bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Effects of Saponins for the Prevention and Treatment of Cancer by Ameliorating Inflammation and Angiogenesis and Inducing Antioxidant and Apoptotic Effects in Human Cells
Authors: Khan Muhammad , Karima Gul , Khan Muhammad , Shin Jin , Kim Jong
Published: September 2022

Saponins are natural compounds found in plants and have a diverse range of applications. However, the therapeutic potential of saponins in regulating cytotoxicity, angiogenesis, and inflammation in mammalian cells is yet to be explored. Here, we investigated the therapeutic effects of saponins from green tea by exploring the cytotoxic effects of saponins by inducing apoptosis in the human cancer cell lines hepatocellular carcinoma (HEPG2) and colorectal adenocarcinoma (HT29). The anti-angiogenesis effect of saponins was also investigated in human umbilical vein endothelial cells (HUVEC). We explored the ability of saponins to attenuate inflammation in a dose-dependent manner in normal human cells. It was found that saponins exhibit cytotoxic effects in cancer cells and not in normal cells at the same concentration. Cytotoxicity was measured by inducing apoptosis by enhancing caspase-3 (cas-3) activation and B-cell lymphoma-2 (Bcl-2)-associated X protein (BAX) gene expression and suppressing the antiapoptotic protein, Bcl-2. The inhibition of HUVEC proliferation was due to the suppression of the phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), vascular endothelial growth factor receptor-2 (VEGFR-2), and nuclear factor kappa B (NF-κB). We also observed the antioxidant potential of green tea-derived saponins against free radicals in reactive oxygen species (ROS)-induced cells. Here we observed that the saponins exhibited free radical scavenging activities and activated nuclear factorerythroid 2-related factor 2 (NRF-2) leading to the upregulation of antioxidant-related genes in human embryonic kidney 293 (HEK293) cells. Furthermore, we demonstrated that the anti-inflammatory effects were due to the suppression of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in HEK293 cells. The significance of the work is we are the first to report on the anti-cancer effects of saponins based on the anti-inflammatory, antioxidant, anti-angiogenesis, and apoptosis induction properties. In conclusion, green tea-derived saponins could be effective therapeutics for the treatment of cancer.
Platelet Hemostasis Reactions at Different Temperatures Correlate with Intracellular Calcium Concentration
Authors: Mindukshev Igor , Fock Ekaterina , Dobrylko Irina , Sudnitsyna Julia , Gambaryan Stepan , Panteleev Mikhail A.
Published: September 2022

Hypo- and hyperthermia affect both primary and secondary hemostasis; however, there are controversial data concerning platelet activation and the underlying mechanisms under hypo- and hyperthermia. The discrepancies in the data could be partly explained by different approaches to hemostatic reactions analysis. We applied a new LaSca-TMF laser particle analyzer for a simultaneous fluorescence and laser scattering analysis of platelet responses at different temperatures. Human platelets were activated by ADP in a wide range of temperatures, and platelet transformations (e.g., a shape change reaction, aggregation and clot formation) and the intracellular calcium concentration ([Ca2+]i) were analyzed by LaSca-TMF and confocal microscopy. The platelet shape change reaction gradually increased with a rising temperature. The platelet aggregation strongly decreased at low ADP concentrations with the augmentation of the temperature and was independent of the temperature at high ADP concentrations. In contrast, the clotting time decreased with a temperature increase. Similar to the aggregation response, a rise in [Ca2+]i triggered by low ADP concentrations was higher under hypothermic conditions and the differences were independent of the temperature at high ADP concentrations. We showed that the key reactions of cellular hemostasis are differentially regulated by temperature and demonstrated for the first time that an accelerated aggregation under hypothermic conditions directly correlated with an increased level in [Ca2+]i in platelets.
A Preliminary Direct Comparison of the Inflammatory Reduction and Growth Factor Production Capabilities of Three Commercially Available Wound Products: Collagen Sheet, Manuka Honey Sheet, and a Novel Bioengineered Collagen Derivative + Manuka Honey + Hydroxyapatite Sheet
Authors: Rodriguez Isaac , Conti Tricia , Bionda Nina
Published: September 2022

Many commercially available wound products focus on improving one stage of the wound healing cascade. While this targeted approach works for specific wounds, there is a need for products that can reliably and comprehensively progress a wound through multiple stages. This preliminary in vitro study was performed to directly compare the inflammatory reduction and growth factor production effects of three commercially available wound care products: a collagen sheet (COL), a Manuka Honey Calcium Alginate sheet (MH), and a novel bioengineered sheet comprised of a collagen derivative (gelatin), Manuka honey, and hydroxyapatite (BCMH). Macrophages and human dermal fibroblasts were directly seeded on all three commercial products, and supernatants were analyzed for inflammatory markers and growth factors, respectively. Comparing the MMP-9/TIMP-1 ratio, BCMH resulted in 11× lower levels of this inflammation biomarker compared to COL, and 3× lower levels compared to MH. Both the COL and BCMH products created an environment conducive to expression and release of relevant growth factors, while the MH product showed the lowest levels of growth factor expression of all three commercially available products tested. The favorable 11× lower MMP-9/TIMP-1 ratio observed with the BCMH product compared to the COL product suggests that the BCMH products provided a superior comprehensive approach to healthy progression of the wounds by providing an additional benefit of reducing the inflammatory response in vitro.
CD73-Adenosinergic Axis Mediates the Protective Effect of Extracellular Vesicles Derived from Mesenchymal Stromal Cells on Ischemic Renal Damage in a Rat Model of Donation after Circulatory Death
Authors: Grignano Maria Antonietta , Bruno Stefania , Viglio Simona , Avanzini Maria Antonietta , Tapparo Marta , Ramus Marina , Croce Stefania , Valsecchi Chiara , Pattonieri Eleonora Francesca , Ceccarelli Gabriele , Manzoni Federica , Asti Annalia , Libetta Carmelo , Sepe Vincenzo , Iadarola Paolo , Gregorini Marilena , Rampino Teresa
Published: September 2022

