bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive Decline in Rheumatoid Arthritis: Insight into the Molecular Pathogenetic Mechanisms
Authors: Basile Maria Sofia , Ciurleo Rosella , Bramanti Alessia , Petralia Maria Cristina , Fagone Paolo , Nicoletti Ferdinando , Cavalli Eugenio
Published: January 2021

Cognitive decline refers to a deterioration of intellectual and learning abilities and related memory problems, and is often associated with behavioral alterations, which prevents sufferers from carrying out the most common daily activities, such as maintaining normal productive interpersonal relationships, communicating, and leading an autonomous life. Numerous studies have highlighted the association between cognitive decline and autoimmune disorders, including rheumatoid arthritis (RA). RA is a chronic, inflammatory, autoimmune disease that involves systems and organs other than the bones and joints, with varying severity among patients. Here, we review the studies investigating the link between cognitive decline and RA, focusing on the main molecular pathogenetic mechanisms involved. The emerging body of data suggests that clinical, psychological, and biological factors may contribute to the pathogenesis of cognitive decline in RA, including cardiovascular complications, chronic pain, depression, inflammatory factors, changes in hormone levels, drug side effects, and genetics. Further studies are warranted in order to fully clarify the basis underlying the association between cognitive decline and RA and to find new possible diagnostic strategies and therapeutic targets for RA patients.
Comparative 2D and 3D Ultrastructural Analyses of Dendritic Spines from CA1 Pyramidal Neurons in the Mouse Hippocampus
Authors: Colombo Maria , Maiellano Greta , Putignano Sabrina , Scandella Lucrezia , Francolini Maura
Published: January 2021

Three-dimensional (3D) reconstruction from electron microscopy (EM) datasets is a widely used tool that has improved our knowledge of synapse ultrastructure and organization in the brain. Rearrangements of synapse structure following maturation and in synaptic plasticity have been broadly described and, in many cases, the defective architecture of the synapse has been associated to functional impairments. It is therefore important, when studying brain connectivity, to map these rearrangements with the highest accuracy possible, considering the affordability of the different EM approaches to provide solid and reliable data about the structure of such a small complex. The aim of this work is to compare quantitative data from two dimensional (2D) and 3D EM of mouse hippocampal CA1 (apical dendrites), to define whether the results from the two approaches are consistent. We examined asymmetric excitatory synapses focusing on post synaptic density and dendritic spine area and volume as well as spine density, and we compared the results obtained with the two methods. The consistency between the 2D and 3D results questions the need—for many applications—of using volumetric datasets (costly and time consuming in terms of both acquisition and analysis), with respect to the more accessible measurements from 2D EM projections.
Comparison of Proteomic Technologies for Blood-Based Detection of Colorectal Cancer
Authors: Bhardwaj Megha , Terzer Tobias , Schrotz-King Petra , Brenner Hermann
Published: January 2021

