bluuebunny/crossref_metadata_2025 huggingface dataset:
BBX24 Interacts with DELLA to Regulate UV-B-Induced Photomorphogenesis in Arabidopsis thaliana
Authors: Huang Yuewei , Xiong Hui , Xie Yuxin , Lyu Suihua , Miao Tingting , Li Tingting , Lyu Guizhen , Li Shaoshan
Published: July 2022

UV-B radiation, sensed by the photoreceptor UVR8, induces signal transduction for plant photomorphogenesis. UV-B radiation affects the concentration of the endogenous plant hormone gibberellin (GA), which in turn triggers DELLA protein degradation through the 26S proteasome pathway. DELLA is a negative regulator in GA signaling, partially relieving the inhibition of hypocotyl growth induced by UV-B in Arabidopsis thaliana. However, GAs do usually not work independently but integrate in complex networks linking to other plant hormones and responses to external environmental signals. Until now, our understanding of the regulatory network underlying GA-involved UV-B photomorphogenesis had remained elusive. In the present research, we investigate the crosstalk between the GA and UV-B signaling pathways in UV-B-induced photomorphogenesis of Arabidopsis thaliana. Compared with wild type Landsberg erecta (Ler), the abundance of HY5, CHS, FLS, and UF3GT were found to be down-regulated in rga-24 and gai-t6 mutants under UV-B radiation, indicating that DELLA is a positive regulator in UV-B-induced photomorphogenesis. Our results indicate that BBX24 interacts with RGA (one of the functional DELLA family members). Furthermore, we also found that RGA interacts with HY5 (the master regulator in plant photomorphogenesis). Collectively, our findings suggest that the HY5–BBX24–DELLA module serves as an important signal regulating network, in which GA is involved in UV-B signaling to regulate hypocotyl inhibition.
Injectable Platelet-Rich Fibrin as a Drug Carrier Increases the Antibacterial Susceptibility of Antibiotic—Clindamycin Phosphate
Authors: Egle Karina , Skadins Ingus , Grava Andra , Micko Lana , Dubniks Viktors , Salma Ilze , Dubnika Arita
Published: July 2022

The aim of this study was to investigate the change in clindamycin phosphate antibacterial properties against Gram-positive bacteria using the platelet-rich fibrin as a carrier matrix, and evaluate the changes in the antibiotic within the matrix. The antibacterial properties of CLP and its combination with PRF were tested in a microdilution test against reference cultures and clinical isolates of Staphylococcus aureus (S. aureus) or Staphylococcus epidermidis (S. epidermidis). Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) analysis was done to evaluate the changes in the PRF_CLP matrix. Release kinetics of CLP was defined with ultra-performance liquid chromatography (UPLC). According to FTIR data, the use of PRF as a carrier for CLP ensured the structural changes in the CLP toward a more active form of clindamycin. A significant decrease in minimal bactericidal concentration values (from 1000 µg/mL to 62 µg/mL) against reference cultures and clinical isolates of S. aureus and S. epidermidis was observed for the CLP and PRF samples if compared to pure CLP solution. In vitro cell viability tests showed that PRF and PRF with CLP have higher cell viability than 70% after 24 h and 48 h time points. This article indicates that CLP in combination with PRF showed higher antibacterial activity against S. aureus and S. epidermidis compared to pure CLP solution. This modified PRF could be used as a novel method to increase drug delivery and efficacy, and to reduce the risk of postoperative infection.
Tissue Engineering Approaches to Uncover Therapeutic Targets for Endothelial Dysfunction in Pathological Microenvironments
Authors: Ntekoumes Dimitris , Gerecht Sharon
Published: July 2022

Endothelial cell dysfunction plays a central role in many pathologies, rendering it crucial to understand the underlying mechanism for potential therapeutics. Tissue engineering offers opportunities for in vitro studies of endothelial dysfunction in pathological mimicry environments. Here, we begin by analyzing hydrogel biomaterials as a platform for understanding the roles of the extracellular matrix and hypoxia in vascular formation. We next examine how three-dimensional bioprinting has been applied to recapitulate healthy and diseased tissue constructs in a highly controllable and patient-specific manner. Similarly, studies have utilized organs-on-a-chip technology to understand endothelial dysfunction’s contribution to pathologies in tissue-specific cellular components under well-controlled physicochemical cues. Finally, we consider studies using the in vitro construction of multicellular blood vessels, termed tissue-engineered blood vessels, and the spontaneous assembly of microvascular networks in organoids to delineate pathological endothelial dysfunction.
Effects of Storage Temperature on Indica-Japonica Hybrid Rice Metabolites, Analyzed Using Liquid Chromatography and Mass Spectrometry
Authors: Zhu Lin , Tian Yu , Ling Jiangang , Gong Xue , Sun Jing , Tong Litao
Published: July 2022

The Yongyou series of indica-japonica hybrid rice has excellent production potential and storage performance. However, little is known about the underlying mechanism of its storage resistance. In this study, Yongyou 1540 rice (Oryza sativa cv. yongyou 1540) was stored at different temperatures, and the storability was validated though measuring nutritional components and apparent change. In addition, a broad-targeted metabolomic approach coupled with liquid chromatography-mass spectrometry was applied to analyze the metabolite changes. The study found that under high temperature storage conditions (35 °C), Yongyou 1540 was not significantly worse in terms of fatty acid value, whiteness value, and changes in electron microscope profile. A total of 19 key differential metabolites were screened, and lipid metabolites related to palmitoleic acid were found to affect the aging of rice. At the same time, two substances, guanosine 3′,5′-cyclophosphate and pipecolic acid, were beneficial to enhance the resistance of rice under harsh storage conditions, thereby delaying the deterioration of its quality and maintaining its quality. Significant regulation of galactose metabolism, alanine, aspartate and glutamate metabolism, butyrate metabolism, and arginine and proline metabolism pathways were probably responsible for the good storage capacity of Yongyou 1540.
Revisiting Epithelial Carcinogenesis
Authors: Méndez-López Luis Fernando
Published: July 2022

