bluuebunny/crossref_metadata_2025 huggingface dataset:
Survivin’ Acute Myeloid Leukaemia—A Personalised Target for inv(16) Patients
Authors: Greiner Jochen , Brown Elliott , Bullinger Lars , Hills Robert K. , Morris Vanessa , Döhner Hartmut , Mills Ken I. , Guinn Barbara-ann
Published: September 2021

Despite recent advances in therapies including immunotherapy, patients with acute myeloid leukaemia (AML) still experience relatively poor survival rates. The Inhibition of Apoptosis (IAP) family member, survivin, also known by its gene and protein name, Baculoviral IAP Repeat Containing 5 (BIRC5), remains one of the most frequently expressed antigens across AML subtypes. To better understand its potential to act as a target for immunotherapy and a biomarker for AML survival, we examined the protein and pathways that BIRC5 interacts with using the Kyoto Encyclopedia of Genes and Genomes (KEGG), search tool for recurring instances of neighbouring genes (STRING), WEB-based Gene Set Analysis Toolkit, Bloodspot and performed a comprehensive literature review. We then analysed data from gene expression studies. These included 312 AML samples in the Microarray Innovations In Leukemia (MILE) dataset. We found a trend between above median levels of BIRC5 being associated with improved overall survival (OS) but this did not reach statistical significance (p = 0.077, Log-Rank). There was some evidence of a beneficial effect in adjusted analyses where above median levels of BIRC5 were shown to be associated with improved OS (p = 0.001) including in Core Binding Factor (CBF) patients (p = 0.03). Above median levels of BIRC5 transcript were associated with improved relapse free survival (p < 0.0001). Utilisation of a second large cDNA microarray dataset including 306 AML cases, again showed no correlation between BIRC5 levels and OS, but high expression levels of BIRC5 correlated with worse survival in inv(16) patients (p = 0.077) which was highly significant when datasets A and B were combined (p = 0.001). In addition, decreased BIRC5 expression was associated with better clinical outcome (p = 0.004) in AML patients exhibiting CBF mainly due to patients with inv(16) (p = 0.007). This study has shown that BIRC5 expression plays a role in the survival of AML patients, this association is not apparent when we examine CBF patients as a cohort, but when those with inv(16) independently indicating that those patients with inv(16) would provide interesting candidates for immunotherapies that target BIRC5.
Autophagy-Related Proteins Are Differentially Expressed in Adrenal Cortical Tumor/Pheochromocytoma and Associated with Patient Prognosis
Authors: Kim Hye Min , Koo Ja Seung
Published: September 2021

The aim of this research was to evaluate the expression and concomitant implications of LC3A, LC3B, beclin-1, and p62, which are key components of autophagy in human adrenal gland tumors. Tissue microarray was made for 321 cases of adrenal gland tumor (adrenal cortical adenoma (ACA): 115, adrenal cortical carcinoma (ACC): 17, and pheochromocytoma (PCC): 189). Immunohistochemical staining was performed for beclin-1, p62, LC3A, and LC3B, and the results were compared with the patients’ clinicopathologic parameters. LC3A, LC3B, beclin-1, and LC3B isolated single positive cells (ISPC) positivity rates were higher in PCC than in adrenal cortical tumor (ACT), whereas p62 positivity was lower in PCC than in ACT. The proportion of positive LC3B (ISPC) was higher in ACC than in ACA. In addition, the proportion of cells positive for p62 and LC3B (ISPC) was significantly higher in PCCs with a GAPP score of ≥3. In univariate Cox analysis, p62 positivity (p = 0.014) and the presence of p62 (ISPC) (p = 0.001) were associated with shorter disease-free survival in PCC. Moreover, p62 positivity was predictive of shorter overall survival (OS) in patients with PCC by multivariate analysis (relative risk, 6.240; 95% CI, 1.434–27.15; p = 0.015). Differences were found in the expression of autophagy-related proteins according to adrenal gland tumor types. Compared to ACT, the proportion of LC3A, LC3B, beclin-1, and LC3B (ISPC) positivity was higher in PCC, whereas p62 positivity was lower. Similarly, p62 positivity in PCC was associated with patient prognosis of OS.
Genome-Wide Identification and Expression Analysis of the Aux/IAA and Auxin Response Factor Gene Family in Medicago truncatula
Authors: Liu Rui , Guo Zhenfei , Lu Shaoyun
Published: September 2021

Aux/IAA and auxin response transcription factor (ARF) genes are key regulators of auxin responses in plants. A total of 25 MtIAA and 40 MtARF genes were identified based on the latest updated Medicago truncatula reference genome sequence. They were clustered into 10 and 8 major groups, respectively. The homologs among M. truncatula, soybean, and Arabidopsis thaliana shared close relationships based on phylogenetic analysis. Gene structure analysis revealed that MtIAA and MtARF genes contained one to four concern motifs and they are localized to eight chromosomes, except chromosome 6 without MtARFs. In addition, some MtIAA and MtARF genes were expressed in all tissues, while others were specifically expressed in specific tissues. Analysis of cis-acting elements in promoter region and expression profiles revealed the potential response of MtIAA and MtARF genes to hormones and abiotic stresses. The prediction protein–protein interaction network showed that some ARF proteins could interact with multiple Aux/IAA proteins, and the reverse is also true. The investigation provides valuable, basic information for further studies on the biological functions of MtIAA and MtARF genes in the regulation of auxin-related pathways in M. truncatula.
Urinary Extracellular Vesicles Are a Novel Tool to Monitor Allograft Function in Kidney Transplantation: A Systematic Review
Authors: Wu Liang , Boer Karin , Woud Wouter W. , Udomkarnjananun Suwasin , Hesselink Dennis A. , Baan Carla C.
Published: September 2021

