bluuebunny/crossref_metadata_2025 huggingface dataset:
Microalgal Biorefinery Concepts’ Developments for Biofuel and Bioproducts: Current Perspective and Bottlenecks
Authors: Sivaramakrishnan Ramachandran , Suresh Subramaniyam , Kanwal Simab , Ramadoss Govindarajan , Ramprakash Balasubramani , Incharoensakdi Aran
Published: February 2022

Microalgae have received much interest as a biofuel feedstock. However, the economic feasibility of biofuel production from microalgae does not satisfy capital investors. Apart from the biofuels, it is necessary to produce high-value co-products from microalgae fraction to satisfy the economic aspects of microalgae biorefinery. In addition, microalgae-based wastewater treatment is considered as an alternative for the conventional wastewater treatment in terms of energy consumption, which is suitable for microalgae biorefinery approaches. The energy consumption of a microalgae wastewater treatment system (0.2 kW/h/m3) was reduced 10 times when compared to the conventional wastewater treatment system (to 2 kW/h/m3). Microalgae are rich in various biomolecules such as carbohydrates, proteins, lipids, pigments, vitamins, and antioxidants; all these valuable products can be utilized by nutritional, pharmaceutical, and cosmetic industries. There are several bottlenecks associated with microalgae biorefinery. Hence, it is essential to promote the sustainability of microalgal biorefinery with innovative ideas to produce biofuel with high-value products. This review attempted to bring out the trends and promising solutions to realize microalgal production of multiple products at an industrial scale. New perspectives and current challenges are discussed for the development of algal biorefinery concepts.
Molecular Fingerprint of BMD Patients Lacking a Portion in the Rod Domain of Dystrophin
Authors: Capitanio Daniele , Moriggi Manuela , Barbacini Pietro , Torretta Enrica , Moroni Isabella , Blasevich Flavia , Morandi Lucia , Mora Marina , Gelfi Cecilia
Published: February 2022

BMD is characterized by a marked heterogeneity of gene mutations resulting in many abnormal dystrophin proteins with different expression and residual functions. The smaller dystrophin molecules lacking a portion around exon 48 of the rod domain, named the D8 region, are related to milder phenotypes. The study aimed to determine which proteins might contribute to preserving muscle function in these patients. Patients were subdivided, based on the absence or presence of deletions in the D8 region, into two groups, BMD1 and BMD2. Muscle extracts were analyzed by 2-D DIGE, label-free LC-ESI-MS/MS, and Ingenuity pathway analysis (IPA). Increased levels of proteins typical of fast fibers and of proteins involved in the sarcomere reorganization characterize BMD2. IPA of proteomics datasets indicated in BMD2 prevalence of glycolysis and gluconeogenesis and a correct flux through the TCA cycle enabling them to maintain both metabolism and epithelial adherens junction. A 2-D DIGE analysis revealed an increase of acetylated proteoforms of moonlighting proteins aldolase, enolase, and glyceraldehyde-3-phosphate dehydrogenase that can target the nucleus promoting stem cell recruitment and muscle regeneration. In BMD2, immunoblotting indicated higher levels of myogenin and lower levels of PAX7 and SIRT1/2 associated with a set of proteins identified by proteomics as involved in muscle homeostasis maintenance.
Anthocyanin-Rich Vegetables for Human Consumption—Focus on Potato, Sweetpotato and Tomato
Authors: Mattoo Autar K. , Dwivedi Sangam L. , Dutt Som , Singh Brajesh , Garg Monika , Ortiz Rodomiro
Published: February 2022

Malnutrition, unhealthy diets, and lifestyle changes have become major risk factors for non-communicable diseases while adversely impacting economic growth and sustainable development. Anthocyanins, a group of flavonoids that are rich in fruits and vegetables, contribute positively to human health. This review focuses on genetic variation harnessed through crossbreeding and biotechnology-led approaches for developing anthocyanins-rich fruit and vegetable crops. Significant progress has been made in identifying genes involved in anthocyanin biosynthesis in various crops. Thus, the use of genetics has led to the development and release of anthocyanin-rich potato and sweet potato cultivars in Europe and the USA. The purple potato ’Kufri Neelkanth’ has been released for cultivation in northern India. In Europe, the anthocyanin-rich tomato cultivar ‘Sun Black’ developed via the introgression of Aft and atv genes has been released. The development of anthocyanin-rich food crops without any significant yield penalty has been due to the use of genetic engineering involving specific transcription factors or gene editing. Anthocyanin-rich food ingredients have the potential of being more nutritious than those devoid of anthocyanins. The inclusion of anthocyanins as a target characteristic in breeding programs can ensure the development of cultivars to meet the nutritional needs for human consumption in the developing world.
An Efficient Way to Screen Inhibitors of Energy-Coupling Factor (ECF) Transporters in a Bacterial Uptake Assay
Authors: Bousis Spyridon , Winkler Steffen , Haupenthal Jörg , Fulco Francesco , Diamanti Eleonora , Hirsch Anna K. H.
Published: February 2022

