bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of post-stroke motor recovery benefits from measures of sub-acute widespread network damages
Authors: Rivier Cyprien , Preti Maria Giulia , Nicolo Pierre , Van De Ville Dimitri , Guggisberg Adrian G , Pirondini Elvira 
Published: March 2023

AbstractFollowing a stroke in regions of the brain responsible for motor activity, patients can lose their ability to control parts of their body. Over time, some patients recover almost completely, while others barely recover at all. It is known that lesion volume, initial motor impairment and cortico-spinal tract asymmetry significantly impact motor changes over time. Recent work suggested that disabilities arise not only from focal structural changes but also from widespread alterations in inter-regional connectivity. Models that consider damage to the entire network instead of only local structural alterations lead to a more accurate prediction of patients’ recovery. However, assessing white matter connections in stroke patients is challenging and time-consuming. Here, we evaluated in a data set of 37 patients whether we could predict upper extremity motor recovery from brain connectivity measures obtained by using the patient’s lesion mask to introduce virtual lesions in 60 healthy streamline tractography connectomes. This indirect estimation of the stroke impact on the whole brain connectome is more readily available than direct measures of structural connectivity obtained with magnetic resonance imaging. We added these measures to benchmark structural features, and we used a ridge regression regularization to predict motor recovery at 3 months post-injury. As hypothesized, accuracy in prediction significantly increased (R2 = 0.68) as compared to benchmark features (R2 = 0.38). This improved prediction of recovery could be beneficial to clinical care and might allow for a better choice of intervention.
Role of inflammation in neurological damage and regeneration following spinal cord injury and its therapeutic implications
Authors: Jin Yan , Song Yixing , Lin Jiaqi , Liu Tianqing , Li Guicai , Lai Biqin , Gu Yun , Chen Gang , Xing Lingyan 
Published: March 2023

AbstractSpinal cord injury (SCI) is an incurable trauma that frequently results in partial or complete loss of motor and sensory function. Massive neurons are damaged after the initial mechanical insult. Secondary injuries, which are triggered by immunological and inflammatory responses, also result in neuronal loss and axon retraction. This results in defects in the neural circuit and a deficiency in the processing of information. Although inflammatory responses are necessary for spinal cord recovery, conflicting evidence of their contributions to specific biological processes have made it difficult to define the specific role of inflammation in SCI. This review summarizes our understanding of the complex role of inflammation in neural circuit events following SCI, such as cell death, axon regeneration and neural remodeling. We also review the drugs that regulate immune responses and inflammation in the treatment of SCI and discuss the roles of these drugs in the modulation of neural circuits. Finally, we provide evidence about the critical role of inflammation in facilitating spinal cord neural circuit regeneration in zebrafish, an animal model with robust regenerative capacity, to provide insights into the regeneration of the mammalian central nervous system.
Nuclear fragile X mental retardation-interacting protein 1-mediated ribophagy protects T lymphocytes against apoptosis in sepsis
Authors: Zhao Peng-Yue , Yao Ren-Qi , Zheng Li-Yu , Wu Yao , Li Yu-Xuan , Dong Ning , Li Jing-Yan , Du Xiao-Hui , Yao Yong-Ming 
Published: March 2023

