bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of antioxidant enzyme activities enhances carotenogenesis in microalga Dactylococcus dissociatus MT1
Authors: Bouzidi Nour Elaimane , Grama Samir Borhane , Khelef Aboubakeur Essedik , Yang Duanpeng , Li Jian
Published: September 2022

Microalgal biotechnology has become a promising field of research for the production of valuable, sustainable and environmentally friendly byproducts, especially for carotenoids. Bulk accumulation of secondary carotenoids in microalgae are mostly induced by oxidative stress of cells. In this research, we investigated the effects of antioxidant enzyme activity inhibition on carotenogenesis in a microalga Dactylococcus dissociatus MT1. The activities of four major antioxidant enzyme families, namely superoxide dismutase (SOD), catalases (CAT), glutathione peroxydases (GPX) and ascorbate perxodases (APX), were inhibited by relevant inhibitors during the stressed cultivation of D. dissociatus to observe the effects on carotenogensis. A 91% decrease in activity was observed for CAT, comparing with controls without any inhibitors added, followed by 65%, 61%, and 47% for the enzymes SOD, APX, and GPX, respectively. Concomitantly, it was found that this partial inhibition had substantial influences on the accumulation of carotenoids, with the highest production levels obtained in CAT inhibition conditions and an increase of 2.6 times of carotenoid concentration observed, comparing with control cultivation conditions. We conclude that the modulation of antioxidant enzyme activities could lead to the overproduction of carotenoids in this microalgal cell culture, and we expect that this novel approach of optimizing carotenogenesis processes for D. dissociatus cell cultures could be transferrable to other cell culture systems and might have an important impact on the carotenoid production industry.
Artificial intelligence in civil infrastructure health monitoring—Historical perspectives, current trends, and future visions
Authors: Mondal Tarutal Ghosh , Chen Genda
Published: September 2022

Over the past 2 decades, the use of artificial intelligence (AI) has exponentially increased toward complete automation of structural inspection and assessment tasks. This trend will continue to rise in image processing as unmanned aerial systems (UAS) and the internet of things (IoT) markets are expected to expand at a compound annual growth rate of 57.5% and 26%, respectively, from 2021 to 2028. This paper aims to catalog the milestone development work, summarize the current research trends, and envision a few future research directions in the innovative application of AI in civil infrastructure health monitoring. A blow-by-blow account of the major technology progression in this research field is provided in a chronological order. Detailed applications, key contributions, and performance measures of each milestone publication are presented. Representative technologies are detailed to demonstrate current research trends. A road map for future research is outlined to address contemporary issues such as explainable and physics-informed AI. This paper will provide readers with a lucid memoir of the historical progress, a good sense of the current trends, and a clear vision for future research.
Digital algorithm-guided insulin therapy in home healthcare for elderly persons with type 2 diabetes: A proof-of-concept study
Authors: Kopanz Julia , Mader Julia K. , Donsa Klaus , Libiseller Angela , Aberer Felix , Pandis Marlene , Reinisch-Gratzer Johanna , Ambrosch Gisela C. , Lackner Bettina , Truskaller Thomas , Sinner Frank Michael , Pieber Thomas R. , Lichtenegger Katharina M.
Published: September 2022

GlucoTab@MobileCare, a digital workflow and decision support system with integrated basal and basal-plus insulin algorithm was investigated for user acceptance, safety and efficacy in persons with type 2 diabetes receiving home health care by nurses. During a three months study nine participants (five female, age 77 ± 10 years, HbA1c 60 ± 13 mmol/mol (study start) vs. 57 ± 12 mmol/mol (study end) received basal or basal-plus insulin therapy as suggested by the digital system. In total 95% of all suggested tasks (blood glucose (BG) measurements, insulin dose calculations, insulin injections) were performed according to the digital system. Mean morning BG was 171 ± 68 mg/dL in the first study month vs. 145 ± 35 mg/dL in the last study month, indicating a reduced glycemic variability of 33 mg/dL (standard deviation). No hypoglycemic episode < 54 mg/dL occurred. User’s adherence was high and the digital system supported a safe and effective treatment. Larger scale studies are needed to confirm findings under routine care.

German Clinical Trials Register ID

DRKS00015059
Exosomal microRNA panel as a diagnostic biomarker in patients with hepatocellular carcinoma
Authors: Yang Jingwen , Dong Weiwei , Zhang He , Zhao Huixia , Zeng Zhiyan , Zhang Fengyun , Li Qiuwen , Duan Xiaohong , Hu Yanyan , Xiao Wenhua
Published: September 2022

Background: Diagnostic tools for hepatocellular carcinoma (HCC) are critical for patient treatment and prognosis. Thus, this study explored the diagnostic value of the exosomal microRNA panel for HCC.

Methods: Expression profiles of microRNAs in exosomes and plasma of HCC and control groups were assessed using microRNA microarray analysis. Reverse transcription-quantitative PCR was applied to evaluate the expression of candidate microRNAs in blood samples from 50 HCC patients, 50 hepatic cirrhosis patients, and 50 healthy subjects. The area calculated the diagnostic accuracy of the microRNAs and microRNA panel under the receiver operating characteristic curve (AUC).