Herein, we report a novel whole-cell screening assay using Lactobacillus casei as a model microorganism to identify inhibitors of energy-coupling factor (ECF) transporters. This promising and underexplored target may have important pharmacological potential through modulation of vitamin homeostasis in bacteria and, importantly, it is absent in humans. The assay represents an alternative, cost-effective and fast solution to demonstrate the direct involvement of these membrane transporters in a native biological environment rather than using a low-throughput in vitro assay employing reconstituted proteins in a membrane bilayer system. Based on this new whole-cell screening approach, we demonstrated the optimization of a weak hit compound (2) into a small molecule (3) with improved in vitro and whole-cell activities. This study opens the possibility to quickly identify novel inhibitors of ECF transporters and optimize them based on structure–activity relationships.
Molecular Interactions of Tannic Acid with Proteins Associated with SARS-CoV-2 Infectivity
Authors: Haddad Mohamed , Gaudreault Roger , Sasseville Gabriel , Nguyen Phuong Trang , Wiebe Hannah , Van De Ven Theo , Bourgault Steve , Mousseau Normand , Ramassamy Charles
Published: February 2022

The overall impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on our society is unprecedented. The identification of small natural ligands that could prevent the entry and/or replication of the coronavirus remains a pertinent approach to fight the coronavirus disease (COVID-19) pandemic. Previously, we showed that the phenolic compounds corilagin and 1,3,6-tri-O-galloyl-β-D-glucose (TGG) inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 target receptor on the cell membrane of the host organism. Building on these promising results, we now assess the effects of these phenolic ligands on two other crucial targets involved in SARS-CoV-2 cell entry and replication, respectively: transmembrane protease serine 2 (TMPRSS2) and 3-chymotrypsin like protease (3CLpro) inhibitors. Since corilagin, TGG, and tannic acid (TA) share many physicochemical and structural properties, we investigate the binding of TA to these targets. In this work, a combination of experimental methods (biochemical inhibition assays, surface plasmon resonance, and quartz crystal microbalance with dissipation monitoring) confirms the potential role of TA in the prevention of SARS-CoV-2 infectivity through the inhibition of extracellular RBD/ACE2 interactions and TMPRSS2 and 3CLpro activity. Moreover, molecular docking prediction followed by dynamic simulation and molecular mechanics Poisson–Boltzmann surface area (MMPBSA) free energy calculation also shows that TA binds to RBD, TMPRSS2, and 3CLpro with higher affinities than TGG and corilagin. Overall, these results suggest that naturally occurring TA is a promising candidate to prevent and inhibit the infectivity of SARS-CoV-2.
A Machine Learning-Based Method for Content Verification in the E-Commerce Domain
Authors: Alexakis Theodoros , Peppes Nikolaos , Demestichas Konstantinos , Adamopoulou Evgenia
Published: February 2022

Analysis of extreme-scale data is an emerging research topic; the explosion in available data raises the need for suitable content verification methods and tools to decrease the analysis and processing time of various applications. Personal data, for example, are a very valuable source of information for several purposes of analysis, such as marketing, billing and forensics. However, the extraction of such data (referred to as person instances in this study) is often faced with duplicate or similar entries about persons that are not easily detectable by the end users. In this light, the authors of this study present a machine learning- and deep learning-based approach in order to mitigate the problem of duplicate person instances. The main concept of this approach is to gather different types of information referring to persons, compare different person instances and predict whether they are similar or not. Using the Jaro algorithm for person attribute similarity calculation and by cross-examining the information available for person instances, recommendations can be provided to users regarding the similarity or not between two person instances. The degree of importance of each attribute was also examined, in order to gain a better insight with respect to the declared features that play a more important role.
The Supercooling Responses of the Solitary Bee Osmia excavata (Hymenoptera: Megachilidae) under the Biological Stress of Its Brood Parasite, Sapyga coma (Hymenoptera: Sapygidae)
Authors: Yan Zhuo , Wang Lina , Reddy Gadi V. P. , Gu Shimin , Men Xingyuan , Xiao Yunli , Su Jianwei , Ge Feng , Ouyang Fang
Published: February 2022

(1) Background: Many insects have evolved different strategies to adapt to subzero temperatures and parasites, but the supercooling response of pollinator populations under the brood parasitism pressure has not been sufficiently investigated. (2) Methods: This study assessed the supercooling traits (supercooling points, fresh weight and fat content) of the solitary bee Osmia excavata Alfken and its brood parasite, Sapyga coma Yasumatsu & Sugihara. We measured 4035 samples (3025 O. excavata and 1010 S. coma, one individual as one sample) and discovered the supercooling traits relations between solitary bee and brood parasite. (3) Results: Significant differences in the supercooling points were found between O. excavata (females: −24.18 (−26.02~−20.07) vs. males: −23.21 (−25.15~−18.65) °C) and S. coma (females: −22.19 (−25.46~−18.38) vs. males: −20.65 (−23.85~−16.15) °C, p < 0.0001) in the same sex, and also between sexes of same species. The two species’ supercooling traits (supercooling points, fresh weight, and fat content) were significantly positively correlated. The supercooling points of the solitary bee varies regularly under brood parasitism pressure. (4) Conclusions: Our study indicates the supercooling traits relationships between a solitary bee and its brood parasite and suggests that the supercooling points of the solitary bee increase under the biological stress of its brood parasite in a certain level.
Correction: Majeed, A.; Lee, S. Towards Privacy Paradigm Shift Due to the Pandemic: A Brief Perspective. Inventions 2021, 6, 24
Authors: Majeed Abdul , Lee Sungchang
Published: February 2022

The authors made a mistake while publishing this paper [...]
Higher Levels of Stress-Related Hair Steroid Hormones Are Associated with the Increased SCORE2 Risk Prediction Algorithm in Apparently Healthy Women
Authors: Mazgelytė Eglė , Burokienė Neringa , Vysocka Agata , Narkevičius Martynas , Petrėnas Tomas , Kaminskas Andrius , Songailienė Jurgita , Utkus Algirdas , Karčiauskaitė Dovilė
Published: February 2022