We propose a new organ-conditioning strategy based on mesenchymal stromal cell (MSCs)/extracellular vesicle (EVs) delivery during hypothermic perfusion. MSCs/EVs marker CD73 is present on renal proximal tubular cells, and it protects against renal ischemia-reperfusion injury by converting adenosine monophosphate into adenosine (ADO). In this study, after checking if CD73-silenced EVs (EVsi) would impact in vitro tubular-cell proliferation, we perfused kidneys of a rat model of donation after circulatory death, with Belzer solution (BS) alone, BS supplemented with MSCs, EVs, or EVsi. The ADO and ATP levels were measured in the effluents and tissues. Global renal ischemic damage score (GRS), and tubular cell proliferation index (IPT) were evaluated in the tissue. EVsi did not induce cell proliferation in vitro. Ex vivo kidneys perfused with BS or BS + EVsi showed the worst GRS and higher effluent ADO levels than the MSC- and EV-perfused kidneys. In the EV-perfused kidneys, the tissue and effluent ATP levels and IPT were the highest, but not if CD73 was silenced. Tissue ATP content was positively correlated with tissue ADO content and negatively correlated with effluent ADO level in all groups. In conclusion, kidney conditioning with EVs protects against ischemic damage by activating the CD73/ADO system.
Hydroquinones Inhibit Biofilm Formation and Virulence Factor Production in Staphylococcus aureus
Authors: Kim Sanghun , Lee Jin-Hyung , Kim Yong-Guy , Tan Yulong , Lee Jintae
Published: September 2022

Staphylococcus aureus is one of the major pathogens responsible for antimicrobial resistance-associated death. S. aureus can secrete various exotoxins, and staphylococcal biofilms play critical roles in antibiotic tolerance and the persistence of chronic infections. Here, we investigated the inhibitory effects of 18 hydroquinones on biofilm formation and virulence factor production by S. aureus. It was found that 2,5-bis(1,1,3,3-tetramethylbutyl) hydroquinone (TBHQ) at 1 µg/mL efficiently inhibits biofilm formation by two methicillin-sensitive and two methicillin-resistant S. aureus strains with MICs of 5 µg/mL, whereas the backbone compound hydroquinone did not (MIC > 400 µg/mL). In addition, 2,3-dimethylhydroquinone and tert-butylhydroquinone at 50 µg/mL also exhibited antibiofilm activity. TBHQ at 1 µg/mL significantly decreased the hemolytic effect and lipase production by S. aureus, and at 5–50 µg/mL was non-toxic to the nematode Caenorhabditis elegans and did not adversely affect Brassica rapa seed germination or growth. Transcriptional analyses showed that TBHQ suppressed the expression of RNAIII (effector of quorum sensing). These results suggest that hydroquinones, particularly TBHQ, are potentially useful for inhibiting S. aureus biofilm formation and virulence.
Connexin Lateralization Contributes to Male Susceptibility to Atrial Fibrillation
Authors: Thibault Simon , Ton Anh-Tuan , Huynh François , Fiset Céline
Published: September 2022

Men have a higher risk of developing atrial fibrillation (AF) than women, though the reason for this is unknown. Here, we compared atrial electrical and structural properties in male and female mice and explored the contribution of sex hormones. Cellular electrophysiological studies revealed that action potential configuration, Na+ and K+ currents were similar in atrial myocytes from male and female mice (4–5 months). Immunofluorescence showed that male atrial myocytes had more lateralization of connexins 40 (63 ± 4%) and 43 (66 ± 4%) than females (Cx40: 45 ± 4%, p = 0.006; Cx43: 44 ± 4%, p = 0.002), with no difference in mRNA expression. Atrial mass was significantly higher in males. Atrial myocyte dimensions were also larger in males. Atrial fibrosis was low and similar between sexes. Orchiectomy (ORC) abolished sex differences in AF susceptibility (M: 65%; ORC: 38%, p = 0.050) by reducing connexin lateralization and myocyte dimensions. Ovariectomy (OVX) did not influence AF susceptibility (F: 42%; OVX: 33%). This study shows that prior to the development of age-related remodeling, male mice have more connexin lateralization and larger atria and atrial myocyte than females. Orchiectomy reduced AF susceptibility in males by decreasing connexin lateralization and atrial myocyte size, supporting a role for androgens. These sex differences in AF substrates may contribute to male predisposition to AF.
Physiological and Biochemical Regulation Mechanism of Exogenous Hydrogen Peroxide in Alleviating NaCl Stress Toxicity in Tartary Buckwheat (Fagopyrum tataricum (L.) Gaertn)
Authors: Yao Xin , Zhou Meiliang , Ruan Jingjun , Peng Yan , Ma Chao , Wu Weijiao , Gao Anjing , Weng Wenfeng , Cheng Jianping
Published: September 2022