The origin of cancer remains one of the most important enigmas in modern biology. This paper presents a hypothesis for the origin of carcinomas in which cellular aging and inflammation enable the recovery of cellular plasticity, which may ultimately result in cancer. The hypothesis describes carcinogenesis as the result of the dedifferentiation undergone by epithelial cells in hyperplasia due to replicative senescence towards a mesenchymal cell state with potentially cancerous behavior. In support of this hypothesis, the molecular, cellular, and histopathological evidence was critically reviewed and reinterpreted when necessary to postulate a plausible generic series of mechanisms for the origin and progression of carcinomas. In addition, the implications of this theoretical framework for the current strategies of cancer treatment are discussed considering recent evidence of the molecular events underlying the epigenetic switches involved in the resistance of breast carcinomas. The hypothesis also proposes an epigenetic landscape for their progression and a potential mechanism for restraining the degree of dedifferentiation and malignant behavior. In addition, the manuscript revisits the gradual degeneration of the nonalcoholic fatty liver disease to propose an integrative generalized mechanistic explanation for the involution and carcinogenesis of tissues associated with aging. The presented hypothesis might serve to understand and structure new findings into a more encompassing view of the genesis of degenerative diseases and may inspire novel approaches for their study and therapy.
Characterisation of 3D Bioprinted Human Breast Cancer Model for In Vitro Drug and Metabolic Targeting
Authors: Dankó Titanilla , Petővári Gábor , Raffay Regina , Sztankovics Dániel , Moldvai Dorottya , Vetlényi Enikő , Krencz Ildikó , Rókusz András , Sipos Krisztina , Visnovitz Tamás , Pápay Judit , Sebestyén Anna
Published: July 2022

Monolayer cultures, the less standard three-dimensional (3D) culturing systems, and xenografts are the main tools used in current basic and drug development studies of cancer research. The aim of biofabrication is to design and construct a more representative in vivo 3D environment, replacing two-dimensional (2D) cell cultures. Here, we aim to provide a complex comparative analysis of 2D and 3D spheroid culturing, and 3D bioprinted and xenografted breast cancer models. We established a protocol to produce alginate-based hydrogel bioink for 3D bioprinting and the long-term culturing of tumour cells in vitro. Cell proliferation and tumourigenicity were assessed with various tests. Additionally, the results of rapamycin, doxycycline and doxorubicin monotreatments and combinations were also compared. The sensitivity and protein expression profile of 3D bioprinted tissue-mimetic scaffolds showed the highest similarity to the less drug-sensitive xenograft models. Several metabolic protein expressions were examined, and the in situ tissue heterogeneity representing the characteristics of human breast cancers was also verified in 3D bioprinted and cultured tissue-mimetic structures. Our results provide additional steps in the direction of representing in vivo 3D situations in in vitro studies. Future use of these models could help to reduce the number of animal experiments and increase the success rate of clinical phase trials.
The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage
Authors: Rossi Chiara , Salvati Antonio , Distaso Mariarosaria , Campani Daniela , Raggi Francesco , Biancalana Edoardo , Tricò Domenico , Brunetto Maurizia Rossana , Solini Anna
Published: July 2022

P2X7R-NLRP3 and AIM2 inflammasomes activate caspase-1 and the release of cytokines involved in viral-related liver disease. Little is known about their role in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steato-hepatitis (NASH). We characterized the role of inflammasomes in NAFLD, NASH, and HCV. Gene expression and subcellular localization of P2X7R/P2X4R-NLRP3 and AIM2 inflammasome components were examined in histopathological preparations of 46 patients with biopsy-proven viral and metabolic liver disease using real-time PCR and immunofluorescence. P2X7R, P2X4R, and Caspase-1 are two- to five-fold more expressed in patients with NAFLD/NASH associated with chronic HCV infection than those with metabolic damage only (p ≤ 0.01 for all comparisons). The AIM2 inflammasome is 4.4 times more expressed in patients with chronic HCV infection, regardless of coexistent metabolic abnormalities (p = 0.0006). IL-2, a cytokine playing a pivotal role during chronic HCV infection, showed a similar expression in HCV and NASH patients (p = 0.77) but was virtually absent in NAFLD. The P2X7R-NLRP3 complex prevailed in infiltrating macrophages, while AIM2 was localized in Kupffer cells. Caspase-1 expression correlated with elastography-based liver fibrosis (r = 0.35, p = 0.02), whereas P2X7R, P2X4R, NRLP3, Caspase-1, and IL-2 expression correlated with circulating markers of disease severity. P2X7R and P2X4R play a major role in liver inflammation accompanying chronic HCV infection, especially when combined with metabolic damage, while AIM2 is specifically expressed in chronic viral hepatitis. We describe for the first time the hepatic expression of IL-2 in NASH, so far considered a peculiarity of HCV-related liver damage.
Biventricular versus Conduction System Pacing after Atrioventricular Node Ablation in Heart Failure Patients with Atrial Fibrillation
Authors: Ivanovski Maja , Mrak Miha , Mežnar Anja Zupan , Žižek David
Published: July 2022