Extracellular vesicles (EVs) are nanoparticles that transmit molecules from releasing cells to target cells. Recent studies link urinary EVs (uEV) to diverse processes such as infection and rejection after kidney transplantation. This, and the unmet need for biomarkers diagnosing kidney transplant dysfunction, has led to the current high level of interest in uEV. uEV provide non-intrusive access to local protein, DNA, and RNA analytics without invasive biopsy. To determine the added value of uEV measurements for detecting allograft dysfunction after kidney transplantation, we systematically included all related literature containing directly relevant information, with the addition of indirect evidence regarding urine or kidney injury without transplantation. According to their varying characteristics, uEV markers after transplantation could be categorized into kidney-specific, donor-specific, and immune response-related (IR-) markers. A few convincing studies have shown that kidney-specific markers (PODXL, ion cotransporters, SYT17, NGAL, and CD133) and IR-markers (CD3, multi-mRNA signatures, and viral miRNA) could diagnose rejection, BK virus-associated nephropathy, and calcineurin inhibitor nephrotoxicity after kidney transplantation. In addition, some indirect proof regarding donor-specific markers (donor-derived cell-free DNA) in urine has been demonstrated. Together, this literature review provides directions for exploring novel uEV markers’ profiling complications after kidney transplantation.
Low-Frequency Harmonic Perturbations Drive Protein Conformational Changes
Authors: Scaramozzino Domenico , Piana Gianfranco , Lacidogna Giuseppe , Carpinteri Alberto
Published: September 2021

Protein dynamics has been investigated since almost half a century, as it is believed to constitute the fundamental connection between structure and function. Elastic network models (ENMs) have been widely used to predict protein dynamics, flexibility and the biological mechanism, from which remarkable results have been found regarding the prediction of protein conformational changes. Starting from the knowledge of the reference structure only, these conformational changes have been usually predicted either by looking at the individual mode shapes of vibrations (i.e., by considering the free vibrations of the ENM) or by applying static perturbations to the protein network (i.e., by considering a linear response theory). In this paper, we put together the two previous approaches and evaluate the complete protein response under the application of dynamic perturbations. Harmonic forces with random directions are applied to the protein ENM, which are meant to simulate the single frequency-dependent components of the collisions of the surrounding particles, and the protein response is computed by solving the dynamic equations in the underdamped regime, where mass, viscous damping and elastic stiffness contributions are explicitly taken into account. The obtained motion is investigated both in the coordinate space and in the sub-space of principal components (PCs). The results show that the application of perturbations in the low-frequency range is able to drive the protein conformational change, leading to remarkably high values of direction similarity. Eventually, this suggests that protein conformational change might be triggered by external collisions and favored by the inherent low-frequency dynamics of the protein structure.
Epigenetic Mechanisms in Type 2 Diabetes Retinopathy: A Systematic Review
Authors: Milluzzo Agostino , Maugeri Andrea , Barchitta Martina , Sciacca Laura , Agodi Antonella
Published: September 2021

Diabetic retinopathy (DR) is one of the main causes of vision loss in middle-aged economically active people. Modifiable (i.e., hyperglycaemia, hypertension, hyperlipidaemia, obesity, and cigarette smoke) and non-modifiable factors (i.e., duration of diabetes, puberty, pregnancy and genetic susceptibility) are involved in the development of DR. Epigenetic mechanisms, modulating the oxidative stress, inflammation, apoptosis, and aging, could influence the course of DR. Herein, we conducted a systematic review of observational studies investigating how epigenetics affects type 2 diabetes retinopathy (T2DR). A total of 23 epidemiological studies were included: 14 studies focused on miRNA, 4 studies on lnc-RNA, one study on both miRNA and lnc-RNA, and 4 studies on global or gene-specific DNA methylation. A direct relation between the dysregulation of miR-21, miR-93, and miR-221 and FPG, HbA1c, and HOMA-IR was identified. A panel of three miRNAs (hsa-let-7a-5p, hsa-miR-novel-chr5_15976, and hsa-miR-28-3p) demonstrated a good sensitivity and specificity for predicting T2DR. Little evidence is available regarding the possible role of the long non-coding MALAT1 dysregulation and MTHFR gene promoter hypermethylation. Despite these initial, encouraging findings potentially suggesting a role of epigenetics in T2DR, the use in clinical practice for the diagnosis and staging of this complication encounters several difficulties and further targeted investigations are still necessary.
Acid Stripping after Infection Improves the Detection of Viral HLA Class I Natural Ligands Identified by Mass Spectrometry
Authors: Lorente Elena , Marcilla Miguel , de la Sota Patricia G. , Quijada-Freire Adriana , Mir Carmen , López Daniel
Published: September 2021

