bluuebunny/crossref_metadata_2025 huggingface dataset:
Nickel Sensitivity Is Associated with GH-IGF1 Axis Impairment and Pituitary Abnormalities on MRI in Overweight and Obese Subjects
Authors: Risi Renata , Masieri Simonetta , Poggiogalle Eleonora , Watanabe Mikiko , Caputi Alessandra , Tozzi Rossella , Gangitano Elena , Masi Davide , Mariani Stefania , Gnessi Lucio , Lubrano Carla
Published: December 2020

Nickel (Ni) is a ubiquitous metal, the exposure of which is implied in the development of contact dermatitis (nickel allergic contact dermatitis (Ni-ACD)) and Systemic Ni Allergy Syndrome (SNAS), very common among overweight/obese patients. Preclinical studies have linked Ni exposure to abnormal production/release of Growth Hormone (GH), and we previously found an association between Ni-ACD/SNAS and GH-Insulin-like growth factor 1 (IGF1) axis dysregulation in obese individuals, altogether suggesting a role for this metal as a pituitary disruptor. We herein aimed to directly evaluate the pituitary gland in overweight/obese patients with signs/symptoms suggestive of Ni allergy, exploring the link with GH secretion; 859 subjects with overweight/obesity and suspected of Ni allergy underwent Ni patch tests. Among these, 106 were also suspected of GH deficiency (GHD) and underwent dynamic testing as well as magnetic resonance imaging for routine follow up of benign diseases or following GHD diagnosis. We report that subjects with Ni allergies show a greater GH-IGF1 axis impairment, a higher prevalence of Empty Sella (ES), a reduced pituitary volume and a higher normalized T2 pituitary intensity compared to nonallergic ones. We hypothesize that Ni may be detrimental to the pituitary gland, through increased inflammation, thus contributing to GH-IGF1 axis dysregulation.
Endurance Exercise Mitigates Immunometabolic Adipose Tissue Disturbances in Cancer and Obesity
Authors: Rosa-Neto José Cesar , Silveira Loreana Sanches
Published: December 2020

Adipose tissue is considered an endocrine organ whose complex biology can be explained by the diversity of cell types that compose this tissue. The immune cells found in the stromal portion of adipose tissue play an important role on the modulation of inflammation by adipocytokines secretion. The interactions between metabolic active tissues and immune cells, called immunometabolism, is an important field for discovering new pathways and approaches to treat immunometabolic diseases, such as obesity and cancer. Moreover, physical exercise is widely known as a tool for prevention and adjuvant treatment on metabolic diseases. More specifically, aerobic exercise training is able to increase the energy expenditure, reduce the nutrition overload and modify the profile of adipocytokines and myokines with paracrine and endocrine effects. Therefore, our aim in this review was to cover the effects of aerobic exercise training on the immunometabolism of adipose tissue in obesity and cancer, focusing on the exercise-related modification on adipose tissue or immune cells isolated as well as their interaction.
Variations in Triterpenoid Deposition in Cuticular Waxes during Development and Maturation of Selected Fruits of Rosaceae Family
Authors: Dashbaldan Soyol , Pączkowski Cezary , Szakiel Anna
Published: December 2020

The process of fruit ripening involves many chemical changes occurring not only in the mesocarp but also in the epicarp, including changes in the triterpenoid content of fruit cuticular waxes that can modify the susceptibility to pathogens and mechanical properties of the fruit surface. The aim of the study was the determination of the ripening-related changes in the triterpenoid content of fruit cuticular waxes of three plant species from the Rosaceae family, including rugosa rose (Rosa rugosa), black chokeberry (Aronia melanocarpa var. “Galicjanka”) and apple (Malus domestica var. “Antonovka”). The triterpenoid and steroid content in chloroform-soluble cuticular waxes was determined by a GC-MS/FID method at four different phenological stages. The profile of identified compounds was rather similar in selected fruit samples with triterpenoids with ursane-, oleanane- and lupane-type carbon skeletons, prevalence of ursolic acid and the composition of steroids. Increasing accumulation of triterpenoids and steroids, as well as the progressive enrichment of the composition of these compounds in cuticular wax during fruit development, was observed. The changes in triterpenoid content resulted from modifications of metabolic pathways, particularly hydroxylation and esterification, that can alter interactions with complementary functional groups of aliphatic constituents and lead to important changes in fruit surface quality.
Chlorinated Guaiane-Type Sesquiterpene Lactones as Cytotoxic Agents against Human Tumor Cells
Authors: Estévez-Sarmiento Francisco , Saavedra Ester , Ruiz-Estévez Mercedes , León Francisco , Quintana José , Brouard Ignacio , Estévez Francisco
Published: December 2020

Guaiane-type sesquiterpene lactones are naturally occurring compounds which have attracted attention due to their array of biological activities. In this study, chlorinated guaianolides 1–8, isolated from plants of the genus Centaurea, were evaluated against the human leukemia cell lines HL-60, U-937, a specific U-937 cell line that overexpresses the anti-apoptotic Bcl-2 protein and the human melanoma cell line SK-MEL-1. This established the relevant structure-growth inhibition relationships. Chlorohyssopifolins A (1), C (3) and D (4) and linichlorin A (6) were the most potent compounds in terms of inducing growth inhibition in the four cell lines. IC50 values were below 10 μM in all cases. Chlorohyssopifolins A (1) and D (4) and linichlorin A (6) were potent apoptotic inducers in human U-937 leukemia cells, as determined by fluorescent microscopy and flow cytometry, and their mechanism of action was associated with cytochrome c release, caspase activation and poly(ADP-ribose)polymerase cleavage. Overall this study shows that guaianolides induce cytotoxicity against human tumor cells and provides important insights into the cell death pathways that are involved.
Non-Destructive Genotyping of Honeybee Queens to Support Selection and Breeding
Authors: Bubnič Jernej , Mole Katarina , Prešern Janez , Moškrič Ajda
Published: December 2020