Conduction system pacing (CSP) modalities, including His-bundle pacing (HBP) and left bundle branch pacing (LBBP), are increasingly used as alternatives to biventricular (BiV) pacing in heart failure (HF) patients scheduled for pace and ablate strategy. The aim of the study was to compare clinical outcomes of HF patients with refractory AF who received either BiV pacing or CSP in conjunction with atrio-ventricular node ablation (AVNA). Fifty consecutive patients (male 48%, age 70 years (IQR 9), left ventricular ejection fraction (LVEF) 39% (IQR 12)) were retrospectively analysed. Thirteen patients (26%) received BiV pacing, 27 patients (54%) HBP and 10 patients (20%) LBBP. All groups had similar baseline characteristics and acute success rate. While New York Heart. Association (NYHA) class improved in both HBP (p < 0.001) and LBBP (p = 0.008), it did not improve in BiV group (p = 0.096). At follow-up, LVEF increased in HBP (form 39% (IQR 15) to 49% (IQR 16), p < 0.001) and LBBP (from 28% (IQR 13) to 40% (IQR 13), p = 0.041), but did not change in BiV group (p = 0.916). Conduction system pacing modalities showed superior symptomatic and echocardiographic improvement compared to BiV pacing after AVNA. With more stable pacing parameters, LBBP could present a more feasible pacing option compared to HBP.
Altered Heart Rate Turbulence and Variability Parameters Predict 1-Year Mortality in Heart Failure with Preserved Ejection Fraction
Authors: Ksela Jus , Rupert Lea , Djordjevic Anze , Antonic Miha , Avbelj Viktor , Jug Borut
Published: July 2022

Background: Heart failure with preserved ejection fraction (HFpEF) is a complex and heterogeneous clinical syndrome. In the absence of effective and potent treatment strategies, the main challenge in HFpEF management remains the availability of strong predictors of unfavourable outcomes. In our study, we sought to evaluate the potential prognostic value of heart rate turbulence (HRT) and variability (HRV) parameters on mortality in ambulatory HFpEF patients. Methods: This was a case–control study comparing HRT and HRV parameters in HFpEF survivors vs. non-survivors. Patients from the RESPOND Heart Failure Registry with HFpEF who underwent 24 h ECG monitoring (Holter) were included; HRT parameters (i.e., turbulence onset (TO) and turbulence slope (TS)) and HRV parameters (i.e., standard deviation of NN intervals (SDNN)) derived from 24 h Holter ECGs were calculated in patients who died within 12 months, and compared to their age-, gender-, LVEF-, ECHO-, aetiology-, and therapy-matched alive controls. Results: A total of 22 patients (mean age 80 ± 7 years, 18% female, mean LVEF 57 ± 9%) were included in the final analysis. In deceased patients, values of TO were significantly higher, and values of TS and SDNN were significantly lower as compared to survivors. Conclusions: HRT and HRV parameters have the ability to differentiate individuals with HFpEF who are at the greatest risk of unfavourable outcomes. The extent of autonomic disbalance as determined by HRT and HRV could potentially assist in the prognostic assessment and risk stratification of HFpEF patients.
Peak Oxygen Uptake on Cardiopulmonary Exercise Test Is a Predictor for Severe Arrhythmic Events during Three-Year Follow-Up in Patients with Complex Congenital Heart Disease
Authors: von Sanden Felix , Ptushkina Svetlana , Hock Julia , Fritz Celina , Hörer Jürgen , Hessling Gabriele , Ewert Peter , Hager Alfred , Wolf Cordula M.
Published: July 2022

Patients with congenital heart disease (CHD) are at increased risk for severe arrhythmia and sudden cardiac death (SCD). Although implantable cardioverter defibrillators (ICD) effectively prevent SCD, risk stratification for primary prophylaxis in patients with CHD remains challenging. Patients with complex CHD undergoing CPET were included in this single-center study. Univariable and backwards stepwise multivariable logistic regression models were used to identify variables associated with the endpoint of severe arrhythmic event during three years of follow-up. Cut-off values were established with receiver operating characteristic (ROC) curve analysis. Survival analysis was conducted via Kaplan–Meier plots. Severe Arrhythmia was documented in 97 of 1194 patients (8.1%/3 years). Independent risk factors for severe arrhythmia during follow-up were old age and a low peak oxygen uptake (V.O2peak) on multivariable analysis. Patients with more advanced age and with V.O2peak values of less than 24.9 mL/min/kg were at significantly increased risk for the occurrence of severe arrhythmias during follow-up. The combined analysis of both risk factors yielded an additional benefit for risk assessment. Age at CPET and V.O2peak predict the risk for severe arrhythmic events and should be considered for risk stratification of SCD in patients with complex CHD.
Efficacy of Oxybrasion in the Treatment of Acne Vulgaris: A Preliminary Report
Authors: Chilicka Karolina , Rogowska Aleksandra M. , Szyguła Renata , Rusztowicz Monika , Nowicka Danuta
Published: July 2022