We aimed to elucidate the physiological and biochemical mechanism by which exogenous hydrogen peroxide (H2O2) alleviates salt stress toxicity in Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn). Tartary buckwheat “Chuanqiao-2” under 150 mmol·L−1 salt (NaCl) stress was treated with 5 or 10 mmol·L−1 H2O2, and seedling growth, physiology and biochemistry, and related gene expression were studied. Treatment with 5 mmol·L−1 H2O2 significantly increased plant height (PH), fresh and dry weights of shoots (SFWs/SDWs) and roots (RFWs/RDWs), leaf length (LL) and area (LA), and relative water content (LRWC); increased chlorophyll a (Chl a) and b (Chl b) contents; improved fluorescence parameters; enhanced antioxidant enzyme activity and content; and reduced malondialdehyde (MDA) content. Expressions of all stress-related and enzyme-related genes were up-regulated. The F3′H gene (flavonoid synthesis pathway) exhibited similar up-regulation under 10 mmol·L−1 H2O2 treatment. Correlation and principal component analyses showed that 5 mmol·L−1 H2O2 could significantly alleviate the toxic effect of salt stress on Tartary buckwheat. Our results show that exogenous 5 mmol·L−1 H2O2 can alleviate the inhibitory or toxic effects of 150 mmol·L−1 NaCl stress on Tartary buckwheat by promoting growth, enhancing photosynthesis, improving enzymatic reactions, reducing membrane lipid peroxidation, and inducing the expression of related genes.
Activation of Alternative Bilirubin Clearance Pathways Partially Reduces Hyperbilirubinemia in a Mouse Model Lacking Functional Ugt1a1 Activity
Authors: Banerjee Bhaswati , Olajide Olayemi Joseph , Bortolussi Giulia , Muro Andrés F.
Published: September 2022

Bilirubin is a heme catabolite and Ugt1a1 is the only enzyme involved in the biological elimination of bilirubin. Partially functional or non-functional Ugt1a1 may result in neuronal damage and death due to the accumulation of unconjugated bilirubin in the brain. The understanding of the role of alternative bilirubin detoxification mechanisms that can reduce bilirubin toxicity risk is crucial for developing novel therapeutic strategies. To provide a proof-of-principle showing whether activation of alternative detoxification pathways could lead to life-compatible bilirubin levels in the absence of Ugt1a1 activity, we used Ugt1−/− hyperbilirubinemic mice devoid of bilirubin glucuronidation activity. We treated adult Ugt1−/− mice with TCPOBOP, a strong agonist of the constitutive androstane receptor (CAR). TCPOBOP treatment decreased plasma and liver tissue bilirubin levels by about 38%, and resulted in the transcriptional activation of a vast array of genes involved in bilirubin transport and metabolism. However, brain bilirubin level was unaltered. We observed ~40% degradation of bilirubin in the liver microsomes from TCPOBOP treated Ugt1−/− mice. Our findings suggest that, in the absence of Ugt1a1, the activation of alternative bilirubin clearance pathways can partially improve hyperbilirubinemic conditions. This therapeutic approach may only be considered in a combinatorial manner along with other treatments.
Sinomenine Hydrochloride Promotes TSHR-Dependent Redifferentiation in Papillary Thyroid Cancer
Authors: Zhang Jing , Zhao Aomei , Jia Xi , Li Xinru , Liang Yiqian , Liu Yan , Xie Xin , Qu Xijie , Wang Qi , Zhang Yuemin , Gao Rui , Yu Yan , Yang Aimin
Published: September 2022

Radioactive iodine (RAI) plays an important role in the diagnosis and treatment of papillary thyroid cancer (PTC). The curative effects of RAI therapy are not only related to radiosensitivity but also closely related to the accumulation of radionuclides in the lesion in PTC. Sinomenine hydrochloride (SH) can suppress tumor growth and increase radiosensitivity in several tumor cells, including PTC. The aim of this research was to investigate the therapeutic potential of SH on PTC cell redifferentiation. In this study, we treated BCPAP and TPC-1 cells with SH and tested the expression of thyroid differentiation-related genes. RAI uptake caused by SH-pretreatment was also evaluated. The results indicate that 4 mM SH significantly inhibited proliferation and increased the expression of the thyroid iodine-handling gene compared with the control group (p < 0.005), including the sodium/iodide symporter (NIS). Furthermore, SH also upregulated the membrane localization of NIS and RAI uptake. We further verified that upregulation of NIS was associated with the activation of the thyroid-stimulating hormone receptor (TSHR)/cyclic adenosine monophosphate (cAMP) signaling pathway. In conclusion, SH can inhibit proliferation, induce apoptosis, promote redifferentiation, and then increase the efficacy of RAI therapy in PTC cells. Thus, our results suggest that SH could be useful as an adjuvant therapy in combination with RAI therapy in PTC.
Toll-like Receptor 2 Is Associated with the Immune Response, Apoptosis, and Angiogenesis in the Mammary Glands of Dairy Cows with Clinical Mastitis
Authors: Bai Xu , Wang Xueying , Lin Ting , Dong Weitao , Gao Yuan , Ji Peng , Zhang Yong , Zhao Xingxu , Zhang Quanwei
Published: September 2022

Toll-like receptor 2 (TLR2) plays a crucial role in bacterial recognition and the host immune response during infection. However, its function and downstream biological processes (BPs) in the mammary glands (MGs) of Holstein cows with clinical mastitis (CM) are not fully understood. This study aimed to comprehensively identify the BPs and differentially expressed proteins (DEPs) associated with the bacterial response and TLR2 using data-independent acquisition (DIA) proteomic data. A possible mechanism for the action of TLR2 was proposed, and the results suggested that the expression levels of TLR2 and caspase 8 (CASP8) were positively correlated with the apoptosis of MGs. The expression patterns of TLR2 and TEK receptor tyrosine kinase 2 (Tie2) were negatively correlated with angiogenesis. These results indicated that TLR2 might promote apoptosis in mammary epithelial cells (MECs) and vascular endothelial cells (VECs) via upregulation of CASP8 expression, and inhibition of angiogenesis in VECs via downregulation of Tie2 expression in dairy cows with CM. In conclusion, TLR2 is associated with inflammation, apoptosis, and angiogenesis in the MGs of dairy cows with bacteria-induced mastitis. These results contribute to a deeper understanding of the pathogenic mechanisms and provide the knowledge needed for developing the prevention and treatment of dairy mastitis.
Involvement of Inflammation and Its Resolution in Disease and Therapeutics
Authors: Alfaro Sebastián , Acuña Vania , Ceriani Ricardo , Cavieres María Fernanda , Weinstein-Oppenheimer Caroline Ruth , Campos-Estrada Carolina
Published: September 2022

