bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Quantitative Detection Methods Based on Molecular Fluorescence Spectroscopy and Chromatographic Techniques Used for the Determination of Bisphenol Compounds
Authors: Orzel Joanna , Swit Pawel
Published: September 2021

Analytical methods using the fluorescence properties of bisphenols (BPA, BPF and BPS) and their complexes with β-cyclodextrin and methyl-β-cyclodextrin were developed. The methods were applied for the analysis of thermal paper and canned food. Their performance was compared with a standard HPLC approach with a diode array and fluorescence detections. For comparison purposes, basic validation parameters (linear range, limit of detection, sensitivity, precision) were evaluated. It was concluded the developed methods facilitate fast and cost-effective determination of three bisphenol species in liquid samples, similar to the HPLC performance. They are also environmentally friendly. BPA, BPF and BPS can be routinely determined with the presented approach.
Protective and Healing Effects of Ghrelin and Risk of Cancer in the Digestive System
Authors: Ginter Grzegorz , Ceranowicz Piotr , Warzecha Zygmunt
Published: September 2021

Ghrelin is an endogenous ligand for the ghrelin receptor, previously known as the growth hormone secretagogue receptor. This hormone is mainly produced by endocrine cells present in the gastric mucosa. The ghrelin-producing cells are also present in other organs of the body, mainly in the digestive system, but in much smaller amount. Ghrelin exhibits a broad spectrum of physiological effects, such as stimulation of growth hormone secretion, gastric secretion, gastrointestinal motility, and food intake, as well as regulation of glucose homeostasis and bone formation, and inhibition of inflammatory processes. This review summarizes the recent findings concerning animal and human data showing protective and therapeutic effects of ghrelin in the gut, and also presents the role of growth hormone and insulin-like growth factor-1 in these effects. In addition, the current data on the possible influence of ghrelin on the carcinogenesis, its importance in predicting the risk of developing gastrointestinal malignances, as well as the potential usefulness of ghrelin in the treatment of cancer, have been presented.
ADSC-Based Cell Therapies for Musculoskeletal Disorders: A Review of Recent Clinical Trials
Authors: Lee Seahyoung , Chae Dong-Sik , Song Byeong-Wook , Lim Soyeon , Kim Sang Woo , Kim Il-Kwon , Hwang Ki-Chul
Published: September 2021

Recently published clinical trials involving the use of adipose-derived stem cells (ADSCs) indicated that approximately one-third of the studies were conducted on musculoskeletal disorders (MSD). MSD refers to a wide range of degenerative conditions of joints, bones, and muscles, and these conditions are the most common causes of chronic disability worldwide, being a major burden to the society. Conventional treatment modalities for MSD are not sufficient to correct the underlying structural abnormalities. Hence, ADSC-based cell therapies are being tested as a form of alternative, yet more effective, therapies in the management of MSDs. Therefore, in this review, MSDs subjected to the ADSC-based therapy were further categorized as arthritis, craniomaxillofacial defects, tendon/ligament related disorders, and spine disorders, and their brief characterization as well as the corresponding conventional therapeutic approaches with possible mechanisms with which ADSCs produce regenerative effects in disease-specific microenvironments were discussed to provide an overview of under which circumstances and on what bases the ADSC-based cell therapy was implemented. Providing an overview of the current status of ADSC-based cell therapy on MSDs can help to develop better and optimized strategies of ADSC-based therapeutics for MSDs as well as help to find novel clinical applications of ADSCs in the near future.
Ocular Therapeutics and Molecular Delivery Strategies for Neovascular Age-Related Macular Degeneration (nAMD)
Authors: Sarkar Aira , Junnuthula Vijayabhaskarreddy , Dyawanapelly Sathish
Published: September 2021

Age-related macular degeneration (AMD) is the leading cause of vision loss in geriatric population. Intravitreal (IVT) injections are popular clinical option. Biologics and small molecules offer efficacy but relatively shorter half-life after intravitreal injections. To address these challenges, numerous technologies and therapies are under development. Most of these strategies aim to reduce the frequency of injections, thereby increasing patient compliance and reducing patient-associated burden. Unlike IVT frequent injections, molecular therapies such as cell therapy and gene therapy offer restoration ability hence gained a lot of traction. The recent approval of ocular gene therapy for inherited disease offers new hope in this direction. However, until such breakthrough therapies are available to the majority of patients, antibody therapeutics will be on the shelf, continuing to provide therapeutic benefits. The present review aims to highlight the status of pre-clinical and clinical studies of neovascular AMD treatment modalities including Anti-VEGF therapy, upcoming bispecific antibodies, small molecules, port delivery systems, photodynamic therapy, radiation therapy, gene therapy, cell therapy, and combination therapies.
Piceatannol, a Structural Analog of Resveratrol, Is an Apoptosis Inducer and a Multidrug Resistance Modulator in HL-60 Human Acute Myeloid Leukemia Cells
Authors: Siedlecka-Kroplewska Kamila , Wrońska Agata , Kmieć Zbigniew
Published: September 2021