Results: MicroRNA microarray analysis revealed that there were more differentially expressed microRNAs in the exosome HCC group than plasma HCC group. Among the 43 differentially expressed microRNAs contained in both exosomes and plasma, we finally decided to testify the expression and diagnostic significance of microRNA-26a, microRNA-29c, and microRNA-199a. The results indicated that expression of the microRNA-26a, microRNA-29c, and microRNA-199a in both exosomes and plasma was significantly lower in HCC patients compared with hepatic cirrhosis and healthy group. Interestingly, exosomal microRNAs were substantially more accurate in diagnosing HCC than microRNAs and alpha-fetoprotein in plasma. Moreover, the exosomal microRNA panel containing microRNA-26a, microRNA-29c, and microRNA-199a showed high accuracy in discriminating HCC from healthy (AUC = 0.994; sensitivity 100%; specificity 96%) and hepatic cirrhosis group (AUC = 0.965; sensitivity 92%; specificity 90%).

Conclusion: This study revealed that the exosomal microRNA panel has high accuracy in diagnosing HCC and has important clinical significance.
Neurotransmitters, neuropeptides and calcium in oocyte maturation and early development
Authors: Alhajeri Maitha M. , Alkhanjari Rayyah R. , Hodeify Rawad , Khraibi Ali , Hamdan Hamdan
Published: September 2022

A primary reason behind the high level of complexity we embody as multicellular organisms is a highly complex intracellular and intercellular communication system. As a result, the activities of multiple cell types and tissues can be modulated resulting in a specific physiological function. One of the key players in this communication process is extracellular signaling molecules that can act in autocrine, paracrine, and endocrine fashion to regulate distinct physiological responses. Neurotransmitters and neuropeptides are signaling molecules that renders long-range communication possible. In normal conditions, neurotransmitters are involved in normal responses such as development and normal physiological aspects; however, the dysregulation of neurotransmitters mediated signaling has been associated with several pathologies such as neurodegenerative, neurological, psychiatric disorders, and other pathologies. One of the interesting topics that is not yet fully explored is the connection between neuronal signaling and physiological changes during oocyte maturation and fertilization. Knowing the importance of Ca2+ signaling in these reproductive processes, our objective in this review is to highlight the link between the neuronal signals and the intracellular changes in calcium during oocyte maturation and embryogenesis. Calcium (Ca2+) is a ubiquitous intracellular mediator involved in various cellular functions such as releasing neurotransmitters from neurons, contraction of muscle cells, fertilization, and cell differentiation and morphogenesis. The multiple roles played by this ion in mediating signals can be primarily explained by its spatiotemporal dynamics that are kept tightly checked by mechanisms that control its entry through plasma membrane and its storage on intracellular stores. Given the large electrochemical gradient of the ion across the plasma membrane and intracellular stores, signals that can modulate Ca2+ entry channels or Ca2+ receptors in the stores will cause Ca2+ to be elevated in the cytosol and consequently activating downstream Ca2+-responsive proteins resulting in specific cellular responses. This review aims to provide an overview of the reported neurotransmitters and neuropeptides that participate in early stages of development and their association with Ca2+ signaling.
Organic electrochromic energy storage materials and device design
Authors: Liu Qingjiang , Yang Liangliang , Ling Wei , Guo Binbin , Chen Lina , Wang Jiaqi , Zhang Jiaolong , Wang Wenhui , Mo Funian
Published: September 2022

While not affecting electrochemical performance of energy storage devices, integrating multi-functional properties such as electrochromic functions into energy storage devices can effectively promote the development of multifunctional devices. Compared with inorganic electrochromic materials, organic materials possess the significant advantages of facile preparation, low cost, and large color contrast. Specifically, most polymer materials show excellent electrochemical properties, which can be widely used in the design and development of energy storage devices. In this article, we focus on the application of organic electrochromic materials in energy storage devices. The working mechanisms, electrochemical performance of different types of organics as well as the shortcomings of organic electrochromic materials in related devices are discussed in detail.
Bioplastics: A new analytical challenge
Authors: Censi Valentina , Saiano Filippo , Bongiorno David , Indelicato Serena , Napoli Anna , Piazzese Daniela
Published: September 2022

Even though petroleum-based plastics are advantageous in complying with the performance requirements in many applications, these are related, throughout their life cycle, to several environmental problems, including greenhouse gas emissions and persistence in marine and terrestrial environments. Therefore, the preservation of natural resources and climate change is considered worldwide, the main reason for which is necessary to reduce consumption and dependence on fossil-based materials. Biopolymers (PLA, PHAs, etc.) are examples of plastics whose use is grown exponentially over the years because of the improvements of their physical and mechanical properties using additives of various nature and depending on the scope of application. This review aims to discuss various ways of biopolymer degradation, to evaluate if they represent a new Frontier in eco-sustainability or rather a re-proposal of old problems. Related to this topic, we also have focussed our attention on the different methods for the quantitative analysis of bioplastics, or their degradation by-products, comparing and evaluating the advantages and disadvantages of each technique.
Heme oxygenase-1 modulates ferroptosis by fine-tuning levels of intracellular iron and reactive oxygen species of macrophages in response to Bacillus Calmette-Guerin infection
Authors: Ma Chenjie , Wu Xiaoling , Zhang Xu , Liu Xiaoming , Deng Guangcun
Published: September 2022