Inflammation plays a critical role in the response to and survival from injuries and/or infections. It occurs in two phases: initiation and resolution; however, when these events do not resolve and persist over time, the inflammatory response becomes chronic, prompting diseases that affect several systems and organs, such as the vasculature and the skin. Here, we reviewed inflammation that occurs in selected infectious and sterile pathologies. Thus, the immune processes induced by bacterial sepsis as well as T. cruzi and SARS-CoV-2 infections are shown. In addition, vaccine adjuvants as well as atherosclerosis are revised as examples of sterile-mediated inflammation. An example of the consequences of a lack of inflammation resolution is given through the revision of wound healing and chronic wounds. Then, we revised the resolution of the latter through advanced therapies represented by cell therapy and tissue engineering approaches, showing how they contribute to control chronic inflammation and therefore wound healing. Finally, new pharmacological insights into the management of chronic inflammation addressing the resolution of inflammation based on pro-resolving mediators, such as lipoxin, maresin, and resolvins, examining their biosynthesis, biological properties, and pharmacokinetic and pharmaceuticals limitations, are given. We conclude that resolution pharmacology and advanced therapies are promising tools to restore the inflammation homeostasis.
Analysis of the Correlation between Mass-Media Publication Activity and COVID-19 Epidemiological Situation in Early 2022
Authors: Yakunin Kirill , Mukhamediev Ravil I. , Yelis Marina , Kuchin Yan , Symagulov Adilkhan , Levashenko Vitaly , Zaitseva Elena , Aubakirov Margulan , Yunicheva Nadiya , Muhamedijeva Elena , Gopejenko Viktors , Popova Yelena
Published: September 2022

The paper presents the results of a correlation analysis between the information trends in the electronic media of Kazakhstan and indicators of the epidemiological situation of COVID-19 according to the World Health Organization (WHO). The developed method is based on topic modeling and some other methods of processing natural language texts. The method allows for calculating the correlations between media topics, moods, the results of full-text search queries, and objective WHO data. The analysis of the results shows how the attitudes of society towards the problems of COVID-19 changed from 2021–2022. Firstly, the results reflect a steady trend of decreasing interest of electronic media in the topic of the pandemic, although to an unequal extent for different thematic groups. Secondly, there has been a tendency to shift the focus of attention to more pragmatic issues, such as remote learning problems, remote work, the impact of quarantine restrictions on the economy, etc.
Angiographic Characteristics of the Vein of Marshall in Patients with and without Atrial Fibrillation
Authors: Ding Lei , Zhang Hongda , Yu Fengyuan , Mi Lijie , Hua Wei , Zhang Shu , Yao Yan , Tang Min
Published: September 2022

Background: Ethanol infusion into the vein of Marshall (Et-VOM) is a novel therapeutic treatment for atrial fibrillation (AF). However, few studies have focused on the difference between AF and non-AF patients (presented other types of arrhythmias) regarding the characteristics of the vein of Marshall (VOM). Objective: This study sought to investigate the incidence, morphology, and angiographic characteristics of the VOM. Methods: Coronary sinus (CS) angiography was performed in all patients. The baseline, angiographic characteristics and measurements of VOM dimensions were compared between the AF and non-AF group. Results: CS angiography was performed in 290 patients. The VOM detection rate was higher in the AF group than in the non-AF group (91.8% vs. 84.1%, p = 0.044). In the right anterior oblique (RAO) projection, AF patients had significant larger VOM ostium, CS ostium, and CS diameter at VOM ostium than non-AF patients (1.9 ± 0.9 vs. 1.7 ± 0.7 mm, p = 0.015; 12.8 ± 4.1 vs. 11.4 ± 3.7 mm, p = 0.016; 9.1 ± 3.1 vs. 8.2 ± 2.9 mm, p = 0.028, respectively). There was a slight linear correlation between the VOM ostium and the CS ostium diameter as well as left atrial volume (LAV). Conclusion: AF patients seem to have a higher incidence of the VOM, larger VOM ostium, CS ostium, and CS lumen in RAO view. Meanwhile, the VOM ostium may correlate with the CS ostium and LAV.
Does Bicanalicular Intubation Improve the Outcome of Endoscopic Dacryocystorhinostomy?
Authors: Matoušek Petr , Lubojacký Jakub , Masárová Michaela , Čábalová Lenka , Červenka Stanislav , Komínek Pavel
Published: September 2022