There are many cosmetic methods to reduce skin eruptions in people with acne vulgaris. As oxybrasion is a safe method of exfoliating dead epidermis, our objective was to investigate its effectiveness in young women with acne vulgaris. The Global Acne Grading System (GAGS) and Derma Unit SSC 3 device (Sebumeter SM 815, Corneometer CM 825) were used to assess acne vulgaris and skin properties. Twenty-four women aged 19–21 years (M = 19.50, SD = 0.66) with diagnosed mild acne vulgaris and a high level of sebum (more than 100 μg/cm2) participated in the study. Women on any dermatological treatment within the last 12 months and/or hormonal contraception were excluded. Probands were randomly assigned to two equal groups. Group A (experimental) was oxybrased with 0.9% sodium chloride solution simultaneously with compressed oxygen. Group B (placebo) was the group treated with non-carbonated mineral water and oxygen from the device (not pure). A series of five treatments was performed at 10-day intervals. Skin parameters were measured before and 30 days after the end of treatment. As a result, in group A (experimental), skin hydration and GAGS improved, while sebum on the epidermis was reduced. No side effects were noted. We concluded that oxybrasion is effective in women with acne and safe, as it improved skin parameters; however, further research is needed.
Anterior Quadratus Lumborum Block at the Lateral Supra-Arcuate Ligament versus Transmuscular Quadratus Lumborum Block for Analgesia after Elective Cesarean Section: A Randomized Controlled Trial
Authors: Guo Min , Lei Bo , Li Huili , Gao Xiaoru , Zhang Tianshu , Liang Ziwei , Wang Yun , Wang Lei
Published: July 2022

Several studies have shown the effectiveness of trans-muscular quadratus lumborum block (TQLB) in analgesia after cesarean delivery. However, the influence of anterior QLB at the lateral supra-arcuate ligament (QLB-LSAL) in this surgery is unclear. This study aimed to compare the analgesic efficacy of bilateral TQLBs with bilateral QLBs-LSAL following cesarean delivery. Ninety-four parturients scheduled for cesarean delivery under spinal anesthesia were enrolled and randomly allocated to undergo either bilateral TQLBs or bilateral QLBs-LSAL with 0.375% of ropivacaine (20 mL each side) following cesarean delivery. Intravenous sufentanil was administered for patient-controlled analgesia (PCA). The primary outcome was postoperative sufentanil consumption during the initial 24 h post-surgery. Secondary endpoints included pain scores, time to the first PCA request, postoperative rescue analgesia, satisfaction scores, and nausea/vomiting events. Sufentanil consumption was significantly reduced in the QLB-LSAL group in the first 24 h compared with the TQLB group after surgery (29.4 ± 5.7 μg vs. 39.4 ± 9.6 μg, p < 0.001). In comparison with TQLB, the time to the first PCA request in the QLB-LSAL group was significantly longer (10.9 ± 4.1 h vs. 6.7 ± 1.8 h, p < 0.001). No differences were observed between two groups regarding pain scores, rescue analgesia after surgery, satisfaction scores, or nausea/vomiting incidence. The significant reduction in opioid consumption in the first 24 h and prolongation in time to first opioid demand in parturients receiving QLB-LSAL compared with TQLB suggest that the QLB-LSAL is a superior choice for multimodal analgesia after cesarean delivery.
Haemodynamic Adaptive Mechanisms at High Altitude: Comparison between European Lowlanders and Nepalese Highlanders
Authors: Salvi Paolo , Grillo Andrea , Gautier Sylvie , Montaguti Luca , Brunacci Fausto , Severi Francesca , Salvi Lucia , Pretolani Enzo , Parati Gianfranco , Benetos Athanase
Published: July 2022

Background: Exposure to high altitudes determines several adaptive mechanisms affecting in a complex way the whole cardiovascular, respiratory, endocrine systems because of the hypobaric hypoxic condition. The aim of our study was to evaluate the circulatory adaptive mechanisms at high altitudes, during a scientific expedition in the Himalayas. Methods: Arterial distensibility was assessed measuring carotid-radial and carotid-femoral pulse wave velocity. Tests were carried out at several altitudes, from 1350 to 5050 m above sea level, on 8 lowlander European researchers and 11 highlander Nepalese porters. Results: In Europeans, systolic blood pressure and pulse pressure increased slightly but significantly with altitude (p < 0.05 and p < 0.001, respectively). Norepinephrine showed a significant increase after the lowlanders had spent some time at high altitude (p < 0.001). With increasing altitude, a progressive increase in carotid-radial and carotid-femoral pulse wave velocity values was observed in lowlanders, showing a particularly significant increase (p < 0.001) after staying at high altitude (carotid-radial pulse wave velocity, median value (interquartile range) from 9.2 (7.9–10.0) to 11.2 (10.9–11.8) m/s and carotid-femoral pulse wave velocity from 8.5 (7.9–9.0) to 11.3 (10.9–11.8) m/s). At high altitudes (3400 and 5050 m above sea level), no significant differences were observed between highlanders and lowlanders in hemodynamic parameters (blood pressure, carotid-radial and carotid-femoral pulse wave velocity). Conclusions: The progressive arterial stiffening with altitude observed in European lowlanders could explain the increase in systolic and pulse pressure values observed at high altitudes in this ethnic group. Further studies are needed to evaluate the role of aortic stiffening in the pathogenesis of acute mountain sickness.
Retinal Glaucoma Public Datasets: What Do We Have and What Is Missing?
Authors: Camara José , Rezende Roberto , Pires Ivan Miguel , Cunha António
Published: July 2022