Identification of a natural human leukocyte antigen (HLA) ligandome is a key element to understand the cellular immune response. Advanced high throughput mass spectrometry analyses identify a relevant, but not complete, fraction of the many tens of thousands of self-peptides generated by antigen processing in live cells. In infected cells, in addition to this complex HLA ligandome, a minority of peptides from degradation of the few proteins encoded by the viral genome are also bound to HLA class I molecules. In this study, the standard immunopeptidomics strategy was modified to include the classical acid stripping treatment after virus infection to enrich the HLA ligandome in virus ligands. Complexes of HLA-B*27:05-bound peptide pools were isolated from vaccinia virus (VACV)-infected cells treated with acid stripping after virus infection. The HLA class I ligandome was identified using high throughput mass spectrometry analyses, yielding 37 and 51 natural peptides processed and presented untreated and after acid stripping treatment VACV-infected human cells, respectively. Most of these virus ligands were identified in both conditions, but exclusive VACV ligands detected by mass spectrometry detected on acid stripping treatment doubled the number of those identified in the untreated VACV-infected condition. Theoretical binding affinity prediction of the VACV HLA-B*27:05 ligands and acute antiviral T cell response characterization in the HLA transgenic mice model showed no differences between HLA ligands identified under the two conditions: untreated and under acid stripping condition. These findings indicated that acid stripping treatment could be useful to identify HLA class I ligands from virus-infected cells.
Possible Roles of Calreticulin in Uterine Decidualization and Receptivity in Rats and Humans
Authors: Yoshie Mikihiro , Kusama Kazuya , Tanaka Risaka , Okubo Takanori , Kojima Junya , Takaesu Yotaro , Isaka Keiichi , Nishi Hirotaka , Tamura Kazuhiro
Published: September 2021

Previous in vitro studies have suggested that calreticulin (CALR), which is responsible for the folding and quality control of glycoproteins, may be associated with decidualization. However, its precise role in regulating decidualization has not been explored in vivo. Here, we used pregnant rat models to examine endometrial CALR expression during the peri-implantation period. We also examined whether polypectomy, a procedure that could ameliorate infertility, alters the endometrial expression levels of CALR and several implantation factors in women diagnosed as infertile. In rats, uterine CALR was expressed at a high level at the implantation site, and a marked increase in CALR expression was observed in decidual cells of normal pregnancy. In addition, endometrial CALR expression was enhanced by either administration of estradiol-17β in the delayed implantation rat model or the artificial induction of decidualization in the pseudopregnant rat. In cultured stromal cells, siRNA-mediated silencing of CALR inhibited the decidual stimulus-induced expression of prolactin, decidual/trophoblast prolactin-related protein, and connexin 43. In humans, the endometrial expression levels of the mRNAs encoding CALR and the implantation-related factor insulin-like growth factor binding protein (IGFBP)-7 tended to increase after polypectomy. The strongest positive correlation between expression levels before polypectomy was observed for IGFBP-7 and CALR, and the strength of this correlation increased after the surgery. Thus, endometrial CALR may play a role in the formation of decidua, and the polypectomy of infertile patients may result in the co-operative expression of endometrial factors, including CALR, that could enhance endometrial receptivity.
State of the Art in the Antibacterial and Antiviral Applications of Carbon-Based Polymeric Nanocomposites
Authors: Díez-Pascual Ana M.
Published: September 2021

The development of novel approaches to prevent bacterial infection is essential for enhancing everyday life. Carbon nanomaterials display exceptional optical, thermal, and mechanical properties combined with antibacterial ones, which make them suitable for diverse fields, including biomedical and food applications. Nonetheless, their practical applications as antimicrobial agents have not been fully explored yet, owing to their relatively poor dispersibility, expensiveness, and scalability changes. To solve these issues, they can be integrated within polymeric matrices, which also exhibit antimicrobial activity in some cases. This review describes the state of the art in the antibacterial applications of polymeric nanocomposites reinforced with 0D fullerenes, 1D carbon nanotubes (CNTs), and 2D graphene (G) and its derivatives such as graphene oxide (GO) and reduced graphene oxide (rGO). Given that a large number of such nanocomposites are available, only the most illustrative examples are described, and their mechanisms of antimicrobial activity are discussed. Finally, some applications of these antimicrobial polymeric nanocomposites are reviewed.
A Novel In Vitro Assay Using Human iPSC-Derived Sensory Neurons to Evaluate the Effects of External Chemicals on Neuronal Morphology: Possible Implications in the Prediction of Abnormal Skin Sensation
Authors: Satoh Masahiko , Suzuki Tamie , Sakurai Tetsuhito , Toyama Sumika , Kamata Yayoi , Kondo Shinya , Suga Yasushi , Tominaga Mitsutoshi , Takamori Kenji
Published: September 2021

Neuronal morphological changes in the epidermis are considered to be one of causes of abnormal skin sensations in dry skin-based skin diseases. The present study aimed to develop an in vitro model optimised for human skin to test the external factors that lead to its exacerbation. Human-induced pluripotent stem cell-derived sensory neurons (hiPSC-SNs) were used as a model of human sensory neurons. The effects of chemical substances on these neurons were evaluated by observing the elongation of nerve fibers, incidence of blebs (bead-like swellings), and the expression of nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2). The nerve fiber length increased upon exposure to two common cosmetic preservatives—methylparaben and phenoxyethanol—but not to benzo[a]pyrene, an air pollutant at the estimated concentrations in the epidermis. Furthermore, the incidence of blebs increased upon exposure to benzo[a]pyrene. However, there was a decrease in the expression of NMNAT2 in nerve fibers, suggesting degenerative changes. No such degeneration was found after methylparaben or phenoxyethanol at the estimated concentrations in the epidermis. These findings suggest that methylparaben and phenoxyethanol promote nerve elongation in hiPSC-SNs, whereas benzo[a]pyrene induces nerve degeneration. Such alterations may be at least partly involved in the onset and progression of sensitive skin.
Single-Incision vs. Multiport Robotic Sacrocolpopexy: 126 Consecutive Cases at a Single Institution
Authors: Nam Gina , Lee Sa-Ra , Roh A-mi , Kim Ju-Hee , Choi Sungwook , Kim Sung-Hoon , Chae Hee-Dong
Published: September 2021