The aim of this study was to compare the success of endoscopic dacryocystorinostomy with and without bicanalicular intubation in the treatment of distal nasolacrimal duct obstruction. Methods: In a prospective, randomized, comparative study, endoscopic dacryocystorinostomy without bicanalicular silicone intubation (Group I) and endoscopic dacryocystorinostomy with intubation (Group II) were performed in patients with distal nasolacrimal duct obstructions. The tubes were removed 3 months after surgery in Group II, and the patients were followed up for 6 months after surgery. Therapeutic success was defined as the fluorescein dye disappearance test grade 0–1 corresponding with a complete resolution of symptoms. Results: Thirty patients, aged 23–86 years, were included in the study. The success rate was 13/15 (86.67%) in Group I and in 14/15 (93.33%) in Group II. The difference between the two groups was not statistically significant (p = 0.483). Most common complications were granulations that occurred in 1/15 (6.67%) patient in Group I and in 2/15 (13.33%) patients in Group II. Adhesions in rhinostomy with epiphora and persistent secretion were observed in 1/15 (6.67%) patient in Group II. Conclusions: Bicanalicular intubation does not significantly increase the success rate of EDCR in distal nasolacrimal obstruction in adults.
The Limited Effect of a History of COVID-19 on Antibody Titers and Adverse Reactions Following BNT162b2 Vaccination: A Single-Center Prospective Study
Authors: Kushima Hisako , Ishii Hiroshi , Kinoshita Yoshiaki , Koide Yohei , Komiya Yukie , Kato Junko , Umehara Mayumi , Sakata Miho , Miyazaki Motoyasu , Ikuta Mikihiro
Published: September 2022

Background and Objectives: The need for, and ideal frequency of, the vaccination against coronavirus disease 2019 (COVID-19) of previously infected individuals have not yet been sufficiently evaluated. The aim of this study was to examine the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody status and adverse reactions after vaccination among medical staff with or without a history of COVID-19. Materials and Methods: A single-center prospective study was performed at Fukuoka University Chikushi Hospital. We investigated the presence of the anti-SARS-CoV-2 antibody titer among medical staff before and after mRNA vaccination with the BNT162b2. The levels of immunoglobulin G antibody were quantitatively measured at six points—before vaccination, after the first vaccination, at three points after the second vaccination, and finally, after the third vaccination—and the levels were then compared based on the COVID-19 infection history. Results: The previously infected (before the first vaccination) subjects (n = 17) showed a marked increase in antibody titers two weeks after the first vaccination and four weeks after the second vaccination. Although they were able to maintain a certain level of antibody titers until 30 weeks after the second vaccination, the titers fell in the same way as observed in the non-infected subjects. The subjects who did not receive the third vaccination due to adverse reactions to previous vaccines (n = 1) or who were positive for COVID-19 prior to the third vaccination (n = 2) were excluded from the subsequent analyses. Among non-infected subjects (n = 36), smokers had lower peak antibody titers than the others. The previously infected subjects had a significantly higher incidence of adverse reactions after the first vaccination but had a similar incidence of adverse reactions after the second and third vaccinations compared to the non-infected subjects. Conclusions: A history of COVID-19 may influence only the initial increase in anti-SARS-CoV-2 antibody titers and the occurrence of adverse reactions after the first vaccination.
Advanced Research on Immune Checkpoint Inhibitor Therapy
Authors: Imai Hisao , Kaira Kyoichi , Kagamu Hiroshi
Published: September 2022

The human body has an inherent immune surveillance mechanism that eliminates cancer cells and suppresses the development of cancer [...]
The Effect of COVID-19 on the Perioperative Course of Acute Coronary Syndrome in Poland: The Estimation of Perioperative Prognosis and Neural Network Analysis in 243,515 Cases from 2020 to 2021
Authors: Kaziród-Wolski Karol , Zając Patrycja , Zabojszcz Michał , Kołodziej Agnieszka , Sielski Janusz , Siudak Zbigniew
Published: September 2022

COVID-19 causes thromboembolic complications that affect the patient’s prognosis. COVID-19 vaccines significantly improve the prognosis for the course of the infection. The aim of this study was to evaluate the impacts of patient characteristics, including COVID-19 vaccinations, on perioperative mortality in acute coronary syndrome in Poland during the pandemic. We analyzed the data of 243,515 patients from the National Registry of Invasive Cardiology Procedures (Ogólnopolski Rejestr Procedur Kardiologii Inwazyjnej [ORPKI]). In this group, 7407 patients (21.74%) had COVID-19. The statistical analysis was based on a neural network that was verified by the random forest method. In 2020, the most significant impact on prognosis came from a diagnosis of unstable angina, a short period (<2 h) from pain occurrence to first medical contact, and a history of stroke. In 2021, the most significant factors were pre-hospital cardiac arrest, female sex, and a short period (<2 h) from first medical contact to coronary angiography. After adjusting for a six-week lag, a diagnosis of unstable angina and psoriasis were found to be relevant in the data from 2020, while in 2021, it was the time from the pain occurrence to the first medical contact (2–12 h) in non-ST segment elevation myocardial infarction and the time from first contact to balloon inflation (2–12 h) in ST-segment elevation myocardial infarction. The number of vaccinations was one of the least significant factors. COVID-19 vaccination does not directly affect perioperative prognosis in patients with acute coronary syndrome.
Deep Learning-Based System for Preoperative Safety Management in Cataract Surgery
Authors: Kiuchi Gaku , Tanabe Mao , Nagata Katsunori , Ishitobi Naofumi , Tabuchi Hitoshi , Oshika Tetsuro
Published: September 2022

