bluuebunny/crossref_metadata_2025 huggingface dataset:
An Integrative Transcriptomic Analysis of Systemic Juvenile Idiopathic Arthritis for Identifying Potential Genetic Markers and Drug Candidates
Authors: Kim Daeun , Song Jaeseung , Lee Sora , Jung Junghyun , Jang Wonhee
Published: January 2021

Systemic juvenile idiopathic arthritis (sJIA) is a rare subtype of juvenile idiopathic arthritis, whose clinical features are systemic fever and rash accompanied by painful joints and inflammation. Even though sJIA has been reported to be an autoinflammatory disorder, its exact pathogenesis remains unclear. In this study, we integrated a meta-analysis with a weighted gene co-expression network analysis (WGCNA) using 5 microarray datasets and an RNA sequencing dataset to understand the interconnection of susceptibility genes for sJIA. Using the integrative analysis, we identified a robust sJIA signature that consisted of 2 co-expressed gene sets comprising 103 up-regulated genes and 25 down-regulated genes in sJIA patients compared with healthy controls. Among the 128 sJIA signature genes, we identified an up-regulated cluster of 11 genes and a down-regulated cluster of 4 genes, which may play key roles in the pathogenesis of sJIA. We then detected 10 bioactive molecules targeting the significant gene clusters as potential novel drug candidates for sJIA using an in silico drug repositioning analysis. These findings suggest that the gene clusters may be potential genetic markers of sJIA and 10 drug candidates can contribute to the development of new therapeutic options for sJIA.
Oxidative Stress Underlies the Ischemia/Reperfusion-Induced Internalization and Degradation of AMPA Receptors
Authors: Achzet Lindsay M. , Davison Clara J. , Shea Moira , Sturgeon Isabella , Jackson Darrell A.
Published: January 2021

Stroke is the fifth leading cause of death annually in the United States. Ischemic stroke occurs when a blood vessel supplying the brain is occluded. The hippocampus is particularly susceptible to AMPA receptor-mediated delayed neuronal death as a result of ischemic/reperfusion injury. AMPA receptors composed of a GluA2 subunit are impermeable to calcium due to a post-transcriptional modification in the channel pore of the GluA2 subunit. GluA2 undergoes internalization and is subsequently degraded following ischemia/reperfusion. The subsequent increase in the expression of GluA2-lacking, Ca2+-permeable AMPARs results in excitotoxicity and eventually delayed neuronal death. Following ischemia/reperfusion, there is increased production of superoxide radicals. This study describes how the internalization and degradation of GluA1 and GluA2 AMPAR subunits following ischemia/reperfusion is mediated through an oxidative stress signaling cascade. U251-MG cells were transiently transfected with fluorescently tagged GluA1 and GluA2, and different Rab proteins to observe AMPAR endocytic trafficking following oxygen glucose-deprivation/reperfusion (OGD/R), an in vitro model for ischemia/reperfusion. Pretreatment with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), a superoxide dismutase mimetic, ameliorated the OGD/R-induced, but not agonist-induced, internalization and degradation of GluA1 and GluA2 AMPAR subunits. Specifically, MnTMPyP prevented the increased colocalization of GluA1 and GluA2 with Rab5, an early endosomal marker, and with Rab7, a late endosomal marker, but did not affect the colocalization of GluA1 with Rab11, a marker for recycling endosomes. These data indicate that oxidative stress may play a vital role in AMPAR-mediated cell death following ischemic/reperfusion injury.
Endothelial Lipase Modulates Paraoxonase 1 Content and Arylesterase Activity of HDL
Authors: Schilcher Irene , Stadler Julia T. , Lechleitner Margarete , Hrzenjak Andelko , Berghold Andrea , Pregartner Gudrun , Lhomme Marie , Holzer Michael , Korbelius Melanie , Reichmann Florian , Springer Anna , Wadsack Christian , Madl Tobias , Kratky Dagmar , Kontush Anatol , Marsche Gunther , Frank Saša
Published: January 2021

Endothelial lipase (EL) is a strong modulator of the high-density lipoprotein (HDL) structure, composition, and function. Here, we examined the impact of EL on HDL paraoxonase 1 (PON1) content and arylesterase (AE) activity in vitro and in vivo. The incubation of HDL with EL-overexpressing HepG2 cells decreased HDL size, PON1 content, and AE activity. The EL modification of HDL did not diminish the capacity of HDL to associate with PON1 when EL-modified HDL was incubated with PON1-overexpressing cells. The overexpression of EL in mice significantly decreased HDL serum levels but unexpectedly increased HDL PON1 content and HDL AE activity. Enzymatically inactive EL had no effect on the PON1 content of HDL in mice. In healthy subjects, EL serum levels were not significantly correlated with HDL levels. However, HDL PON1 content was positively associated with EL serum levels. The EL-induced changes in the HDL-lipid composition were not linked to the HDL PON1 content. We conclude that primarily, the interaction of enzymatically active EL with HDL, rather than EL-induced alterations in HDL size and composition, causes PON1 displacement from HDL in vitro. In vivo, the EL-mediated reduction of HDL serum levels and the consequently increased PON1-to-HDL ratio in serum increase HDL PON1 content and AE activity in mice. In humans, additional mechanisms appear to underlie the association of EL serum levels and HDL PON1 content.
Expression Levels of an Alpha-Synuclein Transcript in Blood May Distinguish between Early Dementia with Lewy Bodies and Parkinson’s Disease
Authors: Marsal-García Laura , Urbizu Aintzane , Arnaldo Laura , Campdelacreu Jaume , Vilas Dolores , Ispierto Lourdes , Gascón-Bayarri Jordi , Reñé Ramón , Álvarez Ramiro , Beyer Katrin
Published: January 2021