Cardiovascular diseases (CVDs) are the major cause of death worldwide. Although the importance of conventional CVD risk factors, including older age, male gender, hypertension, obesity, dyslipidemia and hyperglycemia, is well-studied, psychosocial stress, which is considered an independent CVD risk factor, requires further investigation. Thus, we aimed to investigate the association between long-term secretion of stress-related steroid hormones, including cortisol, cortisone and dehydroepiandrosterone, and the 10-year fatal and non-fatal CVD risk estimated by the SCORE2 risk prediction algorithm, as well as traditional CVD risk factors in a group of apparently healthy women. A total of 145 women (aged 50–64 years) participating in the national CVD prevention program were enrolled in the study. Sociodemographic, lifestyle, health-related characteristics, stress, anxiety and sleep quality indicators were evaluated using specific questionnaires. Anthropometric and arterial blood pressure measures were assessed by trained personnel, lipid and glucose metabolism biomarkers were measured using routine methods, and hair steroid hormone levels were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry. The results showed that higher levels of hair cortisol and cortisone are associated with increased SCORE2 values. Moreover, significant associations between hair glucocorticoids and individual cardiovascular risk factors, including obesity, hypertension, dyslipidemia and hyperglycemia, were found. These findings indicate that stress-related hair steroid hormones might be valuable biomarkers for CVD prediction and prevention.
The Role of Extracellular Matrix Proteins in Breast Cancer
Authors: Lepucki Arkadiusz , Orlińska Kinga , Mielczarek-Palacz Aleksandra , Kabut Jacek , Olczyk Pawel , Komosińska-Vassev Katarzyna
Published: February 2022

The extracellular matrix is a structure composed of many molecules, including fibrillar (types I, II, III, V, XI, XXIV, XXVII) and non-fibrillar collagens (mainly basement membrane collagens: types IV, VIII, X), non-collagenous glycoproteins (elastin, laminin, fibronectin, thrombospondin, tenascin, osteopontin, osteonectin, entactin, periostin) embedded in a gel of negatively charged water-retaining glycosaminoglycans (GAGs) such as non-sulfated hyaluronic acid (HA) and sulfated GAGs which are linked to a core protein to form proteoglycans (PGs). This highly dynamic molecular network provides critical biochemical and biomechanical cues that mediate the cell–cell and cell–matrix interactions, influence cell growth, migration and differentiation and serve as a reservoir of cytokines and growth factors’ action. The breakdown of normal ECM and its replacement with tumor ECM modulate the tumor microenvironment (TME) composition and is an essential part of tumorigenesis and metastasis, acting as key driver for malignant progression. Abnormal ECM also deregulate behavior of stromal cells as well as facilitating tumor-associated angiogenesis and inflammation. Thus, the tumor matrix modulates each of the classically defined hallmarks of cancer promoting the growth, survival and invasion of the cancer. Moreover, various ECM-derived components modulate the immune response affecting T cells, tumor-associated macrophages (TAM), dendritic cells and cancer-associated fibroblasts (CAF). This review article considers the role that extracellular matrix play in breast cancer. Determining the detailed connections between the ECM and cellular processes has helped to identify novel disease markers and therapeutic targets.
Diagnosis of Congenital Uterine Abnormalities: Practical Considerations
Authors: Jayaprakasan Kanna , Ojha Kamal
Published: February 2022

As most congenital uterine abnormalities are asymptomatic, the majority of them are detected incidentally. While most women with uterine anomalies have a normal reproductive outcome, some may experience adverse reproductive outcomes. Accurate diagnosis and correct classification help in the appropriate counselling of women about their potential reproductive prognosis and risks and for planning any intervention. Evaluation of the internal and external contours of the uterus is the key in making a diagnosis and correctly classifying a uterine anomaly. Considering this, the gold standard test has been the combined laparoscopy and hysteroscopy historically, albeit invasive. However, 3D ultrasound has now become the diagnostic modality of choice for uterine anomalies due to its high degree of diagnostic accuracy, less invasive nature and it being comparatively less expensive. While 2D ultrasound and HSG are adequate for screening for uterine anomalies, MRI and combined laparoscopy and hysteroscopy are reserved for diagnosing complex Mullerian anomalies. Imaging for renal anomalies is recommended if a uterine anomaly is diagnosed.
Are Differences in Inflammatory Markers between Patients with and without Hypertension-Mediated Organ Damage Influenced by Circadian Blood Pressure Abnormalities?
Authors: Vazquez-Agra Nestor , Marques-Afonso Ana-Teresa , Cruces-Sande Anton , Novo-Veleiro Ignacio , Lopez-Paz Jose-Enrique , Pose-Reino Antonio , Hermida-Ameijeiras Alvaro
Published: February 2022