Acute myeloid leukemia is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Despite recent advances in the treatment of this disease, the prognosis and overall long-term survival for patients remain poor, which drives the search for new chemotherapeutics and treatment strategies. Piceatannol, a polyphenolic compound present in grapes and wine, appears to be a promising chemotherapeutic agent in the treatment of leukemia. The aim of the present study was to examine whether piceatannol induces autophagy and/or apoptosis in HL-60 human acute myeloid leukemia cells and whether HL-60 cells are able to acquire resistance to piceatannol toxicity. We found that piceatannol at the IC90 concentration of 14 µM did not induce autophagy in HL-60 cells. However, it induced caspase-dependent apoptosis characterized by phosphatidylserine externalization, disruption of the mitochondrial membrane potential, caspase-3 activation, internucleosomal DNA fragmentation, PARP1 cleavage, chromatin condensation, and fragmentation of cell nuclei. Our findings also imply that HL-60 cells are able to acquire resistance to piceatannol toxicity via mechanisms related to MRP1 activity. Our results suggest that the use of piceatannol as a potential chemotherapeutic agent may be associated with the risk of multidrug resistance, warranting its use in combination with other chemotherapeutic agents.
A Method to Monitor the NAD+ Metabolome—From Mechanistic to Clinical Applications
Authors: Giner Maria Pilar , Christen Stefan , Bartova Simona , Makarov Mikhail V. , Migaud Marie E. , Canto Carles , Moco Sofia
Published: September 2021

Nicotinamide adenine dinucleotide (NAD+) and its reduced form (NADH) are coenzymes employed in hundreds of metabolic reactions. NAD+ also serves as a substrate for enzymes such as sirtuins, poly(ADP-ribose) polymerases (PARPs) and ADP-ribosyl cyclases. Given the pivotal role of NAD(H) in health and disease, studying NAD+ metabolism has become essential to monitor genetic- and/or drug-induced perturbations related to metabolic status and diseases (such as ageing, cancer or obesity), and its possible therapies. Here, we present a strategy based on liquid chromatography-tandem mass spectrometry (LC-MS/MS), for the analysis of the NAD+ metabolome in biological samples. In this method, hydrophilic interaction chromatography (HILIC) was used to separate a total of 18 metabolites belonging to pathways leading to NAD+ biosynthesis, including precursors, intermediates and catabolites. As redox cofactors are known for their instability, a sample preparation procedure was developed to handle a variety of biological matrices: cell models, rodent tissues and biofluids, as well as human biofluids (urine, plasma, serum, whole blood). For clinical applications, quantitative LC-MS/MS for a subset of metabolites was demonstrated for the analysis of the human whole blood of nine volunteers. Using this developed workflow, our methodology allows studying NAD+ biology from mechanistic to clinical applications.
IL-33 Enhances IFNγ and TNFα Production by Human MAIT Cells: A New Pro-Th1 Effect of IL-33
Authors: Azzout Mourad , Dietrich Céline , Machavoine François , Gastineau Pauline , Bottier Alix , Lezmi Guillaume , Leite-de-Moraes Maria
Published: September 2021

Mucosal-associated invariant T (MAIT) cells represent a distinct T cell population restricted by the MHC-class-I-related molecule, MR1, which recognizes microbial-derived vitamin B2 (riboflavin) metabolites. Their abundance in humans, together with their ability to promptly produce distinct cytokines including interferon γ (IFNγ) and tumor necrosis factor α (TNFα), are consistent with regulatory functions in innate as well as adaptive immunity. Here, we tested whether the alarmin interleukin 33 (IL-33), which is secreted following inflammation or cell damage, could activate human MAIT cells. We found that MAIT cells stimulated with IL-33 produced high levels of IFNγ, TNFα and Granzyme B (GrzB). The action of IL-33 required IL-12 but was independent of T cell receptor (TCR) cross-linking. MAIT cells expressed the IL-33 receptor ST2 (suppression of tumorigenicity 2) and upregulated Tbet (T-box expressed in T cells) in response to IL-12 or IL-33. Electronically sorted MAIT cells also upregulated the expression of CCL3 (Chemokine C-C motif ligand 3), CD40L (CD40 Ligand), CSF-1 (Colony Stimulating Factor 1), LTA (Lymphotoxin-alpha) and IL-2RA (IL-2 receptor alpha chain) mRNAs in response to IL-33 plus IL-12. In conclusion, IL-33 combined with IL-12 can directly target MAIT cells to induce their activation and cytokine production. This novel mechanism of IL-33 activation provides insight into the mode of action by which human MAIT cells can promote inflammatory responses in a TCR-independent manner.
Synthesis and Characterization of a Novel Biocompatible Alloy, Ti-Nb-Zr-Ta-Sn
Authors: Khrunyk Yuliya Y. , Ehnert Sabrina , Grib Stella V. , Illarionov Anatoly G. , Stepanov Stepan I. , Popov Artemiy A. , Ryzhkov Maxim A. , Belikov Sergey V. , Xu Zeqian , Rupp Frank , Nüssler Andreas K.
Published: September 2021

Many current-generation biomedical implants are fabricated from the Ti-6Al-4V alloy because it has many attractive properties, such as low density and biocompatibility. However, the elastic modulus of this alloy is much larger than that of the surrounding bone, leading to bone resorption and, eventually, implant failure. In the present study, we synthesized and performed a detailed analysis of a novel low elastic modulus Ti-based alloy (Ti-28Nb-5Zr-2Ta-2Sn (TNZTS alloy)) using a variety of methods, including scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and tensile test. Additionally, the in vitro biocompatibility of the TNZTS alloy was evaluated using SCP-1, SaOs-2, and THP-1 cell lines and primary human osteoblasts. Compared to Ti-6Al-4V, the elastic modulus of TNZTS alloy was significantly lower, while measures of its in vitro biocompatibility are comparable. O2 plasma treatment of the surface of the alloy significantly increased its hydrophilicity and, hence, its in vitro biocompatibility. TNZTS alloy specimens did not induce the release of cytokines by macrophages, indicating that such scaffolds would not trigger inflammatory responses. The present results suggest that the TNZTS alloy may have potential as an alternative to Ti-6Al-4V.
Mouse Liver Compensates Loss of Sgpl1 by Secretion of Sphingolipids into Blood and Bile
Authors: Spohner Anna Katharina , Jakobi Katja , Trautmann Sandra , Thomas Dominique , Schumacher Fabian , Kleuser Burkhard , Lütjohann Dieter , El-Hindi Khadija , Grösch Sabine , Pfeilschifter Josef , Saba Julie D. , Meyer zu Heringdorf Dagmar
Published: September 2021