Public databases for glaucoma studies contain color images of the retina, emphasizing the optic papilla. These databases are intended for research and standardized automated methodologies such as those using deep learning techniques. These techniques are used to solve complex problems in medical imaging, particularly in the automated screening of glaucomatous disease. The development of deep learning techniques has demonstrated potential for implementing protocols for large-scale glaucoma screening in the population, eliminating possible diagnostic doubts among specialists, and benefiting early treatment to delay the onset of blindness. However, the images are obtained by different cameras, in distinct locations, and from various population groups and are centered on multiple parts of the retina. We can also cite the small number of data, the lack of segmentation of the optic papillae, and the excavation. This work is intended to offer contributions to the structure and presentation of public databases used in the automated screening of glaucomatous papillae, adding relevant information from a medical point of view. The gold standard public databases present images with segmentations of the disc and cupping made by experts and division between training and test groups, serving as a reference for use in deep learning architectures. However, the data offered are not interchangeable. The quality and presentation of images are heterogeneous. Moreover, the databases use different criteria for binary classification with and without glaucoma, do not offer simultaneous pictures of the two eyes, and do not contain elements for early diagnosis.
Across the Myeloablative Spectrum: Hematopoietic Cell Transplant Conditioning Regimens for Pediatric Patients with Sickle Cell Disease
Authors: Limerick Emily , Abraham Allistair
Published: July 2022

One out of every five hundred African American children in the United States has sickle cell disease (SCD). While multiple disease-modifying therapies are available, hematopoietic cell transplantation (HCT) remains the only curative option for children with SCD. HLA-matched sibling HCT has demonstrated excellent efficacy, but its availability remains limited; alternative donor strategies are increasingly explored. While Busulfan-Cyclophosphamide has become the most widespread conditioning regimen employed in HCT for pediatric SCD, many other regimens have been examined. This review explores different conditioning regimens across the intensity spectrum: from myeloablative to non-myeloablative. We describe survival and organ function outcomes in pediatric SCD patients who have received HCT and discuss the strengths and weaknesses of the various conditioning intensities. Finally, we posit novel directions in allogeneic HCT for SCD.
Should We Use High-Flow Nasal Cannula in Patients Receiving Gastrointestinal Endoscopies? Critical Appraisals through Updated Meta-Analyses with Multiple Methodologies and Depiction of Certainty of Evidence
Authors: Lee Chi Chan , Ju Teressa Reanne , Lai Pei Chun , Lin Hsin-Ti , Huang Yen Ta
Published: July 2022

(1) Background: High-flow nasal cannula (HFNC) therapy or conventional oxygen therapy (COT) are typically applied during gastrointestinal (GI) endoscopic sedation. (2) Methods: We conducted a rigorous systematic review enrolling randomized controlled trials (RCTs) from five databases. Risk of bias was assessed using Cochrane’s RoB 2.0 tool; certainty of evidence (CoE) was assessed using GRADE framework. Meta-analysis was conducted using inverse-variance heterogeneity model and presented as relative risk (RR) with 95% confidence interval (CI). Trial sequential analysis was performed, and sensitivity analysis was conducted with Bayesian approach. (3) Results: Eight RCTs were included. Compared to COT, HFNC did not reduce the overall incidence of hypoxemia (RR 0.51; 95% CI 0.24–1.09; CoE: very low) but might reduce the incidence of hypoxemia in patients at moderate to high risk for hypoxemia (RR 0.54; 95% CI 0.31–0.96; and CoE: very low). HFNC might reduce the incidence of severe hypoxemia (RR 0.38; 95% CI 0.20–0.74; and CoE: low). HFNC might not affect the need of minor airway interventions (RR 0.31; 95% CI 0.08–1.22; and CoE: very low) and had no effect on procedure duration (CoE: very low); (4) Conclusions: During GI endoscopic sedation, HFNC might reduce the incidence of hypoxemia in patients at moderate to high risk for hypoxemia and prevent severe hypoxemia.
Intraoperative Anterior Segment Optical Coherence Tomography in the Management of Cataract Surgery: State of the Art
Authors: Toro Mario Damiano , Milan Serena , Tognetto Daniele , Rejdak Robert , Costagliola Ciro , Zweifel Sandrine Anne , Posarelli Chiara , Figus Michele , Rejdak Magdalena , Avitabile Teresio , Carnevali Adriano , Giglio Rosa
Published: July 2022

Background: The introduction of non-invasive diagnostic tools in ophthalmology has significantly reshaped current clinical practice in different settings. Recently, different anterior segment (AS) intraoperative optical coherence tomography (i-OCT) systems have been employed for different interventional procedures including cataract surgery. Materials and Methods: A review on the use of AS i-OCT in the management of cataract surgery, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The level of evidence according to the Oxford Centre for Evidence-Based Medicine (OCEM) 2011 guidelines, and the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were assessed for all included articles. Results: Out of 6302 articles initially extracted, 6302 abstracts were identified for screening and 32 of these met the inclusion/exclusion criteria for full-text review; 19 articles were excluded. Conclusions: The use of AS i-OCT in cataract surgery, even if only a few studies have a high level or grade of evidence, may represent a useful tool for novel surgeons approaching phacoemulsification but also for expert ones for teaching purposes and to plan and manage complicated cases.
Diversity of Hemodynamic Reactive Profiles across Persons—Psychosocial Implications for Personalized Medicine
Authors: Gandarillas Miguel Ángel , Goswami Nandu
Published: July 2022