We aimed to explore the influence that the circadian blood pressure (BP) profile could exert on the correlation between some inflammatory markers and hypertension-mediated organ damage (HMOD). This was a cross-sectional study that included patients with primary arterial hypertension older than 18 years old. We included some parameters of 24 h ambulatory blood pressure monitoring collection and several inflammatory markers, as follows: platelet count (PTC), erythrocyte sedimentation rate (ESR), ultrasensitive C-reactive-protein, ferritin, fibrinogen, and uric acid. Myocardial hypertrophy, albuminuria, carotid intima-media thicknesses and ankle brachial index were assessed as HMOD presentations. Individuals were divided into two groups: patients with and without HMOD. We included 522 patients (47% women, mean age of 54 years). Multivariate logistic regression analysis showed that male patients older than 50 years old with uric acid levels above 7 mg/dL, ESR higher than 20 mm/h, fibrinogen greater than 320 mg/dL and PTC lower than 275 × 103/µL were associated with HMOD (p < 0.05). The circadian BP profile (dipper versus non-dipper pattern) did reach neither statistical significance nor influence the odds ratio of those inflammatory markers for HMOD. We found that differences in some inflammatory markers between patients with and without HMOD were not explained by a different circadian BP profile.
Chronic Plaque Psoriasis in Poland: Disease Severity, Prevalence of Comorbidities, and Quality of Life
Authors: Purzycka-Bohdan Dorota , Kisielnicka Anna , Zabłotna Monika , Nedoszytko Bogusław , Nowicki Roman J. , Reich Adam , Samotij Dominik , Szczęch Justyna , Krasowska Dorota , Bartosińska Joanna , Narbutt Joanna , Lesiak Aleksandra , Barasińska Paulina , Owczarczyk-Saczonek Agnieszka , Czerwińska Joanna , Szepietowski Jacek C. , Batycka-Baran Aleksandra , Czajkowski Rafał , Górecka-Sokołowska Magdalena , Rudnicka Lidia , Czuwara Joanna , Sobalska-Kwapis Marta , Strapagiel Dominik , Szczerkowska-Dobosz Aneta
Published: February 2022

The epidemiology of psoriasis has not been widely assessed in Polish population so far. This study aimed to investigate psoriasis epidemiological situation by evaluating disease course and severity, management, comorbidities, environmental factors, and knowledge about this disorder among psoriatic patients in Poland. A cross-sectional cohort population-based study enrolled 1080 psoriatic patients and 1200 controls. The mean age of psoriasis onset was 27.6 years; 78.24% had type I psoriasis. Positive family history of psoriasis was reported in 44.81% of patients, whereas itch was reported in vast majority of patients (83.33%). Based on PASI score moderate psoriasis was the most common in studied group (mean 12.63 ± 9.33, range 0–67.2). The DLQI score (12.01 ± 7.41, range 0–30.0) indicated a very large effect of psoriasis on the quality of life. Hypertension was the most prevalent comorbidity (33.80%), followed by obesity (16.85%) and dyslipidemia (11.85%). Stress was the foremost cause of disease exacerbation (66.20%); however, infections (44.07%) and seasonal changes (45.09%) had also an impact on the course of psoriasis. Psoriatic patients were more often smokers (37.59%) vs. general population (27.50%; p < 0.0001). In conclusion, epidemiological studies help clinicians in better disease and patient understanding, which may translate into better management and patient compliance.
Regular School Sport versus Dedicated Physical Activities for Body Posture—A Prospective Controlled Study Assessing the Sagittal Plane in 7–10-Year-Old Children
Authors: Kozinoga Mateusz , Stoliński Łukasz , Korbel Krzysztof , Politarczyk Katarzyna , Janusz Piotr , Kotwicki Tomasz
Published: February 2022

Body posture develops during the growing period and can be documented using trunk photography. The study aims to evaluate the body posture in children aged 7–10 years undergoing a dedicated physical activities program versus regular school sport. A total of 400 children, randomly chosen from a cohort of 9300 participating in a local scoliosis screening program, were evaluated twice at a one-year interval. A total of 167 children were involved in regular school sport (control group), while 233 received both school sport and a dedicated physical activities program (intervention group). Standardized photographic habitual body posture examination was performed at enrollment (T0) and one-year after (T1). Sacral slope (SS), lumbar lordosis (LL), thoracic kyphosis (TK), chest inclination (CI), and head protraction (HP) were measured. At T0, the body posture parameters did not differ between groups. At T1 in the controls, all five parameters tended to deteriorate (insignificant): SS p = 0.758, LL p = 0.38, TK p = 0.328, CI p = 0.081, and HP p = 0.106. At T1 in the intervention group, the SS decreased (p = 0.001), the LL tended to decrease (p = 0.0602), and the TK, CI, and HP remained unaltered. At T1, the SS and LL parameter differed between groups statistically (p = 0.0002 and p = 0.0064, respectively) and clinically (2.52° and 2.58°, respectively). In 7–10-year-old children, participation in dedicated physical activities tends to improve their body posture compared to regular school sport.
Extracorporeal Membrane Oxygenation in Infarct-Related Cardiogenic Shock
Authors: Freund Anne , Desch Steffen , Pöss Janine , Sulimov Dmitry , Sandri Marcus , Majunke Nicolas , Thiele Holger
Published: February 2022

Mortality in infarct-related cardiogenic shock (CS) remains high, reaching 40–50%. In refractory CS, active mechanical circulatory support devices including veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are rapidly evolving. However, supporting evidence of VA-ECMO therapy in infarct-related CS is low. The current review aims to give an overview on the basics of VA-ECMO therapy, current evidence, ongoing trials, patient selection and potential complications.
Tumor Microenvironment and Microvascular Density in Follicular Lymphoma
Authors: Tamma Roberto , Ingravallo Giuseppe , Annese Tiziana , Gaudio Francesco , Perrone Tommasina , Musto Pellegrino , Specchia Giorgina , Ribatti Domenico
Published: February 2022