AbstractBackgroundRibophagy is a selective autophagic process that specifically degrades dysfunctional or superfluous ribosomes to maintain cellular homeostasis. Whether ribophagy can ameliorate the immunosuppression in sepsis similar to endoplasmic reticulum autophagy (ERphagy) and mitophagy remains unclear. This study was conducted to investigate the activity and regulation of ribophagy in sepsis and to further explore the potential mechanism underlying the involvement of ribophagy in T-lymphocyte apoptosis.MethodsThe activity and regulation of nuclear fragile X mental retardation-interacting protein 1 (NUFIP1)-mediated ribophagy in T lymphocytes during sepsis were first investigated by western blotting, laser confocal microscopy and transmission electron microscopy. Then, we constructed lentivirally transfected cells and gene-defective mouse models to observe the impact of NUFIP1 deletion on T-lymphocyte apoptosis and finally explored the signaling pathway associated with T-cell mediated immune response following septic challenge.ResultsBoth cecal ligation and perforation-induced sepsis and lipopolysaccharide stimulation significantly induced the occurrence of ribophagy, which peaked at 24 h. When NUFIP1 was knocked down, T-lymphocyte apoptosis was noticeably increased. Conversely, the overexpression of NUFIP1 exerted a significant protective impact on T-lymphocyte apoptosis. Consistently, the apoptosis and immunosuppression of T lymphocytes and 1-week mortality rate in NUFIP1 gene-deficient mice were significantly increased compared with those in wild-type mice. In addition, the protective effect of NUFIP1-mediated ribophagy on T lymphocytes was identified to be closely related to the endoplasmic reticulum stress apoptosis pathway, and PERK–ATF4–CHOP signaling was obviously involved in downregulating T-lymphocyte apoptosis in the setting of sepsis.ConclusionsNUFIP1-mediated ribophagy can be significantly activated to alleviate T lymphocyte apoptosis through the PERK–ATF4–CHOP pathway in the context of sepsis. Thus, targeting NUFIP1-mediated ribophagy might be of importance in reversing the immunosuppression associated with septic complications.
Efficacy and safety of extracorporeal membrane oxygenation for burn patients: a comprehensive systematic review and meta-analysis
Authors: Heng Xue , Cai Peng , Yuan Zhiqiang , Peng Yizhi , Luo Gaoxing , Li Haisheng 
Published: March 2023

AbstractBackgroundRespiratory and circulatory dysfunction are common complications and the leading causes of death among burn patients, especially in severe burns and inhalation injury. Recently, extracorporeal membrane oxygenation (ECMO) has been increasingly applied in burn patients. However, current clinical evidence is weak and conflicting. This study aimed to comprehensively evaluate the efficacy and safety of ECMO in burn patients.MethodsA comprehensive search of PubMed, Web of Science and Embase from inception to 18 March 2022 was performed to identify clinical studies on ECMO in burn patients. The main outcome was in-hospital mortality. Secondary outcomes included successful weaning from ECMO and complications associated with ECMO. Meta-analysis, meta-regression and subgroup analyses were conducted to pool the clinical efficacy and identify influencing factors.ResultsFifteen retrospective studies with 318 patients were finally included, without any control groups. The commonest indication for ECMO was severe acute respiratory distress syndrome (42.1%). Veno–venous ECMO was the commonest mode (75.29%). Pooled in-hospital mortality was 49% [95% confidence interval (CI) 41–58%] in the total population, 55% in adults and 35% in pediatrics. Meta-regression and subgroup analysis found that mortality significantly increased with inhalation injury but decreased with ECMO duration. For studies with percentage inhalation injury ≥50%, pooled mortality (55%, 95% CI 40–70%) was higher than in studies with percentage inhalation injury &lt;50% (32%, 95% CI 18–46%). For studies with ECMO duration ≥10 days, pooled mortality (31%, 95% CI 20–43%) was lower than in studies with ECMO duration &lt;10 days (61%, 95% CI 46–76%). In minor and major burns, pooled mortality was lower than in severe burns. Pooled percentage of successful weaning from ECMO was 65% (95% CI 46–84%) and inversely correlated with burn area. The overall rate of ECMO-related complications was 67.46%, and infection (30.77%) and bleedings (23.08%) were the two most common complications. About 49.26% of patients required continuous renal replacement therapy.ConclusionsECMO seems to be an appropriate rescue therapy for burn patients despite the relatively high mortality and complication rate. Inhalation injury, burn area and ECMO duration are the main factors influencing clinical outcomes.
Myocardial injury: where inflammation and autophagy meet
Authors: Liu Chunping , Liu Yanjiao , Chen Huiqi , Yang Xiaofei , Lu Chuanjian , Wang Lei , Lu Jiahong 
Published: March 2023

AbstractAutophagy is a highly conserved bulk degradation mechanism that degrades damaged organelles, aged proteins and intracellular contents to maintain the homeostasis of the intracellular microenvironment. Activation of autophagy can be observed during myocardial injury, during which inflammatory responses are strongly triggered. Autophagy can inhibit the inflammatory response and regulate the inflammatory microenvironment by removing invading pathogens and damaged mitochondria. In addition, autophagy may enhance the clearance of apoptotic and necrotic cells to promote the repair of damaged tissue. In this paper, we briefly review the role of autophagy in different cell types in the inflammatory microenvironment of myocardial injury and discuss the molecular mechanism of autophagy in regulating the inflammatory response in a series of myocardial injury conditions, including myocardial ischemia, ischemia/reperfusion injury and sepsis cardiomyopathy.
Melatonin influences the biological characteristics of keloid fibroblasts through the Erk and Smad signalling pathways
Authors: Huang Shaobin , Deng Wuguo , Dong Yunxian , Hu Zhicheng , Zhang Yi , Wang Peng , Cao Xiaoling , Chen Miao , Cheng Pu , Xu Hailin , Zhu Wenkai , Tang Bing , Zhu Jiayuan 
Published: March 2023