Macrophages are the host cells and the frontline defense against Mycobacterium tuberculosis (Mtb) infection, and the form of death of infected macrophages plays a pivotal role in the outcome of Mtb infections. Ferroptosis, a programmed necrotic cell death induced by overwhelming lipid peroxidation, was confirmed as one of the mechanisms of Mtb spread following infection and the pathogenesis of tuberculosis (TB). However, the mechanism underlying the macrophage ferroptosis induced by Mtb infection has not yet been fully understood. In the present study, transcriptome analysis revealed the upregulation of heme oxygenase-1 (HMOX1) and pro-ferroptosis cytokines, but downregulation of glutathione peroxidase 4 (GPX4) and other key anti-lipid peroxidation factors in the peripheral blood of both patients with extra-pulmonary tuberculosis (EPTB) and pulmonary tuberculosis (PTB). This finding was further corroborated in mice and RAW264.7 murine macrophage-like cells infected with Bacillus Calmette-Guerin (BCG). A mechanistic study further demonstrated that heme oxygenase-1 protein (HO-1) regulated the production of reactive oxygen species (ROS) and iron metabolism, and ferroptosis in BCG-infected murine macrophages. The knockdown of Hmox1 by siRNA resulted in a significant increase of intracellular ROS, Fe2+, and iron autophagy-mediated factor Ncoa4, along with the reduction of antioxidant factors Gpx4 and Fsp1 in macrophages infected with BCG. The siRNA-mediated knockdown of Hmox1 also reduced cell survival rate and increased the release of intracellular bacteria in BCG-infected macrophages. By contrast, scavenging ROS by N-acetyl cysteine led to the reduction of intracellular ROS, Fe2+, and Hmox1 concentrations, and subsequently inhibited ferroptosis and the release of intracellular BCG in RAW264.7 cells infected with BCG. These findings suggest that HO-1 is an essential regulator of Mtb-induced ferroptosis, which regulates ROS production and iron accretion to alter macrophage death against Mtb infections.
Meningococcal virulence in zebrafish embryos depends on capsule polysaccharide structure
Authors: Schipper Kim , Preusting Lisanne C. , van Sorge Nina M. , Pannekoek Yvonne , van der Ende Arie
Published: September 2022

Neisseria meningitidis or the meningococcus, can cause devasting diseases such as sepsis and meningitis. Its polysaccharide capsule, on which serogrouping is based, is the most important virulence factor. Non-encapsulated meningococci only rarely cause disease, due to their sensitivity to the host complement system. How the capsular polysaccharide structure of N. meningitidis relates to virulence is largely unknown. Meningococcal virulence can be modeled in zebrafish embryos as the innate immune system of the zebrafish embryo resembles that of mammals and is fully functional two days post-fertilization. In contrast, the adaptive immune system does not develop before 4 weeks post-fertilization. We generated isogenic meningococcal serogroup variants to study how the chemical composition of the polysaccharide capsule affects N. meningitidis virulence in the zebrafish embryo model. H44/76 serogroup B killed zebrafish embryos in a dose-dependent manner, whereas the non-encapsulated variant was completely avirulent. Neutrophil depletion was observed after infection with encapsulated H44/76, but not with its non-encapsulated variant HB-1. The survival of embryos infected with isogenic capsule variants of H44/76 was capsule specific. The amount of neutrophil depletion differed accordingly. Both embryo killing capacity and neutrophil depletion after infection correlated with the number of carbons used per repeat unit of the capsule polysaccharide during its biosynthesis (indicative of metabolic cost).

Conclusion

Meningococcal virulence in the zebrafish embryo largely depends on the presence of the polysaccharide capsule but the extent of the contribution is determined by its structure. The observed differences between the meningococcal isogenic capsule variants in zebrafish embryo virulence may depend on differences in metabolic cost.
Application of metagenomic next-generation sequencing in cutaneous tuberculosis
Authors: Kong Min , Li Wei , Kong Qingsheng , Dong Haixin , Han Aizhong , Jiang Liqing
Published: September 2022

Tuberculous infection in a skin wound is a rare but well-known condition. This study describes a child infected with tuberculosis after being wounded. Because of swelling and pain in his wrist tissue, he was admitted to the Affiliated Hospital of Jining Medical University of Shandong Province on 16 October 2021. His medical history only included a wound. He was discharged after debridement. The laboratory data were normal. Two months after surgery, his wound was still swollen and painful. Secretions from the wound were sent for metagenomic next-generation sequencing (mNGS), which revealed three reads related to the Mycobacterium tuberculosis complex group (MTBC). A diagnosis of cutaneous tuberculosis (TB) was made. The wound disappeared after anti-TB drugs were administered. This case demonstrates that, while TB presenting as a severe cutaneous wound is rare, it should be considered in the clinical diagnosis. Clinicians should also pay attention to extrapulmonary infection with MTBC in patients, particularly in some long-suffering patients, and identify the specific pathogen as soon as possible. mNGS could help to identify pathogens and facilitate early treatment, thereby improving the prognosis.
Drug resistant tuberculosis: Implications for transmission, diagnosis, and disease management
Authors: Liebenberg Dale , Gordhan Bhavna Gowan , Kana Bavesh Davandra
Published: September 2022