Follicular lymphoma (FL) is a slowly progressive disease and constitutes the second most common non-Hodgkin lymphoma. Biological factors, such as the tumor microenvironment and the host response, are determinants in the outcome of FL but the experimental data about microenvironment and tumor cells in FL are variable and contradictory. In this morphometric study, we analyzed by immunohistochemistry the cellular components of the tumor microenvironment and correlated these data with the microvascular vascular density in three different grades of FL lymph node biopsies, comparing the results to healthy lymph node controls. The results indicated a significant increase in the number of CD68+ and CD163+ macrophages in all three analyzed FL grades. Tryptase+ mast cells resulted in an increase only in grade 1. PDL-1+ cells, CD4- and CD8-lymphocytes number results were reduced in FL samples. The higher number of CD34+ microvessels in the FL grades 1 and 2 of samples positively correlated with CD68+ and CD163+ cells, underlining the important angiogenic potential of this subset of macrophages.
Superiority of a Novel Multifunctional Amorphous Hydrogel Containing Olea europaea Leaf Extract (EHO-85) for the Treatment of Skin Ulcers: A Randomized, Active-Controlled Clinical Trial
Authors: Verdú-Soriano José , de Cristino-Espinar Marisol , Luna-Morales Silvia , Dios-Guerra Caridad , Caballero-Villarraso Javier , Moreno-Moreno Paloma , Casado-Díaz Antonio , Berenguer-Pérez Miriam , Guler-Caamaño Ipek , Laosa-Zafra Olga , Rodríguez-Mañas Leocadio , Lázaro-Martínez José Luis
Published: February 2022

This 8-week, multicenter, randomized, active-controlled, observer-blinded clinical trial was designed to demonstrate the accelerating effect on wound healing of the novel Olea europaea leaf extract hydrogel (EHO-85) by comparing it to a widely used amorphous hydrogel. Results showed that EHO-85 significantly accelerated wound healing, regardless of ulcer etiology (pressure, venous leg or diabetic foot) and prognosis, doubling the median wound area reduction compared with a reference amorphous hydrogel (79.4% vs. 39.7%; difference: −39.7%, 95% CI: −71.1 to −21.3%; p < 0.001). The intention-to-treat analysis was conducted on 195 patients from 23 Spanish health centers/nursing homes. This novel treatment balances the ulcer microenvironment by modulating reactive oxygen species and pH. These actions complement the moistening and barrier functions inherent to amorphous hydrogels, whilst also conferring EHO-85 its documented granulation formation and pain relief properties. Furthermore, efficacy was achieved safely and in a cost-efficient manner due to its multi-dose format, which reduced the amount of product needed by 85.8% over 8 weeks compared to single-use hydrogel. The present randomized controlled trial is a relevant milestone in evidence-based practice for being the first to demonstrate (i) the effectiveness of an amorphous hydrogel in accelerating wound healing and (ii) the superiority of a specific hydrogel over another.
Epigenetic Alterations in Inborn Errors of Immunity
Authors: Romano Roberta , Cillo Francesca , Moracas Cristina , Pignata Laura , Nannola Chiara , Toriello Elisabetta , De Rosa Antonio , Cirillo Emilia , Coppola Emma , Giardino Giuliana , Brunetti-Pierri Nicola , Riccio Andrea , Pignata Claudio
Published: February 2022

The epigenome bridges environmental factors and the genome, fine-tuning the process of gene transcription. Physiological programs, including the development, maturation and maintenance of cellular identity and function, are modulated by intricate epigenetic changes that encompass DNA methylation, chromatin remodeling, histone modifications and RNA processing. The collection of genome-wide DNA methylation data has recently shed new light into the potential contribution of epigenetics in pathophysiology, particularly in the field of immune system and host defense. The study of patients carrying mutations in genes encoding for molecules involved in the epigenetic machinery has allowed the identification and better characterization of environment-genome interactions via epigenetics as well as paving the way for the development of new potential therapeutic options. In this review, we summarize current knowledge of the role of epigenetic modifications in the immune system and outline their potential involvement in the pathogenesis of inborn errors of immunity.
Parenting Children with Autism Spectrum Disorder during Crises: Differential Responses between the Financial and the COVID-19 Pandemic Crisis
Authors: Papanikolaou Katerina , Ntre Vassiliki , Gertsou Ioanna-Maria , Tagkouli Evdokia , Tzavara Chara , Pehlivanidis Artemios , Kolaitis Gerasimos
Published: February 2022

Parenting a child with autism can be particularly stressful and challenging, especially during periods of crises. This study focuses on parenting children with autism during the COVID-19 pandemic in comparison to the economic crisis, six years ago. We administered the same set of questionnaires (CES-D, F-COPES, PSI-SF, and WHOQoL-BREF), along with a demographic characteristic and a COVID-19-related questionnaire to the same group of parents of children with autism as we did six years ago. Results indicated that during the COVID-19 crisis, the level of parenting stress and the distress due to personal factors related to demands of parenting, were significantly lower compared to the economic crisis, while the environment facet of quality of life was significantly higher. The depressive symptomatology was elevated during both periods. Finally, when addressing the pandemic crisis, parents were more likely to passively accept problematic issues, less able to obtain social support, and less able to acquire and accept help from others. In our sample, findings differentiate the genre of crises through the parents’ responses regarding the sense of competence in their parental role, their quality of life, and the coping strategies they implemented. The study implies that each crisis must be confronted with particular responses to particular needs.
The Usefulness of Vanin-1 and Periostin as Markers of an Active Autoimmune Process or Renal Fibrosis in Children with IgA Nephropathy and IgA Vasculitis with Nephritis—A Pilot Study
Authors: Mizerska-Wasiak Małgorzata , Płatos Emilia , Cichoń-Kawa Karolina , Demkow Urszula , Pańczyk-Tomaszewska Małgorzata
Published: February 2022