Sphingosine 1 phosphate (S1P) lyase (Sgpl1) catalyses the irreversible cleavage of S1P and thereby the last step of sphingolipid degradation. Loss of Sgpl1 in humans and mice leads to accumulation of sphingolipids and multiple organ injuries. Here, we addressed the role of hepatocyte Sgpl1 for regulation of sphingolipid homoeostasis by generating mice with hepatocyte-specific deletion of Sgpl1 (Sgpl1HepKO mice). Sgpl1HepKO mice had normal body weight, liver weight, liver structure and liver enzymes both at the age of 8 weeks and 8 months. S1P, sphingosine and ceramides, but not glucosylceramides or sphingomyelin, were elevated by ~1.5–2-fold in liver, and this phenotype did not progress with age. Several ceramides were elevated in plasma, while plasma S1P was normal. Interestingly, S1P and glucosylceramides, but not ceramides, were elevated in bile of Sgpl1HepKO mice. Furthermore, liver cholesterol was elevated, while LDL cholesterol decreased in 8-month-old mice. In agreement, the LDL receptor was upregulated, suggesting enhanced uptake of LDL cholesterol. Expression of peroxisome proliferator-activated receptor-γ, liver X receptor and fatty acid synthase was unaltered. These data show that mouse hepatocytes largely compensate the loss of Sgpl1 by secretion of accumulating sphingolipids in a specific manner into blood and bile, so that they can be excreted or degraded elsewhere.
Vanadium(V) Complexes with Siderophore Vitamin E-Hydroxylamino-Triazine Ligands
Authors: Loizou Maria , Hadjiadamou Ioanna , Drouza Chryssoula , Keramidas Anastasios D. , Simos Yannis V. , Peschos Dimitrios
Published: September 2021

Novel vitamin E chelate siderophore derivatives and their VV and FeIII complexes have been synthesised and the chemical and biological properties have been evaluated. In particular, the α- and δ-tocopherol derivatives with bis-methyldroxylamino triazine (α-tocTHMA) and (δ-tocDPA) as well their VV complexes, [V2VO3(α-tocTHMA)2] and [V2IVO3(δ-tocTHMA)2], have been synthesised and characterised by infrared (IR), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and ultra violet-visible (UV-Vis) spectroscopies. The dimeric vanadium complexes in solution are in equilibrium with their respefrctive monomers, H2O + [V2VO2(μ-O)]4+ = 2 [VVO(OH)]2+. The two amphiphilic vanadium complexes exhibit enhanced hydrolytic stability. EPR shows that the complexes in lipophilic matrix are mild radical initiators. Evaluation of their biological activity shows that the compounds do not exhibit any significant cytotoxicity to cells.
Assay Optimization Can Equalize the Sensitivity of Real-Time PCR with ddPCR for Detection of Helicoverpa armigera (Lepidoptera: Noctuidae) in Bulk Samples
Authors: Oliveira Thayssa M. R. , Zink Frida A. , Menezes Renato C. , Dianese Érico C. , Albernaz-Godinho Karina C. , Cunha Marcos G. , Timm Alicia E. , Gilligan Todd M. , Tembrock Luke R.
Published: September 2021

Helicoverpa armigera (Hübner) is one of the most important agricultural pests in the world. This historically Old World species was first reported in Brazil in 2013 and has since spread throughout much of South America and into the Caribbean. Throughout North America, H. armigera surveys are ongoing to detect any incursions. Each trap is capable of capturing hundreds of native Helicoverpa zea (Boddie). The two species cannot be separated without genitalic dissection or molecular methods. A ddPCR assay is currently used to screen large trap samples, but this equipment is relatively uncommon and expensive. Here, we optimized a newly designed assay for accurate and repeatable detection of H. armigera in bulk samples across both ddPCR and less costly, and more common, real-time PCR methods. Improvements over previously designed assays were sought through multiple means. Our results suggest bulk real-time PCR assays can be improved through changes in DNA extraction and purification, so that real-time PCR can be substituted for ddPCR in screening projects. While ddPCR remains a more sensitive method for detection of H. armigera in bulk samples, the improvements in assay design, DNA extraction, and purification presented here also enhance assay performance over previous protocols.
Sex Pheromone of the Introduced Pine Sawfly, Diprion similis, Revisited to Define a Useful Monitoring Lure: Deviating Chiral Composition and Behavioural Responses Compared to Earlier Reports
Authors: Anderbrant Olle , Lyons D. Barry , Bång Joakim , Hedenström Erik , Högberg Hans-Erik
Published: September 2021