Lewy body diseases (LBD) including dementia with Lewy bodies (DLB) and Parkinson disease (PD) are characterized by alpha-synuclein pathology. DLB is difficult to diagnose and peripheral biomarkers are urgently needed. Therefore, we analyzed the expression of five alpha-synuclein gene (SNCA) transcripts, SNCAtv1, SNCAtv2, SNCAtv3, SNCA126, and SNCA112, in 45 LBD and control temporal cortex samples and in the blood of 72 DLB, 59 PD, and 54 control subjects. The results revealed overexpression of SNCAtv1 and SNCA112 in DLB, and SNCAtv2 in PD temporal cortices. In DLB blood, diminution of all SNCA transcripts was observed. SNCAtv1 and SNCAtv2 were diminished in PD with disease onset before 70 years. SNCAtv3, driven by its own promoter, showed opposite expression in early DLB and PD, suggesting that its amount may be an early, DLB specific biomarker. Correlation between blood transcript levels and disease duration was positive in DLB and negative in PD, possibly reflecting differences in brain alpha-synuclein aggregation rates associated with differences in disease courses. In conclusion, SNCA transcripts showed a disease-specific increase in the brain and were diminished in blood of LBD patients. SNCAtv3 expression was decreased in early DLB and increased in early PD and could be a biomarker for early DLB diagnosis.
Cholesterol and Sphingolipid Enriched Lipid Rafts as Therapeutic Targets in Cancer
Authors: Codini Michela , Garcia-Gil Mercedes , Albi Elisabetta
Published: January 2021

Lipid rafts are critical cell membrane lipid platforms enriched in sphingolipid and cholesterol content involved in diverse cellular processes. They have been proposed to influence membrane properties and to accommodate receptors within themselves by facilitating their interaction with ligands. Over the past decade, technical advances have improved our understanding of lipid rafts as bioactive structures. In this review, we will cover the more recent findings about cholesterol, sphingolipids and lipid rafts located in cellular and nuclear membranes in cancer. Collectively, the data provide insights on the role of lipid rafts as biomolecular targets in cancer with good perspectives for the development of innovative therapeutic strategies.
A Micellar Formulation of Quercetin Prevents Cisplatin Nephrotoxicity
Authors: Casanova Alfredo G. , Prieto Marta , Colino Clara I. , Gutiérrez-Millán Carmen , Ruszkowska-Ciastek Barbara , de Paz Esther , Martín Ángel , Morales Ana I. , López-Hernández Francisco J.
Published: January 2021

The antioxidant flavonoid quercetin has been shown to prevent nephrotoxicity in animal models and in a clinical study and is thus a very promising prophylactic candidate under development. Quercetin solubility is very low, which handicaps clinical application. The aim of this work was to study, in rats, the bioavailability and nephroprotective efficacy of a micellar formulation of Pluronic F127-encapsulated quercetin (P-quercetin), with improved hydrosolubility. Intraperitoneal administration of P-quercetin leads to an increased plasma concentration and bioavailability of quercetin compared to the equimolar administration of natural quercetin. Moreover, P-quercetin retains overall nephroprotective properties, and even slightly improves some renal function parameters, when compared to natural quercetin. Specifically, P-quercetin reduced the increment in plasma creatinine (from 3.4 ± 0.5 to 1.2 ± 0.3 mg/dL) and urea (from 490.9 ± 43.8 to 184.1 ± 50.1 mg/dL) and the decrease in creatinine clearance (from 0.08 ± 0.02 to 0.58 ± 0.19 mL/min) induced by the nephrotoxic chemotherapeutic drug cisplatin, and it ameliorated histological evidence of tubular damage. This new formulation with enhanced kinetic and biopharmaceutical properties will allow for further exploration of quercetin as a candidate nephroprotector at lower dosages and by administration routes oriented towards its clinical use.
Omics Analysis of Blood-Responsive Regulon in Bordetella pertussis Identifies a Novel Essential T3SS Substrate
Authors: Drzmisek Jakub , Stipl Daniel , Petrackova Denisa , Vecerek Branislav , Dienstbier Ana
Published: January 2021

Bacterial pathogens sense specific cues associated with different host niches and integrate these signals to appropriately adjust the global gene expression. Bordetella pertussis is a Gram-negative, strictly human pathogen of the respiratory tract and the etiological agent of whooping cough (pertussis). Though B. pertussis does not cause invasive infections, previous results indicated that this reemerging pathogen responds to blood exposure. Here, omics RNA-seq and LC–MS/MS techniques were applied to determine the blood-responsive regulon of B. pertussis. These analyses revealed that direct contact with blood rewired global gene expression profiles in B. pertussis as the expression of almost 20% of all genes was significantly modulated. However, upon loss of contact with blood, the majority of blood-specific effects vanished, with the exception of several genes encoding the T3SS-secreted substrates. For the first time, the T3SS regulator BtrA was identified in culture supernatants of B. pertussis. Furthermore, proteomic analysis identified BP2259 protein as a novel secreted T3SS substrate, which is required for T3SS functionality. Collectively, presented data indicate that contact with blood represents an important cue for B. pertussis cells.
AhR and Cancer: From Gene Profiling to Targeted Therapy
Authors: Paris Anaïs , Tardif Nina , Galibert Marie-Dominique , Corre Sébastien
Published: January 2021