Blood-based protein biomarkers are increasingly being explored as supplementary or efficient alternatives for population-based screening of colorectal cancer (CRC). The objective of the current study was to compare the diagnostic potential of proteins measured with different proteomic technologies. The concentrations of protein biomarkers were measured using proximity extension assays (PEAs), liquid chromatography/multiple reaction monitoring–mass spectrometry (LC/MRM-MS) and quantibody microarrays (QMAs) in plasma samples of 56 CRC patients and 99 participants free of neoplasms. In another approach, proteins were measured in serum samples of 30 CRC cases and 30 participants free of neoplasm using immunome full-length functional protein arrays (IpAs). From all the measurements, 9, 6, 35 and 14 protein biomarkers overlapped for comparative evaluation of (a) PEA and LC/MRM-MS, (b) PEA and QMA, (c) PEA and IpA, and (d) LC/MRM-MS and IpA measurements, respectively. Correlation analysis was performed, along with calculation of the area under the curve (AUC) for assessing the diagnostic potential of each biomarker. DeLong’s test was performed to assess the differences in AUC. Evaluation of the nine biomarkers measured with PEA and LC/MRM-MS displayed correlation coefficients >+0.6, similar AUCs and DeLong’s p-values indicating no differences in AUCs for biomarkers like insulin-like growth factor binding protein 2 (IGFBP2), matrix metalloproteinase 9 (MMP9) and serum paraoxonase lactonase 3 (PON3). Comparing six proteins measured with PEA and QMA showed good correlation and similar diagnostic performance for only one protein, growth differentiation factor 15 (GDF15). The comparison of 35 proteins measured with IpA and PEA and 14 proteins analyzed with IpA and LC/MRM-MS revealed poor concordance and comparatively better AUCs when measured with PEA and LC/MRM-MS. The comparison of different proteomic technologies suggests the superior performance of novel technologies like PEA and LC/MRM-MS over the assessed array-based technologies in blood-protein-based early detection of CRC.
High Potential of Pichia kluyveri and Other Pichia Species in Wine Technology
Authors: Vicente Javier , Calderón Fernando , Santos Antonio , Marquina Domingo , Benito Santiago
Published: January 2021

The surfaces of grapes are covered by different yeast species that are important in the first stages of the fermentation process. In recent years, non-Saccharomyces yeasts such as Torulaspora delbrueckii, Lachancea thermotolerans, Metschnikowia pulcherrima, and Pichia kluyveri have become popular with regard to winemaking and improved wine quality. For that reason, several manufacturers started to offer commercially available strains of these non-Saccharomyces species. P. kluyveri stands out, mainly due to its contribution to wine aroma, glycerol, ethanol yield, and killer factor. The metabolism of the yeast allows it to increase volatile molecules such as esters and varietal thiols (aroma-active compounds), which increase the quality of specific varietal wines or neutral ones. It is considered a low- or non-fermentative yeast, so subsequent inoculation of a more fermentative yeast such as Saccharomyces cerevisiae is indispensable to achieve a proper fermented alcohol. The impact of P. kluyveri is not limited to the grape wine industry; it has also been successfully employed in beer, cider, durian, and tequila fermentation, among others, acting as a promising tool in those fermentation processes. Although no Pichia species other than P. kluyveri is available in the regular market, several recent scientific studies show interesting improvements in some wine quality parameters such as aroma, polysaccharides, acid management, and color stability. This could motivate yeast manufacturers to develop products based on those species in the near future.
Microbiome-Derived Metabolites in Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Masetti Riccardo , Zama Daniele , Leardini Davide , Muratore Edoardo , Turroni Silvia , Brigidi Patrizia , Pession Andrea
Published: January 2021

The gut microbiome has emerged as a major character in the context of hematopoietic stem cell transplantation. The biology underpinning this relationship is still to be defined. Recently, mounting evidence has suggested a role for microbiome-derived metabolites in mediating crosstalk between intestinal microbial communities and the host. Some of these metabolites, such as fiber-derived short-chain fatty acids or amino acid-derived compounds, were found to have a role also in the transplant setting. New interesting data have been published on this topic, posing a new intriguing perspective on comprehension and treatment. This review provides an updated comprehensive overview of the available evidence in the field of gut microbiome-derived metabolites and hematopoietic stem cell transplantation.
Micellar Carriers of Active Substances Based on Amphiphilic PEG/PDMS Heterograft Copolymers: Synthesis and Biological Evaluation of Safe Use on Skin
Authors: Odrobińska Justyna , Skonieczna Magdalena , Neugebauer Dorota
Published: January 2021