Robot-assisted laparoscopic sacrocolpopexy (RSC) has gained popularity as a method for easier intracorporeal suturing than conventional laparoscopic sacrocolpopexy. However, few studies have compared multiport RSC (MP-RSC) and single-incision RSC (SI-RSC). We aimed to compare perioperative outcomes between these techniques for advanced pelvic organ prolapse (POP). We analyzed 126 patients who underwent RSC for POP quantification (all stage III to IV) between March 2019 and May 2021 at Seoul Asan Medical Center. We prospectively collected operation-related data, including total operation time (OT; from skin incision to closure) and perioperative outcomes. A total of 106 and 20 patients underwent MP-RSC and SI-RSC, respectively. The mean ages were 57.49 ± 10.89 and 56.20 ± 10.30 years in the MP-RSC and SI-RSC groups, respectively. The mean total OT was significantly shorter for MP-RSC than for SI-RSC (105.43 ± 24.03 vs. 121.10 ± 26.28 min). The OT difference was 15.67 min (95% confidence interval, 3.90–25.85, p = 0.009). No statistically significant differences were observed in terms of perioperative variables (estimated blood loss, hospital stay) and postoperative adverse events (POP recurrence, mesh erosion). SI-RSC had comparable intraoperative and postoperative outcomes to MP-RSC, with additional cosmetic benefits. MP-RSC had significantly shorter OT than SI-RSC.
Surgical Approaches and Oncological Outcomes in the Management of Duodenal Gastrointestinal Stromal Tumors (GIST)
Authors: Vassos Nikolaos , Perrakis Aristotelis , Hohenberger Werner , Croner Roland S.
Published: September 2021

Background: Duodenal gastrointestinal stromal tumors (GIST) are a rare subset of GIST. Their surgical management in this anatomically complex region consists of varied approaches, and the administration of imatinib mesylate (IM) has not been clarified. Methods: We retrospectively reviewed patients with duodenal GIST treated during a 10-year-period. We analysed the clinicopathological characteristics and survival factors and evaluated the perioperative and long-term outcomes based on the extent of resection ((ocal-resection (LR) versus pancreaticoduodenectomy (PD)) and the IM-administration. The median follow-up period was 60 months (range, 12–140). Results: A total of thirteen patients (M:F = 7:6) with median age of 64 years (range, 42–77) underwent resection of duodenal GIST. Median tumor size was 5.2 cm (range, 1.5–13.3). Eight patients (61.5%) underwent LR and five patients (38.5%) PD. R0-resection was achieved in 92.5%. Neoadjuvant IM-therapy was administered in five patients leading to tumor downsizing and in 40% to less-extended resection. The PD group consisted of larger tumors with higher mitotic count, mostly located in D2 (p = 0.031). The PD group had longer operative time (p = 0.026), longer hospital stay (p = 0.016), and higher rate of postoperative complications (p = 0.128). The actuarial 1-, 3-, and 5-year overall survival were 92.5%, 84%, and 73.5%, respectively, whereas the disease-free survival rates at 1, 3, and 5 years were 91.5%, 83%, and 72%, respectively. A tendency towards increased risk of disease recurrence was demonstrated for patients with tumor >5 cm and high-risk potential. There was not statistic survival benefit for one or the other surgical approach. Conclusion: The type of resection depends on duodenal site of origin and tumor size. LR can be the treatment of choice for duodenal GIST whenever technically feasible. Recurrence of duodenal GIST is dependent on tumor biology rather than surgical approach. Administration of IM in neaodjuvant setting should be considered in cases with high-risk GIST scheduled for PD since it might facilitate less-extended resection.
Impact on the Mental and Physical Health of the Portuguese Population during the COVID-19 Confinement
Authors: Frade Fátima , Jacobsohn Lia , Gómez-Salgado Juan , Martins Rosário , Allande-Cussó Regina , Ruiz-Frutos Carlos , Frade João
Published: September 2021

Confinement of the population has been one of the measures implemented by different governments to address the COVID-19 health crisis, and it has led to social isolation together with a disruption of daily activities. The aim of the study is to analyze psychological distress during the COVID-19 pandemic in Portugal. During the quarantine, a cross-sectional study was carried out on a sample of 2120 subjects over 18 years of age, resident and born in Portugal. Data were collected using a self-developed questionnaire that considered socio-demographic variables, physical symptoms, health conditions, and history of contact with COVID-19, as well as psychological alterations. The General Health Questionnaire (GHQ-12) was also included. Univariate and bivariate statistical analyses were performed. Predictive capacity was studied using logistic regression models. The results showed a higher percentage of individuals presenting psychological distress (57.2.0%), with a higher percentage identified among women (79.0%), and in people with a higher educational level (bachelor’s + master’s and doctorate) (75.8%). The predictor variables with the greatest weight were sex, educational level (graduation, master’s, and doctorate), living with children or under 16 years of age, presence of symptoms, and quarantine in the last 14 days for having symptoms. Good self-assessment of health and working at home appear to be protective against psychological distress. These results highlight the impact of the COVID-19 pandemic on psychological distress and provide an opportunity to consider the need to implement specific multidisciplinary public health and mental health interventions in this pandemic situation.
Native Kidney Hydronephrosis Is Associated with Upper Urinary Tract Urothelial Carcinoma in Post-Kidney Transplantation Patients
Authors: Ho Cheng-Ju , Huang Yu-Hui , Hsieh Tzuo-Yi , Yang Min-Hsin , Wang Shao-Chuan , Chen Wen-Jung , Lee Tsung-Hsien , Sung Wen-Wei , Chen Sung-Lang
Published: September 2021