Drug resistant tuberculosis contributes significantly to the global burden of antimicrobial resistance, often consuming a large proportion of the healthcare budget and associated resources in many endemic countries. The rapid emergence of resistance to newer tuberculosis therapies signals the need to ensure appropriate antibiotic stewardship, together with a concerted drive to develop new regimens that are active against currently circulating drug resistant strains. Herein, we highlight that the current burden of drug resistant tuberculosis is driven by a combination of ongoing transmission and the intra-patient evolution of resistance through several mechanisms. Global control of tuberculosis will require interventions that effectively address these and related aspects. Interrupting tuberculosis transmission is dependent on the availability of novel rapid diagnostics which provide accurate results, as near-patient as is possible, together with appropriate linkage to care. Contact tracing, longitudinal follow-up for symptoms and active mapping of social contacts are essential elements to curb further community-wide spread of drug resistant strains. Appropriate prophylaxis for contacts of drug resistant index cases is imperative to limit disease progression and subsequent transmission. Preventing the evolution of drug resistant strains will require the development of shorter regimens that rapidly eliminate all populations of mycobacteria, whilst concurrently limiting bacterial metabolic processes that drive drug tolerance, mutagenesis and the ultimate emergence of resistance. Drug discovery programs that specifically target bacterial genetic determinants associated with these processes will be paramount to tuberculosis eradication. In addition, the development of appropriate clinical endpoints that quantify drug tolerant organisms in sputum, such as differentially culturable/detectable tubercle bacteria is necessary to accurately assess the potential of new therapies to effectively shorten treatment duration. When combined, this holistic approach to addressing the critical problems associated with drug resistance will support delivery of quality care to patients suffering from tuberculosis and bolster efforts to eradicate this disease.
Real-time visualization of phagosomal pH manipulation by Cryptococcus neoformans in an immune signal-dependent way
Authors: Santiago-Burgos Emmanuel J. , Stuckey Peter V. , Santiago-Tirado Felipe H.
Published: September 2022

Understanding of how intracellular pathogens survive in their host cells is important to improve management of their diseases. This has been fruitful for intracellular bacteria, but it is an understudied area in fungal pathogens. Here we start elucidating and characterizing the strategies used by one of the commonest fungal pathogens, Cryptococcus neoformans, to survive intracellularly. The ability of the fungus to survive inside host cells is one of the main drivers of disease progression, yet it is unclear whether C. neoformans resides in a fully acidified, partially acidic, or neutral phagosome. Using a dye that only fluoresce under acidic conditions to stain C. neoformans, a hypha-defective Candida albicans mutant, and the nonpathogenic Saccharomyces cerevisiae, we characterized the fungal behaviors in infected macrophages by live microscopy. The main behavior in the C. albicans mutant strain and S. cerevisiae-phagosomes was rapid acidification after internalization, which remained for the duration of the imaging. In contrast, a significant number of C. neoformans-phagosomes exhibited alternative behaviors distinct from the normal phagosomal maturation: some phagosomes acidified with subsequent loss of acidification, and other phagosomes never acidified. Moreover, the frequency of these behaviors was affected by the immune status of the host cell. We applied the same technique to a flow cytometry analysis and found that a substantial percentage of C. neoformans-phagosomes showed impaired acidification, whereas almost 100% of the S. cerevisiae-phagosomes acidify. Lastly, using a membrane-damage reporter, we show phagosome permeabilization correlates with acidification alterations, but it is not the only strategy that C. neoformans uses to manipulate phagosomal acidification. The different behaviors described here provide an explanation to the confounding literature regarding cryptococcal-phagosome acidification and the methods can be applied to study other intracellular fungal pathogens.
Identification of amino acid domains of Borrelia burgdorferi P66 that are surface exposed and important for localization, oligomerization, and porin function of the protein
Authors: Curtis Michael W. , Fierros Christa H. , Hahn Beth L. , Surdel Matthew C. , Kessler Julie , Anderson Phillip N. , Vandewalle-Capo Marine , Bonde Mari , Zhu Jieqing , Bergström Sven , Coburn Jenifer
Published: September 2022

P66, a bifunctional integral outer membrane protein, is necessary for Borrelia burgdorferi to establish initial infection and to disseminate in mice. The integrin binding function of P66 facilitates extravasation and dissemination, but the role of its porin function during murine infection has not been investigated. A limitation to studying P66 porin function during mammalian infection has been the lack of structural information for P66. In this study, we experimentally characterized specific domains of P66 with regard to structure and function. First, we aligned the amino acid sequences of P66 from Lyme disease-causing Borrelia and relapsing fever-causing Borrelia to identify conserved and unique domains between these disease-causing clades. Then, we examined whether specific domains of P66 are exposed on the surface of the bacteria by introducing c-Myc epitope tags into each domain of interest. The c-Myc epitope tag inserted C-terminally to E33 (highly conserved domain), to T187 (integrin binding region domain and a non-conserved domain), and to E334 (non-conserved domain) were all detected on the surface of Borrelia burgdorferi. The c-Myc epitope tag inserted C-terminally to E33 and D303 in conserved domains disrupted P66 oligomerization and porin function. In a murine model of infection, the E33 and D303 mutants exhibited decreased infectivity and dissemination. Taken together, these results suggest the importance of these conserved domains, and potentially P66 porin function, in vivo.
Non-thermal plasma causes Pseudomonas aeruginosa biofilm release to planktonic form and inhibits production of Las-B elastase, protease and pyocyanin
Authors: Kašparová Petra , Vaňková Eva , Paldrychová Martina , Svobodová Alžběta , Hadravová Romana , Jarošová Kolouchová Irena , Masák Jan , Scholtz Vladimir
Published: September 2022