This study aimed to evaluate the usefulness of vanin-1 and periostin in urine as markers of the autoimmune process in kidneys and renal fibrosis in IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAVN). From a group of 194 patients from the Department of Pediatrics and Nephrology, who were included in the Polish Pediatric Registry of IgAN and IgAVN, we qualified 51 patients (20 with IgAN and 31 with IgAVN) between the ages of 3 and 17, diagnosed based on kidney biopsy, for inclusion in the study. All of the patients received glucocorticosteroids, immunosuppressive drugs, or renoprotective therapy. The control group consisted of 18 healthy individuals. The concentration of vanin was significantly higher in the IgAN and IgAVN groups than in the control group. The concentration of vanin/creatinine correlates positively with the level of IgA and negatively with the serum level of C3 at the end of the observation. Urinary vanin-1 concentration may be useful as a marker of the active autoimmune process in IgAN and IgAVN in children, but the study needs confirmation on a larger group of children, along with evaluation of the dynamics of this marker. Urinary periostin is not a good marker for children with IgAN and IgAVN, especially in stage 1 and 2 CKD.
Risk Assessment after ST-Segment Elevation Myocardial Infarction: Can Biomarkers Improve the Performance of Clinical Variables?
Authors: Garcia-Osuna Alvaro , Sans-Rosello Jordi , Ferrero-Gregori Andreu , Alquezar-Arbe Aitor , Sionis Alessandro , Ordóñez-Llanos Jordi
Published: February 2022

Introduction: Myocardial infarction with ST-segment elevation (STEMI) is the coronary artery disease associated with the highest risk of morbimortality; however, this risk is heterogeneous, usually being evaluated by clinical scores. Risk assessment is a key factor in personalized clinical management of patients with this disease. Aim: The aim of this study was to assess whether some new cardiac biomarkers considered alone, combined in a multibiomarker model or in association with clinical variables, improve the short- and long-term risk stratification of STEMI patients. Materials and Methods: This was a retrospective observational study of 253 patients with STEMI. Blood samples were obtained before or during the angiography. The assessed biomarkers were C-terminal fragment of insulin-like growth factor binding protein-4 (CT-IGFBP4), high sensitive cardiac troponin T (hs-cTnT), N-terminal fragment of probrain natriuretic peptide (NT-proBNP), and growth differentiation factor 15 (GDF-15); they reflect different cardiovascular (CV) physiopathological pathways and underlying pathologies. We registered in-hospital and follow-up mortalities and their causes (cardiovascular and all-cause) and major adverse cardiac events (MACE) during a two year follow-up. Discrimination, survival analysis, model calibration, and reclassification of the biomarkers were comprehensively evaluated. Results and Discussion: In total, 55 patients (21.7%) died, 33 in-hospital and 22 during the follow-up, most of them (69.1%) from CV causes; 37 MACE occurred during follow-up. Biomarkers showed good prognostic ability to predict mortality, alone and combined with the multibiomarker model. A predictive clinical model based on age, Killip–Kimball class, estimated glomerular filtration rate (eGFR), and heart rate was derived by multivariate analysis. GDF-15 and NT-proBNP significantly improved risk assessment of the clinical model, as shown by discrimination, calibration, and reclassification of all the end-points except for all-cause mortality. The combination of NT-proBNP and hs-cTnT improved CV mortality prediction. Conclusions: GDF-15 and NT-proBNP added value to the usual risk assessment of STEMI patients.
Efficacy of Percutaneous Transarterial Embolization in Patients with Spontaneous Abdominal Wall Hematoma and Comparison between Blind and Targeted Embolization Approaches
Authors: Di Pietro Stefano , Tiralongo Francesco , Desiderio Carla Maria , Vacirca Francesco , Palmucci Stefano , Giurazza Francesco , Venturini Massimo , Basile Antonio
Published: February 2022

Background: Endovascular treatment of abdominal wall hematomas (AWHs) has been increasingly used when conservative treatments were not sufficiently effective, and it is often preferred to surgical interventions. The aim of our study was to evaluate the safety and technical and clinical success of percutaneous transarterial treatment of AWH and to evaluate the efficacy of blind embolization compared to targeted embolization. Materials and Methods: We retrospectively enrolled 43 patients (23 men and 20 females) with spontaneous AWH who underwent digital subtraction angiography (DSA) and embolization, focusing on the presence of signs of bleeding at pre-procedural CT-Angiography (CTA) and at DSA. Furthermore, we divided patients into two groups depending on blind or targeted embolization approaches. Results: The mean age of the study population was 71 ± 12 years. CTA revealed signs of active bleeding in 31 patients (72%). DSA showed signs of active bleeding in 34 patients (79%). In nine patients (21%), blind embolization was performed. The overall technical success rate was 100%. Clinical success was achieved in 33 patients (77%), while 10 patients (23%) rebled within 96 h, and all of them were re-treated. No major peri-procedural complication was reported. The comparison between blind and targeted embolization showed no statistically significant differences for characteristics of groups and for clinical success rates (78% and 77%, respectively, −p = 0.71). The technical success was 100% in both groups. Conclusions: Our study confirms that transarterial embolization is a safe and effective option for the treatment of spontaneous AWHs, and it suggests that the efficacy and safety of blind embolization is comparable to non-blind.
A Multinational Pilot Study on Patients’ Perceptions of Advanced Neuroendocrine Neoplasms on the EORTC QLQ-C30 and EORTC QLQ-GINET21 Questionnaires
Authors: van Leeuwaarde Rachel S. , González-Clavijo Angélica M. , Pracht Marc , Emelianova Galina , Cheung Winson Y. , Thirlwell Christina , Öberg Kjell , Spada Francesca
Published: February 2022