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that has been shown to be an essential regulator of a broad spectrum of biological activities required for maintaining the body’s vital functions. AhR also plays a critical role in tumorigenesis. Its role in cancer is complex, encompassing both pro- and anti-tumorigenic activities. Its level of expression and activity are specific to each tumor and patient, increasing the difficulty of understanding the activating or inhibiting roles of AhR ligands. We explored the role of AhR in tumor cell lines and patients using genomic data sets and discuss the extent to which AhR can be considered as a therapeutic target.
A Closer Look at Estrogen Receptor Mutations in Breast Cancer and Their Implications for Estrogen and Antiestrogen Responses
Authors: Clusan Léa , Le Goff Pascale , Flouriot Gilles , Pakdel Farzad
Published: January 2021

Breast cancer (BC) is the most common cancer among women worldwide. More than 70% of BC cases express estrogen receptor alpha (ERα), a central transcription factor that stimulates the proliferation of breast cancer cells, usually in the presence of estrogen. While most cases of ER-positive BC initially respond to antiestrogen therapies, a high percentage of cases develop resistance to treatment over time. The recent discovery of mutated forms of ERα that result in constitutively active forms of the receptor in the metastatic-resistance stage of BC has provided a strong rationale for the development of new antiestrogens. These molecules targeting clinically relevant ERα mutants and a combination with other pharmacological inhibitors of specific pathways may constitute alternative treatments to improve clinical practice in the fight against metastatic-resistant ER-positive BC. In this review, we summarize the latest advances regarding the particular involvement of point mutations of ERα in endocrine resistance. We also discuss the involvement of synonymous ERα mutations with respect to co-translational folding of the receptor and ribosome biogenesis in breast carcinogenesis.
The Landscape of AhR Regulators and Coregulators to Fine-Tune AhR Functions
Authors: Gargaro Marco , Scalisi Giulia , Manni Giorgia , Mondanelli Giada , Grohmann Ursula , Fallarino Francesca
Published: January 2021

The aryl-hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates numerous cellular responses. Originally investigated in toxicology because of its ability to bind environmental contaminants, AhR has attracted enormous attention in the field of immunology in the last 20 years. In addition, the discovery of endogenous and plant-derived ligands points to AhR also having a crucial role in normal cell physiology. Thus, AhR is emerging as a promiscuous receptor that can mediate either toxic or physiologic effects upon sensing multiple exogenous and endogenous molecules. Within this scenario, several factors appear to contribute to the outcome of gene transcriptional regulation by AhR, including the nature of the ligand as such and its further metabolism by AhR-induced enzymes, the local tissue microenvironment, and the presence of coregulators or specific transcription factors in the cell. Here, we review the current knowledge on the array of transcription factors and coregulators that, by interacting with AhR, tune its transcriptional activity in response to endogenous and exogenous ligands.
Liquid Baits with Oenococcus oeni Increase Captures of Drosophila suzukii
Authors: Ðurović Gordana , Alawamleh Amani , Carlin Silvia , Maddalena Giuseppe , Guzzon Raffaele , Mazzoni Valerio , Dalton Daniel T. , Walton Vaughn M. , Suckling David M. , Butler Ruth C. , Angeli Sergio , De Cristofaro Antonio , Anfora Gianfranco
Published: January 2021

The spotted-wing drosophila (SWD), Drosophila suzukii Matsumura (Diptera: Drosophilidae), native to Eastern Asia, is an invasive alien species in Europe and the Americas, where it is a severe pest of horticultural crops, including soft fruits and wine grapes. The conventional approach to controlling infestations of SWD involves the use of insecticides, but the frequency of application for population management is undesirable. Consequently, alternative strategies are urgently needed. Effective and improved trapping is important as an early risk detection tool. This study aimed to improve Droskidrink® (DD), a commercially available attractant for SWD. We focused on the chemical and behavioral effects of adding the bacterium Oenococcus oeni (Garvie) to DD and used a new trap design to enhance the effects of attractive lures. We demonstrate that microbial volatile compounds produced by O. oeni are responsible for the increase in the attractiveness of the bait and could be later utilized for the development of a better trapping system. Our results showed that the attractiveness of DD was increased up to two-fold by the addition of commercially available O. oeni when combined with an innovative trap design. The new trap-bait combination increased the number of male and especially female catches at low population densities.
Success Rates of Monitoring for Healthcare Professionals with a Substance Use Disorder: A Meta-Analysis
Authors: Geuijen Pauline M. , van den Broek Sophie J. M. , Dijkstra Boukje A. G. , Kuppens Joanneke M. , de Haan Hein A. , de Jong Cornelis A. J. , Schene Aart H. , Atsma Femke , Schellekens Arnt F. A.
Published: January 2021

In the past decades, monitoring programs have been developed for healthcare professionals with substance use disorders. We aimed to explore estimates of abstinence and work retention rates after participation in such monitoring programs. A literature search was performed using PubMed, Embase, PsycINFO, and CINAHL. Twenty-nine observational studies reporting on success rates (abstinence and work retention) of monitoring for healthcare professionals with a substance use disorder were included in the meta-analysis. Quality-effects models calculated pooled success rates and corresponding 95%-Confidence Intervals (CI), with subgroup analyses on monitoring elements and patient characteristics. Pooled success rates were 72% for abstinence (95%-CI = 63–80%) and 77% for work retention (95%-CI = 61–90%). Heterogeneity across studies was partly explained by the starting moment of monitoring, showing higher abstinence rates for studies that started monitoring after treatment completion (79%; 95%-CI = 72–85%) compared to studies that started monitoring with treatment initiation (61%; 95%-CI = 50–72%). About three-quarters of healthcare professionals with substance use disorders participating in monitoring programs are abstinent during follow-up and working at the end of the follow-up period. Due to selection and publication bias, no firm conclusions can be drawn about the effectiveness of monitoring for healthcare professionals with SUD.
Head-to-Head Comparison of Rapid and Automated Antigen Detection Tests for the Diagnosis of SARS-CoV-2 Infection
Authors: Favresse Julien , Gillot Constant , Oliveira Maxime , Cadrobbi Julie , Elsen Marc , Eucher Christine , Laffineur Kim , Rosseels Catherine , Van Eeckhoudt Sandrine , Nicolas Jean-Baptiste , Morimont Laure , Dogné Jean-Michel , Douxfils Jonathan
Published: January 2021