The increasing risk of antibiotic failure in the treatment of Pseudomonas aeruginosa infections is largely related to the production of a wide range of virulence factors. The use of non-thermal plasma (NTP) is a promising alternative to antimicrobial treatment. Nevertheless, there is still a lack of knowledge about the effects of NTP on the virulence factors production. We evaluated the ability of four NTP-affected P. aeruginosa strains to re-form biofilm and produce Las-B elastase, proteases, lipases, haemolysins, gelatinase or pyocyanin. Highly strains-dependent inhibitory activity of NTP against extracellular virulence factors production was observed. Las-B elastase activity was reduced up to 82% after 15-min NTP treatment, protease activity and pyocyanin production by biofilm cells was completely inhibited after 60 min, in contrast to lipases and gelatinase production, which remained unchanged. However, for all strains tested, a notable reduction in biofilm re-development ability was depicted using spinning disc confocal microscopy. In addition, NTP exposure of mature biofilms caused disruption of biofilm cells and their dispersion into the environment, as shown by transmission electron microscopy. This appears to be a key step that could help overcome the high resistance of P. aeruginosa and its eventual elimination, for example in combination with antibiotics still highly effective against planktonic cells.
Indigenous perceptions and adaptive responses to the impacts of climate variability in the Sierra Nevada de Santa Marta, Colombia
Authors: Guáqueta-Solórzano Victoria-Eugenia , Postigo Julio C.
Published: September 2022

The exposure, risks, and impacts of climatic changes are most acute for marginalized and disenfranchised groups, particularly Indigenous Peoples. Worldwide, Indigenous Peoples are exposed to a wide range of climate threats that generate a broad spectrum of risks to their wellbeing. Responding to a request from the Arhuaco, this paper examines Arhuaco Indigenous perceptions of climatic variability, the impacts of this variability, and the response to such impacts. The empirical basis of the paper is the fieldwork on four Arhuaco settlements in the Sierra Nevada de Santa Marta, Colombia. We gathered data through surveys, semi-structured interviews, and focus groups. The results of our qualitative and quantitative analyses are: (1) Indigenous perception of climatic variability is consistent with meteorological data; (2) Loss of traditional crops is the most relevant impact; (3) Social and cultural capitals are the most used for adaptation strategies to climate variability; and (4) vulnerability results from non-climatic factors which shape the response capacity to environmental change. Insights from our work contribute to generate new knowledge about impacts of climate variability on Indigenous livelihoods, the responses to such impacts, and to understanding the linkages among climate, capitals, and adaptive responses from marginalized groups in Western society. Finally, our results provide valuable Indigenous practices and perspectives for improving policies to adapt to climate change and strengthen the resilience of local populations.
Blazing fire or breezy wind? A story-driven playful experience for annotating dance movement
Authors: Kougioumtzian Lori , El Raheb Katerina , Katifori Akrivi , Roussou Maria
Published: September 2022

The annotation of animated motion-captured segments is a challenging, interdisciplinary task, especially when it comes to characterizing movement qualitatively. The lack of intuitive, easy-to-learn-and-use frameworks is considered to be one of the biggest challenges in this process; another is the lack of approaches able to motivate a wide audience of users, from the broader public to dance experts, researchers and performers, to contribute with annotations. In this paper we present Motion Hollow, a story-driven playful experience that uses metaphors based on Laban Movement Analysis, an established framework for movement analysis and annotation, to familiarize novice users with the process of qualitative characterization of dance moves. This work proposes a first step into introducing movement annotation to non-expert users, and as such, its main goal is to explore the implications and potential of such an approach. The evaluation of the experience confirms its potential to transform the annotation of dance movement segments into an engaging and enjoyable experience as well as to foster a deeper understanding of movement annotation both as a concept and process.
Cardiotoxicity is mitigated after a supervised exercise program in HER2-positive breast cancer undergoing adjuvant trastuzumab
Authors: Jacquinot Quentin , Meneveau Nathalie , Falcoz Antoine , Bouhaddi Malika , Roux Pauline , Degano Bruno , Chatot Marion , Curtit Elsa , Mansi Laura , Paillard Marie-Justine , Bazan Fernando , Chaigneau Loïc , Dobi Erion , Meynard Guillaume , Vernerey Dewi , Pivot Xavier , Mougin Fabienne
Published: September 2022

Background

Trastuzumab is used, alone or in conjunction with standard chemotherapy, to treat HER2-positive breast cancer (BC). Although it improves cancer outcomes, trastuzumab. can lead to cardiotoxicity. Physical exercise is a safe and effective supportive therapy in the management of side effects, but the cardioprotective effects of exercise are still unclear.

Objectives

The primary aim of this study was to test whether trastuzumab-induced cardiotoxicity [left ventricular ejection fraction (LVEF) under 50%, or an absolute drop in LVEF of 10%] was reduced after a supervised exercise program of 3 months in patients with HER2-positive breast cancer. Secondary endpoints were to evaluate (i) cardiotoxicity rates using other criteria, (ii) cardiac parameters, (iii) cardiorespiratory fitness and (iv) whether a change in LVEF influences the cardiorespiratory fitness.

Methods

89 women were randomized to receive adjuvant trastuzumab in combination with a training program (training group: TG; n = 46) or trastuzumab alone (control group: CG; n = 43). The primary and secondary endpoints were evaluated at the end of the supervised exercise program of 3 months (T3).