Amphiphilic copolymers containing polydimethylsiloxane (PDMS) and polyethylene glycol methyl ether (MPEG) were obtained via an azide-alkyne cycloaddition reaction between alkyne-functionalized copolymer of MPEG methacrylate and azide-functionalized PDMS. “Click” reactions were carried out with an efficiency of 33–47% increasing grafting degrees. The grafted copolymers were able to carry out the micellization and encapsulation of active substances, such as vitamin C (VitC), ferulic acid (FA) and arginine (ARG) with drug loading content (DLC) in the range of 2–68% (VitC), and 51–89% (FA or ARG). In vitro release studies (phosphate buffer saline, PBS; pH = 7.4 or 5.5) demonstrated that the maximum release of active substances was mainly after 1–2 h. The permeability of released active substances through membrane mimicking skin evaluated by transdermal tests in Franz diffusion cells indicated slight diffusion into the solution (2–16%) and their remaining in the membrane. Studies on the selected carrier with FA showed no negative effect on cell viability, proliferation capacity or senescence, as well as cell apoptosis/necrosis differences or cell cycle interruption in comparison with control cells. These results indicated that the presented micellar systems are good candidates for carriers of cosmetic substances according to physicochemical characterization and biological studies.
New Insights into Development of Female Reproductive Tract—Hedgehog-Signal Response in Wolffian Tissues Directly Contributes to Uterus Development
Authors: Haraguchi Ryuma , Yamada Gen , Murashima Aki , Matsumaru Daisuke , Kitazawa Riko , Kitazawa Sohei
Published: January 2021

The reproductive tract in mammals emerges from two ductal systems during embryogenesis: Wolffian ducts (WDs) and Mullerian ducts (MDs). Most of the female reproductive tract (FRT) including the oviducts, uterine horn and cervix, originate from MDs. It is widely accepted that the formation of MDs depends on the preformed WDs within the urogenital primordia. Here, we found that the WD mesenchyme under the regulation of Hedgehog (Hh) signaling is closely related to the developmental processes of the FRT during embryonic and postnatal periods. Deficiency of Sonic hedgehog (Shh), the only Hh ligand expressed exclusively in WDs, prevents the MD mesenchyme from affecting uterine growth along the radial axis. The in vivo cell tracking approach revealed that after WD regression, distinct cells responding to WD-derived Hh signal continue to exist in the developing FRT and gradually contribute to the formation of various tissues such as smooth muscle, endometrial stroma and vascular vessel, in the mouse uterus. Our study thus provides a novel developmental mechanism of FRT relying on WD.
Puparia Cleaning Techniques for Forensic and Archaeo-Funerary Studies
Authors: Pradelli Jennifer , Tuccia Fabiola , Giordani Giorgia , Vanin Stefano
Published: January 2021

Diptera puparia may represent both in forensic and archaeo-funerary contexts the majority of the entomological evidence useful to reconstruct the peri and post-mortem events. Puparia identification is quite difficult due to the lack of identification keys and descriptions. In addition, external substances accumulated during the puparia permanence in the environment make the visualization of the few diagnostic characters difficult, resulting in a wrong identification. Six different techniques based on physical and chemical treatments have been tested for the removal of external substances from puparia to make identification at species level feasible. Furthermore, the effects of these methods on successful molecular analyses have also been tested as molecular identification is becoming an important tool to complement morphological identifications. The results of this study indicate that cleaning via warm water/soap, the sonication and treatment with a sodium hydroxide solution are the best methods to achieve a good quality of the samples.
NAFLD and Cardiovascular Diseases: Epidemiological, Mechanistic and Therapeutic Considerations
Authors: Niederseer David , Wernly Bernhard , Aigner Elmar , Stickel Felix , Datz Christian
Published: January 2021