Among the available neuroendocrine neoplasm (NEN)-specific HR-QoL scales, only the EORTC QLQ-C30 and EORTC QLQ-G.I.NET21 questionnaires have been validated in several languages. We aim to assess patients’ perceptions of these questionnaires. A cross-sectional qualitative pilot study was conducted among 65 adults from four countries with well-differentiated advanced gastro-entero-pancreatic (GEP) or unknown primary NENs. Patients completed the EORTC QLQ-C30 and EORTC QLQ-G.I.NET21 questionnaires and then a survey containing statements concerning the questionnaires. The majority of patients had a small intestine NET (52%). Most tumors were functioning (55%) and grade 2 NET (52%). Almost half of the patients identified limitations in the questionnaires, with nine (14%) patients scoring the questionnaires as poor and 16 (25%) patients as moderate. Overall, 37 (57%) patients were positive towards the questionnaires. Approximately a quarter of patients considered the questionnaires not suitable for all ages, missing some of their complaints, not representative of their overall HR-QoL regarding the treatment of their NET and too superficial. The current validated EORTC QLQ-C30 and EORTC QLQ-G.I.NET21 questionnaires may show some limitations in the design of questions and the patients’ final satisfaction reporting of the questionnaire. Large-scale, high-quality prospective studies are required in HR-QoL assessment regarding NETs.
Role and Impact of Cerebrolysin for Ischemic Stroke Care
Authors: Mureșanu Dafin F. , Livinț Popa Livia , Chira Diana , Dăbală Victor , Hapca Elian , Vlad Irina , Văcăraș Vitalie , Popescu Bogdan Ovidiu , Cherecheș Răzvan , Strilciuc Ștefan , Brainin Michael
Published: February 2022

Stroke is still a significant health problem that affects millions of people worldwide, as it is the second-leading cause of death and the third-leading cause of disability. Many changes have occurred in the treatment of acute ischemic stroke. Although the innovative concepts of neuroprotection and neurorecovery have been vigorously investigated in a substantial number of clinical studies in the past, only a few trials managed to increase the number of promising outcomes with regard to the multidimensional construct of brain protection and rehabilitation. In terms of pharmacological therapies with proven benefits in the post-ischemic process, drugs with neurorestorative properties are thought to be effective in both the acute and chronic phases of stroke. One significant example is Cerebrolysin, a combination of amino acids and peptides that mimic the biological functions of neurotrophic factors, which has been shown to improve outcomes after ischemic stroke, while preserving a promising safety profile. The purpose of this paper is to offer an overview on the role and impact of Cerebrolysin for ischemic stroke care, by touching on various aspects, from its complex, multimodal and pleiotropic mechanism of action, to its efficacy and safety, as well as cost effectiveness.
Outcomes of Vitrectomy with Fovea-Sparing and Inverted ILM Flap Technique for Myopic Foveoschisis
Authors: Wakatsuki Yu , Nakashizuka Hiroyuki , Tanaka Koji , Mori Ryusaburo , Shimada Hiroyuki
Published: February 2022

Surgical treatment of myopic foveoschisis (MF) can result in a macular hole in 11–17% of patients that may lead to poor visual outcomes and progression to macular hole retinal detachment. We evaluated the benefit of vitrectomy to treat MF using the inverted internal limiting membrane (ILM) flap and fovea-sparing ILM techniques. We studied 20 eyes of 20 patients (7 men, 13 women) with high MF (mean axial length, 29.3 ± 1.7 mm). MF was classified by optical coherence tomography findings: retinoschisis (7 eyes) or foveal detachment (13 eyes). Between October 2013 and June 2021, we performed vitreous surgery in all 20 patients, employing both techniques. Air tamponade was used in 4 eyes, SF6 gas in 10 eyes, and C3F8 gas in 6 eyes. All patients stayed in the face-down position for one full day postoperatively. Visual acuity and foveal contour were analyzed using optical coherence tomography before surgery and at 3 and 6 months postoperatively. LogMAR visual acuity was 0.46 before surgery, with a significant improvement at 3 months (0.34) and at 6 months (0.2) postoperatively (p = 0.024, p < 0.001, respectively). In all patients, the foveal contour showed improvement without macular hole formation after surgery. These results show that vitrectomy, performed using the inverted ILM flap and fovea-sparing ILM technique, is effective for treating MF.
QRS Narrowing Following CRT Implantation: Predictors, Dynamics, and Association with Improved Long-Term Outcome
Authors: Lapidot Daniel , Rav-Acha Moshe , Bdolah-Abram Tali , Farkash Rivka , Glikson Michael , Hasin Tal
Published: February 2022