An artificial intelligence-based system was implemented for preoperative safety management in cataract surgery, including facial recognition, laterality (right and left eye) confirmation, and intraocular lens (IOL) parameter verification. A deep-learning model was constructed with a face identification development kit for facial recognition, the You Only Look Once Version 3 (YOLOv3) algorithm for laterality confirmation, and the Visual Geometry Group-16 (VGG-16) for IOL parameter verification. In 171 patients who were undergoing phacoemulsification and IOL implantation, a mobile device (iPad mini, Apple Inc.) camera was used to capture patients’ faces, location of surgical drape aperture, and IOL parameter descriptions on the packages, which were then checked with the information stored in the referral database. The authentication rates on the first attempt and after repeated attempts were 92.0% and 96.3% for facial recognition, 82.5% and 98.2% for laterality confirmation, and 67.4% and 88.9% for IOL parameter verification, respectively. After authentication, both the false rejection rate and the false acceptance rate were 0% for all three parameters. An artificial intelligence-based system for preoperative safety management was implemented in real cataract surgery with a passable authentication rate and very high accuracy.
Mechanisms Leading to Gut Dysbiosis in COVID-19: Current Evidence and Uncertainties Based on Adverse Outcome Pathways
Authors: Clerbaux Laure-Alix , Filipovska Julija , Muñoz Amalia , Petrillo Mauro , Coecke Sandra , Amorim Maria-Joao , Grenga Lucia
Published: September 2022

Alteration in gut microbiota has been associated with COVID-19. However, the underlying mechanisms remain poorly understood. Here, we outlined three potential interconnected mechanistic pathways leading to gut dysbiosis as an adverse outcome following SARS-CoV-2 presence in the gastrointestinal tract. Evidence from the literature and current uncertainties are reported for each step of the different pathways. One pathway investigates evidence that intestinal infection by SARS-CoV-2 inducing intestinal inflammation alters the gut microbiota. Another pathway links the binding of viral S protein to angiotensin-converting enzyme 2 (ACE2) to the dysregulation of this receptor, essential in intestinal homeostasis—notably for amino acid metabolism—leading to gut dysbiosis. Additionally, SARS-CoV-2 could induce gut dysbiosis by infecting intestinal bacteria. Assessing current evidence within the Adverse Outcome Pathway framework justifies confidence in the proposed mechanisms to support disease management and permits the identification of inconsistencies and knowledge gaps to orient further research.
Association between High Lipid Burden of Target Lesion and Slow TIMI Flow in Coronary Interventions
Authors: Lim Subin , Cha Jung-Joon , Hong Soon Jun , Kim Ju Hyeon , Joo Hyung Joon , Park Jae Hyoung , Yu Cheol Woong , Ahn Tae Hoon , Lim Do-Sun
Published: September 2022

Decreased thrombolysis in myocardial infarction (TIMI) flow is associated with poor clinical outcomes. However, its predictors are not fully known. A combination of near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) could be used to detect lesions at high risk of slow TIMI flow. This study evaluated 636 consecutive patients undergoing target-lesion NIRS-IVUS imaging prior to percutaneous coronary intervention (PCI). The maximal lipid core burden index over 4-mm segments (maxLCBI4mm) per target vessel was calculated. The primary endpoint was the association between maxLCBI4mm and post-interventional TIMI flow. A high lipid core burden index (LCBI) cut-off point was determined using receiver-operating characteristic analysis. Decreased TIMI flow (TIMI less than 3) occurred in 90 patients and normal TIMI flow in 546 patients. The decreased TIMI flow group showed significantly higher incidence of cardiovascular events (5.6% vs. 1.5%, log-rank p = 0.010) in three months of composite events including cardiac death, myocardial infarction, stent thrombosis, and target lesion revascularization. In multivariable analysis, a high LCBI (≥354) was independently associated with slow TIMI flow (OR, 2.59 (95% CI, 1.33–5.04), p = 0.005). High LCBI measured using NIRS-IVUS imaging was an independent predictor of decreased post-PCI TIMI flow. Performing PCI for high-LCBI lesions may necessitate adjunctive measures to prevent suboptimal post-PCI reperfusion.
Preventive Impella® Support in High-Risk Patients Undergoing Cardiac Surgery
Authors: Benke Kálmán , Korça Edina , Boltjes Anniek , Stengl Roland , Hofmann Britt , Matin Meradjoddin , Krohe Katharina , Yakobus Yuliana , Michaelsen Jens , Khizaneishvili Levan , Szabó Gábor , Veres Gábor
Published: September 2022

Background: Patients with severely reduced LV-EF ≤ 30% undergoing CABG have a high risk for postoperative cardiogenic shock. The optimal timing of an adequate hemodynamic support has an impact on short- and midterm mortality after CABG. This study aimed to assess the prophylactic use of the Impella pump in high-risk patients undergoing elective cardiac surgery. Methods: In this single-center retrospective study, 14 patients with LV-EF (≤30%) undergoing cardiac surgery received a prophylactic, perioperative Impella (5.0, 5.5) support between 2020 and 2022. Results: The mean age at surgery was 64.2 ± 2.6 years, the mean preoperative LV-EF was 20.7% ± 1.56%. The duration of Impella support was 4 (3–7.8) days and the 30-day survival rate was 92.85%. Acute renal failure occurred in four patients who were dialyzed on average for 1.2 ± 0.7 days. Mechanical ventilation was needed for 1.75 (0.9–2.7) days. Time to inotrope/vasopressor independence was 2 (0.97–7.25) days with a highest lactate level (24 h postoperatively) of 3.8 ± 0.6 mmol/l. Postoperative LV-EF showed a significant improvement when compared to preoperative LV-EF (29.1% ± 2.6% vs. 20.7% ± 1.56% (p = 0.022)). Conclusion: The prophylactic Impella application seems to be a safe approach to improve the outcomes of this patient population.
Characteristics and Ablation Outcomes of Atrial Tachycardia in Patients with Prior Cardiac Surgery vs. Spontaneous Scars: Where Are the Differences?
Authors: Wang Junqi , Li Sainan , Liang Ming , Sun Mingyu , Jin Zhiqing , Ding Jian , Han Yaling , Wang Zulu
Published: September 2022

(1) Background: Atrial scars play an important role in atrial tachycardia (AT). They can not only be found in patients with prior cardiac surgery (PCS) but also in patients without PCS or significant structural heart disease, in which case the scar is called a spontaneous scar (SS). This study aims to compare the characteristics, mechanisms and ablation outcomes of AT in patients with PCS and SS. (2) Methods: We retrospectively reviewed electrophysiological and ablative characteristics of ATs in 46 patients with PCS and 18 patients with SS. (3) Results: There were averages of 1.52 and 2.33 ATs per patient in the PCS group and SS group, respectively (p < 0.01). Cavo-tricuspid isthmus dependent atrial flutter (CTI-AFL) was presented in most patients in both groups (93.50% vs. 77.80%, p = 0.17), whereas the SS group had a higher occurrence of scar-mediated reentrant AT (SMAT) and focal AT (FAT) compared with the PCS group (88.90% vs. 39.10%, p < 0.01; 22.2% vs. 2.2%, p < 0.05). There were no significant differences in acute success rate between the two groups, whereas patients with SS had lower long-term success rate (87.0% vs. 61.1%, p < 0.05) and higher occurrence of sinus node dysfunction (SND) (4.3% vs. 22.2%, p < 0.05). (4) Conclusions: CTI-AFL is common in both patients with PCS and SS, and routine CTI ablation is recommended. Compared with patients with PCS, patients with SS have more ATs, especially with higher occurrence of SMAT and FAT, and had a lower long-term success rate and higher incidence of SND.
Open Innovation as the Catalyst in the Personalized Medicine to Personalized Digital Medicine Transition
Authors: Cesario Alfredo , D’Oria Marika , Simone Irene , Patarnello Stefano , Valentini Vincenzo , Scambia Giovanni
Published: September 2022

Personalized medicine (PM) bridges several disciplines for understanding and addressing prevalent, complex, or rare situations in human health (e.g., complex phenotyping, risk stratification, etc.); therefore, digital and technological solutions have been integrated in the field to boost innovation and new knowledge generation. The open innovation (OI) paradigm proposes a method by which to respectfully manage disruptive change in biomedical organizations, as experienced by many organizations during digital transformation and the COVID-19 pandemic. In this article, we focus on how this paradigm has catalyzed the transition from PM to personalized digital medicine in a large-volume research hospital. Methods, challenges, and results are discussed. This case study is an endeavor to confirm that OI strategies could help manage urgent needs from the healthcare environment, while achieving sustainability-oriented, accountable innovation.
Impact of Early Limitation of Therapeutic Effort in Elderly COVID-19 Patients Admitted to the Intensive Care Unit—A Cohort Study
Authors: Lacoste-Palasset Thomas , Sutterlin Laetitia , M’Rad Aymen , Modestin Louis , Mourman Vianney , Pepin-Lehalleur Adrien , Malissin Isabelle , Naim Giulia , Grant Caroline , Guérin Emmanuelle , Ekhérian Jean-Michel , Deye Nicolas , Mégarbane Bruno , Voicu Sebastian
Published: September 2022

(1) Background: Admission to the ICU and intensity of care provided to elderly COVID-19 patients are difficult choices guided by the expected patient-centered benefits. However, the impact of an early discussion of limitation of therapeutic effort (LTE) has been poorly investigated. (2) Methods: We performed a single-center retrospective cohort study including all ≥70-year-old COVID-19 patients admitted to the ICU. Factors associated with early LTE discussion (defined as before or up to 2 days post-ICU admission) and in-hospital mortality were evaluated. (3) Results: Eighty-two patients (59 M/23 F; 78 years (74–82) [median (interquartile range)]; 43/82 with LTE) were included. The in-hospital mortality rate was 55%. Early LTE was decided upon for 22/82 patients (27%), more frequently in older (p < 0.001) and frailer patients (p = 0.004). Using a multivariable logistic regression model including clinical frailty scale grade ≥4, hospital acquisition of COVID-19, ventilation support modality and SOFA score on admission, early LTE was not associated with mortality (adjusted odds ratio = 0.57 (0.15–2.00), p = 0.39). LTE resulted in less frequent invasive mechanical ventilation (23% versus 65%, p = 0.001), renal replacement therapy (5% versus 27%, p = 0.03) and norepinephrine infusion (23% versus 60%, p = 0.005), and shorter ICU stay (6 days (2–12) versus 14 days (7–24), p = 0.001). (4) Conclusions: In this small sample exploratory study, we were unable to demonstrate any increase in in-hospital mortality associated with early LTE discussion in elderly COVID-19 patients while reducing the use of organ support techniques. These findings require confirmation in larger studies.
Patient-Specific Image-Based Computational Fluid Dynamics Analysis of Abdominal Aorta and Branches
Authors: Totorean Alin-Florin , Totorean Iuliana-Claudia , Bernad Sandor Ianos , Ciocan Tiberiu , Malita Daniel Claudiu , Gaita Dan , Bernad Elena Silvia
Published: September 2022