Overwhelming evidence suggests an association of cardiovascular disease (CVD) with non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanisms remain largely speculative. It is, however, likely that common mechanisms contribute to the development of CVD and NAFLD, with lifestyle factors such as smoking, sedentary lifestyle with poor nutrition habits and physical inactivity being major candidates. These behavioral factors, on a predisposing genetic background, trigger changes in gut microbiota, inflammation, dyslipidemia and oxidative stress, leading to metabolic syndrome, diabetes and obesity as well as atherosclerosis. Treatment options to counteract both the progression and development of CVD and NAFLD include lifestyle interventions, optimal medical therapy of comorbid conditions and, as final possibility, bariatric surgery. As no causal pharmacotherapy of NAFLD is available, further research is urgently needed to address the unmet need of a growing population with NAFLD and CVD.
Pharmacogenomics of Allopurinol and Sulfamethoxazole/Trimethoprim: Case Series and Review of the Literature
Authors: Ikediobi Ogechi , Schneider Jeremy A.
Published: January 2021

Severe cutaneous adverse drug reactions (SCAR) such as the Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DIHS) can be induced by a plethora of medications. The field of pharmacogenomics aims to prevent severe adverse drug reactions by using our knowledge of the inherited or acquired genetic risk of drug metabolizing enzymes, drug targets, or the human leukocyte antigen (HLA) genotype. Dermatologists are experts in the diagnosis and management of severe cutaneous adverse drug reactions (SCAR) in both the inpatient and outpatient setting. However, most dermatologists in the US have not focused on the prevention of SCAR. Therefore, this paper presents a case series and review of the literature highlighting salient examples of how dermatologists can apply pharmacogenomics in the diagnosis and especially in the prevention of SCAR induced by allopurinol and sulfamethoxazole/trimethoprim, two commonly prescribed medications.
Optimizing the Required Cathodic Protection Current for Pre-Buried Pipelines Using Electrochemical Acceleration Methods
Authors: Chung Nguyen-Thuy , Hong Min-Sung , Kim Jung-Gu
Published: January 2021

Several corrosion mitigation methods are generally applied to pipelines exposed to corrosive environments. However, in the case of pre-buried pipelines, the only option for corrosion inhibition is cathodic protection (CP). To apply CP, the required current should be defined even though the pipeline is covered with various oxide layers. In this study, an electrochemical acceleration test was used to investigate the synthetic soil corrosion of a pre-buried pipeline. Potentiodynamic polarization experiments were first conducted to ascertain the corrosion current density in the environment, and galvanostatic measurements were performed to accelerate corrosion according to the operating time. In addition, corrosion current density and the properties of the rust layer were investigated via potentiodynamic polarization tests and electrochemical impedance spectroscopy (EIS) tests. The variation in surface corrosion was subsequently analyzed via optical microscopy (OM) and X-ray diffraction (XRD) measurements. Finally, an empirical equation for the optimized CP current requirement, according to the pipeline service time, was derived. This equation can be applied to any corroded pipeline.
Long-Term Compressive Strength Development of Steel Fiber Shotcrete from Cores Based on Accelerator Types at Tunnel Site
Authors: Yun Kyong Ku , Choi Seunghak , Ha Taeho , Kim Seong Kwon , Hossain Mohammad Shakhawat , Han Seungyeon
Published: January 2021

In this study, cement minerals, aluminates, and alkali-free accelerators incorporated with steel fiber were used to scrutinize the influence of accelerating agents on the long-term performance of tunneling shotcrete. Performance tests were identified based on the core compressive strength of mix shotcrete specimens with different types of accelerating agents throughout timeframes of 1, 3, 6, and 12 months. Here, 37 kg of steel fiber was incorporated into the cement mineral and aluminate mixes, and 40 kg of steel fiber was incorporated in an alkali-free mix for the shotcrete mix design. The KSF 2784 and ASTM 214 standards were followed for specimen fabrication and core cutting. For all specimens, shotcrete test panels of 250 × 600 × 500 mm were manufactured for core compressive strength tests conducted using 100, 75 and 55 mm diameter cylindrical molds and a length-to-diameter ratio of 2. The 1-month compressive strength of all test variables satisfied the Korea Expressway Co. standard of 21 MPa. The core compressive strength of the shotcrete specimens showed a tendency to increase with age, but a strength reduction occurred in 6 months and increased again at 12 months. Moreover, the impact of the diameter changes in the shotcrete core specimens was analyzed based on the mixing. For 12 months, a large increase in the core compressive strength occurred, particularly in the alkali-free specimens. The comparison also focused on the relative strength compared with a cast concrete mold and shotcrete core specimens. It is necessary to use alkali-free accelerators considering the long-term performance of tunnels and worker safety.
Chemical Synthesis and NMR Solution Structure of Conotoxin GXIA from Conus geographus
Authors: Armstrong David A. , Jin Ai-Hua , Braga Emidio Nayara , Lewis Richard J. , Alewood Paul F. , Rosengren K. Johan
Published: January 2021