(1) Background: The detection of SARS-CoV-2 RNA in nasopharyngeal samples through real-time reverse transcription-polymerase chain reaction (RT-PCR) is considered the standard gold method for the diagnosis of SARS-CoV-2 infection. Antigen detection (AD) tests are more rapid, less laborious, and less expensive alternatives but still require clinical validation. (2) Methods: This study compared the clinical performance of five AD tests, including four rapid AD (RAD) tests (biotical, Panbio, Healgen, and Roche) and one automated AD test (VITROS). For that purpose, 118 (62.8%) symptomatic patients and 70 (37.2%) asymptomatic subjects were tested, and results were compared to RT-PCR. (3) Results: The performance of the RAD tests was modest and allowed us to identify RT-PCR positive patients with higher viral loads. For Ct values ≤25, the sensitivity ranged from 93.1% (95% CI: 83.3–98.1%) to 96.6% (95% CI: 88.1–99.6%), meaning that some samples with high viral loads were missed. Considering the Ct value proposed by the CDC for contagiousness (i.e., Ct values ≤33) sensitivities ranged from 76.2% (95% CI: 65.4–85.1%) to 88.8% (95% CI: 79.7–94.7%) while the specificity ranged from 96.3% (95% CI: 90.8–99.0%) to 99.1% (95% CI: 95.0–100%). The VITROS automated assay showed a 100% (95% CI: 95.5–100%) sensitivity for Ct values ≤33, and had a specificity of 100% (95% CI: 96.6–100%); (4) Conclusions: Compared to RAD tests, the VITROS assay fully aligned with RT-PCR for Ct values up to 33, which might allow a faster, easier and cheaper identification of SARS-CoV-2 contagious patients.
Incidence of Atrial Fibrillation in Postmenopausal Women with Endometrial Cancer
Authors: Parahuleva Mariana S. , Kreutz Julian , Euler Gerhild , Terzieva Dora , Mardini Amar , Uchikova Ekaterina , Parahuleva Nikoleta
Published: January 2021

Endometrial cancer (EC) has been associated with an increased risk of cardiovascular disease, including atrial fibrillation (AF). We performed a prospective, case-controlled analysis among 310 Bulgarian women with new-onset, histologically confirmed EC, free of AF at the baseline survey, and women with normal (senile) endometrium/endometrial hyperplasia as a control group (n = 205). The risk of AF as well as relationship of adiponectin (APN) and high sensitivity C-reactive protein (hs-CRP) levels with AF in women with EC were calculated by Cox proportional hazards models. During the mean follow-up of 2.5 ± 0.5 years, new-onset AF had occurred in 11.7% of women with EC vs. 5.8% in the control group (p < 0.01). The risk of AF was highest in the first 6 months after new-onset EC, with an incidence rate ratio (IRR) of 1.19 (95% CI 1.10–1.29; p = 0.01). Women with EC, who were obese (body mass index (BMI) > 30 kg/m2) and younger (age < 60) were found to be more likely to develop AF (HR 1.95; 95% CI 1.18–3.32; p = 0.05). APN levels were not significantly associated with new-onset AF (95% CI 0.87–1.21; p = 0.063). However, the secondary analysis showed evidence of APN–AF association when adjusted for BMI (2.05; 95% CI 1.04–4.04; p = 0.037). We conclude that EC was significantly associated with the incidence of AF.
Genital Prolapse Surgery: What Options Do We Have in the Age of Mesh Issues?
Authors: Noé Guenter K.
Published: January 2021

Here, we describe the current laparoscopic procedures for prolapse surgery and report data based on the application of these procedures. We also evaluate current approaches in vaginal prolapse surgery. Debates concerning the use of meshes have seriously affected vaginal surgery and threaten to influence reconstructive laparoscopic surgery as well. We describe the option of using autologous tissue in combination with the laparoscopic approach. Study data and problematic issues concerning the existing techniques are highlighted, and future options addressed.
Serum Albumin Concentrations in Stable Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis
Authors: Zinellu Elisabetta , Fois Alessandro G. , Sotgiu Elisabetta , Mellino Sabrina , Mangoni Arduino A. , Carru Ciriaco , Zinellu Angelo , Pirina Pietro
Published: January 2021