Background: Heart failure (HF) patients with wide QRS often benefit from cardiac resynchronization therapy (CRT), although QRS narrowing does not always occur. The current study investigates the incidence and predictors for QRS narrowing following CRT and its long-term impact on clinical outcomes. Methods: Among individuals undergoing clinically indicated CRT, pre-and post-implantation electrocardiographs were meticulously analyzed for QRS duration change. All-cause mortality and the composite of mortality and HF hospitalizations were retrieved. Results: For 104 patients, mean age 67 years, 25% females, QRS narrowed within days by 20.2 ± 24.7 ms. In 55/104 (53%) QRS narrowed by ≥20 ms (“acute narrowing”). Female gender and baseline QRS predicted acute narrowing. Acute narrowing persisted for 1–6 weeks in 18/20 (90%) and 3–12 months in 21/31 (68%) of patients. During the average follow-up of 41 months, 29/104 (28%) died and 50/104 (48%) met the composite outcome. In a multivariable analysis including comorbidities and cardiac history, prolonged baseline PR interval (HR 1.015, CI 1.008–1.021, p < 0.001) and acute narrowing < 20 ms (HR 3.243, CI 1.593–6.603, p = 0.001) were significant and independent predictors for the composite outcome. Conclusions: Post-CRT acute QRS narrowing ≥ 20 ms is independently associated with favorable long-term outcomes and might be considered as a novel measure for procedural success.
Gene Therapy of Chronic Limb-Threatening Ischemia: Vascular Medical Perspectives
Authors: Simon Florian , Duran Mansur , Garabet Waseem , Schelzig Hubert , Jacobs Michael , Gombert Alexander
Published: February 2022

A decade ago, gene therapy seemed to be a promising approach for the treatment of chronic limb-threatening ischemia, providing new perspectives for patients without conventional, open or endovascular therapeutic options by potentially enabling neo-angiogenesis. Yet, until now, the results have been far from a safe and routine clinical application. In general, there are two approaches for inserting exogenous genes in a host genome: transduction and transfection. In case of transduction, viral vectors are used to introduce genes into cells, and depending on the selected strain of the virus, a transient or stable duration of protein production can be achieved. In contrast, the transfection of DNA is transmitted by chemical or physical processes such as lipofection, electro- or sonoporation. Relevant risks of gene therapy may be an increasing neo-vascularization in undesired tissue. The risks of malignant transformation and inflammation are the potential drawbacks. Additionally, atherosclerotic plaques can be destabilized by the increased angiogenesis, leading to arterial thrombosis. Clinical trials from pilot studies to Phase II and III studies on angiogenic gene therapy show mainly a mixed picture of positive and negative final results; thus, the role of gene therapy in vascular occlusive disease remains unclear.
Astaxanthin Relieves Testicular Ischemia-Reperfusion Injury—Immunohistochemical and Biochemical Analyses
Authors: Bašković Marko , Krsnik Dajana , Himelreich Perić Marta , Katušić Bojanac Ana , Sinčić Nino , Sonicki Zdenko , Ježek Davor
Published: February 2022

Testicular torsion potentially leads to acute scrotum and testicle loss, and requires prompt surgical intervention to restore testicular blood flow, despite the paradoxical negative effect of reperfusion. While no drug is yet approved for this condition, antioxidants are promising candidates. This study aimed to determine astaxanthin’s (ASX), a potent antioxidant, effect on rat testicular torsion−detorsion injury. Thirty-two prepubertal male Fischer rats were divided into four groups. Group 1 underwent sham surgery. In group 2, the right testis was twisted at 720° for 90 min. After 90 min of reperfusion, the testis was removed. ASX was administered intraperitoneally at the time of detorsion (group 3) and 45 min after detorsion (group 4). Quantification of caspase-3 positive cells and oxidative stress markers detection were determined immunohistochemically, while the malondialdehyde (MDA) value, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were determined by colorimetric assays. The number of apoptotic caspase-3 positive cells and the MDA value were lower in group 4 compared to group 2. A significant increase in the SOD and GPx activity was observed in group 4 compared to groups 2 and 3. We conclude that ASX has a favorable effect on testicular ischemia-reperfusion injury in rats.
Clinical Outcomes of Shunting in Normal Pressure Hydrocephalus: A Multicenter Prospective Observational Study
Authors: Trungu Sokol , Scollato Antonio , Ricciardi Luca , Forcato Stefano , Polli Filippo Maria , Miscusi Massimo , Raco Antonino
Published: February 2022

Background: Normal pressure hydrocephalus (NPH) is characterized by the triad of dementia, gait disturbance and urinary incontinence, all potentially reversible following a ventriculoperitoneal shunt (VPS). This study aims to evaluate the clinical outcomes of shunting in normal pressure hydrocephalus following a new standardized protocol. Methods: This study is designed according to the STROBE guidelines. Demographical, clinical, surgical and radiological data were collected from May 2015 to November 2019. Gait, balance and incontinence data based on the NPH European scale were collected before and after one, six and twelve months of treatment with a VPS. Clinical symptoms and changes of the stoke volume, measured on phase-contrast MRI, were used to evaluate improvement after VPS surgery. Results: One hundred and eighty-one consecutive patients met the inclusion criteria. The mean age was 73.1 years (59–86) and mean follow-up was 38.3 months (13–50). The gait (58.5 ± 14.3 to 70.1 ± 13.4, p < 0.001), the balance (66.7 ± 21.5 to 71.7 ± 22.1, p = 0.001), continence domain (69.9 ± 20.5 to 76 ± 20, p = 0.002) scores and neuropsychological scales showed a statistically significant improvement over the follow-up. The overall improvement after 12 months was present in 91.2% of patients. An overall complication rate of 8.8% and a reoperation rate of 9.4% were recorded, respectively. Conclusions: Surgical treatment by VPS for NPH improves symptoms in most patients, when accurately selected. A standardized protocol and a multidisciplinary team dedicated to this disorder is needed to achieve an early and correct diagnosis of NPH. Follow-up with stroke volume measurement is a valuable tool for the early diagnosis of shunt malfunction or the need for valve adjustment.