Conotoxins are disulfide-rich peptides found in the venom of cone snails. Due to their exquisite potency and high selectivity for a wide range of voltage and ligand gated ion channels they are attractive drug leads in neuropharmacology. Recently, cone snails were found to have the capability to rapidly switch between venom types with different proteome profiles in response to predatory or defensive stimuli. A novel conotoxin, GXIA (original name G117), belonging to the I3-subfamily was identified as the major component of the predatory venom of piscivorous Conus geographus. Using 2D solution NMR spectroscopy techniques, we resolved the 3D structure for GXIA, the first structure reported for the I3-subfamily and framework XI family. The 32 amino acid peptide is comprised of eight cysteine residues with the resultant disulfide connectivity forming an ICK+1 motif. With a triple stranded β-sheet, the GXIA backbone shows striking similarity to several tarantula toxins targeting the voltage sensor of voltage gated potassium and sodium channels. Supported by an amphipathic surface, the structural evidence suggests that GXIA is able to embed in the membrane and bind to the voltage sensor domain of a putative ion channel target.
The Role of New Technologies to Prevent Suicide in Adolescence: A Systematic Review of the Literature
Authors: Forte Alberto , Sarli Giuseppe , Polidori Lorenzo , Lester David , Pompili Maurizio
Published: January 2021

Background and objectives: Suicide in adolescents represents a major public health concern. To date, a growing number of suicide preventive strategies based on the use of new technologies are emerging. We aimed to provide an overview of the present literature on the use of new technologies in adolescent suicide prevention. Materials and methods: An electronic search was run using the following keywords: Technology OR Technologies OR APP OR Application OR mobile application) AND (Adolescent OR youth OR puberty) AND (Suicid* OR Self-harm OR self-destruction). Inclusion criteria were: English language, published in a peer-reviewed journal, suicide prevention with the use of new technologies among adolescents. Results: Our search strategy yielded a total of 12 studies on the use of telemedicine, 7 on mobile applications, and 3 on language detection. We also found heterogeneity regarding the study design: 3 are randomized controlled trials (RCT), 13 are open-label single group trials, 2 are randomized studies, and 1 is a cross-sectional study. Telemedicine was the most adopted tool, especially web-based approaches. Mobile applications mostly focused on screening of depressive symptoms and suicidal ideation, and for clinical monitoring through the use of text messages. Although telepsychiatry and mobile applications can provide a fast and safe tool, supporting and preceding a face-to-face clinical assessment, only a few studies demonstrated efficacy in preventing suicide among adolescents through the use of these interventions. Some studies suggested algorithms able to recognize people at risk of suicide from the exploration of the language on social media posts. Conclusions: New technologies were found to be well accepted and tolerated supports for suicide prevention in adolescents. However, to date, few data support the use of such interventions in clinical practice and preventive strategies. Further studies are needed to test their efficacy in suicide prevention among adolescents and young adults.
Review of Medical Therapies for the Management of Pulmonary Embolism
Authors: Panahi Ladan , Udeani George , Horseman Michael , Weston Jaye , Samuel Nephy , Joseph Merlyn , Mora Andrea , Bazan Daniela
Published: January 2021