Results

After exercise program, 90.5 % of TG patients and 81.8% of CG patients did not exhibit cardiotoxicity. Furthermore, whatever the used criterion, percentage of patients without cardiotoxicity were greater in TG (97.6 and 100% respectively) than in CG (90.9 and 93.9% respectively). LVEF and GLS values remained stable in both groups without any difference between the groups. In contrast, at T3, peak VO2 (+2.6 mL.min−1.kg−1; 95%CI, 1.8 to 3.4) and maximal power (+21.3 W; 95%CI, 17.3 to 25.3) increased significantly in TG, whereas they were unchanged in CG (peak VO2: +0.2 mL.min−1.kg−1; 95%CI, −0.5 to 0.9 and maximal power: +0.7 W, 95%CI, −3.6 to 5.1) compared to values measured at T0. No correlation between LVEF changes and peak VO2 or maximal power was observed.

Conclusion

A 12-week supervised exercise regimen was safe and improved the cardiopulmonary fitness in particular peak VO2, in HER2-positive BC patients treated with adjuvant trastuzumab therapy. The study is under powered to come to any conclusion regarding the effect on cardiotoxicity.

Clinical trial registration

www.ClinicalTrials.gov, identifier: NCT02433067.
Persistent Liver Dysfunction in Pediatric Patients After Total Cavopulmonary Connection Surgery
Authors: Luo Qipeng , Jia Yuan , Su Zhanhao , Wang Hongbai , Li Yinan , Wu Xie , Liu Qiao , Liu Xiaoguang , Yuan Su , Yan Fuxia
Published: September 2022

Background

Studies have reported early liver dysfunction (LD) after cardiac surgery is associated with short and long-term mortality. In this study, we aimed to investigate risk factors for persistent LD after total cavopulmonary connection (TCPC) surgery.

Methods

This is a retrospective case-control study. We defined persistent LD as LDs occurring between postoperative day 1 (POD1) and POD7 and sustaining at least on POD7, while transient LD as LDs occurring between POD1 and POD7 and recovering at least on POD7. Multivariable logistic regression analysis was applied and central venous pressure (CVP) was considered continuously or in quantiles.

Results

Postoperative LD occurred in 111 (27.1%) patients. Transient and persistent LD occurred in 65 (15.9%) and 46 (11.2%) patients, respectively. Aortic cross-clamping (ACC) (odds ratio [OR] 2.55, 95% CI 1.26–5.14) and postoperative CVP (OR 1.34, 95% CI 1.18–1.51) were risk factors for persistent LD, also identified for postoperative any LD and transient LD. Adding postoperative CVP to the model only including ACC significantly improved persistent LD prediction (△AUC 0.15, p = 0.002). Compared with CVP ≤ 14 mmHg, adjusted ORs and 95% CI of persistent LD for CVP of 14–16 and >16 mmHg were 3.11 (1.24, 7.81) and 10.55 (3.72, 29.93), respectively. Patients with persistent LD might have a longer length of mechanical ventilation (mean difference, 13.5 h) and postoperative hospital stay (mean difference, 7 days), and higher postoperative costs (mean difference, 6.7 thousand dollars) compared to those with transient LD.

Conclusions

Intra-operative application of ACC and postoperative elevated CVP were independent risk factors for persistent LD in pediatric patients following TCPC surgery. Compared to patients with transient LD, patients with persistent LD might have a longer length of mechanical ventilation and postoperative hospital stay, and higher postoperative costs. We should pay more attention to patients with high postoperative CVP to prevent their persistent LD occurrence.
Effect of metformin on adverse outcomes in T2DM patients: Systemic review and meta-analysis of observational studies
Authors: Xu Zhicheng , Zhang Haidong , Wu Chenghui , Zheng Yuxiang , Jiang Jingzhou
Published: September 2022

Background

The cardiovascular protection effect of metformin on patients with type 2 diabetes mellitus (T2DM) remains inconclusive. This systemic review and meta-analysis were to estimate the effect of metformin on mortality and cardiovascular events among patients with T2DM.

Methods

A search of the Pubmed and EMBASE databases up to December 2021 was performed. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled by a random-effects model with an inverse variance method.

Results

A total of 39 studies involving 2473009 T2DM patients were adopted. Compared to non-metformin therapy, the use of metformin was not significantly associated with a reduced risk of major adverse cardiovascular event (MACE) (HR = 1.06, 95%CI 0.91–1.22; I2 = 82%), hospitalization (HR = 0.85, 95%CI 0.64–1.13; I2 = 98%), heart failure (HR = 0.86, 95%CI 0.60–1.25; I2 = 99%), stroke (HR = 1.16, 95%CI 0.88–1.53; I2 = 84%), and risk of AMI (HR = 0.88, 95%CI 0.69–1.14; I2 = 88%) in T2DM patients. Metformin was also not associated with significantly lowered risk of MACE compared to dipeptidyl peptidase-4 inhibitor (DPP-4i) in T2DM patients (HR = 0.95, 95%CI 0.73–1.23; I2 = 84%).

Conclusions

The effect of metformin on some cardiovascular outcomes was not significantly better than the non-metformin therapy or DPP-4i in T2DM patients based on observational studies.
Effect of social app-assisted education and support on glucose control in patients with coronary heart disease and diabetes mellitus
Authors: Zhong Jing , Zhang Huimin , Li Zhuyu , Qian Dehui , Zhang Yingqian , Li Chao , Song Yuanbin , Qin Zhexue , Yu Jie , Bian Shi-zhu , Yu Yang , Wang Ke , Li Jing-Wei
Published: September 2022

Background

Social app-assisted education and support may facilitate diabetes self-management. We aim to evaluate the effect of WeChat, a popular social app, on glycemic control in patients with coronary heart disease (CHD) and diabetes mellitus (DM).