This study analyzed the individual differences in hemodynamic time patterns and reactivity to cognitive and emotional tasks, and explored the diversity of psycho-physiological profiles that could be used for the personalized prediction of different diseases. An analysis of heart rate (HR)—blood pressure (BP) relationship patterns across time using cross-correlations (CCs) during a logical-mathematical task and a task recalling negative emotions (rumination) was carried out in a laboratory setting on 45 participants. The results showed maximum HR–BP CCs during the mathematical task significantly more positive than the maximum HR–BP CCs during the rumination task. Furthermore, our results showed a large variety of hemodynamic reactivity profiles across the participants, even when carrying out the same tasks. The most frequent type showed positive HR–BP CCs under cognitive activity, and several positive–negative HR–BP CCs cycles under negative emotional activity. In general terms, our results supported the main hypothesis. We observed some distinct time-based “coordination strategies” in the reactivity of the autonomic nervous system under emotional vs. cognitive loading. Overall, large individual, as well as situational, specificities in hemodynamic reactivity time patterns were seen. The possible relationships between this variety of profiles and different psychosocial characteristics, and the potential for integrative predictive health within the provision of highly personalized medicine, are discussed.
Prognostic Factors in Patients with Sudden Cardiac Arrest and Acute Myocardial Infarction Undergoing Percutaneous Interventions with the LUCAS-2 System for Mechanical Cardiopulmonary Resuscitation
Authors: Chyrchel Michał , Hałubiec Przemysław , Duchnevič Olgerd , Łazarczyk Agnieszka , Okarski Michał , Januszek Rafał , Rzeszutko Łukasz , Bartuś Stanisław , Surdacki Andrzej
Published: July 2022

Sudden cardiac arrest (SCA) is one of the most perilous complications of acute myocardial infarction (AMI). For years, the return of spontaneous circulation (ROSC) has had to be achieved before the patient could be treated at the catheterization laboratory, as simultaneous manual chest compression and angiography were mutually exclusive. Mechanical chest compression devices enabled simultaneous resuscitation and invasive percutaneous procedures. The aim was to characterize the poorer responders that would allow one to predict the positive outcome of such a treatment. We retrospectively analyzed the medical charts of 94 patients with SCA due to AMI, who underwent mechanical cardiopulmonary resuscitation during angiography. In total, 48 patients, 8 (17%) of which survived the event, were included in the final analysis, which revealed that 83% of the survivors had mild to moderate hyperkalemia (potassium 5.0–6.0 mmol/L), in comparison to 15% of non-survivors (p = 0.002). In the age- and sex-adjusted model, patients with serum potassium > 5.0 mmol/L had 4.61-times higher odds of survival until discharge from the hospital (95% CI: 1.41–15.05, p = 0.01). Using the highest Youden index, we identified the potassium concentration of 5.1 mmol/L to be the optimal cut-off value for prediction of survival until hospital discharge (83.3% sensitivity and 87.9% specificity). The practical implications of these findings are that patients with potassium levels between 5.0 and 6.0 mmol/L may actually benefit most from percutaneous coronary interventions with ongoing mechanical chest compressions and that they do not need immediate correction for this electrolyte abnormality.
Exercise Capacity Is Independent of Respiratory Muscle Strength in Patients with Chronic Heart Failure
Authors: Albarrati Ali , Aseeri Abdulrahman , Taher Mohammed , Aldhahi Monira I. , Nazer Rakan I.
Published: July 2022

Background: Exercise intolerance in patients with chronic heart failure (CHF) is associated with a number of factors, including breathlessness and respiratory muscle weakness. However, many studies reported controversial results, and as yet there is no study on Arabic patients with CHF. This study aimed to examine the impact of breathlessness and respiratory muscle strength on exercise capacity in Arabic patients with CHF. Methods: This was a cross-sectional study, involving 42 stable adult male patients with CHF with a reduced ejection fraction and 42 controls who were free from cardiorespiratory and neuromuscular diseases. Patients with CHF and the controls underwent respiratory muscle strength tests and a six-minute walk test (6MWT), and the measurements were taken. Dyspnea was recorded using the modified Medical Research Council (mMRC) scale, along with the number of comorbidities. Results: Patients with CHF and controls were similar in age and sex. Patients with CHF had a greater number of comorbidities, a higher dyspnea score, a lower 6MWT score, and lower respiratory muscle strength (p < 0.001). Only 7% of patients with CHF had weak inspiratory muscle strength (<60% of that predicted) and 40% terminated the 6MWT due to dyspnea. The 6MWT was associated with mMRC (rs = −0.548, p < 0.001) but not with respiratory muscle strength (p > 0.05). Conclusions: Exercise intolerance in patients with CHF was associated with dyspnea and was independent of respiratory muscle strength.
Hypothyroidism Is Correlated with Ventilator Complications and Longer Hospital Days after Coronary Artery Bypass Grafting Surgery in a Relatively Young Population: A Nationwide, Population-Based Study
Authors: Lin Jiun-Yu , Kao Pei-Chi , Tsai Yi-Ting , Chung Chi-Hsiang , Chien Wu-Chien , Lin Chih-Yuan , Lu Chieh-Hua , Tsai Chien-Sung
Published: July 2022

Background: Some research indicated that hypothyroidism has huge adverse effects for the metabolic, cardiovascular, respiratory, and immune systems. However, there is no confirmed conclusion for the effect of cardiovascular surgery. This cohort study aims to investigate the prognosis of hypothyroidism patient at the age under 65-year-old after coronary artery bypass grafting (CABG) surgery. Method: From the National Health Insurance Research Database of Taiwan, 1586 patients with hypothyroidism who underwent elective CABG surgery were selected, along with 6334 patients who underwent surgery in a ratio of 1:4 sex-, age- and index year-matched controls, who were out of hypothyroidism. We used Cox proportional hazard analysis to compare the rate of 30-day, 5-year mortality, post-operative atrial fibrillation, respiratory complication during an average of 10-year follow-up. Result: Post-CABG patients had more hospital days, which was associated with hypothyroidism, male, DM and higher CCI_R (p < 0.001). Post-CABG patients had more inpatient respiratory complications, which was associated with hypothyroidism (p = 0.041), DM and CCI_R (p < 0.001, p = 0.046), and there was no difference in 1-year respiratory complication, tracheostomy in the same hospital course and within 1 year, repeated PCI, Af, CVVH, cerebral infarction, 30-day and 5-year mortality rate. Conclusions: Hypothyroidism correlates to post-CABG ventilator-related complications and pneumonia, and prolonged hospital days, but no effect on 30-day, 5-year mortality, post-operative atrial fibrillation and cerebral infarction rate. Thyroid function survey might include routinely preoperative survey for CABG outcome prognosis.
Antisense Oligonucleotides and Small Interfering RNA for the Treatment of Dyslipidemias
Authors: Gareri Clarice , Polimeni Alberto , Giordano Salvatore , Tammè Laura , Curcio Antonio , Indolfi Ciro
Published: July 2022