Extracts of Diprion similis females contained about 15 ng of the sex pheromone precursor 3,7-dimethylpentadecan-2-ol per female. After derivatisation with (S)-2-acetoxypropanoyl chloride, we found that the major stereoisomer in the extract was (2S,3R,7R)-3,7-dimethylpentadecan-2-ol. Small amounts of other stereoisomers of 3,7-dimethylpentadecan-2-ol were also identified in the extract, namely 1% of (2R,3S,7S), 0.3% (2R,3R,7R) and 0.4% of (2R,3R,7S). An unknown fifth substance showed a very similar spectrum to 3,7-dimethylpentadecan-2-ol, both in SIM and full scan mode. None of the earlier suggested behavioural synergistic isomers ((2S,3S,7S), (2S,3S,7R) and (2S,3R,7S)) were detected in the extracts. In field tests in Ontario, Canada, the earlier identified main pheromone component, viz. the propanoate of (2S,3R,7R)-3,7-dimethylpentadecan-2-ol, was tested alone and in combination with other stereoisomers, earlier reported to be synergistic. No synergistic effects were detected and the threo four-isomer blend was as attractive as the pure main compound. Thus, one of the few examples of a diprionid sawfly using more than one substance in its sex pheromone could not be confirmed. The results also suggest that monitoring programs can use the more easily synthesized threo-blend without losing efficiency. Furthermore, the study suggests that other diprionid pheromones may benefit from a reinvestigation, to clarify possible synergistic effects of stereoisomers.
Postnatal Repair of Open Neural Tube Defects: A Single Center with 90-Month Interdisciplinary Follow-Up
Authors: Hagemann Christian , Krajewski Kara , Henne Thomas , Stücker Ralf , Kunkel Philip
Published: September 2021

After publication of the Management of Myelomeningocele Study (MOMS) there is confusion regarding which treatment of open neural tube defects (NTD) is best. We report our results of postnatally repaired open NTDs born between 2007–2018 (n = 36) in critical reflection of the MOMS study. Neurosurgical, orthopedic, and urologic data were assessed. We also introduce a new entity: “status post prenatal repair”. FU ranged from 29 to 161 months (mean: 89.1 m) in 7 cases of myeloschisis and 24 myelomeningoceles in the final collective n = 31. The shunt rate was 41.9%, and the endoscopic third ventriculostomy rate was 16.1%. Hydrocephalus requiring treatment was not associated with the anatomical level, but with premature birth (p = 0.048). Myeloschisis was associated with shunt placement (p = 0.008). ROC analysis revealed birth <38.5th week predicts the necessity for hydrocephalus treatment (sensitivity: 89%; specificity: 77%; AUC= 0.71; p = 0.055). Eight (25.8%), patients are wheelchair-bound, 2 (6.5%) ambulate with a posterior walker, 10 (32.3%) with orthosis and 11 (35.5%) independently. One (3.2%) patient underwent detethering at 5.5 years. A total of three patients underwent five Chiari decompressions (9.6%). Further, nineteen orthopedic procedures were performed in nine patients (29.0%). A total of 17 (54.8%) patients self-catheterize, which was associated with an anatomical lesion at L3 or below (p = 0.032) and 23 (74.2%) take anticholinergic medication. In conclusion, shunt dependency is associated with myeloschisis, not with the anatomical defect level. Hydrocephalus treatment is associated with premature birth. In this postnatal cohort with significantly longer follow-up data than the MOMs study, the ambulation rate is better, the shunt rate lower and the secondary tethered cord rate better compared to the MOMS study.
The Role of Immunotherapy in the Treatment of Advanced Cervical Cancer: Current Status and Future Perspectives
Authors: Walsh Robert J. , Tan David S. P.
Published: September 2021

Cervical cancer remains one of the most common cancers in women around the world however therapeutic options in the advanced and recurrent setting are limited. Immune checkpoint inhibitors (ICI) have been considered an attractive option given the viral etiology of cervical cancer although the majority of patients do not benefit from their use. This review summarises current knowledge and use of immune checkpoint blockade in cervical cancer as well as discussing the challenges faced in their clinical application, namely, the role of biomarker-driven ICI use, potential mechanisms of resistance, strategies to overcome such resistance and additional immunotherapy options beyond ICI.
Challenges Related to Surgical Site Infection Prevention—Results after Standardized Bundle Implementation
Authors: Jurt Jonas , Hübner Martin , Clerc Daniel , Curchod Pauline , Abd El Aziz Mohamed A. , Hahnloser Dieter , Senn Laurence , Demartines Nicolas , Grass Fabian
Published: September 2021

Aim: The aim of this study was to assess the implementation of an intraoperative standardized surgical site infection (SSI) prevention bundle. Methods: The multimodal, evidence-based care bundle included nine intraoperative items (antibiotic type, timing, and re-dosing; disinfection; induction temperature control > 36.5°; glove change; intra-cavity lavage; wound protection; and closure strategy). The bundle was applied to all consecutive patients undergoing colonic resections. The primary outcome, SSI, was independently assessed by the National Infection Surveillance Committee for up to 30 postoperative days. A historical, institutional pre-implementation control group (2012–2017) with an identical methodology was used for comparison. Findings: In total, 1516 patients were included, of which 1256 (82.8%) were in the control group and 260 (17.2%) were in the post-implementation group. After 2:1 propensity score matching, the groups were similar for all items (p > 0.05). Overall compliance with the care bundle was 77% (IQR 77–88). The lowest compliance rates were observed for temperature control (53% overall), intra-cavity lavage (64% overall), and wound protection and closure (68% and 63% in the SSI group, respectively). Surgical site infections were reported in 58 patients (22.2%) vs. 21.4% in the control group (p = 0.79). Infection rates were comparable throughout the Centers for Disease Control and Prevention (CDC) categories: superficial, 12 patients (4.5%) vs. 4.2%, p = 0.82; deep incisional, 10 patients (3.7%) vs. 5.1%, p = 0.34; organ space, 36 (14%) vs. 12.4%, p = 0.48. After propensity score matching, rates remained comparable throughout all comparisons (all p > 0.05). Conclusions: The implementation of an intraoperative standardized care bundle had no impact on SSI rates. This may be explained by insufficient compliance with the individual measures.
Impact of Serum Uric Acid Level on Systemic Endothelial Dysfunction in Patients with a Broad Spectrum of Ischemic Heart Disease
Authors: Hiraga Takashi , Saito Yuichi , Mori Naoto , Tateishi Kazuya , Kitahara Hideki , Kobayashi Yoshio
Published: September 2021