Background: Upper urinary tract urothelial carcinoma (UTUC) is the most common malignancy occurring after kidney transplantation (KT) in Taiwan. The aim of this study was to investigate the association between native kidney hydronephrosis and UTUC in post-KT patients. Methods: From 2003 to 2018, we conducted a retrospective cohort study that enrolled 1005 post-KT patients, 67 of whom were subsequently diagnosed with UTUC. We divided patients into two groups based on whether or not they had UTUC. Multivariate analysis and Kaplan-Meier plot were used to evaluate if native kidney hydronephrosis was associated with post-KT UTUC. Results: The total cohort consisted of 612 men (60.9%) and 393 women (39.1%) with a mean age of 48.2 ± 12.0 at KT. The mean follow-up time was 118.6 ± 70.2 months, and mean time from KT to UTUC was 7.53 years. There was a significant gender difference with a female predominance among the UTUC patients (73.1% versus 26.9%, p < 0.001). Native kidney hydronephrosis occurred more frequently in the UTUC group (68.7% versus 4.8%, p < 0.001). Multivariate analysis showed that native kidney hydronephrosis and female gender were significantly associated with UTUC with odds ratios of 35.32 (95% CI, 17.99–69.36; p < 0.001) and 3.37 (95% CI, 1.55–7.29; p = 0.002), respectively. UTUC in the post-KT patients also showed aggressive pathological characteristics and a tendency toward bilateral lesions (41.8%). Conclusions: Native kidney hydronephrosis is significantly associated with post-KT UTUC patients in Taiwan. Native kidney hydronephrosis may be a deciding factor for standard nephroureterectomy and bladder cuff excision in selected patients. Nevertheless, almost half of the patients with kidney hydronephrosis do not present with UTUC at the end of our study.
Use of a Pre-Trained Neural Network for Automatic Classification of Arterial Doppler Flow Waveforms: A Proof of Concept
Authors: Guilcher Antoine , Laneelle Damien , Mahé Guillaume
Published: September 2021

Background: Arterial Doppler flow waveform analysis is a tool recommended for the management of lower extremity peripheral arterial disease (PAD). To standardize the waveform analysis, classifications have been proposed. Neural networks have shown a great ability to categorize data. The aim of the present study was to use an existing neural network to evaluate the potential for categorization of arterial Doppler flow waveforms according to a commonly used classification. Methods: The Pareto efficient ResNet-101 (ResNet-101) neural network was chosen to categorize 424 images of arterial Doppler flow waveforms according to the Simplified Saint-Bonnet classification. As a reference, the inter-operator variability between two trained vascular medicine physicians was also assessed. Accuracy was expressed in percentage, and agreement was assessed using Cohen’s Kappa coefficient. Results: After retraining, ResNet-101 was able to categorize waveforms with 83.7 ± 4.6% accuracy resulting in a kappa coefficient of 0.79 (0.75–0.83) (CI 95%), compared with a kappa coefficient of 0.83 (0.79–0.87) (CI 95%) between the two physicians. Conclusion: This study suggests that the use of transfer learning on a pre-trained neural network is feasible for the automatic classification of images of arterial Doppler flow waveforms.
Cardioplegia between Evolution and Revolution: From Depolarized to Polarized Cardiac Arrest in Adult Cardiac Surgery
Authors: Francica Alessandra , Tonelli Filippo , Rossetti Cecilia , Tropea Ilaria , Luciani Giovanni Battista , Faggian Giuseppe , Dobson Geoffrey Phillip , Onorati Francesco
Published: September 2021

Despite current advances in perioperative care, intraoperative myocardial protection during cardiac surgery has not kept the same pace. High potassium cardioplegic solutions were introduced in the 1950s, and in the early 1960s they were soon recognized as harmful. Since that time, surgeons have minimized many of the adverse effects by lowering the temperature of the heart, lowering K+ concentration, reducing contact K+ time, changing the vehicle from a crystalloid solution to whole-blood, adding many pharmacological protectants and modifying reperfusion conditions. Despite these attempts, high potassium remains a suboptimalway to arrest the heart. We briefly review the historical advances and failures of finding alternatives to high potassium, the drawbacks of a prolonged depolarized membrane, altered Ca2+ intracellular circuits and heterogeneity in atrial-ventricular K+ repolarization during reanimation. Many of these untoward effects may be alleviated by a polarized membrane, and we will discuss the basic science and clinical experience from a number of institutions trialling different alternatives, and our institution with a non-depolarizing adenosine, lidocaine and magnesium (ALM) cardioplegia. The future of polarized arrest is an exciting one and may play an important role in treating the next generation of patients who are older, and sicker with multiple comorbidities and require more complex operations with prolonged cross-clamping times.
Ankle Osteoarthritis Aetiology
Authors: Herrera-Pérez Mario , González-Martín David , Vallejo-Márquez Mercedes , Godoy-Santos Alexandre L. , Valderrabano Victor , Tejero Sergio
Published: September 2021