The burden of atherosclerotic disease worldwide necessitates implementing the treatment of its risk factors. Among them, hypercholesterolemia has a central role. In addition to conventional small organic compounds and the recently introduced monoclonal antibodies, new technologies are arising such as the antisense oligonucleotides and small interfering RNAs (siRNAs) that operate upstream, blocking the mRNA translation of the proteins specifically involved in lipid metabolism. In this review, we briefly explain the mechanisms of action of these molecules and discuss the difficulties related to their in vivo use as therapeutical agents. We go over the oligonucleotides tested in clinical trials that could potentially revolutionize the care of patients by acting on proteins involved in the lipoprotein metabolism and regulation, namely: angiopoietin-like protein 3 (ANGPTL3); lipoprotein a (Lp(a)); apolipoprotein B (Apo B); apolipoprotein C III (Apo C-III); and proprotein convertase subtilisin–kexin type 9 (PCSK9). Finally, the differences between ASOs and siRNAs, their future possible clinical applications, and the role of Inclisiran, a siRNA direct against PCSK9 to reduce LDL-C, were reviewed in detail.
Monomorphic VT Non-Inducibility after Electrical Storm Ablation Reduces Mortality and Recurrences
Authors: Vătășescu Radu , Cojocaru Cosmin , Năstasă Alexandrina , Popescu Sorin , Iorgulescu Corneliu , Bogdan Ștefan , Gondoș Viviana , Berruezo Antonio
Published: July 2022

Background: Electrical storm (ES) is defined by clustering episodes of ventricular tachycardia (VT) and is associated with severe long-term outcomes. We sought to evaluate the prognostic impact of radiofrequency catheter ablation (RFCA) in ES as assessed by aggressive programmed ventricular stimulation (PVS). Methods: Single-center retrospective longitudinal study with 82 consecutive ES patients referred for RFCA with a median follow-up (IQR 25–75%) of 45.43 months (15–69.86). All-cause mortality and VT recurrences were assessed in relation to RFCA outcomes defined by 4-extrastimuli PVS: Class 1—no ventricular arrhythmia; Class 2—no sustained monomorphic VTs (mVT) inducible, but non-sustained mVTs, polymorphic VTs, or VF inducible; Class 3—clinical VT non-inducible, other sustained mVTs inducible; and Class 4—clinical VT inducible. Results: Class 1, Class 2, Class 3, and Class 4 were achieved in 56.1%, 13.4%, 23.2%, and 7.4% of cases, respectively. The combined outcome of Class 1 + Class 2 (no sustained monomorphic VT inducible) led to improved survival (log-rank p < 0.001) and reduced VT recurrence (log-rank p < 0.001). Residual monomorphic VT inducibility (HR 6.262 (95% CI: 2.165–18.108, p = 0.001), NYHA IV heart failure symptoms (HR 20.519 (95% CI: 1.623–259.345), p = 0.02)), and age (HR 1.009 (95% CI: 1.041–1.160), p = 0.001)) independently predicted death during follow-up. LVEF was not predictive of death (HR 1.003 (95% CI: 0.946–1.063) or recurrences (HR 0.988 (95% CI: 0.955–1.021)). Conclusions: Non-inducibility for sustained mVTs after aggressive PVS post-RFCA leads to improved survival in ES, independently of LVEF.
How Old Is Old? An Age-Stratified Analysis of Elderly Liver Donors above 65
Authors: Houben Philipp , Bormann Eike , Kneifel Felicia , Katou Shadi , Morgül Mehmet , Vogel Thomas , Bahde Ralf , Radünz Sonia , Pascher Andreas , Schmidt Hartmut , Brockmann Jens , Becker Felix
Published: July 2022

In liver transplantation, older donor age is a well-known risk factor for dismal outcomes, especially due to the high susceptibility of older grafts to ischemia-reperfusion injury. However, whether the factors correlating with impaired graft and patient survival following the transplantation of older grafts follow a linear trend among elderly donors remains elusive. In this study, liver transplantations between January 2006 and May 2018 were analyzed retrospectively. Ninety-two recipients of grafts from donors ≥65 years were identified and divided into two groups: (1) ≥65–69 and (2) ≥ 70 years. One-year patient survival was comparable between recipients of grafts from donors ≥65–69 and ≥70 years (78.9% and 70.0%). One-year graft survival was 73.1% (donor ≥65–69) and 62.5% (donor ≥ 70), while multivariate analysis revealed superior one-year graft survival to be associated with a donor age of ≥65–69. No statistically significant differences were found for rates of primary non-function. The influence of donor age on graft and patient survival appears not to have a distinct impact on dismal outcomes in the range of 65–70 years. The impact of old donor age needs to be balanced with other risk factors, as these donors provide grafts that offer a lifesaving graft function.
Cerebrovascular Events after Transcatheter Aortic Valve Replacement: The Difficulty in Predicting the Unpredictable
Authors: Maier Oliver , Bosbach Georg , Piayda Kerstin , Afzal Shazia , Polzin Amin , Westenfeld Ralf , Jung Christian , Kelm Malte , Zeus Tobias , Veulemans Verena
Published: July 2022