In traditional bee breeding, the honeybee queen is chosen for breeding based on the performance of the colony produced by its mother. However, we cannot be entirely certain that a specific queen will produce offspring with desirable traits until we observe the young queen’s new colony. Collecting the queen’s genetic material enables quick and reliable determination of the relevant information. We sampled exuviae, feces, and wingtips for DNA extraction to avoid fatally injuring the queen when using tissue samples. Quantity and purity of extracted DNA were measured. Two mitochondrial markers were used to determine the lineage affiliation and exclude possible contamination of DNA extracts with non-honeybee DNA. dCAPS (derived Cleaved Amplified Polymorphic Sequences) markers allowed detection of single nucleotide polymorphisms (SNPs) in nuclear DNA regions presumably associated with Varroa sensitive hygiene and set the example of successful development of genotyping protocol from non-destructive DNA sources. One of the logical future steps in honeybee breeding is introducing genomic selection and non-destructive sampling methods of genetic material may be the prerequisite for successful genotyping. Our results demonstrate that the extraction of DNA from feces and exuviae can be introduced into practice. The advantage of these two sources over wingtips is reducing the time window for processing the samples, thus enabling genotyping directly after the queen’s emergence.
Patients with Single-Ventricle Physiology over the Age of 40 Years
Authors: Pujol Claudia , Schiele Sandra , Maurer Susanne J. , Hock Julia , Fritz Celina , Hager Alfred , Ewert Peter , Tutarel Oktay
Published: December 2020

Background: Single-ventricle physiology (SVP) is associated with significant morbidity and mortality at a young age. However, survival prospects have improved and risk factors for a negative outcome are well described in younger cohorts. Data regarding older adults is scarce. Methods: In this study, SVP patients under active follow-up at our center who were ≥40 years of age at any point between January 2005 and December 2018 were included. Demographic data, as well as medical/surgical history were retrieved from hospital records. The primary end-point was all-cause mortality. Results: Altogether, 49 patients (19 female (38.8%), mean age 49.2 ± 6.4 years) were included. Median follow-up time was 4.9 years (interquartile range (IQR): 1.8–8.5). Of these patients, 40 (81.6%) had undergone at least one cardiac surgery. The most common extracardiac comorbidities were thyroid dysfunction (n = 27, 55.1%) and renal disease (n = 15, 30.6%). During follow-up, 10 patients (20.4%) died. On univariate analysis, renal disease and liver cirrhosis were predictors of all-cause mortality. On multivariate analysis, only renal disease (hazard ratio (HR): 12.5, 95% confidence interval (CI): 1.5–106.3, p = 0.021) remained as an independent predictor. Conclusions: SVP patients ≥40 years of age are burdened with significant morbidity and mortality. Renal disease is an independent predictor of all-cause mortality.
Plasma Endocan as a Predictor of Cardiovascular Event in Patients with End-Stage Renal Disease on Hemodialysis
Authors: Kim Jin Sug , Ko Gang Jee , Kim Yang Gyun , Lee So Young , Lee Dong Young , Jeong Kyung Hwan , Lee Sang Ho
Published: December 2020

Endocan, a potential biomarker of endothelial dysfunction, is associated with increased cardiovascular risk. We investigated the utility of plasma endocan for predicting cardiovascular risk in end-stage renal disease (ESRD) patients undergoing hemodialysis. Of the 452 patients in the K-cohort, 354 with available plasma endocan levels were enrolled. The correlation between plasma endocan levels and the clinical characteristics of a study population were analyzed. We divided patients into two groups, according to plasma endocan levels, and investigated the predictive value of endocan for the occurrence of cardiovascular events. In a multiple linear regression analysis, plasma endocan levels were positively correlated with previous cardiovascular events and negatively correlated with body mass index, albumin, and triglyceride. Patients with higher plasma endocan levels experienced more frequent cardiovascular events than those with lower plasma endocan levels (12.9% in the lower group vs. 22.7% in the higher group, p = 0.016). Cox proportional hazard models showed that higher plasma endocan levels were an independent predictor of cardiovascular events in ESRD patients on hemodialysis ((hazard ration) HR 1.949, 95% (confidence interval) CI 1.144–3.319, p = 0.014). Our results suggest that plasma endocan level might be a useful biomarker for predicting cardiovascular events in ESRD patients on hemodialysis.
Comparisons of the Nonlinear Relationship of Cerebral Blood Flow Response and Cerebral Vasomotor Reactivity to Carbon Dioxide under Hyperventilation between Postural Orthostatic Tachycardia Syndrome Patients and Healthy Subjects
Authors: Lin Shyan-Lung , Yeh Shoou-Jeng , Chen Ching-Kun , Hsu Yu-Liang , Kuo Chih-En , Chen Wei-Yu , Hsieh Cheng-Pu
Published: December 2020