Traditionally, the management of patients with pulmonary embolism has been accomplished with anticoagulant treatment with parenteral heparins and oral vitamin K antagonists. Although the administration of heparins and oral vitamin K antagonists still plays a role in pulmonary embolism management, the use of these therapies are limited due to other options now available. This is due to their toxicity profile, clearance limitations, and many interactions with other medications and nutrients. The emergence of direct oral anticoagulation therapies has led to more options now being available to manage pulmonary embolism in inpatient and outpatient settings conveniently. These oral therapeutic options have opened up opportunities for safe and effective pulmonary embolism management, as more evidence and research is now available about reversal agents and monitoring parameters. The evolution of the pharmacological management of pulmonary embolism has provided us with better understanding regarding the selection of anticoagulants. There is also a better understanding and employment of anticoagulants in pulmonary embolism in special populations, such as patients with liver failure, renal failure, malignancy, and COVID-19.
High-Temperature Oxidation Resistance of Alumina-Forming Austenitic Stainless Steels Optimized by Refractory Metal Alloying
Authors: Zhang Shuqi , Dong Dandan , Wang Qing , Dong Chuang , Yang Rui
Published: January 2021

Alumina-forming austenitic stainless steels are known for their superior high-temperature oxidation resistance. Following our previous work that solved the matching of major alloying elements in their specific 16-atom cluster formula, we here focus on the 800 °C air-oxidation resistance of 0.08 wt. % C alloy series satisfying cluster formula [(Al0.89Si0.05NbxTa0.06−x)-(Fe11.7−yNiyMn0.3)]Cr3.0−z(Mo,W)z, x = 0.03 or 0.06, y = 3.0 or 3.2, z = 0.07 or 0.2, to explore the effect of minor alloying elements Mo, Nb, Ta and W. This cluster formula is established particularly based on alloys which were originally developed by Oak Ridge National Laboratory. All samples are graded as complete oxidation resistance level according to Chinese standard HB 5258-2000, as their oxidation rate and oxidation-peeling mass are generally below 0.1 g/m2 × h and 1.0 g/m2, respectively. In alloys without Ta and W, a Cr2O3-type oxide layer is formed on the surface and Al2O3 particles of sizes up to 4 μm are distributed beneath it. In contrast, in Ta/W-containing alloys, a continuous protective Al2O3 layer is formed beneath the outer Cr2O3 layer, which prevents internal oxidation and provides the lowest weight gain. Instead of internal Al2O3 particles, AlN is formed in Ta/W-containing alloys. The W-containing alloy possesses the thinnest internal nitride zone, indicating the good inhibition effect of W on nitrogen diffusion.
Mechanism of Phosphorus Enrichment in Dephosphorization Slag Produced Using the Technology of Integrating Dephosphorization and Decarburization
Authors: Xue Haimeng , Li Jie , Xia Yunjin , Wan Yong , Chen Liangjun , Lv Changji
Published: January 2021

In order to better understand and develop the technology of integrating dephosphorization and decarburization in a single converter (abbreviated as IDDSC), the relevant thermodynamic issues were discussed by calculation. Based on the thermodynamic calculation, the bridges between the phosphorus distribution ratio, temperature, and slag composition were constructed. Besides, the connections between the dephosphorization behavior and the microstructure of slag were also established by investigating four heats of hot metal smelt using IDDSC technology. As a result, the mechanism of phosphorus enrichment in the dephosphorization slag was revealed. Also, the results show that the dephosphorization efficiency increases gradually with increasing slag basicity. While the dephosphorization efficiency increases first and then decreases with the increase of FeO content in slag. There is a competition relationship between P2O5 and FeO in reacting with CaO and SiO2. When CaO/FeO is relatively high, not enough FeO is provided. Thus P2O5 is in priority to react with CaO and SiO2 through [3n + 2](CaO) + 2SiO2 + n(P2O5) = n(3CaO·P2O5)-2CaO·SiO2(s), generating P2O5-rich nC2S-C3P solid solution which promotes the removal of [P] from the hot metal. When CaO/FeO is relatively low, FeO competes over P2O5 in reacting with CaO and SiO2 through a(CaO) + b(SiO2) + c(FeO) = aCaO·bSiO2·cFeO(s), generating CaFeSiO4 instead of P2O5-rich solid solution. As a consequence, the slag with low CaO/FeO shows a poor dephosphorization ability.
Influence of the Thickness of the Reaction Zone in Aluminum/Stainless Steel Brazed Joints on the Mechanical Properties
Authors: Fedorov Vasilii , Uhlig Thomas , Wagner Guntram
Published: January 2021