Background: Cerebrovascular events (CVE) are feared complications following transcatheter aortic valve replacement (TAVR). We aimed to develop a new risk model for CVE prediction with the application of multimodal imaging. Methods: From May 2011 to August 2019, a total of 2015 patients underwent TAVR at our institution. The study cohort was subdivided into a derivation cohort (n = 1365) and a validation cohort (n = 650) for risk model development. Results: Of 2015 patients, 72 (3.6%) developed TAVR-related CVE. Pre-procedural factors of our risk model were history of prior CVE, a larger aortic valve area (≥0.55 cm2), a large aortic angulation (≥48.5°), and enhanced calcification of the right coronary cusp (≥447.2 AU), left ventricular outflow tract (≥262.4 AU), and ascending thoracic aorta (≥116.4 AU). Our risk model was superior for in-hospital CVE prediction following TAVR in the establishment cohort (AUC 0.73, 95% CI 0.66–0.80; p < 0.001) compared to other risk scores, such as the EuroSCORE II or the CHA2DS2-VASc score. Conclusions: Although CVE prediction in patients undergoing TAVR is challenging due to the complex nature of the TAVR procedure, our study highlights that multimodal imaging is a promising approach to generate a more accurate risk model for CVE prediction.
The Role of the Histone Variant H2A.Z in Metazoan Development
Authors: Dijkwel Yasmin , Tremethick David J.
Published: July 2022

During the emergence and radiation of complex multicellular eukaryotes from unicellular ancestors, transcriptional systems evolved by becoming more complex to provide the basis for this morphological diversity. The way eukaryotic genomes are packaged into a highly complex structure, known as chromatin, underpins this evolution of transcriptional regulation. Chromatin structure is controlled by a variety of different epigenetic mechanisms, including the major mechanism for altering the biochemical makeup of the nucleosome by replacing core histones with their variant forms. The histone H2A variant H2A.Z is particularly important in early metazoan development because, without it, embryos cease to develop and die. However, H2A.Z is also required for many differentiation steps beyond the stage that H2A.Z-knockout embryos die. H2A.Z can facilitate the activation and repression of genes that are important for pluripotency and differentiation, and acts through a variety of different molecular mechanisms that depend upon its modification status, its interaction with histone and nonhistone partners, and where it is deposited within the genome. In this review, we discuss the current knowledge about the different mechanisms by which H2A.Z regulates chromatin function at various developmental stages and the chromatin remodeling complexes that determine when and where H2A.Z is deposited.
Experimental and Numerical Investigation of Floating Large Woody Debris Impact on a Masonry Arch Bridge
Authors: Majtan Eda , Cunningham Lee S. , Rogers Benedict D.
Published: July 2022

Masonry arch bridges form an essential part of existing transport infrastructure around the world, including mainland Europe and the northeastern US. Recent extreme flood events highlight that masonry arch bridges spanning watercourses are vulnerable to flood-induced hydrodynamic and debris impact loads. When the flow interacts with the bridge superstructure, with or without discrete floating debris, a complex interaction is observed. This paper presents both experimental and numerical studies to investigate this complex phenomenon, including fluid–structure and structure–structure interactions. A typical single-span masonry arch bridge and large woody debris representing a tree log are investigated. Experimental observations from a scaled hydraulic model, with and without debris in the flow, are first presented for the case where the abutment of the bridge is fully submerged. Next, the capability of the numerical method smoothed particle hydrodynamics (SPH) in simulating the hydrodynamic behaviour and debris impact observed in the experiment is discussed. Following this, both hydrodynamic and debris-induced pressure–time histories on the bridge are obtained using the SPH model. Results reveal that the debris impact leads to a significantly more localised load on the bridge compared to the situation with hydrodynamic load only.
Numerical Study of Circulation and Seasonal Variability in the Southwestern Yellow Sea
Authors: He Zhanyuan , Zhu Shouxian , Sheng Jinyu
Published: July 2022

A nested-grid ocean circulation modelling system (NGMS-swYS) is used for examining the impact of tides and winds on the three-dimensional (3D) circulation, hydrography and seasonal variability over the southwestern Yellow Sea (swYS). The modelling system is based on the Princeton Ocean Model (POM) and uses a nested-grid setup, with a fine-resolution (~2.7 km) inner model nested inside a coarse-resolution (~9.0 km) outer model. The domain of the outer model covers the China Seas and adjacent deep ocean waters. The domain of the fine-resolution inner model covers the swYS and adjacent waters. The NGMS-swYS is driven by a suite of external forcings, including the atmospheric forcing, tides, freshwater discharge and currents specified at the lateral open boundaries. A comparison of model results with observations and previous numerical studies demonstrates the satisfactory performance of the NGMS-swYS in simulating tides, seasonal mean circulation and distribution of temperature and salinity. Five additional numerical experiments were conducted using NGMS-swYS with different combinations of external forcing. Analysis of model results demonstrates that the monthly mean circulation over the swYS is affected significantly by tides and winds, with large seasonal variability. The northward Subei Shoal Current occurred in both winter and summer months in 2015, with persistent strong southeastward mean currents induced by tides along the 50 m isobath. Model results also demonstrated that strong wind-induced currents occurred with large sea surface cooling during Typhoon Chan-Hom.