Postural orthostatic tachycardia syndrome (POTS) typically occurs in youths, and early accurate POTS diagnosis is challenging. A recent hypothesis suggests that upright cognitive impairment in POTS occurs because reduced cerebral blood flow velocity (CBFV) and cerebrovascular response to carbon dioxide (CO2) are nonlinear during transient changes in end-tidal CO2 (PETCO2). This novel study aimed to reveal the interaction between cerebral autoregulation and ventilatory control in POTS patients by using tilt table and hyperventilation to alter the CO2 tension between 10 and 30 mmHg. The cerebral blood flow velocity (CBFV), partial pressure of end-tidal carbon dioxide (PETCO2), and other cardiopulmonary signals were recorded for POTS patients and two healthy groups including those aged >45 years (Healthy-Elder) and aged <45 years (Healthy-Youth) throughout the experiment. Two nonlinear regression functions, Models I and II, were applied to evaluate their CBFV-PETCO2 relationship and cerebral vasomotor reactivity (CVMR). Among the estimated parameters, the curve-fitting Model I for CBFV and CVMR responses to CO2 for POTS patients demonstrated an observable dissimilarity in CBFVmax (p = 0.011), mid-PETCO2 (p = 0.013), and PETCO2 range (p = 0.023) compared with those of Healthy-Youth and in CBFVmax (p = 0.015) and CVMRmax compared with those of Healthy-Elder. With curve-fitting Model II for POTS patients, the fit parameters of curvilinear (p = 0.036) and PETCO2 level (p = 0.033) displayed significant difference in comparison with Healthy-Youth parameters; range of change (p = 0.042), PETCO2 level, and CBFVmax also displayed a significant difference in comparison with Healthy-Elder parameters. The results of this study contribute toward developing an early accurate diagnosis of impaired CBFV responses to CO2 for POTS patients.
Correlation between Fecal Calprotectin Levels in Meconium and Vitamin D Levels in Cord Blood: Association with Intestinal Distress
Authors: Jung Jae Hoon , Park Sook Hyun
Published: December 2020

We aimed to investigate the correlation between vitamin D status in cord blood and fecal calprotectin concentrations in meconium, and also find their association with intestinal distress symptoms during the first two weeks of life. Two hundred and twenty-eight newborns were enrolled in the study who were delivered at Kyungpook National University Children’s Hospital between July 2016 and August 2017. The first passed meconium samples were collected for fecal calprotectin analysis. Intestinal distress involved infants with necrotizing enterocolitis (NEC) and other feeding interruption signs. The median gestational age of the population was 37.0 (34.3–38.4) weeks, and the median birth weight was 2635 (2100–3268) g. The median fecal calprotectin levels in meconium were 134.1 (55.6–403.2) μg/g (range: 11.5–2000 μg/g) and the median 25-hydroxyvitamin D (25-OHD) concentrations in cord blood were 21.0 (15.5–28.8) ng/mL. Sixty infants (26.3%) had intestinal distress, including four patients (1.8%) diagnosed as having NEC. Higher fecal calprotectin concentrations (398.2 (131.8–900.2) μg/g vs. 105.6 (39.4–248.5) μg/g, p < 0.001) and lower 25-OHD levels (17.9 (12.8–22.1) ng/mL vs. 23.2 (17.2–33.0) ng/mL, p < 0.001) were found in infants with intestinal distress compared to infants without intestinal distress. The cut-off value was set at 359.8 μg/g with a sensitivity of 0.53 and a specificity of 0.82 for the development of intestinal distress in the first two weeks of life. Serum 25-OHD levels in cord blood were inversely correlated with fecal calprotectin concentrations in meconium.
Medicine and Phlebolymphology: Time to Change?
Authors: Cavezzi Attilio
Published: December 2020

Biomedical science is undergoing a reappraisal of its scientific advancement process and of the related healthcare management. Progress in medicine should combine improvements of knowledge, efficacy, and safety of diagnostic/therapeutic procedures, with adequate cost-effectiveness profiles. This narrative review is aimed at assessing in medicine, more specifically in phlebology and lymphology: (a) scientific literature possible biases, (b) the level of evidence, comprehensiveness, and cost-effectiveness of the main therapeutic options, and (c) the possible contribution of integrative and translational medicine. Current medical research may have cognitive biases, or industry-tied influences, which impacts clinical practice. Some reductionism, with an increasing use of drugs and technology, often neglecting the understanding and care of the root causative pathways of the diseases, is affecting biomedical science as well. Aging brings a relevant burden of chronic degenerative diseases and disabilities, with relevant socio-economic repercussions; thus, a major attention to cost-effectiveness and appropriateness of healthcare is warranted. In this scenario, costly and innovative but relatively validated therapies may tend to be adopted in venous and lymphatic diseases, such as varicose veins, leg venous ulcer, post-thrombotic syndrome, pelvic congestion syndrome, and lymphedema. Conversely, a more comprehensive approach to the basic pathophysiology of chronic venous and lymphatic insufficiency and the inclusion of pharmacoeconomics analyses would benefit overall patients’ management. Erroneous lifestyle and nutrition, together with chronic stress-induced syndromes, significantly influence chronic degenerative phlebo-lymphatic diseases. The main active epigenetic socio-biologic factors are obesity, dysfunctions of musculo-respiratory-vascular pumps, pro-inflammatory nutrition, hyperactivation of stress axis, and sedentarism. An overall critical view of the scientific evidence and innovations in phebolymphology could be of help to improve efficacy, safety, and sustainability of current practice. Translational and integrative medicine may contribute to a patient-centered approach. Conversely, reductionism, eminence/reimbursement-based decisional processes, patients’ lack of education, industry-influenced science, and physician’s improvable awareness, may compromise efficacy, safety, appropriateness, and cost-effectiveness of future diagnostic and therapeutic patterns of phlebology and lymphology.
Energy Metabolism Disturbances in Cell Models of PARK2 CNV Carriers with ADHD
Authors: Palladino Viola Stella , Chiocchetti Andreas G. , Frank Lukas , Haslinger Denise , McNeill Rhiannon , Radtke Franziska , Till Andreas , Haupt Simone , Brüstle Oliver , Günther Katharina , Edenhofer Frank , Hoffmann Per , Reif Andreas , Kittel-Schneider Sarah
Published: December 2020