Methods

We conducted a parallel-group, open-label, randomized clinical trial that included 160 patients with both CHD and diabetes mellitus from a tertiary hospital in China. The intervention group (n = 80) received educational materials (information on glucose monitoring, drug usage, medication, and lifestyle) and reminders in response to individual blood glucose values via WeChat. The control group (n = 80) received usual care. The primary outcome was a change in glycated hemoglobin (HbA1C) levels over 3 months. Secondary outcomes included fasting blood glucose (FBG), systolic blood pressure, and low-density lipoprotein (LDL) cholesterol from baseline to 3 months. Analysis was conducted using a linear mixed model.

Results

The intervention group had a greater reduction in HbA1C (−0.85 vs. 0.15%, between-group difference: −1.00%; 95% CI −1.31 to −0.69%; p < 0.001) compared with the control group. Change in fasting blood glucose was larger in the intervention group (−1.53 mmol/L; 95% CI −1.90 to −1.17; p < 0.001) and systolic blood pressure (−9.06 mmHg; 95% CI −12.38 to −5.73; p < 0.001), but not LDL (between-group difference, −0.08 mmol/L; 95% CI −0.22 to 0.05; p = 0.227).

Conclusion

The combination of social app with education and support resulted in better glycemic control in patients with CHD and DM. These results suggest that education and support interaction via social app may benefit self-management in CHD and DM.
Identifying novel phenotypes of elevated left ventricular end diastolic pressure using hierarchical clustering of features derived from electromechanical waveform data
Authors: Burton Timothy , Ramchandani Shyam , Bhavnani Sanjeev P. , Khedraki Rola , Cohoon Travis J. , Stuckey Thomas D. , Steuter John A. , Meine Frederick J. , Bennett Brett A. , Carroll William S. , Lange Emmanuel , Fathieh Farhad , Khosousi Ali , Rabbat Mark , Sanders William E.
Published: September 2022

Introduction

Elevated left ventricular end diastolic pressure (LVEDP) is a consequence of compromised left ventricular compliance and an important measure of myocardial dysfunction. An algorithm was developed to predict elevated LVEDP utilizing electro-mechanical (EM) waveform features. We examined the hierarchical clustering of selected features developed from these EM waveforms in order to identify important patient subgroups and assess their possible prognostic significance.

Materials and methods

Patients presenting with cardiovascular symptoms (N = 396) underwent EM data collection and direct LVEDP measurement by left heart catheterization. LVEDP was classified as non-elevated ( ≤ 12 mmHg) or elevated (≥25 mmHg). The 30 most contributive features to the algorithm output were extracted from EM data and input to an unsupervised hierarchical clustering algorithm. The resultant dendrogram was divided into five clusters, and patient metadata overlaid.

Results

The cluster with highest LVEDP (cluster 1) was most dissimilar from the lowest LVEDP cluster (cluster 5) in both clustering and with respect to clinical characteristics. In contrast to the cluster demonstrating the highest percentage of elevated LVEDP patients, the lowest was predominantly non-elevated LVEDP, younger, lower BMI, and males with a higher rate of significant coronary artery disease (CAD). The next adjacent cluster (cluster 2) to that of the highest LVEDP (cluster 1) had the second lowest LVEDP of all clusters. Cluster 2 differed from Cluster 1 primarily based on features extracted from the electrical data, and those that quantified predictability and variability of the signal. There was a low predictability and high variability in the highest LVEDP cluster 1, and the opposite in adjacent cluster 2.

Conclusion

This analysis identified subgroups of patients with varying degrees of LVEDP elevation based on waveform features. An approach to stratify movement between clusters and possible progression of myocardial dysfunction may include changes in features that differentiate clusters; specifically, reductions in electrical signal predictability and increases in variability. Identification of phenotypes of myocardial dysfunction evidenced by elevated LVEDP and knowledge of factors promoting transition to clusters with higher levels of left ventricular filling pressures could permit early risk stratification and improve patient selection for novel therapeutic interventions.
Direct autotransfusion in the management of acute pericardial tamponade during catheter ablation for atrial fibrillation: An imperfect but practical method
Authors: Zhao Xin , Liu Jian-feng , Su Xin , Long De-yong , Sang Cai-hua , Tang Ri-bo , Yu Rong-Hui , Liu Nian , Jiang Chen-xi , Li Song-nan , Guo Xue-yuan , Wang Wei , Zuo Song , Dong Jian-zeng , Ma Chang-sheng
Published: September 2022

Background

Acute pericardial tamponade (APT) is one of the most serious complications of catheter ablation for atrial fibrillation (AF-CA). Direct autotransfusion (DAT) is a method of reinjecting pericardial blood directly into patients through vein access without a cell-salvage system. Data regarding DAT for APT are rare and provide limited information. Our present study aims to further investigate the safety and feasibility of DAT in the management of APT during the AF-CA procedure.