Ankle osteoarthritis affects 1% of the population and, unlike gonarthrosis or coxarthrosis, is secondary to previous trauma in more than 75% of cases. Another peculiarity of this disease is that it affects a younger and active population, with socio-occupational implications. Mechanical factors, such as incongruity, instability, malalignment, and impacts, which increase stress on isolated areas of the ankle cartilage, have been clearly associated with the development of osteoarthritis. However, we cannot ignore the importance of pro-inflammatory mediators present from the moment of fracture as triggers of the cascade that eventually causes chondrocyte cell death, ultimately responsible for ankle osteoarthritis.
Heart Rate Variability and Its Associations with Organ Complications in Adults after Fontan Operation
Authors: Okólska Magdalena , Łach Jacek , Matusik Paweł T. , Pająk Jacek , Mroczek Tomasz , Podolec Piotr , Tomkiewicz-Pająk Lidia
Published: September 2021

Reduction of heart rate variability (HRV) parameters may be a risk factor and precede the occurrence of arrhythmias or the development of heart failure and complications in people with postinfarct left ventricular dysfunction and after coronary artery bypass grafting. Data on this issue in adults after a Fontan operation (FO) are scarce. This study assessed the association between HRV, exercise capacity, and multiorgan complications in adults after FO. Data were obtained from 30 FO patients (mean age 24 ± 5.4 years) and 30 healthy controls matched for age and sex. HRV was investigated in all patients by clinical examination, laboratory tests, echocardiography, a cardiopulmonary exercise test, and 24-h electrocardiogram. The HRV parameters were reduced in the FO group. Reduced HRV parameters were associated with patients’ age at the time of FO, time since surgery, impaired exercise capacity, chronotropic incompetence parameters, and multiorgan complications. Univariate analysis showed that saturated O2 at rest, percentage difference between adjacent NN intervals of >50 ms duration, and peak heart rate were associated with chronotropic index. Multivariable analysis revealed that all three variables were independent predictors of the chronotropic index. The results of this study suggest novel pathophysiological mechanisms that link HRV, physical performance, and organ damage in patients after FO.
Correlation between α1-Antitrypsin Deficiency and SARS-CoV-2 Infection: Epidemiological Data and Pathogenetic Hypotheses
Authors: Vianello Andrea , Guarnieri Gabriella , Braccioni Fausto , Molena Beatrice , Lococo Sara , Achille Alessia , Lionello Federico , Salviati Leonardo , Caminati Marco , Senna Gianenrico
Published: September 2021

The most common hereditary disorder in adults, α1-antitrypsin deficiency (AATD), is characterized by reduced plasma levels or the abnormal functioning of α1-antitrypsin (AAT), a major human blood serine protease inhibitor, which is encoded by the SERine Protein INhibitor-A1 (SERPINA1) gene and produced in the liver. Recently, it has been hypothesized that the geographic differences in COVID-19 infection and fatality rates may be partially explained by ethnic differences in SERPINA1 allele frequencies. In our review, we examined epidemiological data on the correlation between the distribution of AATD, SARS-CoV-2 infection, and COVID-19 mortality rates. Moreover, we described shared pathogenetic pathways that may provide a theoretical basis for our epidemiological findings. We also considered the potential use of AAT augmentation therapy in patients with COVID-19.
Attenuative Effects of Platelet-Rich Plasma on 30 kDa Fibronectin Fragment-Induced MMP-13 Expression Associated with TLR2 Signaling in Osteoarthritic Chondrocytes and Synovial Fibroblasts
Authors: Lu Hsien-Tsung , Lu Jeng-Wei , Lee Chian-Her , Peng Yi-Jen , Lee Herng-Sheng , Chu You-Hsiang , Ho Yi-Jung , Liu Feng-Cheng , Shen Pei-Hung , Wang Chih-Chien
Published: September 2021

Proteolytic fragments of fibronectin can have catabolic effects on cartilage, menisci, and synovium. Previous studies have reported that Toll-like receptor (TLR) signaling pathways might be associated with joint inflammation and joint destruction. Platelet-rich plasma (PRP) is increasingly being used to treat a range of joint conditions; however, it has yet to be determined whether PRP influences fibronectin fragment (FN-f) procatabolic activity and TLRs. In this study, human primary culture cells were treated with 30 kDa FN-f with/without PRP co-incubation, and then analyzed using real-time PCR to determine gene expression levels in articular chondrocytes, meniscal fibrochondrocytes, and synovial fibroblasts. Protein levels were evaluated by Western immunoblotting. This study observed an increase in the protein expression of matrix metalloproteinases (MMPs), Toll-like receptor 2 (TLR2), nitric oxide synthase 2 (NOS2), prostaglandin-endoperoxide synthase (PTGS2), and cyclooxygenase 2 (COX2) in articular chondrocytes, meniscal fibrochondrocytes, and synovial fibroblasts following insult with 30 kDa FN-f. Upregulation of these genes was significantly attenuated by PRP treatment. TLR2 and matrix metalloproteinase 13 (MMP-13) were also significantly attenuated by cotreatment with 30 kDa FN-f + PRP + TLR2 inhibitor. PRP treatment was shown to attenuate the 30 kDa FN-f-induced MMP-13 expression associated with the decreased expression of TLR2 in osteoarthritic chondrocytes and synovial fibroblasts. PRP treatment was also shown to attenuate procatabolic activity associated with MMP-13 expression via the TLR2 signaling pathway.
Heart Failure in Type 1 Diabetes: A Complication of Concern? A Narrative Review
Authors: Gómez-Perez Ana María , Damas-Fuentes Miguel , Cornejo-Pareja Isabel , Tinahones Francisco J.
Published: September 2021

Heart failure (HF) has been a hot topic in diabetology in the last few years, mainly due to the central role of sodium-glucose cotransporter 2 inhibitors (iSGLT2) in the prevention and treatment of cardiovascular disease and heart failure. It is well known that HF is a common complication in diabetes. However, most of the knowledge about it and the evidence of cardiovascular safety trials with antidiabetic drugs refer to type 2 diabetes (T2D). The epidemiology, etiology, and pathophysiology of HF in type 1 diabetes (T1D) is still not well studied, though there are emerging data about it since life expectancy for T1D has increased in the last decades and there are more elderly patients with T1D. The association of T1D and HF confers a worse prognosis than in T2D, thus it is important to investigate the characteristics, risk factors, and pathophysiology of this disease in order to effectively design prevention strategies and therapeutic tools.
Educational Differences in Diabetes Mortality among Hispanics in the United States: An Epidemiological Analysis of Vital Statistics Data (1989–2018)
Authors: Barcelo Alberto , Valdivia Alfredo , Sabag Angelo , Rey-Lopez Juan Pablo , Galil Arise Garcia de Siqueira , Colugnati Fernando A.B. , Pastor-Valero María
Published: September 2021

Background: Diabetes accounted for approximately 10% of all-cause mortality among those 20–79 years of age worldwide in 2019. In 1986–1989, Hispanics in the United States of America (USA) represented 6.9% of the national population with diabetes, and this proportion increased to 15.1% in 2010–2014. Recently published findings demonstrated the impact of attained education on amenable mortality attributable to diabetes among Non-Hispanic Whites (NHWs) and Non-Hispanic Blacks (HNBs). Previous cohort studies have shown that low education is also a detrimental factor for diabetes mortality among the Hispanic population in the USA. However, the long-term impact of low education on diabetes mortality among Hispanics in the USA is yet to be determined. Aims and methods: The aim of this study was to measure the impact of achieving a 12th-grade education on amenable mortality due to diabetes among Hispanics in the USA from 1989 to 2018. We used a time-series designed to analyze death certificate data of Hispanic-classified men and women, aged 25 to 74 years, whose underlying cause of death was diabetes, between 1989 and 2018. Death certificate data from the USA National Center for Health Statistics was downloaded, as well as USA population estimates by age, sex, and ethnicity from the USA Census Bureau. The analyses were undertaken using JointPoint software and the Age–Period–Cohort Web Tool, both developed by the USA National Cancer Institute. Results: The analyses showed that between 1989 to 2018, age- and sex-standardized diabetes mortality rates among the least educated individuals were higher than those among the most educated individuals (both sexes together, p = 0.036; males, p = 0.053; females, p = 0.036). The difference between the least and most educated individuals became more pronounced in recent years, as shown by independent confidence intervals across the study period. Sex-based analyses revealed that the age-adjUSAted diabetes mortality rate had increased to a greater extent among the least educated males and females, respectively, than among the most educated. Conclusions: The results of the analyses demonstrated a powerful effect of low education on amenable mortality attributable to diabetes among the Hispanic population in the USA. As an increasing prevalence of diabetes among the least educated Hispanics has been reported, there is a great need to identify and implement effective preventive services, self-management, and quality care practices, that may assist in reducing the growing disparity among those most vulnerable, such as minority populations.
Biomarkers Associated with Failure of Liberation from Oxygen Therapy in Severe COVID-19: A Pilot Study
Authors: Kweon Oh Joo , Cha Min Jae , Baek Moon Seong , Choi Seong-Ho , Kim Won-Young
Published: September 2021

This study aimed to investigate whether clinical and laboratory biomarkers can identify patients with COVID-19 who are less likely to be liberated from oxygen therapy. This was a retrospective study comparing 18 patients in the weaning failure group with 38 patients in the weaning success group. Weaning failure was defined as death or discharge with an oxygen device before day 28 after hospital admission or requiring oxygen support as of day 28. The median quick Sequential Organ Failure Assessment (qSOFA) score was significantly higher and the median SpO2/FiO2 was significantly lower in the weaning failure group. The laboratory biomarkers, procalcitonin (PCT) and D-dimer, were significantly higher in the weaning failure group, as were the biomarkers of endothelial injury, such as angiopoietin-2 (Ang-2) and Ang-2/Ang-1, and tumor necrosis factor-α (TNF-α). Patients’ qSOFA scores, SpO2/FiO2, and PCT, D-dimer, Ang-2, Ang-2/Ang-1, endocan (4-day and 7-day increases), and TNF-α levels predicted weaning failure; 7-day endocan levels were the best predictor of weaning failure with an AUC of 0.81 (95% CI, 0.67–0.94). We identified clinical and laboratory parameters, including plasma biomarkers of endothelial injury, that may be considered as biomarkers for predicting failure of liberation from oxygen therapy in patients with severe COVID-19.
Post-Mastectomy Pain: An Updated Overview on Risk Factors, Predictors, and Markers
Authors: Calapai Marco , Esposito Emanuela , Puzzo Luisa , Vecchio Daniele Alfio , Blandino Rosario , Bova Giuseppe , Quattrone Domenico , Mannucci Carmen , Ammendolia Ilaria , Mondello Cristina , Gangemi Sebastiano , Calapai Gioacchino , Cardia Luigi
Published: September 2021