AbstractBackgroundKeloids are abnormal fibrous hyperplasias that are difficult to treat. Melatonin can be used to inhibit the development of certain fibrotic diseases but has never been used to treat keloids. We aimed to discover the effects and mechanisms of melatonin in keloid fibroblasts (KFs).MethodsFlow cytometry, CCK-8 assays, western blotting, wound-healing assays, transwell assays, collagen gel contraction assays and immunofluorescence assays were applied to demonstrate the effects and mechanisms of melatonin in fibroblasts derived from normal skin, hypertrophic scars and keloids. The therapeutic potential of the combination of melatonin and 5-fluorouracil (5-FU) was investigated in KFs.ResultsMelatonin significantly promoted cell apoptosis and inhibited cell proliferation, migration and invasion, contractile capability and collagen production in KFs. Further mechanistic studies demonstrated that melatonin could inhibit the cAMP/PKA/Erk and Smad pathways through the membrane receptor MT2 to alter the biological characteristics of KFs. Moreover, the combination of melatonin and 5-FU remarkably promoted cell apoptosis and inhibited cell migration and invasion, contractile capability and collagen production in KFs. Furthermore, 5-FU suppressed the phosphorylation of Akt, mTOR, Smad3 and Erk, and melatonin in combination with 5-FU markedly suppressed the activation of the Akt, Erk and Smad pathways.ConclusionsCollectively, melatonin may inhibit the Erk and Smad pathways through the membrane receptor MT2 to alter the cell functions of KFs, while combination with 5-FU could exert even more inhibitory effects in KFs through simultaneous suppression of multiple signalling pathways.
Efficacy and Safety of Advanced Therapies for Moderately to Severely Active Ulcerative Colitis at Induction and Maintenance: An Indirect Treatment Comparison Using Bayesian Network Meta-analysis
Authors: Panaccione Remo , Collins Eric B , Melmed Gil Y , Vermeire Severine , Danese Silvio , Higgins Peter D R , Kwon Christina S , Zhou Wen , Ilo Dapo , Sharma Dolly , Sanchez Gonzalez Yuri , Wang Si-Tien 
Published: March 2023

AbstractBackgroundGiven rapid innovation in advanced therapies for moderately to severely active ulcerative colitis (UC), we investigated their comparative efficacy and safety during induction and maintenance through network meta-analysis.MethodsUsing Bayesian methods, endpoints of clinical remission and clinical response per Full Mayo score, and endoscopic improvement were assessed in bio-naive and -exposed populations. Safety was assessed in overall populations by all adverse events (AEs), serious AEs, discontinuation due to AEs, and serious infections. Phase 3 randomized controlled trials were identified via systematic literature review, including the following advanced therapies: infliximab, adalimumab, vedolizumab, golimumab, tofacitinib, ustekinumab, filgotinib, ozanimod, and upadacitinib. Random effects models were used to address between-study heterogeneity. Intent-to-treat (ITT) efficacy rates were calculated by adjusting maintenance outcomes by likelihood of induction response.ResultsOut of 48 trials identified, 23 were included. Across all outcomes and regardless of prior biologic exposure, ITT efficacy rates were highest for upadacitinib, owing to its highest ranking for all efficacy outcomes in induction and for all but clinical remission during maintenance among bio-naive induction responders. For all advanced therapies versus placebo, there were no significant differences in serious AEs or serious infections across therapies. For all AEs, golimumab had higher odds versus placebo during maintenance; for discontinuation due to AEs, upadacitinib had lower odds versus placebo during induction, while ustekinumab and vedolizumab had lower odds versus placebo during maintenance.ConclusionsUpadacitinib may be the most efficacious therapy for moderately to severely active UC based on ITT analyses, with similar safety across advanced therapies.
Phospholamban pentamerization increases sensitivity and dynamic range of cardiac relaxation
Authors: Funk Florian , Kronenbitter Annette , Hackert Katarzyna , Oebbeke Matthias , Klebe Gerhard , Barth Mareike , Koch Daniel , Schmitt Joachim P 
Published: March 2023