Methods and results

We retrospectively reviewed 73 cases of APT in the perioperative period of AF-CA from January 2014 to October 2021 at our institution, among whom 46 were treated with DAT. All included patients successfully received emergency pericardiocentesis through subxiphoid access guided by X-ray. Larger volumes of aspirated pericardial blood (658.4 ± 545.2 vs. 521.2 ± 464.9 ml), higher rates of bridging anticoagulation (67.4 vs. 37.0%), and surgical repair (6 vs. 0) were observed in patients with DAT than without. Moreover, patients with DAT were less likely to complete AF-CA procedures (32/46 vs. 25/27) and had a lower incidence of APT first presented in the ward (delayed presentation) (8/46 vs. 9/27). There was no difference in major adverse events (death/disseminated intravascular coagulation/multiple organ dysfunction syndrome and clinical thrombosis) (0/0/1/0 vs. 1/0/0/0), other potential DAT-related complications (fever/infection and deep venous thrombosis) (8/5/2 vs. 5/3/1), and length of hospital stay (11.4 ± 11.6 vs. 8.3 ± 4.7 d) between two groups.

Conclusion

DAT could be a feasible and safe method to deal with APT during AF-CA procedure.
Are cardiovascular comorbidities always associated with a worse prognosis in patients with lung cancer?
Authors: Mędrek Sabina , Szmit Sebastian
Published: September 2022

Many factors contribute to mortality in lung cancer, including the presence of concomitant cardiovascular disease. In the treatment of early stage of lung cancer, the presence of comorbidities and occurence of cardiotoxicity may be prognostic. The effect of cardiotoxicity of radiotherapy and chemoradiotherapy on overall survival has been documented. Acute arterial and venous thromboembolic events seem to correlate with the degree of the histological malignancy, its clinical advancement, and even with optimal cardiac treatment, they may influence the survival time. In the case of high-grade and advanced lung cancer stage especially in an unresectable stadium, the prognosis depends primarily on the factors related to the histopathological and molecular diagnosis. Electrocardiographic and echocardiographic abnormalities may be prognostic factors, as they seem to correlate with the patient's performance status as well as tumor localization and size.
Integrating diverse layers of omic data to identify novel drug targets in Listeria monocytogenes
Authors: Palumbo Miranda , Sosa Ezequiel , Castello Florencia , Schottlender Gustavo , Serral Federico , Turjanski Adrián , Palomino María Mercedes , Do Porto Darío Fernández
Published: September 2022

Listeriamonocytogenes (Lm) is a Gram-positive bacillus responsible for listeriosis in humans. Listeriosis has become a major foodborne illness in recent years. This illness is mainly associated with the consumption of contaminated food and ready-to-eat products. Recently, Lm has developed resistances to a broad range of antimicrobials, including those used as the first choice of therapy. Moreover, multidrug-resistant strains have been detected in clinical isolates and settings associated with food processing. This scenario punctuates the need for novel antimicrobials against Lm. On the other hand, increasingly available omics data for diverse pathogens has created new opportunities for rational drug discovery. Identification of an appropriate molecular target is currently accepted as a critical step of this process. In this work, we generated multiple layers of omics data related to Lm, aiming to prioritize proteins that could serve as attractive targets for antimicrobials against L. monocytogenes. We generated genomic, transcriptomic, metabolic, and protein structural information, and this data compendium was integrated onto a freely available web server (Target Pathogen). Thirty targets with desirable features from a drug development point of view were shortlisted. This set of target proteins participates in key metabolic processes such as fatty acid, pentose, rhamnose, and amino acids metabolism. Collectively, our results point towards novel targets for the control of Lm and related bacteria. We invite researchers working in the field of drug discovery to follow up experimentally on our revealed targets.
Controlling effect of source-reservoir assemblage on natural gas accumulation: A case study of the upper triassic xujiahe formation in the sichuan basin
Authors: Tan Kaijun , Yao Jun , Chen Juan , Tang Dahai , Qin Yang , Wu Qingpeng
Published: September 2022

The enrichment law of tight sandstone gas in the Upper Triassic Xujiahe Formation in the Sichuan Basin has not been fully revealed. In this study, the controlling effect of source-reservoir assemblage on gas accumulation in the Xujiahe Formation was systematically investigated. The results show that pores and fractures are developed in the tight sandstone reservoirs of the Xujiahe Formation. The main pore types are intragranular dissolved and intergranular pores. The quality of sandstone reservoirs in the Xujiahe Formation is controlled by sedimentation, diagenesis and tectonic processes. Underwater distributary river channels and estuary bars are favorable microfacies for reservoir development, and chlorite cemented facies and dissolution-kaolinite cemented facies are the most favorable diagenetic facies. In addition, the natural gas composition and carbon isotope characteristics of the Xujiahe Formation are significantly different in different intervals of the same gas field and the same interval of adjacent gas fields. This shows that the natural gas has no obvious vertical mixing and lateral migration, and it has the distribution characteristics of “local enrichment”. Then, the natural gas will be preferentially charged in the feldspar lithic sandstone and feldspar quartz sandstone with large thickness and good physical properties by means of short-range migration. According to the research, the hydrocarbon supply capacity of the single layer in each interval is weak, and it leads to the low filling degree of the gas reservoir and the insufficient separation of gas and water. On the whole, four sets of extra-source “lower generation and upper storage” assemblages and two sets of “self-generation and self-storage” source-reservoir assemblages are developed in the Xujiahe Formation. The development scale of natural gas is mainly controlled by the type of source-reservoir combination, and the areas with close source-reservoir contact and high hydrocarbon generation intensity are high-quality reservoir development areas.