The main goal of the present study was the identification of cellular phenotypes in attention-deficit-/hyperactivity disorder (ADHD) patient-derived cellular models from carriers of rare copy number variants (CNVs) in the PARK2 locus that have been previously associated with ADHD. Human-derived fibroblasts (HDF) were cultured and human-induced pluripotent stem cells (hiPSC) were reprogrammed and differentiated into dopaminergic neuronal cells (mDANs). A series of assays in baseline condition and in different stress paradigms (nutrient deprivation, carbonyl cyanide m-chlorophenyl hydrazine (CCCP)) focusing on mitochondrial function and energy metabolism (ATP production, basal oxygen consumption rates, reactive oxygen species (ROS) abundance) were performed and changes in mitochondrial network morphology evaluated. We found changes in PARK2 CNV deletion and duplication carriers with ADHD in PARK2 gene and protein expression, ATP production and basal oxygen consumption rates compared to healthy and ADHD wildtype control cell lines, partly differing between HDF and mDANs and to some extent enhanced in stress paradigms. The generation of ROS was not influenced by the genotype. Our preliminary work suggests an energy impairment in HDF and mDAN cells of PARK2 CNV deletion and duplication carriers with ADHD. The energy impairment could be associated with the role of PARK2 dysregulation in mitochondrial dynamics.
Surgical Stress Promotes Tumor Progression: A Focus on the Impact of the Immune Response
Authors: Onuma Amblessed E. , Zhang Hongji , Gil Lindsay , Huang Hai , Tsung Allan
Published: December 2020

Despite advances in systemic therapies, surgery is crucial for the management of solid malignancy. There is increasing evidence suggesting that the body’s response to surgical stress resulting from tumor resection has direct effects on tumor cells or can alter the tumor microenvironment. Surgery can lead to the activation of early and key components of the innate and adaptative immune systems. Platelet activation and the subsequent pro-coagulation state can accelerate the growth of micrometastases. Neutrophil extracellular traps (NETs), an extracellular network of DNA released by neutrophils in response to inflammation, promote the adhesion of circulating tumor cells and the growth of existing micrometastatic disease. In addition, the immune response following cancer surgery can modulate the tumor immune microenvironment by promoting an immunosuppressive state leading to impaired recruitment of natural killer (NK) cells and regulatory T cells (Tregs). In this review, we will summarize the current understanding of mechanisms of tumor progression secondary to surgical stress. Furthermore, we will describe emerging and novel peri-operative solutions to decrease pro-tumorigenic effects from surgery.
What Is the Diagnosis in Patients with Type 2 Diabetes Who Have a Painful Shoulder? Results from a Prospective Cross-Sectional Study
Authors: Alabdali Login , Jaeken Jasmien , van Alfen Nens , Dinant Geert-Jan , Borghans Rob , Ottenheijm Ramon
Published: December 2020

Background: Patients with diabetes mellitus have higher risk of developing shoulder pathology. However, only adhesive capsulitis is addressed in shoulder pain guidelines as a disorder associated with diabetes. Yet, patients with diabetes are at risk of having several other shoulder disorders, including focal neuropathy. Our aim was to quantify the presence of shoulder disorders using physical examination and ultrasound imaging in patients with type 2 diabetes (T2DM) suffering from shoulder pain in general practice. Methods: In this prospective cross-sectional study, patients with T2DM who had had a painful shoulder for at least four weeks were included. Patients filled out a questionnaire and underwent a physical examination of the shoulders and feet and ultrasound imaging of the shoulder. Results: A total of 66 patients were included, of whom 40.9% (n = 27) had bilateral complaints resulting in 93 symptomatic shoulders. Subacromial pain syndrome was most frequently diagnosed by physical examination (66.6%, 95% CI 51.6–72.0%; p < 0.0001), while ultrasound imaging showed that subacromial disorders were statistically significantly the most prevalent (90.3%, 95% CI 81.9–95.2%). Only two patients (3%) were diagnosed with neuropathic shoulder pain. Conclusion: When choosing treatment, general practitioners should be aware that in patients with T2DM the subacromial region is most frequently affected.
Is Ovarian Tissue Transplantation Safe in Patients with Central Nervous System Primitive Neuroectodermal Tumors?
Authors: Nguyen Thu Yen Thi , Camboni Alessandra , Masciangelo Rossella , Donnez Jacques , Dolmans Marie-Madeleine
Published: December 2020

The risk of reseeding malignancy harbored in cryopreserved and transplanted ovarian tissue has been a source of concern. This study aimed to determine the potential relationship between frozen–thawed ovarian tissue transplantation and primary cancer recurrence. Three patients with cerebral primitive neuroectodermal tumors (PNET) were included in this study. One woman gave birth to three healthy babies following reimplantation of her cryopreserved ovarian tissue, but subsequently died due to cancer relapse six years after ovarian tissue transplantation. The second subject died from progressive cancer, while the third is still alive and awaiting reimplantation of her ovarian tissue in due course. Frozen ovarian cortex from all three patients was analyzed and xenotransplanted to immunodeficient mice for five months. Main outcomes were the presence of cancer cells in the thawed and xenografted ovarian tissue at histology, immunostaining (expression of neuron-specific enolase and glial fibrillary acidic protein (GFAP)), and reverse-transcription droplet digital polymerase chain reaction (RT-ddPCR) (levels of enolase 2 and GFAP). In conclusion, no malignant cells were detected in ovarian tissue from patients with PNET, even in those who experienced recurrence of the disease, meaning that the risk of reseeding cancer cells with ovarian tissue transplantation in these patients can be considered low.
The Tryptophan System in Cocaine-Induced Depression
Authors: Fonseca Francina , Mestre-Pintó Joan-Ignasi , Gómez-Gómez Àlex , Martinez-Sanvisens Diana , Rodríguez-Minguela Rocío , Papaseit Esther , Pérez-Mañá Clara , Langohr Klaus , Valverde Olga , Pozo Óscar , Farré Magí , Torrens Marta ,   on behalf of NEURODEP GROUP
Published: December 2020

Major depression disorder (MDD) is the most prevalent psychiatric comorbid condition in cocaine use disorder (CUD). The comorbid MDD might be primary-MDD (CUD-primary-MDD) or cocaine-induced MDD (CUD-induced-MDD), and their accurate diagnoses and treatment is a challenge for improving prognoses. This study aimed to assess the tryptophan/serotonin (Trp/5-HT) system with the acute tryptophan depletion test (ATD), and the kynurenine pathway in subjects with CUD-primary-MDD, CUD-induced-MDD, MDD and healthy controls. The ATD was performed with a randomized, double-blind, crossover, and placebo-controlled design. Markers of enzymatic activity of indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase, kynurenine aminotransferase (KAT) and kynureninase were also established. Following ATD, we observed a decrease in Trp levels in all groups. Comparison between CUD-induced-MDD and MDD revealed significant differences in 5-HT plasma concentrations (512 + 332 ng/mL vs. 107 + 127 ng/mL, p = 0.039) and the Kyn/5-HT ratio (11 + 15 vs. 112 + 136; p = 0.012), whereas there were no differences between CUD-primary-MDD and MDD. Effect size coefficients show a gradient for all targeted markers (d range 0.72–1.67). Results suggest different pathogenesis for CUD-induced-MDD, with lower participation of the tryptophan system, probably more related to other neurotransmitter pathways and accordingly suggesting the need for a different pharmacological treatment approach.
AKR1C3 Is Associated with Better Survival of Patients with Endometrial Carcinomas
Authors: Hojnik Marko , Kenda Šuster Nataša , Smrkolj Špela , Frković Grazio Snježana , Verdenik Ivan , Rižner Tea Lanišnik
Published: December 2020

The aldo-keto reductase (AKR) superfamily is gaining attention in cancer research. AKRs are involved in important biochemical processes and have crucial roles in carcinogenesis and chemoresistance. The enzyme AKR1C3 has many functions, which include production of prostaglandins, androgens and estrogens, and metabolism of different chemotherapeutics; AKR1C3 is thus implicated in the pathophysiology of different cancers. Endometrial and ovarian cancers represent the majority of gynecological malignancies in developed countries. Personalized treatments for these cancers depend on identification of prognostic and predictive biomarkers that allow stratification of patients. In this study, we evaluated the immunohistochemical (IHC) staining of AKR1C3 in 123 paraffin-embedded samples of endometrial cancer and 99 samples of ovarian cancer, and examined possible correlations between expression of AKR1C3 and other clinicopathological data. The IHC expression of AKR1C3 was higher in endometrial cancer compared to ovarian cancer. In endometrioid endometrial carcinoma, high AKR1C3 IHC expression correlated with better overall survival (hazard ratio, 0.19; 95% confidence interval, 0.06−0.65, p = 0.008) and with disease-free survival (hazard ratio, 0.328; 95% confidence interval, 0.12–0.88, p = 0.027). In patients with ovarian cancer, there was no correlation between AKR1C3 IHC expression and overall and disease-free survival or response to chemotherapy. These results demonstrate that AKR1C3 is a potential prognostic biomarker for endometrioid endometrial cancer.
The Influence of Sex on Clinical Outcomes after Surgical Mitral Valve Replacement in Spain (2001–2015)
Authors: Muñoz-Rivas Nuria , López-de-Andrés Ana , Méndez-Bailón Manuel , Andrès Emmanuel , Hernández-Barrera Valentín , de Miguel-Yanes José María , Miguel-Díez Javier de , Lorenzo-Villalba Noel , Jiménez-García Rodrigo
Published: December 2020

(1) Background: Mitral regurgitation (MR) is the second most prevalent valvular heart disease in developed countries. Mitral valve (MV) disease is a common cause of heart failure and a leading cause of morbidity and mortality in the U.S.A. and Europe. (2) Methods: We performed a retrospective study using the Spanish National Hospital Discharge Database, 2001–2015. We included patients that had surgical mitral valve replacement (SMVR) listed as a procedure in their discharge report. We sought to (i) examine trends in incidence of SMVR among women and men in Spain, (ii) compare in-hospital outcomes for mechanical and bioprosthetic SMVR by sex, and (iii) identify factors associated with in-hospital mortality (IHM) after SMVR. (3) Results: We identified 44,340 hospitalizations for SMVR (84% mechanical, 16% bioprosthetic). The incidence of SMVR was higher in women (IRR 1.51; 95% CI 1.48–1.54). The use of mechanical SMVR decreased over time in both sexes and the use of bioprosthetic valves increased over time in both sexes. Men who underwent mechanical and bioprosthetic SMVR had higher comorbidity than women. IHM was significantly lower in women who underwent SMVR than in men (10% vs. 12% p < 0.001 for mechanical and 14% vs. 16% p = 0.025 for bioprosthetic valve, respectively). Major adverse cardiovascular and cerebrovascular events (MACCE) were also significantly lower in women who underwent mechanical and bioprosthetic SMVR. A significant reduction in both in-hospital MACCEs and IHM was observed over the study period regardless of sex. After multivariable logistic regression, male sex was associated with increased IHM only in bioprosthetic SMVR (OR 1.28; 95% CI 1.1–1.5). (4) Conclusions: This nationwide analysis over 15 years of sex-specific outcomes after SMVR showed that incidences are significantly higher in women than men for mechanical and bioprosthetic SMVR. IHM and MACCE have improved over time for SMVR in both sexes. Male sex was independently associated with higher mortality after bioprosthetic SMVR.
Expression of FFAR3 and FFAR4 Is Increased in Gastroesophageal Reflux Disease
Authors: Fabisiak Adam , Bartoszek Adrian , Talar Marcin , Binienda Agata , Dziedziczak Katarzyna , Krajewska Julia B. , Mosińska Paula , Niewinna Karolina , Tarasiuk Aleksandra , Mokrowiecka Anna , Wierzchniewska-Ławska Agnieszka , Małecka-Panas Ewa , Salaga Maciej , Fichna Jakub
Published: December 2020

Background: The negative impact of a high-fat diet on the course of gastroesophageal reflux disease (GERD) has been previously reported. Free fatty acid receptors (FFARs) may be mediators of this phenomenon. The aim of this study was to characterize the role of FFARs in the course of nonerosive (NERD) and erosive (ERD) reflux disease. Methods: Collectively, 73 patients (62 with GERD and 11 healthy controls (HCs)) were recruited to the study. Esophageal biopsies were drawn from the lower third of the esophagus and kept for further experiments. Quantitative, real-time polymerase chain reaction was used to assess the expression of FFAR1, FFAR2, FFAR3, and FFAR4 in biopsies. Histological evaluation of dilated intracellular spaces (DISs) was also performed. Results: FFAR3 exhibited the highest expression, and FFAR4 exhibited the lowest expression in all esophageal samples. Higher relative expression of FFAR1 and FFAR2 and significantly higher expression of FFAR3 (p = 0.04) was noted in patients with GERD compared to respective HCs. Patients with nonerosive GERD (NERD) presented higher expression of all FFARs compared to patients with erosive GERD (ERD) and respective HCs. Interestingly, in patients with ERD, the expression of FFAR3 was lower than in HCs. Significant, weak, positive correlation was found for FFAR3 and FFAR4 expression and DIS scores (r = 0.36, p < 0.05 for FFAR 3, and r = 0.39, p < 0.05 for FFAR4). Conclusions: In this study, we show that FFARs may play a role in GERD pathogenesis, particularly in the NERD type. It may be assumed that FFARs, in particular FFAR3 and FFAR4, may have diagnostic and therapeutic potential in GERD.
Fractal-Based Analysis of Bone Microstructure in Crohn’s Disease: A Pilot Study
Authors: Haschka Judith , Kraus Daniel Arian , Behanova Martina , Huber Stephanie , Bartko Johann , Schanda Jakob E. , Meier Philip , Bahrami Arian , Zandieh Shahin , Zwerina Jochen , Kocijan Roland
Published: December 2020

Crohn’s disease (CD) is associated with bone loss and increased fracture risk. TX-Analyzer™ is a new fractal-based technique to evaluate bone microarchitecture based on conventional radiographs. The aim of the present study was to evaluate the TX-Analyzer™ of the thoracic and lumbar spine in CD patients and healthy controls (CO) and to correlate the parameters to standard imaging techniques. 39 CD patients and 39 age- and sex-matched CO were analyzed. Demographic parameters were comparable between CD and CO. Bone structure value (BSV), bone variance value (BVV) and bone entropy value (BEV) were measured at the vertebral bodies of T7 to L4 out of lateral radiographs. Bone mineral density (BMD) and trabecular bone score (TBS) by dual energy X-ray absorptiometry (DXA) were compared to TX parameters. BSV and BVV of the thoracic spine of CD were higher compared to controls, with no difference in BEV. Patients were further divided into subgroups according to the presence of a history of glucocorticoid treatment, disease duration > 15 years and bowel resection. BEV was significantly lower in CD patients with these prevalent risk factors, with no differences in BMD at all sites. Additionally, TBS was reduced in patients with a history of glucocorticoid treatment. Despite a not severely pronounced bone loss in this population, impaired bone quality in CD patients with well-known risk factors for systemic bone loss was assessed by TX-Analyzer™.
Brain-Specific Biomarkers as Mortality Predictors after Aneurysmal Subarachnoid Haemorrhage
Authors: Kedziora Jaroslaw , Burzynska Malgorzata , Gozdzik Waldemar , Kübler Andrzej , Uryga Agnieszka , Kasprowicz Magdalena , Adamik Barbara
Published: December 2020

Aneurysmal subarachnoid haemorrhage (aSAH) is a serious condition with a high mortality and high permanent disability rate for those who survive the initial haemorrhage. The purpose of this study was to investigate markers specific to the central nervous system as potential in-hospital mortality predictors after aSAH. In patients with an external ventricular drain, enolase, S100B, and GFAP levels were measured in the blood and cerebrospinal fluid (CSF) on days 1, 2, and 3 after aSAH. Compared to survivors, non-survivors showed a significantly higher peak of S100B and enolase levels in the blood (S100B: 5.7 vs. 1.5 ng/mL, p = 0.031; enolase: 6.1 vs. 1.4 ng/mL, p = 0.011) and the CSF (S100B: 18.3 vs. 0.9 ng/mL, p = 0.042; enolase: 109.2 vs. 6.1 ng/mL, p = 0.015). Enolase showed the highest level of predictability at 1.8 ng/mL in the blood (AUC of 0.873) and 80.0 ng/mL in the CSF (AUC of 0.889). The predictive ability of S100B was also very good with a threshold of 5.7 ng/mL in the blood (AUC 0.825) and 4.5 ng/mL in the CSF (AUC 0.810). In conclusion, enolase and S100B, but not GFAP, might be suitable as biomarkers for the early prediction of in-hospital mortality after aSAH.
To Shunt or Not to Shunt Patients with Idiopathic Normal Pressure Hydrocephalus? A Reappraisal of an Old Question
Authors: Sahuquillo Juan , Poca Maria A.
Published: December 2020

The possibility that the cerebral ventricles can dilate without any increase in the pressure of the cerebrospinal fluid (CSF) was recognized in 1935 by Penfield who reported a patient in whom “…the cerebrospinal fluid spaces are closed and the ventricles progressively enlarge without the measured intraventricular pressure rising above 150 to 200 mm of water” [...]
A Real-World Comparative Analysis of Lenvatinib and Sorafenib as a Salvage Therapy for Transarterial Treatments in Unresectable HCC
Authors: Lee Jaejun , Sung Pil Soo , Yang Hyun , Lee Soon Kyu , Nam Hee Chul , Yoo Sun Hong , Lee Hae Lim , Kim Hee Yeon , Lee Sung Won , Kwon Jung Hyun , Jang Jeong Won , Kim Chang Wook , Nam Soon Woo , Bae Si Hyun , Choi Jong Young , Yoon Seung Kew
Published: December 2020

Background/Aims: Lenvatinib was recently approved as a first-line oral multikinase inhibitor for unresectable hepatocellular carcinoma (HCC). In this study, we aimed to compare the efficacy and safety of lenvatinib and sorafenib for the treatment of unresectable HCC in patients with prior failure of transarterial treatment. Methods: Between January 2019 and September 2020, 98 unresectable HCC patients treated with lenvatinib or sorafenib as salvage therapy were enrolled from five Korean university-affiliated hospitals. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate were calculated to assess the antitumor response. Results: A total of 43 and 55 patients were treated with lenvatinib and sorafenib, respectively, as salvage therapy after the failure of transarterial treatments. The median PFS was 4.97 months in the lenvatinib group and 2.47 months in the sorafenib group (p = 0.001, log-rank test). The ORR was significantly higher in the lenvatinib group (25.6%) than in the sorafenib group (3.6%, p = 0.002). Use of lenvatinib over sorafenib (hazard ratio: 0.359, 95% confidence interval: 0.203–0.635, p < 0.001) was the most significant factor for a favorable PFS after the failure of transarterial treatments in all enrolled patients. For favorable OS, achieving objective response was the significant factor (hazard ratio 0.356, 95% confidence interval: 0.132–0.957, p = 0.041). There were no significant differences in the safety profile between the two groups. Conclusions: In this real-world study, lenvatinib was demonstrated to be more efficacious than sorafenib as a salvage therapy for transarterial treatments in unresectable HCC.
The Role of Bone Scintigraphy with SPECT/CT in the Characterization and Early Diagnosis of Stage 0 Charcot Neuroarthropathy
Authors: Ahluwalia Raju , Bilal Ahmad , Petrova Nina , Boddhu Krishna , Manu Chris , Vas Prashanth , Bates Maureen , Corcoran Ben , Reichert Ines , Mulholland Nicola , Kavarthapu Venu , Vivian Gill , Edmonds Michael
Published: December 2020

We describe the use of Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) in the investigation and diagnosis of Charcot neuroarthropathy (CN) in patients with a hot swollen foot but normal radiographs and clinical suspicion of CN, usually termed Stage 0. This was a retrospective cohort review of 46 diabetes patients who underwent 3 phase bone scintigraphy with “High Resolution” SPECT/CT. The imaging demonstrated that Stage 0 Charcot foot has a distinct bone pathology, which can be classified into three groups: (1) fractures on Computed Tomography (CT) with accompanying focal uptake of tracer on SPECT, (2) bony abnormalities apart from fracture on CT with focal uptake of tracer on SPECT, and (3) normal CT but focal bony uptake of tracer on SPECT. The CT component of SPECT/CT detected bony fractures in 59% of patients. Early treatment with below knee cast and follow-up for 24 months showed only 4 patients who developed Stage 1 Eichenholtz Charcot foot. Our findings support the use of 3 phase bone scintigraphy with SPECT/CT in the characterization and early diagnosis of CN. Stage 0 Charcot foot has a distinct bone pathology which requires urgent treatment to prevent progression to Stage 1 Eichenholtz Charcot foot. If SPECT/CT is unavailable, CT alone will detect bone fracture in 59% patients.
Can Proteomics Be Considered as a Valuable Tool to Assess the Toxicity of Nanoparticles in Marine Bivalves?
Authors: De Felice Beatrice , Parolini Marco
Published: December 2020

Exposure to nanoparticles (NPs) has been identified as a major concern for marine ecosystems. Because of their peculiar physico-chemical features, NPs are accumulated in marine organisms, which suffer a variety of adverse effects. In particular, bivalve mollusks represent a unique target for NPs, mainly because they are suspension-feeders with highly developed processes for cellular internalization of nano- and micrometric particles. Several studies have demonstrated that the uptake and the accumulation of NPs can induce sub-lethal effects towards marine bivalves. However, to understand the real risk of NP exposures the application of the so-called “omics” techniques (e.g., proteomics, genomics, metabolomics, lipidomics) has been suggested. In particular, proteomics has been used to study the effects of NPs and their mechanism(s) of action in marine bivalves, but to date its application is still limited. The present review aims at summarizing the state of the art concerning the application of proteomics as a tool to investigate the effects of nanoparticles on the proteome of marine bivalves, and to critically discuss the advantages and limitations of proteomics in this field of research. Relying on results obtained by studies that applied proteomics on bivalve tissues, proteomics application needs to be considered cautiously as a promising and valuable tool to shed light on toxicity and mechanism(s) of action of NPs. Although on one hand, the analysis of the current literature demonstrated undeniable strengths, potentiality and reliability of proteomics, on the other hand a number of limitations suggest that some gaps of knowledge need to be bridged, and methodological and technical improvements are necessary before proteomics can be readily and routinely applied to nanotoxicology studies.
Numerical Study on Wave Radiation by a Barge with Large Amplitudes and Frequencies
Authors: Li Yajie , Long Yun
Published: December 2020

A two-dimensional boundary element method is used to study the hydrodynamics of a single barge with prescribed motions of large amplitudes and high frequencies. The wave radiation problem is solved in the time domain based on the fully nonlinear potential flow theory. For numerical simulations, special treatments like plunging wave cutting and remeshing approaches are presented in detail. The numerical schemes are verified through comparing with analytical results. Both the generated outgoing wave amplitudes and hydrodynamic coefficients can be calculated with sufficient accuracy. Then, we focus on large heave, sway and roll motions to investigate the nonlinear effects on hydrodynamic forces, respectively. In particular, the heave motion with two frequencies is also simulated to study the interactions between results at different frequencies. It is interesting to see the sum and difference frequency components and the envelopes in time histories as a result. For forces caused by forced sway or roll motions, there are only even-order harmonics for vertical forces and only odd-order harmonics for horizontal forces. Finally, a single body with combined sway, heave and roll motion is studied to examine the interactions between motion modes.
An Operational Supporting System for Oil Spill Emergencies Addressed to the the Italian Coast Guard
Authors: Sorgente Roberto , La Guardia Dario , Ribotti Alberto , Arrigo Marco , Signa Alessandro , Pessini Federica , Oliva Gennaro , Pes Andrea , Perilli Angelo , Di Maio Antonia
Published: December 2020

Oil spill models are used to simulate the evolution of an oil slick that occurs after an accidental ship collision, malfunctioning of oil extraction platforms, or illegal discharges intentionally released by ships into the marine environment. We present an integrated operational oil spill prediction system that improves capacities in preventing and mitigating maritime risks from oil spills. The objective is to provide forecast information about the transport and the fate of a hypothetical oil spill under Nearly-Real Time hydrodynamic conditions in the western and central Mediterranean Sea. This complex forecast system is developed in the framework of the project SOS-Piattaforme & Impatti Off-Shore to the needs of Italian Coast Guard and other institutions, such as the Ministry of the Environment. This service has been operational since July 2020. The innovative aspect of this work is a graphical user interface (the GUI), which allows to select properties, time, and location of a potential oil spill and show the evolution of oil slick concentration and oil fate parameters. This platform represents the first component of a future Decision Support System aimed to identify the risk assessment of oil spills in order to better manage emergencies and minimize economic damages.
The Tidal Stream Energy Resource of the Fromveur Strait—A Review
Authors: Guillou Nicolas , Charpentier Jean-Frédéric , Benbouzid Mohamed
Published: December 2020

Refined assessments of the available tidal stream energy resource are required to optimize turbines design and guarantee successful implementations and operations of devices in the marine environment. Investigations primary focused on identifying areas with maximum current speeds. However, further information may be reached by exhibiting (i) resource temporal variability, (ii) superimposed effects of meteo-oceanographic conditions (including especially wind-generated surface-gravity waves), and (iii) potential environmental impacts of operating turbines at the regional (e.g., changes in sediment transport and surrounding seabed features, effects on marine water quality, etc.) and local (wake-wake interactions and energy output) scales. These aspects are here investigated by reviewing a series of research studies dedicated to the Fromveur Strait off western Brittany, a region with strong potential for tidal array development along the coast of France. Particular attention is dedicated to the exploitation of combined in-situ and remote-sensing observations and numerical simulations. Beyond a site specific characterization of the tidal stream energy resource, this review promotes a series of original approaches and analysis methods for turbines optimization, thus complementing technical specifications to secure the key steps of a tidal energy project and promote the growth of a reliable tidal stream energy exploitation.