Background: Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by chronic airway inflammation and lung parenchyma damage. Systemic inflammation and oxidative stress also play a role in the pathogenesis of COPD. Serum albumin is a negative acute-phase protein with antioxidant effects and an important marker of malnutrition. The aim of this meta-analysis was to investigate differences in serum albumin concentrations between patients with stable COPD and non-COPD subjects. Methods: A systematic search was conducted, using the terms “albumin” and “chronic obstructive pulmonary disease” or “COPD”, in the electronic databases PubMed and Web of Science, from inception to May 2020. Results: Twenty-six studies were identified on a total of 2554 COPD patients and 2055 non-COPD controls. Pooled results showed that serum albumin concentrations were significantly lower in COPD patients (standard mean difference, SMD = −0.50, 95% CI −0.67 to −0.32; p < 0.001). No significant differences were observed in SMD of serum albumin concentrations between COPD patients with forced expiratory volume in the 1st second (FEV1) < 50% and those with FEV1 > 50%. Conclusions: Our systematic review and meta-analysis showed that serum albumin concentrations are significantly lower in patients with stable COPD compared to non-COPD controls. This supports the presence of a deficit in systemic anti-inflammatory and antioxidant defense mechanisms in COPD.
Analgesic Efficacy of Nefopam as an Adjuvant in Patient-Controlled Analgesia for Acute Postoperative Pain After Laparoscopic Colorectal Cancer Surgery
Authors: Oh Eun Jung , Sim Woo Seog , Wi Won Gook , Kim Jeayoun , Kim Woo Jin , Lee Jin Young
Published: January 2021

Despite rapid advancements in laparoscopic surgical techniques and perioperative management, postoperative pain remains a significant clinical issue. We examined the analgesic efficacy of nefopam as an adjuvant in patient-controlled analgesia (PCA) for acute postoperative pain in patients undergoing laparoscopic colorectal cancer surgery. We retrospectively analyzed the medical records of 120 patients who did or did not receive 80 mg of nefopam as an adjuvant in fentanyl PCA; they were allocated to the nefopam (n = 60) or non-nefopam group (n = 60). The demographic, clinical, and anesthetic data, with data on pain severity and opioid administration at the postoperative anesthesia care unit (PACU) on postoperative days (PODs) 1, 3, and 5, were compared between the groups. The pain score and opioid administration did not differ at the PACU or on PODs 1, 3, or 5. The day of PCA discontinuation, time to pass flatus, length of the hospital stay, and incidence of nausea/vomiting, dizziness, and headache also did not differ between the groups. Fentanyl PCA with 80 mg of nefopam as an adjuvant did not have a superior analgesic effect after laparoscopic colorectal cancer surgery.
Alterations in Small Intestine and Liver Morphology, Immunolocalization of Leptin, Ghrelin and Nesfatin-1 as Well as Immunoexpression of Tight Junction Proteins in Intestinal Mucosa after Gastrectomy in Rat Model
Authors: Puzio Iwona , Muszyński Siemowit , Dobrowolski Piotr , Kapica Małgorzata , Pawłowska-Olszewska Marta , Donaldson Janine , Tomaszewska Ewa
Published: January 2021

The stomach is responsible for the processing of nutrients as well as for the secretion of various hormones which are involved in many activities throughout the gastrointestinal tract. Experimental adult male Wistar rats (n = 6) underwent a modified gastrectomy, while control rats (n = 6) were sham-operated. After six weeks, changes in small intestine (including histomorphometrical parameters of the enteric nervous plexuses) and liver morphology, immunolocalization of leptin, ghrelin and nesfatin-1 as well as proteins forming adherens and tight junctions (E-cadherin, zonula occludens-1, occludin, marvelD3) in intestinal mucosa were evaluated. A number of effects on small intestine morphology, enteric nervous system ganglia, hormones and proteins expression were found, showing intestinal enteroplasticity and neuroplasticity associated with changes in gastrointestinal tract condition. The functional changes in intestinal mucosa and the enteric nervous system could be responsible for the altered intestinal barrier and hormonal responses following gastrectomy. The results suggest that more complicated regulatory mechanisms than that of compensatory mucosal hypertrophy alone are involved.
Favipiravir in Therapy of Viral Infections
Authors: Łagocka Ryta , Dziedziejko Violetta , Kłos Patrycja , Pawlik Andrzej
Published: January 2021

Favipiravir (FPV) is a novel antiviral drug acting as a competitive inhibitor of RNA-dependent RNA polymerase (RdRp), preventing viral transcription and replication. FPV was approved in Japan in 2014 for therapy of influenza unresponsive to standard antiviral therapies. FPV was also used in the therapy of Ebola virus disease (EVD) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this review, we discuss the mechanisms of action, pharmacokinetic parameters, toxicity, and adverse effects of FPV, as well as clinical studies evaluating the use of FPV in the therapy of influenza virus (IV) infection, EVD, and SARS-CoV-2 infection, along with its effectiveness in treating other human RNA infections.
Factors that Influence PRNU-Based Camera-Identification via Videos
Authors: de Roos Lars , Geradts Zeno
Published: January 2021

The Photo Response Non-Uniformity pattern (PRNU-pattern) can be used to identify the source of images or to indicate whether images have been made with the same camera. This pattern is also recognized as the “fingerprint” of a camera since it is a highly characteristic feature. However, this pattern, identically to a real fingerprint, is sensitive to many different influences, e.g., the influence of camera settings. In this study, several previously investigated factors were noted, after which three were selected for further investigation. The computation and comparison methods are evaluated under variation of the following factors: resolution, length of the video and compression. For all three studies, images were taken with a single iPhone 6. It was found that a higher resolution ensures a more reliable comparison, and that the length of a (reference) video should always be as high as possible to gain a better PRNU-pattern. It also became clear that compression (i.e., in this study the compression that Snapchat uses) has a negative effect on the correlation value. Therefore, it was found that many different factors play a part when comparing videos. Due to the large amount of controllable and non-controllable factors that influence the PRNU-pattern, it is of great importance that further research is carried out to gain clarity on the individual influences that factors exert.
Strategies to Better Target Fungal Squalene Monooxygenase
Authors: Sagatova Alia A.
Published: January 2021