Abstract

Aims
A key event in the regulation of cardiac contraction and relaxation is the phosphorylation of phospholamban (PLN) that relieves the inhibition of the sarco/endoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a). PLN exists in an equilibrium between monomers and pentamers. While only monomers can inhibit SERCA2a by direct interaction, the functional role of pentamers is still unclear. This study investigates the functional consequences of PLN pentamerization.

Methods and results
We generated transgenic mouse models expressing either a PLN mutant that cannot form pentamers (TgAFA-PLN) or wild-type PLN (TgPLN) in a PLN-deficient background. TgAFA-PLN hearts demonstrated three-fold stronger phosphorylation of monomeric PLN, accelerated Ca2+ cycling of cardiomyocytes, and enhanced contraction and relaxation of sarcomeres and whole hearts in vivo. All of these effects were observed under baseline conditions and abrogated upon inhibition of protein kinase A (PKA). Mechanistically, far western kinase assays revealed that PLN pentamers are phosphorylated by PKA directly and independent of any subunit exchange for free monomers. In vitro phosphorylation of synthetic PLN demonstrated that pentamers even provide a preferred PKA substrate and compete with monomers for the kinase, thereby reducing monomer phosphorylation and maximizing SERCA2a inhibition. However, β-adrenergic stimulation induced strong PLN monomer phosphorylation in TgPLN hearts and sharp acceleration of cardiomyocyte Ca2+ cycling and haemodynamic values that now were indistinguishable from TgAFA-PLN and PLN-KO hearts. The pathophysiological relevance of PLN pentamerization was evaluated using transverse aortic constriction (TAC) to induce left ventricular pressure overload. Compared to TgPLN, TgAFA-PLN mice demonstrated reduced survival after TAC, impaired cardiac haemodynamics, failure to respond to adrenergic stimulation, higher heart weight, and increased myocardial fibrosis.

Conclusions
The findings show that PLN pentamerization greatly impacts on SERCA2a activity as it mediates the full range of PLN effects from maximum inhibition to full release of SERCA2a function. This regulation is important for myocardial adaptation to sustained pressure overload.
Pyruvate dehydrogenase kinase regulates vascular inflammation in atherosclerosis and increases cardiovascular risk
Authors: Forteza Maria J , Berg Martin , Edsfeldt Andreas , Sun Jangming , Baumgartner Roland , Kareinen Ilona , Casagrande Felipe Beccaria , Hedin Ulf , Zhang Song , Vuckovic Ivan , Dzeja Petras P , Polyzos Konstantinos A , Gisterå Anton , Trauelsen Mette , Schwartz Thue W , Dib Lea , Herrmann Joerg , Monaco Claudia , Matic Ljubica , Gonçalves Isabel , Ketelhuth Daniel F J 
Published: March 2023

Abstract

Aims
Recent studies have revealed a close connection between cellular metabolism and the chronic inflammatory process of atherosclerosis. While the link between systemic metabolism and atherosclerosis is well established, the implications of altered metabolism in the artery wall are less understood. Pyruvate dehydrogenase kinase (PDK)-dependent inhibition of pyruvate dehydrogenase (PDH) has been identified as a major metabolic step regulating inflammation. Whether the PDK/PDH axis plays a role in vascular inflammation and atherosclerotic cardiovascular disease remains unclear.

Methods and results
Gene profiling of human atherosclerotic plaques revealed a strong correlation between PDK1 and PDK4 transcript levels and the expression of pro-inflammatory and destabilizing genes. Remarkably, the PDK1 and PDK4 expression correlated with a more vulnerable plaque phenotype, and PDK1 expression was found to predict future major adverse cardiovascular events. Using the small-molecule PDK inhibitor dichloroacetate (DCA) that restores arterial PDH activity, we demonstrated that the PDK/PDH axis is a major immunometabolic pathway, regulating immune cell polarization, plaque development, and fibrous cap formation in Apoe−/− mice. Surprisingly, we discovered that DCA regulates succinate release and mitigates its GPR91-dependent signals promoting NLRP3 inflammasome activation and IL-1β secretion by macrophages in the plaque.