Previous studies indicated that serum uric acid (SUA) level is a marker of endothelial function in subsets of ischemic heart disease (IHD). In the present study, we aimed to evaluate the relation between the SUA level and endothelial function in patients with a broad spectrum of IHD, including obstructive coronary artery disease (CAD) and ischemia with no obstructive CAD (INOCA). Three prospective studies and one retrospective study were pooled, in which the SUA level was measured, and systemic endothelial function was assessed using the reactive hyperemia index (RHI). The primary endpoint of the present study was a correlation of the SUA level with RHI. A total of 181 patients with a broad spectrum of IHD were included, among whom, 46 (25%) had acute coronary syndrome presentation and 15 (8%) had INOCA. Overall, the SUA level was negatively correlated with the RHI (r = −0.22, p = 0.003). Multivariable analysis identified the SUA level and INOCA as significant factors associated with RHI values. In conclusion, in patients with a broad spectrum of IHD, including obstructive epicardial CAD (chronic and acute coronary syndromes) and INOCA, the SUA level was significantly and negatively correlated with systemic endothelial function assessed with the RHI. INOCA, rather than obstructive CAD, was more associated with endothelial dysfunction.
Do Redox Balance and Inflammatory Events Take Place in Mild Bronchiectasis? A Hint to Clinical Implications
Authors: Qin Liyun , Guitart Maria , Admetlló Mireia , Esteban-Cucó Sandra , Maiques José María , Xia Yingchen , Zha Jianhua , Carbullanca Santiago , Duran Xavier , Wang Xuejie , Barreiro Esther
Published: September 2021

We hypothesized that in mild bronchiectasis patients, increased systemic inflammation and redox imbalance may take place and correlate with clinical parameters. In plasma samples from patients with very mild bronchiectasis, inflammatory cells and molecules and redox balance parameters were analyzed. In the patients, lung function and exercise capacity, nutritional status, bacterial colonization, and radiological extension were assessed. Correlations between biological and clinical variables were determined. Compared to healthy controls, levels of acute phase reactants, neutrophils, IgG, IgA, myeloperoxidase, protein oxidation, and GSH increased and lung function and exercise capacity were mildly reduced. GSH levels were even greater in ex-smoker and Pseudomona-colonized patients. Furthermore, radiological extension inversely correlated with airway obstruction and, disease severity, and positively correlated with neutrophil numbers in mild bronchiectasis patients with no nutritional abnormalities. In stable patients with mild bronchiectasis, several important inflammatory and oxidative stress events take place in plasma. These findings suggest that the extension of bronchiectasis probably plays a role in the development of redox imbalance and systemic inflammation in patients with mild bronchiectasis. These results have therapeutic implications in the management of bronchiectasis patients.
Clinical Early-Onset Sepsis Is Equally Valid to Culture-Proven Sepsis in Predicting Outcome in Infants after Preterm Rupture of Membranes
Authors: Grill Agnes , Olischar Monika , Weber Michael , Unterasinger Lukas , Berger Angelika , Leitich Harald
Published: September 2021

Background: Culture-proven sepsis is the gold standard in early-onset neonatal sepsis diagnosis. Infants born ≤29 weeks gestation after preterm rupture of membranes in the years 2009–2015 were included in a retrospective cohort study performed at a level III fetal-maternal unit. The study aimed to compare culture-proven sepsis, clinical sepsis and positive laboratory biomarkers ≤72 h as predictors of mortality before discharge and the combined outcome of mortality or severe short-term morbidity (severe cerebral morbidity, bronchopulmonary dysplasia and retinopathy). Results: Of the 354 patients included, culture-proven sepsis, clinical sepsis and laboratory biomarkers were positive in 2.3%, 8.5% and 9.6%, respectively. The mortality rate was 37.5% for patients with culture-proven sepsis (3/8), 33.3% for patients with clinical sepsis (10/30) and 8.8% for patients with positive laboratory biomarkers (3/34), respectively. Mortality or severe morbidity occurred in 75.0% of patients with culture-proven sepsis (6/8), 80.0% of patients with clinical sepsis (24/30) and 44.1% of patients with positive laboratory biomarkers (15/34), respectively. Conclusion: In preterm infants after preterm rupture of membranes, clinical sepsis was almost four times more common and at least equally valuable in predicting mortality and mortality or severe morbidity compared to culture-proven sepsis.
Epidemiology and Management of Chronic Thromboembolic Pulmonary Hypertension in Greece. Real-World Data from the Hellenic Pulmonary Hypertension Registry (HOPE)
Authors: Demerouti Eftychia , Karyofyllis Panagiotis , Voudris Vassilios , Boutsikou Maria , Anastasiadis George , Anthi Anastasia , Arvanitaki Alexandra , Athanassopoulos George , Avgeropoulou Aikaterini , Brili Styliani , Feloukidis Christos , Frantzeskaki Frantzeska , Karatasakis George , Karvounis Haralambos , Konstantonis Dimitrios , Mitrouska Ioanna , Mouratoglou Sophia , Naka Katerina K. , Orfanos Stylianos E. , Panagiotidou Evangelia , Pitsiou Georgia , Pitsis Antonios , Stamatopoulou Vagia , Stanopoulos Ioannis , Thomaidis Adina , Tsangaris Iraklis , Tsiapras Dimitrios , Giannakoulas George , Manginas Athanassios ,   on behalf of the Hellenic Society for the Study of Pulmonary Hypertension (HSSPH)
Published: September 2021