Fungal pathogens present a challenge in medicine and agriculture. They also harm ecosystems and threaten biodiversity. The allylamine class of antimycotics targets the enzyme squalene monooxygenase. This enzyme occupies a key position in the sterol biosynthesis pathway in eukaryotes, catalyzing the rate-limiting reaction by introducing an oxygen atom to the squalene substrate converting it to 2,3-oxidosqualene. Currently, terbinafine—the most widely used allylamine—is mostly used for treating superficial fungal infections. The ability to better target this enzyme will have significant implications for human health in the treatment of fungal infections. The human orthologue can also be targeted for cholesterol-lowering therapeutics and in cancer therapies. This review will focus on the structural basis for improving the current therapeutics for fungal squalene monooxygenase.
Dynamics of Erosion and Deposition in a Partially Restored Valley-Bottom Gully
Authors: Alfonso-Torreño Alberto , Gómez-Gutiérrez Álvaro , Schnabel Susanne
Published: January 2021

Gullies are sources and reservoirs of sediments and perform as efficient transfers of runoff and sediments. In recent years, several techniques and technologies emerged to facilitate monitoring of gully dynamics at unprecedented spatial and temporal resolutions. Here we present a detailed study of a valley-bottom gully in a Mediterranean rangeland with a savannah-like vegetation cover that was partially restored in 2017. Restoration activities included check dams (gabion weirs and fascines) and livestock exclosure by fencing. The specific objectives of this work were: (1) to analyze the effectiveness of the restoration activities, (2) to study erosion and deposition dynamics before and after the restoration activities using high-resolution digital elevation models (DEMs), (3) to examine the role of micro-morphology on the observed topographic changes, and (4) to compare the current and recent channel dynamics with previous studies conducted in the same study area through different methods and spatio-temporal scales, quantifying medium-term changes. Topographic changes were estimated using multi-temporal, high-resolution DEMs produced using structure-from-motion (SfM) photogrammetry and aerial images acquired by a fixed-wing unmanned aerial vehicle (UAV). The performance of the restoration activities was satisfactory to control gully erosion. Check dams were effective favoring sediment deposition and reducing lateral bank erosion. Livestock exclosure promoted the stabilization of bank headcuts. The implemented restoration measures increased notably sediment deposition.
Machine Learning Algorithms Applied to Identify Microbial Species by Their Motility
Authors: Riekeles Max , Schirmack Janosch , Schulze-Makuch Dirk
Published: January 2021

(1) Background: Future missions to potentially habitable places in the Solar System require biochemistry-independent methods for detecting potential alien life forms. The technology was not advanced enough for onboard machine analysis of microscopic observations to be performed in past missions, but recent increases in computational power make the use of automated in-situ analyses feasible. (2) Methods: Here, we present a semi-automated experimental setup, capable of distinguishing the movement of abiotic particles due to Brownian motion from the motility behavior of the bacteria Pseudoalteromonas haloplanktis, Planococcus halocryophilus, Bacillus subtilis, and Escherichia coli. Supervised machine learning algorithms were also used to specifically identify these species based on their characteristic motility behavior. (3) Results: While we were able to distinguish microbial motility from the abiotic movements due to Brownian motion with an accuracy exceeding 99%, the accuracy of the automated identification rates for the selected species does not exceed 82%. (4) Conclusions: Motility is an excellent biosignature, which can be used as a tool for upcoming life-detection missions. This study serves as the basis for the further development of a microscopic life recognition system for upcoming missions to Mars or the ocean worlds of the outer Solar System.
Chitin Synthases Are Critical for Reproduction, Molting, and Digestion in the Salmon Louse (Lepeophtheirus salmonis)
Authors: Harðardóttir Hulda , Male Rune , Nilsen Frank , Dalvin Sussie
Published: January 2021

Chitin synthase (CHS) is a large transmembrane enzyme that polymerizes Uridine diphosphate N-acetylglucosamine into chitin. The genomes of insects often encode two chitin synthases, CHS1 and CHS2. Their functional roles have been investigated in several insects: CHS1 is mainly responsible for synthesizing chitin in the cuticle and CHS2 in the midgut. Lepeophtheirus salmonis is an ectoparasitic copepod on salmonid fish, which causes significant economic losses in aquaculture. In the present study, the tissue-specific localization, expression, and functional role of L. salmonis chitin synthases, LsCHS1 and LsCHS2, were investigated. The expressions of LsCHS1 and LsCHS2 were found in oocytes, ovaries, intestine, and integument. Wheat germ agglutinin (WGA) chitin staining signals were detected in ovaries, oocytes, intestine, cuticle, and intestine in adult female L. salmonis. The functional roles of the LsCHSs were investigated using RNA interference (RNAi) to silence the expression of LsCHS1 and LsCHS2. Knockdown of LsCHS1 in pre-adult I lice resulted in lethal phenotypes with cuticle deformation and deformation of ovaries and oocytes in adult lice. RNAi knockdown of LsCHS2 in adult female L. salmonis affected digestion, damaged the gut microvilli, reduced muscular tissues around the gut, and affected offspring. The results demonstrate that both LsCHS1 and LsCHS2 are important for the survival and reproduction in L. salmonis.
Obstructive Sleep Apnea as a Risk Factor of Insulin Resistance in Nondiabetic Adults
Authors: Michalek-Zrabkowska Monika , Macek Piotr , Martynowicz Helena , Gac Pawel , Mazur Grzegorz , Grzeda Magda , Poreba Rafal
Published: January 2021