The complicated abdominal aorta and its branches are a portion of the circulatory system prone to developing atherosclerotic plaque and aneurysms. These disorders are closely connected to the changing blood flow environment that the area’s complicated architecture produces (between celiac artery and iliac artery bifurcation); this phenomenon is widespread at arterial bifurcations. Based on computed tomography angiography (CTA) scans, this current work offers a numerical analysis of a patient-specific reconstruction of the abdominal aorta and its branches to identify and emphasize the most likely areas to develop atherosclerosis. The simulations were run following the heart cycle and under physiological settings. The wall shear stress (WSS), velocity field, and streamlines were examined. According to the findings, complex flow is primarily present at the location of arterial bifurcations, where abnormal flow patterns create recirculation zones with low and fluctuating WSS (<0.5 Pa), which are known to affect endothelial homeostasis and cause adverse vessel remodeling. The study provides a patient-specific hemodynamic analysis model, which couples in vivo CT imaging with in silico simulation under physiological circumstances. The study offers quantitative data on the range fluctuations of important hemodynamic parameters, such as WSS and recirculation region expansion, which are directly linked to the onset and progression of atherosclerosis. The findings could also help drug targeting at this vascular level by understanding blood flow patterns in the abdominal aorta and its branches.
Landscape of Secondary Findings in Chinese Population: A Practice of ACMG SF v3.0 List
Authors: Huang Yingzhao , Liu Bowen , Shi Jile , Zhao Sen , Xu Kexin , Sun Liying , Chen Na , Tian Wen , Zhang Jianguo , Wu Nan
Published: September 2022

Clinical exome sequencing (CES) has shown great utility in the diagnosis of Mendelian disorders. CES can unravel secondary findings (SFs) unrelated to the primary diagnosis but with potential health implications. The American College of Medical Genetics and Genomics (ACMG) has published a guideline for reporting secondary findings and recently updated an ACMG SF v3.0 list comprising 73 genes. Several studies have been performed to explore the prevalence of SFs. However, the data were limited in the Chinese population. In this study, we evaluated the genetic data of 2987 individuals from the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study group in accordance with the ACMG SF v3.0 list. The detected variants were evaluated using the ACMG classification guidelines, HGMD, and ClinVar database. Totally, 157 (157/2987, 5.3%) individuals had reportable variants within genes associated with cancer, cardiovascular, metabolic, and miscellaneous phenotypes. We identified 63 known pathogenic (KP) variants in 72 individuals (72/2987, 2.4%) and 96 expected pathogenic (EP) variants in 105 individuals (3.5%). Forty-five individuals carried SFs in v3.0 newly added genes, which accounted for 1.5% of our cohort. Our findings could contribute to existing knowledge of secondary findings in different ethnicities and indicate the necessity for clinicians to update the SFs gene list.
Experiences of Barriers to Self-Compassion in Women Experiencing Weight Difficulties: An Interpretative Phenomenological Analysis
Authors: Jeziorek Anna , Riazi Afsane
Published: September 2022

There is currently little understanding of why some individuals find it difficult to engage in self-compassion (SC), defined as a form of self-kindness, self-acceptance, and courage to face one’s distress. This is especially true for women experiencing weight difficulties, despite the emergence of promising results from compassion-focused approaches to weight management. Consequently, this study undertakes a qualitative study to explore the experiences of barriers to self-compassion in women who were actively trying to manage their weight, using interpretative phenomenological analysis (IPA). A qualitative study was employed using an interpretive approach. Using purposive sampling, 10 women were recruited from London-based weight loss groups. Three super-ordinate themes emerged: (I) feeling unable to prioritise own needs over others’ needs; (II) having to learn and sustain a new approach to weight loss; and (III) having very high standards. The emergent themes suggest that women who face weight difficulties have numerous barriers to self-compassion. To fully utilise compassionate-based weight loss interventions for women, it is important to recognise these barriers and implement strategies to lessen their impact.
How Rising Water Levels Altered Ecosystem Provisioning Services of the Area around Qinghai Lake from 2000 to 2020: An InVEST-RF-GTWR Combined Method
Authors: Wang Lei , Mao Xufeng , Song Xiuhua , Tang Wenjia , Wang Wenying , Yu Hongyan , Deng Yanfang , Zhang Ziping , Zhang Zhijun , Zhou Huakun
Published: September 2022

The water level of Qinghai Lake, the largest saltwater lake in China, has been rising consistently, which has altered the lake’s ecosystem service patterns and produced an unpredictable impact on local ecological security and sustainable development. To explore the changes in the area around Qinghai Lake’s ecosystem provisioning services that respond to the rise in water level, the spatial and temporal changes of three ecosystem services (water yield, soil conservation, and habitat quality) from 2000 to 2020 were calculated by the InVEST model. Then, the ecosystem service transformation of the rise in Qinghai Lake’s underwater level was evaluated, and the trade-off and synchrony among the three ecosystem services were discussed. Finally, Random Forest and Geographically and Temporally Weighted Regression models were used, to reveal the driving factors and spatial differentiation of ecosystem service change. Results showed that: (1) Although three ecosystem provisioning services were increased by 3.21%, 31.67%, and 6.19%, respectively, in 2000–2020, an overall change trend was observed that they increased first and then decreased. After reaching their peak values in 2005 (444.68 mm), 2015 (341.89 t·hm−2·a−1) and 2015 (0.67), three ecosystem provisioning services decreased to 349.27 mm, 271.82 t·hm−2·a−1, and 0.66 in 2020, respectively. (2) Three ecosystem provisioning services, as well as ecosystem services among different land use types, presented a synchronous relationship during the research periods. (3) Natural factors, such as precipitation and NDVI (Normalized Difference Vegetation Index), accounted for 30.0% of ecosystem services changes, and Social-economic factors, such as GDP (Gross Domestic Product) and population accounted for 28.0% of three ecosystem provisioning services changes. These driving factors exhibited significant spatial heterogeneity (adjusted R2 > 0.6). There were limitations in the scope of ecosystem services evaluation and insufficient consideration of the value of aquatic habitats, which deserved further exploration. This study may provide a scientific basis for the evaluation and management of the plateau lake ecosystem under the background of climate change.