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare disease with poor prognosis if left untreated, characterized by pulmonary vascular bed obstruction due to unresolving thromboembolic material. The Hellenic pulmonary hypertension registry (HOPE) was launched in Greece in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. In total, 98 patients with CTEPH were enrolled from January 2015 until November 2019. Of these patients, 55.1% represented incident population, 50% were classified in the World Health Organization functional class II and 49% had a history of acute pulmonary embolism. The median values of pulmonary vascular resistance (PVR) and cardiac index were 7.4 (4.8) WU and 2.4 (1.0) L/min/m2, respectively, the mean diffusing capacity for carbon monoxide was 74.8 ± 20.6%, the median 6-minute walk distance was 347 (220) meters and the median value of N Terminal-pro brain natriuretic peptide was 506.0 (1450.0) pg/mL. In total, 60.2% of the patients were under pulmonary arterial hypertension-targeted therapy at the time of enrolment; specifically, riociguat was received by 35.7% of the patients and combination therapy was the preferred strategy for 16% of the patients. In total, 74 patients were evaluated for pulmonary endarterectomy (PEA), 34 (45.9%) were assessed as operable but only 23 of those (31.1%) finally underwent PEA. The remaining 40 patients were ineligible for PEA according to the operability assessment and 13 (17.6%) of them underwent balloon pulmonary angioplasty. The age of the non-operable patients was significantly higher than the operable patients (p < 0.001), while there was no significant difference with regard to the history of coagulopathies between the operable and non-operable patients (p = 0.33).
Levels of Impulsivity, Hyperactivity, and Inattention and the Association with Mental Health and Substance Use Severity in Opioid-Dependent Patients Seeking Treatment with Extended-Release Naltrexone
Authors: Karlsson Ann Tarja , Vederhus John-Kåre , Clausen Thomas , Weimand Bente , Solli Kristin Klemmetsby , Tanum Lars
Published: September 2021

The level of impulsivity, hyperactivity, and inattention (IHI) is higher among patients with substance use disorder (SUD) than in the general population. However, the prevalence of such symptoms in patients seeking treatment with an opioid antagonist, such as extended-release naltrexone (XR-NTX), is unknown. We screened 162 patients with opioid use disorder (OUD) seeking treatment with XR-NTX in Norway using the Adult ADHD Self-Report Scale (ASRS) to estimate the prevalence of IHI alongside an assessment of mental and physical health and substance use. Sixty-six patients scored above the clinical cut-off on the ASRS. Higher levels of IHI were significantly associated with a longer history of frequent amphetamine use, current alcohol use, and greater mental distress. Mental distress was the strongest factor associated with higher levels of IHI. The introduction of screening for IHI and mental distress in opioid maintenance treatment and XR-NTX would likely improve the quality of care and enable clinicians to tailor interventions to the needs of patients with high levels of IHI to prevent treatment discontinuation.
Hydrocarbon-Contaminated Sites: Is There Something More Than Exophiala xenobiotica? New Insights into Black Fungal Diversity Using the Long Cold Incubation Method
Authors: Isola Daniela , Scano Alessandra , Orrù Germano , Prenafeta-Boldú Francesc Xavier , Zucconi Laura
Published: September 2021

Human-made hydrocarbon-rich environments are important reservoirs of microorganisms with specific degrading abilities and pathogenic potential. In particular, black fungi are of great interest, but their presence in the environment is frequently underestimated because they are difficult to isolate. In the frame of a biodiversity study from fuel-contaminated sites involving 30 diesel car tanks and 112 fuel pump dispensers (52 diesel and 60 gasoline, respectively), a total of 181 black fungal strains were isolated. The long cold incubation (LCI) of water-suspended samples, followed by plating on Dichloran Rose Bengal Chloramphenicol Agar (DRBC), gave isolation yields up to six times (6.6) higher than those of direct plating on DRBC, and those of enrichment with a phenolic mix. The sequencing of ITS and LSU-rDNA confirmed the dominance of potentially pathogenic fungi from the family Herpotrichiellaceae and Exophiala xenobiotica. Moreover, other opportunistic species were found, including E. opportunistica, E. oligosperma, E. phaeomuriformis, and Rhinocladiella similis. The recurrent presence of E. crusticola, Knufia epidermidis, Aureobasidium melanogenum, Cladosporium spp., and Scolecobasidium spp. was also recorded. Interestingly, 12% of total isolates, corresponding to 50% of taxa found (16/32), represent new species. All the novel taxa in this study were isolated by LCI. These findings suggest that black fungal diversity in hydrocarbon-rich niches remains largely unexplored and that LCI can be an efficient tool for further investigations.
Soft-Tissue Simulation for Computational Planning of Orthognathic Surgery
Authors: Alcañiz Patricia , Pérez Jesús , Gutiérrez Alessandro , Barreiro Héctor , Villalobos Ángel , Miraut David , Illana Carlos , Guiñales Jorge , Otaduy Miguel A.
Published: September 2021

Simulation technologies offer interesting opportunities for computer planning of orthognathic surgery. However, the methods used to date require tedious set up of simulation meshes based on patient imaging data, and they rely on complex simulation models that require long computations. In this work, we propose a modeling and simulation methodology that addresses model set up and runtime simulation in a holistic manner. We pay special attention to modeling the coupling of rigid-bone and soft-tissue components of the facial model, such that the resulting model is computationally simple yet accurate. The proposed simulation methodology has been evaluated on a cohort of 10 patients of orthognathic surgery, comparing quantitatively simulation results to post-operative scans. The results suggest that the proposed simulation methods admit the use of coarse simulation meshes, with planning computation times of less than 10 seconds in most cases, and with clinically viable accuracy.
Insulin as Monotherapy and in Combination with Other Glucose-Lowering Drugs Is Related to Increased Risk of Diagnosis of Pneumonia: A Longitudinal Assessment over Two Years
Authors: Leutner Michael , Kaleta Michaela , Bellach Luise , Kautzky Alexander , Thurner Stefan , Klimek Peter , Kautzky-Willer Alexandra
Published: September 2021

Objective: Patients with type 2 diabetes mellitus (T2DM) are at an increased risk of developing infectious diseases such as pneumonia. Hitherto, there has been uncertainty as to whether there is a relationship between different antidiabetic drug combinations and development of pneumonia in this specific cohort. Research Design and Methods: In this longitudinal retrospective study we used multiple logistic regression analysis to assess the odds ratios (ORs) of pneumonia during an observational period of 2 years in 31,397 patients with T2DM under previously prescribed stable antidiabetic drug combinations over a duration of 4 years in comparison to 6568 T2DM patients without drug therapy over 4 years adjusted for age, sex and hospitalization duration. Results: Of the 37,965 patients with T2DM, 3720 patients underwent stable monotherapy treatment with insulin (mean age: 66.57 ± 9.72 years), 2939 individuals (mean age: 70.62 ± 8.95 y) received stable statin and insulin therapy, and 1596 patients were treated with a stable combination therapy of metformin, insulin and statins (mean age: 68.27 ± 8.86 y). In comparison to the control group without antidiabetic drugs (mean age: 72.83 ± 9.96 y), individuals undergoing insulin monotherapy (OR: 2.07, CI: 1.54–2.79, p < 0.001); insulin and statin combination therapy (OR: 2.24, CI: 1.68–3.00, p < 0.001); metformin, insulin and statin combination therapy (OR: 2.27, CI: 1.55–3.31, p < 0.001); statin, insulin and dipeptidyl peptidase-4 inhibitor (DPP-IV inhibitor) combination therapy (OR: 4.31, CI: 1.80–10.33, p = 0.001); as well as individuals treated with metformin and sulfonylureas (OR: 1.70, CI: 1.08–2.69, p = 0.02) were at increased risk of receiving a diagnosis of pneumonia. Conclusions: Stable monotherapy with insulin, but also in combination with other antidiabetic drugs, is related to an increased risk of being diagnosed with pneumonia during hospital stays in patients with type 2 diabetes mellitus compared to untreated controls.
RNA-Sequencing-Based Transcriptomic Score with Prognostic and Theranostic Values in Multiple Myeloma
Authors: Alaterre Elina , Vikova Veronika , Kassambara Alboukadel , Bruyer Angélique , Robert Nicolas , Requirand Guilhem , Bret Caroline , Herbaux Charles , Vincent Laure , Cartron Guillaume , Elemento Olivier , Moreaux Jérôme
Published: September 2021

Multiple myeloma (MM) is the second most frequent hematological cancer and is characterized by the clonal proliferation of malignant plasma cells. Genome-wide expression profiling (GEP) analysis with DNA microarrays has emerged as a powerful tool for biomedical research, generating a huge amount of data. Microarray analyses have improved our understanding of MM disease and have led to important clinical applications. In MM, GEP has been used to stratify patients, define risk, identify therapeutic targets, predict treatment response, and understand drug resistance. In this study, we built a gene risk score for 267 genes using RNA-seq data that demonstrated a prognostic value in two independent cohorts (n = 674 and n = 76) of newly diagnosed MM patients treated with high-dose Melphalan and autologous stem cell transplantation. High-risk patients were associated with the expression of genes involved in several major pathways implicated in MM pathophysiology, including interferon response, cell proliferation, hypoxia, IL-6 signaling pathway, stem cell genes, MYC, and epigenetic deregulation. The RNA-seq-based risk score was correlated with specific MM somatic mutation profiles and responses to targeted treatment including EZH2, MELK, TOPK/PBK, and Aurora kinase inhibitors, outlining potential utility for precision medicine strategies in MM.
Machine Learning-Based Radiomics of the Optic Chiasm Predict Visual Outcome Following Pituitary Adenoma Surgery
Authors: Zhang Yang , Chen Chaoyue , Huang Wei , Cheng Yangfan , Teng Yuen , Zhang Lei , Xu Jianguo
Published: September 2021

Preoperative prediction of visual recovery after pituitary adenoma surgery remains a challenge. We aimed to investigate the value of MRI-based radiomics of the optic chiasm in predicting postoperative visual field outcome using machine learning technology. A total of 131 pituitary adenoma patients were retrospectively enrolled and divided into the recovery group (N = 79) and the non-recovery group (N = 52) according to visual field outcome following surgical chiasmal decompression. Radiomic features were extracted from the optic chiasm on preoperative coronal T2-weighted imaging. Least absolute shrinkage and selection operator regression were first used to select optimal features. Then, three machine learning algorithms were employed to develop radiomic models to predict visual recovery, including support vector machine (SVM), random forest and linear discriminant analysis. The prognostic performances of models were evaluated via five-fold cross-validation. The results showed that radiomic models using different machine learning algorithms all achieved area under the curve (AUC) over 0.750. The SVM-based model represented the best predictive performance for visual field recovery, with the highest AUC of 0.824. In conclusion, machine learning-based radiomics of the optic chiasm on routine MR imaging could potentially serve as a novel approach to preoperatively predict visual recovery and allow personalized counseling for individual pituitary adenoma patients.
FinTech: Ecosystem, Opportunities and Challenges in Saudi Arabia
Authors: Albarrak Mansour Saleh , Alokley Sara Ali
Published: September 2021

FinTech is a disruptive international phenomenon that is expected to shape the future of the financial sector. This study describes the features and characteristics of the current Saudi Arabian FinTech landscape and ecosystem. Examples of innovative financial startups in Saudi Arabia, including online banking, transfer and payment services, crowdfunding platforms, peer-to-peer lending, and blockchain initiatives, are discussed. Several changes have occurred within the ecosystem in the last five years; for example, Saudi banks are taking a more cautious approach. However, FinTech initiatives are also being internally developed, encouraging technology companies and startups to focus their efforts on innovations aimed at improving current processes rather than novelty. The government directs its effort mainly toward initiatives related to regulations and laws. Customers are interested in new products that are convenient and easy to use. We compare the Saudi FinTech ecosystem to the United Arab Emirates’ FinTech ecosystem and conclude with recommendations for the different stakeholders.
Effect of Free Volume on Curcumin Release from Various Polymer-Based Composite Films Analyzed Using Positron Annihilation Lifetime Spectroscopy
Authors: Rhim Jong-Whan , Kuzeci Saygin , Roy Swarup , Akti Necmettin , Tav Cumali , Yahsi Ugur
Published: September 2021

This work reports the effects of free volume on curcumin release in various polymer-based composite films. Curcumin-reinforced biocomposite films were fabricated with natural biopolymers (carrageenan and chitosan) and bioplastics (poly(lactide) (PLA) and poly (butylene adipate-co-terephthalate) (PBAT)) via the solvent casting method. The curcumin release test was performed using an aqueous medium, and it was found that it was released the fastest in the carrageenan film, followed by the chitosan, PLA, and PBAT films, presumably owing to the dissimilarity of the polymer matrix. The free volume of the polymer films was determined using positron annihilation lifetime spectroscopy (PALS) to understand the release phenomena of curcumin. The free volume fraction was varied and reliant on the type of polymer, with the highest in the PBAT-based film followed by the PLA-, chitosan-, and carrageenan-based films. The free volume method helps analyze the release of bioactive compounds in a polymer matrix and may help to achieve a better understanding of the release of bioactive compounds.
A Calculation Model for Cooling Rate of Aluminum Alloy Melts during Continuous Rheo-Extrusion
Authors: Wang Yu , Gao Minqiang , Yang Bowei , Bai Jingyuan , Guan Renguo
Published: September 2021

The melt temperature of aluminum alloys plays a significant role in determining the microstructure characteristic during continuous rheo-extrusion. However, it is difficult to measure the actual melt temperature in the roll-shoe gap. In this work, based on the basic theory of heat transfer, a calculation model for heat transfer coefficient of cooling water/roll interface and melt/roll interface is established. In addition, the relationship between the temperature at the melt/roll interface and the velocity of cooling water is investigated. Combined with the CALPHAD calculation, the melt temperature during solidification in the continuous rheo-extrusion process is calculated. Using this model, the cooling rate of an Al–6Mg (wt.%) alloy melt prepared by continuous rheo-extrusion is estimated to be 10.3 K/s. This model used to determine the melt parameters during solidification provides a reference for optimizing the production process of continuous rheo-extrusion technology.
Multilayer Casting of Eco-Efficient Self-Compacting Concrete with Reduced Binder Content
Authors: Dybeł Piotr , Kucharska Milena
Published: September 2021

In the study, experiments were performed on two eco-efficient self-compacting concrete mixes of reduced binder content containing supplementary cementitious materials. The behaviour of the eco-efficient self-compacting concrete (SCC) mixture was examined to determine whether it is suitable for multilayer casting. It is recommended that the SCC should be poured in an uninterrupted manner. However, it is not uncommon that contractors are forced to take breaks as a result of delivery delays. Casting the elements in multiple poorly prepared layers may cause the creation of cold joints between them. Two technological variants of the multilayer casting of eco-efficient SCC on beam elements were analysed: pouring the mixture from a minor height on the previously placed layer and placing the subsequent layer on the mechanically disturbed surface of the underlying material. Different delay times were used: 15, 30, 45 and 60 min between the execution of two layers of eco-efficient SCC. The load-bearing capacity of the joint was determined using a splitting tensile strength test on cubic elements. It was observed that, regardless of the mixture and casting variant, the interlayer bond strength decreased as the delay time increased. This effect was less pronounced when the first layer was mechanically disturbed. It was also demonstrated that concrete with reduced binder content is characterized by a lower drop in bond strength between successive layers. Finally, it is noted that the current recommendations and normative guidelines for the multilayer casting of self-compacting concrete should be specified with regard to the time delay allowed for the execution of the next layer in the absence of interference with the previously placed layer. Lack of clarity in this respect may result in the creation of a cold joint and hence a reduction in the load-bearing capacity between layers.