Objective: The aim of this research was to assess the relationship between prevalence and severity of obstructive sleep apnea (OSA) and insulin resistance among patients with increased risk of OSA without diabetes mellitus. Method and materials: our study group involved 102 individuals with suspected OSA, mean age 53.02 ± 12.37 years. Data on medical history, medication usage, sleep habits, sleep quality and daytime sleepiness, were obtained using questionnaires. All patients underwent standardized full night polysomnography. Serum fasting insulin and glucose concentration were analyzed, the homeostatic model assessment-insulin resistance (HOMA-IR) index was calculated. Results: polysomnographic study indicated that in the group with OSA mean values of apnea–hypopnea index (AHI), oxygen desaturation index (ODI), duration of SpO2 < 90% and average desaturation drop were significantly higher compared to the group without OSA, while the minimum SpO2 was significantly lower. The carbohydrate metabolism parameters did not differ within those groups. Significantly higher fasting insulin concentration and HOMA-IR index were found in the group with AHI ≥ 15 compared to the group with AHI < 15 and in the group with AHI ≥ 30 compared to the group with AHI < 30. Higher AHI and ODI were independent risk factors for higher fasting insulin concentration and higher HOMA-IR index. Increased duration of SpO2 < 90% was an independent risk factor for higher fasting glucose concentration. Conclusions: Individuals with moderate to severe OSA without diabetes mellitus had a higher prevalence of insulin resistance.
Implication of Contactins in Demyelinating Pathologies
Authors: Kalafatakis Ilias , Savvaki Maria , Velona Theodora , Karagogeos Domna
Published: January 2021

Demyelinating pathologies comprise of a variety of conditions where either central or peripheral myelin is attacked, resulting in white matter lesions and neurodegeneration. Myelinated axons are organized into molecularly distinct domains, and this segregation is crucial for their proper function. These defined domains are differentially affected at the different stages of demyelination as well as at the lesion and perilesion sites. Among the main players in myelinated axon organization are proteins of the contactin (CNTN) group of the immunoglobulin superfamily (IgSF) of cell adhesion molecules, namely Contactin-1 and Contactin-2 (CNTN1, CNTN2). The two contactins perform their functions through intermolecular interactions, which are crucial for myelinated axon integrity and functionality. In this review, we focus on the implication of these two molecules as well as their interactors in demyelinating pathologies in humans. At first, we describe the organization and function of myelinated axons in the central (CNS) and the peripheral (PNS) nervous system, further analyzing the role of CNTN1 and CNTN2 as well as their interactors in myelination. In the last section, studies showing the correlation of the two contactins with demyelinating pathologies are reviewed, highlighting the importance of these recognition molecules in shaping the function of the nervous system in multiple ways.
Human Umbilical Cord: Information Mine in Sex-Specific Medicine
Authors: Campesi Ilaria , Franconi Flavia , Montella Andrea , Dessole Salvatore , Capobianco Giampiero
Published: January 2021

Biological differences between sexes should be considered in all stages of research, as sexual dimorphism starts in utero leading to sex-specific fetal programming. In numerous biomedical fields, there is still a lack of stratification by sex despite primary cultured cells retaining memory of the sex and of the donor. The sex of donors in biological research must be known because variations in cells and cellular components can be used as endpoints, biomarkers and/or targets of pharmacological studies. This selective review focuses on the current findings regarding sex differences observed in the umbilical cord, a widely used source of research samples, both in the blood and in the circulating cells, as well as in the different cellular models obtainable from it. Moreover, an overview on sex differences in fetal programming is reported. As it emerges that the sex variable is still often forgotten in experimental models, we suggest that it should be mandatory to adopt sex-oriented research, because only awareness of these issues can lead to innovative research.
Advances in Elastomers
Authors: Sedlačík Michal
Published: January 2021

Elastomer materials are characteristic for their high elongation and (entropy) elasticity, which makes them indispensable for widespread applications in various engineering areas, medical applications or consumer goods [...]
Effects of MOVPE Growth Conditions on GaN Layers Doped with Germanium
Authors: Schiavon Dario , Litwin-Staszewska Elżbieta , Jakieła Rafał , Grzanka Szymon , Perlin Piotr
Published: January 2021

The effect of growth temperature and precursor flow on the doping level and surface morphology of Ge-doped GaN layers was researched. The results show that germanium is more readily incorporated at low temperature, high growth rate and high V/III ratio, thus revealing a similar behavior to what was previously observed for indium. V-pit formation can be blocked at high temperature but also at low V/III ratio, the latter of which however causing step bunching.
A Bio-Inspired Nanotubular Na2MoO4/TiO2 Composite as a High-Performance Anodic Material for Lithium-Ion Batteries
Authors: Yu Bo , Lin Zehao , Huang Jianguo
Published: January 2021

A train of bio-inspired nanotubular Na2MoO4/TiO2 composites were synthesized by using a natural cellulose substance (e.g., commercial ordinary filter paper) as the structural template. The TiO2 gel films were coated on the cellulose nanofiber surfaces via a sol-gel method firstly, followed with the deposition of the poly(diallyldimethylammonium chloride)/Na2MoO4 (PDDA/Na2MoO4) bi-layers several times, through the layer-by-layer self-assembly route, yielding the (PDDA/Na2MoO4)n/TiO2-gel/cellulose composite, which was calcined in air to give various Na2MoO4/TiO2 nanocomposites containing different Na2MoO4 contents (15.4, 24.1, and 41.4%). The resultant nanocomposites all inherited the three-dimensionally porous network structure of the premier cellulose substance, which were formed by hierarchical TiO2 nanotubes anchored with the Na2MoO4 layers. When employed as anodic materials for lithium-ion batteries, those Na2MoO4/TiO2 nanocomposites exhibited promoted electrochemical performances in comparison with the Na2MoO4 powder and pure TiO2 nanotubes, which was resulted from the high capacity of the Na2MoO4 component and the buffering effects of the TiO2 nanotubes. Among all the nanotubular Na2MoO4/TiO2 composites, the one with a Na2MoO4 content of 41.4% showed the best electrochemical properties, such as the cycling stability with a capacity of 180.22 mAh g−1 after 200 charge/discharge cycles (current density: 100 mA g−1) and the optimal rate capability.
Research on the Mechanism of Interaction between Styrene–Butadiene–Styrene (SBS) and Asphalt Based on Molecular Vibration Frequency
Authors: Zeng Yuqin , Liu Qicheng , Zeng Qing , He Yuhao , Xu Zhenghong
Published: January 2021

Based on the four-component theory of asphalt, molecular models of the saturate, aromatic, resin, and asphaltene were constructed, respectively. The styrene–butadiene–styrene (SBS) polymer was used as the modifier. Using density functional theory (DFT) to study the effect of SBS on the molecular vibration of each component of asphalt, the vibration spectrums and binding energy of the systems composed of SBS and each component molecule of asphalt were calculated. Prepared SBS modified asphalt and measured Fourier transform infrared spectroscopy (FTIR) before and after the experiment. The results show that after SBS was added to asphalt, no chemical reaction occurred, and the system was mainly physical blending. The vibrational peak intensity of SBS and the light components of asphalt (saturate and aromatic) is stronger than that of SBS and the heavy components of asphalt (resin and asphaltene). The interaction strengths of asphalt components and polybutadiene (PB) blocks, polystyrene (PS) blocks of SBS are different. The binding energy of SBS and the saturate is the lowest and the bonding of the system is weakest. The bonding of the systems of SBS and the aromatic, resin, asphaltene is stable, and the stability of these systems are all stronger than that of SBS and the saturate.
Effect of Acid Leaching Pre-Treatment on Gold Extraction from Printed Circuit Boards of Spent Mobile Phones
Authors: Ippolito Nicolò Maria , Medici Franco , Pietrelli Loris , Piga Luigi
Published: January 2021

The effect of a preliminary acid leaching for the recovery of gold by thiourea from printed circuit boards (PCBs) of spent mobile phones, was investigated. Preliminary leaching is aimed to recover copper in the leachate that would compete with gold in the successive leaching of the residue with thiourea, thus preventing the formation of the gold-thiourea complex. Two hydrometallurgical routes were tested for the recovery of copper first, and gold after. The first one was based on a two-step leaching that utilizes sulfuric acid and hydrogen peroxide in the preliminary leaching and then thiourea for the recovery of gold in the successive leaching: A copper and gold recovery of 81% and 79% were obtained, respectively. In the second route, nitric acid was used: 100% of copper was recovered in the leachate and 85% of gold in the thiourea successive leaching. The main operative parameters, namely thiourea and ferric sulphate concentrations, leach time, liquid-solid ratio, and temperature were studied according to a factorial plan strategy. A flowsheet of the processes was proposed, and a mass balance of both routes was obtained. Finally, qualitative considerations on the technical and economic feasibility of the different routes were made.
Cesium Doping for Performance Improvement of Lead(II)-acetate-Based Perovskite Solar Cells
Authors: Han Min-Seok , Liu Zhihai , Liu Xuewen , Yoon Jinho , Lee Eun-Cheol
Published: January 2021

Lead(II)-acetate (Pb(Ac)2) is a promising lead source for the preparation of organolead trihalide perovskite materials, which avoids the use of inconvenient anti-solvent treatment. In this study, we investigated the effect of cesium doping on the performance of Pb(Ac)2-based perovskite solar cells (PSCs). We demonstrate that the quality of the CH3NH3PbI3 perovskite film was improved with increased crystallinity and reduced pinholes by doping the perovskite with 5 mol% cesium. As a result, the power conversion efficiency (PCE) of the PSCs was improved from 14.1% to 15.57% (on average), which was mainly induced by the significant enhancements in short-circuit current density and fill factor. A PCE of 18.02% was achieved for the champion device of cesium-doped Pb(Ac)2-based PSCs with negligible hysteresis and a stable output. Our results indicate that cesium doping is an effective approach for improving the performance of Pb(Ac)2-based PSCs.
Residual Stress Distribution Design for Gear Surfaces Based on Genetic Algorithm Optimization
Authors: Chen Zhou , Jiang Yibo , Tong Zheming , Tong Shuiguang
Published: January 2021

The rolling contact fatigue of gear surfaces in a heavy loader gearbox is investigated under various working conditions using the critical plane-based multiaxial Fatemi–Socie criterion. The mechanism for residual stress to increase the fatigue initiation life is that the compressive residual stress has a negative normal component on the critical plane. Based on this mechanism, the genetic algorithm is used to search the optimum residual stress distribution that can maximize the fatigue initiation life for a wide range of working conditions. The optimum residual stress distribution is more effective in increasing the fatigue initiation life when the friction coefficient is larger than its critical value, above which the fatigue initiation moves from the subsurface to the surface. Finally, the effect on the fatigue initiation life when the residual stress distribution deviates from the optimum distribution is analyzed. A sound physical explanation for this effect is provided. This yields a useful guideline to design the residual stress distribution.