Conclusions
We have demonstrated for the first time that the PDK/PDH axis is associated with vascular inflammation in humans and particularly that the PDK1 isozyme is associated with more severe disease and could predict secondary cardiovascular events. Moreover, we demonstrate that targeting the PDK/PDH axis with DCA skews the immune system, inhibits vascular inflammation and atherogenesis, and promotes plaque stability features in Apoe−/− mice. These results point toward a promising treatment to combat atherosclerosis.
Diagnosis and Clinical Features of Perianal Lesions in Newly Diagnosed Crohn’s Disease: Subgroup Analysis from Inception Cohort Registry Study of Patients with Crohn’s Disease (iCREST-CD)
Authors: Yamamoto Takayuki , Nakase Hiroshi , Watanabe Kenji , Shinzaki Shinichiro , Takatsu Noritaka , Fujii Toshimitsu , Okamoto Ryuichi , Matsuoka Katsuyoshi , Yamada Akihiro , Kunisaki Reiko , Matsuura Minoru , Shiga Hisashi , Bamba Shigeki , Mikami Yohei , Shimoyama Takahiro , Motoya Satoshi , Torisu Takehiro , Kobayashi Taku , Ohmiya Naoki , Saruta Masayuki , Matsuda Koichiro , Matsumoto Takayuki , Maemoto Atsuo , Murata Yoko , Yoshigoe Shinichi , Nagasaka Shinya , Yajima Tsutomu , Hisamatsu Tadakazu ,   iCREST-CD Study Group, Nagahori Masakazu , Yukawa Tatsu , Saito Daisuke , Kawai Mikio , Masamune Atsushi , Nagasaka Mitsuo , Kazama Tomoe 
Published: March 2023

Abstract

Background and Aims
Perianal lesion is a refractory phenotype of Crohn’s disease [CD] with significantly diminished quality of life. We evaluated the clinical characteristics of perianal lesions in newly diagnosed CD patients and the impact of perianal lesions on the quality of life in Japanese patients with CD.

Methods
Patients newly diagnosed with CD after June 2016 were included between December 2018 and June 2020 from the Inception Cohort Registry Study of Patients with CD [iCREST-CD].

Results
Perianal lesions were present in 324 [48.2%] of 672 patients with newly diagnosed CD; 71.9% [233/324] were male. The prevalence of perianal lesions was higher in patients aged &lt;40 years vs ≥40 years, and it decreased with age. Perianal fistula [59.9%] and abscess [30.6%] were the most common perianal lesions. In multivariate analyses, male sex, age &lt;40 years and ileocolonic disease location were significantly associated with a high prevalence of perianal lesions, whereas stricturing behaviour and alcohol intake were associated with low prevalence. Fatigue was more frequent [33.3% vs 21.6%] while work productivity and activity impairment-work time missed [36.3% vs 29.5%] and activity impairment [51.9% vs 41.1%] were numerically higher in patients with than those without perianal lesions.

Conclusions
At the time of CD diagnosis, approximately half of the patients had perianal lesions; perianal abscesses and perianal fistulas were the most common. Young age, male sex, disease location and behaviour were significantly associated with the presence of perianal lesions. The presence of perianal lesion was associated with fatigue and impairment of daily activities.

Clinical trials registry
University Hospital Medical Information Network Clinical Trials Registry System [UMIN-CTR, UMIN000032237].
Successful percutaneous transvenous approach for pinch-off syndrome: a case report
Authors: Matta Anthony , Chavernac Pascal , Pouche Marion , Cantié Philippe 
Published: March 2023

AbstractBackgroundPinch-off syndrome is a rare late complication characterized by the occurrence of spontaneous fracture and embolization of a port-a-cath implanted via subclavian venous access. It may lead to serious cardiovascular outcomes.Case presentationWe report a successful percutaneous transvenous removal of intravascular fractured port catheter embolized into the right ventricle by using the ‘lasso’ technique in an 85-year-old man with type B non-Hodgkin lymphoma undergoing chemotherapy and long estimated life expectancy.DiscussionKnowledge of pinch-off syndrome among physicians is essential for early intervention, thereby preventing adverse events. Percutaneous approach seems an effective, safe, and simple procedure.