The study deals with the characterization of the relationship between the microstructure of the reaction zone and the mechanical properties in the brazed joints of aluminum alloy 3003 and stainless steel AISI 304 in order to determine the influence of the intermetallic layers on the tensile shear strength of the joints. The joints were produced by induction brazing using an AlSi10 filler in an argon atmosphere at a temperature of 600 °C. Due to the local heat input into the liquid brazing filler during a short brazing time, a thin reaction zone is formed in the brazed joints (~1 µm), which ensures good mechanical properties of the joints. In order to observe the growth kinetics of the reaction zone in the brazed joints and to investigate the influence of the thickness of the reaction zone on the mechanical properties of the brazed joints, the joints were aged at temperatures of 200 °C and 500 °C for 6, 48 and 120 h. The results have shown that the thickness of this layer increases to a maximum of 2 µm depending on the duration of the thermal aging at a temperature of 200 °C. The results of the tensile shear strength tests have shown that the brazed joints with this thin layer ensure a high strength. The thermal aging at a temperature of 500 °C influences the growth of the reaction zone in the brazed joints significantly. The total thickness of the reaction zone increases to a maximum of 12 µm during the thermal aging. The results of the tensile shear tests of these joints have shown that the thermal aging at a higher temperature leads to a decrease of the tensile shear strength of the brazed joints to 67% due to the growth of the existing intermetallic layer and the formation of a new intermetallic layer in the reaction zone.
Identification of Circulating Endocan-1 and Ether Phospholipids as Biomarkers for Complications in Thalassemia Patients
Authors: Botta Amy , Forest Anik , Daneault Caroline , Pantopoulos Kostas , Tantiworawit Adisak , Phrommintikul Arintaya , Chattipakorn Siriporn , Chattipakorn Nipon , Des Rosiers Christine , Sweeney Gary
Published: January 2021

Despite advances in our knowledge and attempts to improve therapies, β-thalassemia remains a prevalent disorder with increased risk for the development of cardiomyopathy. Using an untargeted discovery-based lipidomic workflow, we uncovered that transfusion-dependent thalassemia (TDT) patients had a unique circulating lipidomic signature consisting of 387 lipid features, allowing their significant discrimination from healthy controls (Q-value < 0.01). In particular, TDT patients had elevated triacylglycerols and long-chain acylcarnitines, albeit lower ether phospholipids or plasmalogens, sphingomyelins, and cholesterol esters, reminiscent of that previously characterized in cardiometabolic diseases resulting from mitochondrial and peroxisomal dysfunction. Discriminating lipid (sub)classes correlated differentially with clinical parameters, reflecting blood (ether phospholipids) and iron (cholesterol ester) status or heart function (triacylglycerols). We also tested 15 potential serum biomarkers related to cardiometabolic disease and found that both lipocalin-2 and, for the first time, endocan-1 levels were significantly elevated in TDT patients and showed a strong correlation with blood parameters and three ether diacylglycerophosphatidylcholine species. In conclusion, this study identifies new characteristics of TDT patients which may have relevance in developing biomarkers and therapeutics.
Reproducibility of Baseline Tumour Metabolic Volume Measurements in Diffuse Large B-Cell Lymphoma: Is There a Superior Method?
Authors: Eude Florian , Toledano Mathieu Nessim , Vera Pierre , