a dehydration reaction between two hydroxy groups without loss of optical purity. The racemization barrier and optical properties of the chiral compound 3 were scrutinized.
Mechanistic characterization of waterborne selenite uptake in the water flea, Daphnia magna, indicates water chemistry affects toxicity in coal mine-impacted waters
Authors: Klaczek Chantelle E , Goss Greg G , Glover Chris N 
Published: January 2024

Abstract
Concentrations of selenium that exceed regulatory guidelines have been associated with coal mining activities and have been linked to detrimental effects on aquatic ecosystems and the organisms therein. Although the major route of selenium uptake in macroinvertebrates is via the diet, the uptake of waterborne selenite (HSeO3−), the prominent form at circumneutral pH, can be an important contributor to selenium body burden and thus selenium toxicity. In the current study, radiolabelled selenite (Se75) was used to characterize the mechanism of selenite uptake in the water flea, Daphnia magna. The concentration dependence (1–32 μM) of selenite uptake was determined in 1-hour uptake assays in artificial waters that independently varied in bicarbonate, chloride, sulphate, phosphate and selenate concentrations. At concentrations representative of those found in highly contaminated waters, selenite uptake was phosphate-dependent and inhibited by foscarnet, a phosphate transport inhibitor. At higher concentrations, selenite uptake was dependent on waterborne bicarbonate concentration and inhibited by the bicarbonate transporter inhibitor DIDS (4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid). These findings suggest that concentrations of phosphate in coal mining-affected waters could alter selenite uptake in aquatic organisms and could ultimately affect the toxic impacts of selenium in such waters.
Deciphering the relationship between temperature and immunity
Authors: Maloney Elizabeth , Duffy Darragh 
Published: January 2024

Summary
Fever is a hallmark symptom of disease across the animal kingdom. Yet, despite the evidence linking temperature fluctuation and immune response, much remains to be discovered about the molecular mechanisms governing these interactions. In patients with rheumatoid arthritis, for instance, it is clinically accepted that joint temperature can predict disease progression. But it was only recently demonstrated that the mitochondria of stimulated T cells can rise to an extreme 50°C, potentially indicating a cellular source of these localized ‘fevers’. A challenge to dissecting these mechanisms is a bidirectional interplay between temperature and immunity. Heat shock response is found in virtually all organisms, activating protective pathways when cells are exposed to elevated temperatures. However, the temperature threshold that activates these pathways can vary within the same organism, with human immune cells, in particular, demonstrating differential sensitivity to heat. Such inter-cellular variation may be clinically relevant given the small but significant temperature differences seen between tissues, ages, and sexes. Greater understanding of how such small temperature perturbations mediate immune responses may provide new explanations for persistent questions in disease such as sex disparity in disease prevalence. Notably, the prevalence and severity of many maladies are rising with climate change, suggesting temperature fluctuations can interact with disease on multiple levels. As global temperatures are rising, and our body temperatures are falling, questions regarding temperature–immune interactions are increasingly critical. Here, we review this aspect of environmental interplay to better understand temperature’s role in immune variation and subsequent risk of disease.
A case report of heterozygous familial hypercholesterolaemia with LDLR gene mutation complicated by premature coronary artery disease detected in primary care
Authors: Abdul-Halim Mohamad Abu Zar , Abdul-Hamid Hasidah , Baharudin Noorhida , Mohamed-Yassin Mohamed-Syarif , Kasim Sazzli Shahlan , Nawawi Hapizah , Qureshi Nadeem , Ramli Anis Safura 
Published: January 2024

Abstract

Background
Familial hypercholesterolaemia (FH) is an autosomal dominant genetic condition predominantly caused by the low-density lipoprotein receptor (LDLR) gene mutation.

Case summary
This is the case of a 54-year-old Malay woman with genetically confirmed FH complicated by premature coronary artery disease (PCAD). She was clinically diagnosed in primary care at 52 years old, fulfilling the Simon Broome Criteria (possible FH), Dutch Lipid Clinic Criteria (score of 8: probable FH), and Familial Hypercholesterolaemia Case Ascertainment Tool (relative risk score of 9.51). Subsequently, she was confirmed to have a heterozygous LDLR c.190+4A&gt;T intron 2 pathogenic variant at the age of 53 years. She was known to have hypercholesterolaemia and was treated with statin since the age of 25. However, the lipid-lowering agent was not intensified to achieve the recommended treatment target. The delayed FH diagnosis has caused this patient to have PCAD and percutaneous coronary intervention (PCI) at the age of 29 years and a second PCI at the age of 49 years. She also has a very strong family history of hypercholesterolaemia and PCAD, where seven out of eight of her siblings were affected. Despite this, FH was not diagnosed early, and cascade screening of family members was not conducted, resulting in a missed opportunity to prevent PCAD.

Discussion
Familial hypercholesterolaemia can be clinically diagnosed in primary care to identify those who may require genetic testing. Multidisciplinary care focuses on improving identification, cascade screening, and management of FH, which is vital to improving prognosis and ultimately preventing PCAD.
A case report of coronary artery aneurysms with restenosis and stent fractures developed 14 years after sirolimus eluting stents implantation successfully treated with drug-coated balloons
Authors: Fujita Takanari , Tazaki Junichi , Toyofuku Mamoru 
Published: January 2024

Abstract

Background
Coronary aneurysms following drug-eluting stent implantation are rare but associated with adverse events.

Case summary
An 80-year-old male admitted to our hospital with resting chest discomfort. He had undergone percutaneous coronary interventions (PCIs) with first-generation sirolimus-eluting stent (SES) implantation to the right coronary artery (RCA) and left anterior descending artery (LAD) 14 years ago. Coronary angiography revealed coronary aneurysms and stent fractures in the RCA and LAD where SES was implanted. The aneurysm sizes of the RCA and LAD were 7 × 8 and 7 × 10 mm, respectively. Moreover, in-stent restenosis (ISR) with ischaemia were found in the LAD. The patient was at high risk for cardiac surgery and the coronary aneurysms were not suitable for percutaneous interventions. Therefore, we treated only ISR lesions using drug-coated balloons (DCBs) without intervention for coronary aneurysms. Intravascular ultrasound (IVUS) revealed that the first guide wire went outside the malapposed stents. After rewiring using a double-lumen microcatheter with another guide wire, IVUS confirmed the second guide wire passed entirely inside the stents. Then, the ISR lesions were dilated with high-pressure balloons and DCBs. The post-procedural course was uneventful and his symptoms were relieved.

Discussion
This case demonstrated coronary aneurysms with ISR and stent fractures 14 years after SES implantation. Depending on patient background and lesion morphology, DCB can be one of the treatment options. Intravascular imaging is useful to guide PCI in patients with coronary aneurysms.
Ubiquitin-specific protease 38 promotes inflammatory atrial fibrillation induced by pressure overload
Authors: Xiao Zheng , Pan Yucheng , Kong Bin , Meng Hong , Shuai Wei , Huang He 
Published: January 2024

Abstract

Aims
Atrial structural and electrical remodelling is a major reason for the initiation and perpetuation of atrial fibrillation (AF). Ubiquitin-specific protease 38 (USP38) is a deubiquitinating enzyme, but its function in the heart remains unknown. The aim of this study was to investigate the effect of USP38 in pressure overload-induced AF.

Methods and results
Cardiac-specific knockout USP38 and cardiac-specific transgenic USP38 mice and their corresponding control mice were used in this study. After 4 weeks with or without aortic banding (AB) surgery, atrial echocardiography, atrial histology, electrophysiological study, and molecular analysis were assessed. Ubiquitin-specific protease 38 knockout mice showed a remarkable improvement in vulnerability to AF, atrial weight and diameter, atrial fibrosis, and calcium-handling protein expression after AB surgery. Conversely, USP38 overexpression further increased susceptibility to AF by exacerbating atrial structural and electrical remodelling. Mechanistically, USP38 interacted with and deubiquitinated nuclear factor-kappa B (NF-κB), and USP38 overexpression increased the level of p-NF-κB in vivo and in vitro, accompanied by the upregulation of NOD-like receptor protein 3 (NLRP3) and inflammatory cytokines, suggesting that USP38 contributes to adverse effects by driving NF-κB/NLRP3-mediated inflammatory responses.

Conclusion
Overall, our study indicates that USP38 promotes pressure overload-induced AF through targeting NF-κB/NLRP3-mediated inflammatory responses.
Yield of molecular autopsy in sudden cardiac death in athletes: data from a large registry in the UK
Authors: Finocchiaro Gherardo , Radaelli Davide , Johnson David , Bhatia Raghav T , Westaby Joseph , D’Errico Stefano , Papadakis Michael , Sharma Sanjay , Sheppard Mary N , Behr Elijah R 
Published: January 2024

Abstract

Aims
Sudden cardiac death (SCD) may occur in apparently healthy individuals, including athletes. The aim was to investigate the diagnostic role of post-mortem genetic testing, molecular autopsy (MA), in elucidating the cause of SCD in athletes.

Methods and results
We reviewed a database of 6860 consecutive cases of SCD referred to our specialist cardiac pathology centre. All cases underwent detailed cardiac autopsy, and 748 were deemed to be athletes. Of these, 42 (6%) were investigated with MA (28 using a targeted sequencing, 14 exome sequencing). Variants were classified as pathogenic, likely pathogenic, or variant of unknown significance using international guidelines. Clinical information was obtained from referring coroners who completed a detailed health questionnaire. Out of the 42 decedents (average age 35 years old, 98% males) who were investigated with MA, the autopsy was in keeping with a structurally normal heart [sudden arrhythmic death syndrome (SADS)] in n = 33 (78%) cases, followed by arrhythmogenic cardiomyopathy (ACM) in eight (19%) individuals and idiopathic left ventricular fibrosis in one (2%). Death occurred during exercise and at rest in 26 (62%) and 16 (38%) individuals, respectively. Variants that were adjudicated clinically actionable were present in seven cases (17%). There was concordance between the genetic and phenotypic findings in two cases of ACM (in FLNC and TMEM43 genes). None of the variants identified in SADS cases were previously linked to channelopathies. Clinically actionable variants in cardiomyopathy-associated genes were found in five cases of SADS.

Conclusion
The yield of MA in athletes who died suddenly is 17%. In SADS cases, clinically actionable variants were found in cardiomyopathy-associated genes and not in channelopathy-associated genes. Arrhythmogenic cardiomyopathy is a common cause of SCD in athletes, and one in four decedents with this condition had a clinically actionable variant in FLNC and TMEM43 genes.
Economic analyses in cardiac electrophysiology: from clinical efficacy to cost utility
Authors: Frausing Maria Hee Jung Park , Nielsen Jens Cosedis , Westergaard Caroline Louise , Gerdes Christian , Kjellberg Jakob , Boriani Giuseppe , Kronborg Mads Brix 
Published: January 2024

Abstract
Cardiac electrophysiology is an evolving field that relies heavily on costly device- and catheter-based technologies. An increasing number of patients with heart rhythm disorders are becoming eligible for cardiac interventions, not least due to the rising prevalence of atrial fibrillation and increased longevity in the population. Meanwhile, the expansive costs of healthcare face finite societal resources, and a cost-conscious approach to new technologies is critical. Cost-effectiveness analyses support rational decision-making in healthcare by evaluating the ratio of healthcare costs to health benefits for competing therapies. They may, however, be subject to significant uncertainty and bias. This paper aims to introduce the basic concepts, framework, and limitations of cost-effectiveness analyses to clinicians including recent examples from clinical electrophysiology and device therapy.
Practical Guide on Left Atrial Appendage Closure for the Non-implanting Physician. An International Consensus Paper
Authors: Potpara Tatjana , Grygier Marek , Haeusler Karl Georg , Nielsen-Kudsk Jens Erik , Berti Sergio , Genovesi Simonetta , Marijon Eloi , Boveda Serge , Tzikas Apostolos , Boriani Giuseppe , Boersma Lucas V A , Tondo Claudio , De Potter Tom , Lip Gregory Y H , Schnabel Renate B , Bauersachs Rupert , Senzolo Marco , Basile Carlo , Bianchi Stefano , Osmancik Pavel , Schmidt Boris , Landmesser Ulf , Doehner Wolfram , Hindricks Gerhard , Kovac Jan , Camm A John 
Published: January 2024

Abstract
A significant proportion of patients who suffer from atrial fibrillation and are in need of thromboembolic protection are not treated with oral anticoagulation or discontinue this treatment shortly after its initiation. This undertreatment has not improved sufficiently despite the availability of direct oral anticoagulants which are associated with less major bleeding than vitamin K antagonists. Multiple reasons account for this, including bleeding events or ischaemic strokes whilst on anticoagulation, a serious risk of bleeding events, poor treatment compliance despite best educational attempts or aversion to drug therapy.
An alternative interventional therapy, which is not associated with long-term bleeding and is as effective as vitamin K anticoagulation, was introduced over 20 years ago. Because of significant improvements in procedural safety over the years left atrial appendage closure, predominantly achieved using a catheter-based, device implantation approach, is increasingly favoured for the prevention of thromboembolic events in patients who cannot achieve effective anticoagulation.
This management strategy is well-known to the interventional cardiologist/electrophysiologist but is not more widely appreciated within cardiology or internal medicine. This article introduces the devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described.
Almost all physicians who care for adult patients will have many with atrial fibrillation. This practical guide, written within guideline/guidance boundaries, is aimed at those non-implanting physicians who may need to refer patients for consideration of this new therapy, which is becoming increasingly popular.
Transitional Justice and Redress for Racial Injustices against Marginalized Minorities: Lessons from Indigenous Twa People in Post-Genocide Rwanda
Authors: Sentama Ezechiel 
Published: January 2024

ABSTRACT∞
This article addresses the question of how countries respond to racial injustices through transitional justice. It draws on the case of Rwanda and explores the experiences of the marginalized indigenous Twa minorities with transitional justice implemented after the 1994 genocide through the National Unity and Reconciliation Commission and Gacaca courts. The lessons from Rwanda highlight the limitations of transitional justice in providing redress for racial injustices of marginalized minorities when it is practised within an authoritarian political context. The article discusses how the transitional justice approach in Rwanda contributed to the construction of a flawed record of the past and marginalized the racial realities of Rwandans by imposing an official historical narrative. It was also used as a tool of the government to negate racial injustices against the most marginalized communities of Twa people but also to preserve racial injustices and human rights violations against them by denying their ethnic identity and indigenous way of life.