After breast surgery, women frequently develop chronic post-mastectomy pain (PMP). PMP refers to the occurrence of pain in and around the area of the mastectomy lasting beyond three months after surgery. The nature of factors leading to PMP is not well known. When PMP is refractory to analgesic treatment, it negatively impacts the lives of patients, increasing emotional stress and disability. For this reason, optimizing the quality of life of patients treated for this pathology has gained more importance. On the basis of the findings and opinions above, we present an overview of risk factors and predictors to be used as potential biomarkers in the personalized management of individual PMP. For this overview, we discuss scientific articles published in peer-reviewed journals written in the English language describing risk factors, predictors, and potential biomarkers associated with chronic pain after breast surgery. Our overview confirms that the identification of women at risk for PMP is fundamental to setting up the best treatment to prevent this outcome. Clinical practice can be planned through the interpretation of genotyping data, choosing drugs, and tailoring doses for each patient with the aim to provide safer and more effective individual analgesic treatment.
Stability Loss Analysis for Thin-Walled Shells with Elliptical Cross-Sectional Area
Authors: Kostka Ján , Bocko Jozef , Frankovský Peter , Delyová Ingrid , Kula Tomáš , Varga Patrik
Published: September 2021

The aim of the scientific contribution is to point out the possibility of applicability of cylindrical shells with a constant elliptical cross-sectional shape for stability loss analysis. The solution to the problem consists of two approaches. The first approach is the experimental measurement of critical force levels, where the work also describes the method of production of the sample and jigs that cause the desired elliptical shape. The second approach is solving the problem in the use of numerical methods—the finite strip method together with the finite element method.
Experimental Determination of the Coefficient of Restitution for Selected Modern Hybrid Composites
Authors: Skórski Witold Wojciech , Obszański Marcin , Zawisza Maciej
Published: September 2021

Composite materials (fiber reinforced plastics, FRPs) are successfully utilized in the production of various mechanical devices, including land vehicles, marine vessels, and aircrafts. They are primarily used for the production of body parts and hulls. Due to their importance, certain requirements relating to the mechanical properties of the materials used must be met for such applications. One aspect of the passive safety of vehicles is the effects of a possible collision with another object. The behavior of the structure in such a case can be determined based on the coefficient of restitution, which is a measure of energy dissipation after an impact. This paper presents the results of measuring the value of the coefficient of restitution for the selected composite materials, utilizing various reinforcement materials including different types of fibers and wooden veneer. The selected materials included glass, carbon, Kevlar fibers, and veneer from exotic wood in an epoxy resin matrix. The tested samples were made using various methods in order to understand the influence of the technology on the value of the coefficient. The authors determined the coefficient values utilizing two methods based on the measurement of two different physical quantities. In the first case, the height of the rebound of the ram was measured using a fast digital camera; in the second case, the time between successive rebounds of the tool was measured, determined based on the signal from the acceleration sensor. The authors compared the results of the coefficient values obtained using these methods and examined the relationship between the rebound energy and the value of the coefficient of restitution. The results have been discussed, and some conclusions have been made. Among other things, it seems that both methods of measurement are interchangeable with regard to lower impact velocities corresponding to lower heights (up to 300 mm) of the drop of the ram used in the tests.
Oil Spill Sorber Based on Extrinsically Magnetizable Porous Geopolymer
Authors: Silveira Maranhão Fabíola da , Gomes Fernando , Thode Sérgio , Das Diganta B. , Pereira Emiliane , Lima Nathali , Carvalho Fernanda , Aboelkheir Mostafa , Costa Vitor , Pal Kaushik
Published: September 2021

Environmental impacts are increasingly due to the human polluting activities. Therefore, there is a need to develop technologies capable of removing contamination and driving the impacted environment as close as possible to its inherent characteristics. One of the major problems still faced is the spill of oil into water. Therefore, to solve the environmental problem, this work shows the use of magnetically modified geopolymer materials as an oil remover from water with a magnet’s aid. The results obtained were outstanding since the average intrinsic oil removal capability (IORC) was 150 g/g. The presented IORC is the largest found in the materials produced by our research group, constituting an extremely encouraging result, mainly because of the ease of preparing the magnetic geopolymer system. Furthermore, the low cost of production and the material’s capability to be reused as filler of polymer or even cementitious matrices allows us to project that this nanocomposite can be widely used, constituting an economically viable alternative for more efficient environmental recovery processes.
Effect of the Degree of Conversion on Mechanical Properties and Monomer Elution from Self-, Dual- and Light-Cured Core Composites
Authors: Petronijevic Sarcev Branislava , Balos Sebastian , Markovic Dubravka , Sarcev Ivan , Vukcevic Marija , Labus Zlatanovic Danka , Miletic Vesna
Published: September 2021

The objective of this work was to measure and correlate the degree of conversion (DC), mechanical properties and monomer elution from self-, dual- and light-cured core composites. Five samples of each of the following materials were prepared for each test: Clearfil (Core, Photo Core, Automix), Bisco (Core-Flo, Light-Core and Bis-Core). DC was determined using FTIR, compressive and flexural strength and modulus of elasticity using a universal testing machine and microhardness using Vickers hardness. Elution was measured using HPLC. One-way ANOVA with Tukey’s post-test and Pearson’s correlation were used to statistically analyze the data. DC of Clearfil-Dual (70.1%) and Clerafil-Photo (66.8%) were higher than Clearfil-Self (55.4%) and all Bisco materials (51.4–55.3%). Flexural strength of Clearfilwas higher than that of Bisco composites. The Microhardness of Clearfil-Dual (119.8VHN) and Clearfil-Photo (118.0VHN) were higher compared to other materials. The greatest elution was detected from self-cured materials. DC positively correlated to microhardness and compressive/flexural strength and negatively to BisGMA elution. Clearfil-Photo and Automix showed higher conversion, lower monomer elution and, generally, better mechanical properties. Self-cured composites should not be recommended for routine clinical use as their performance was inferior to dual- and light-cured composites. Microhardness may be used as an indicator of elution.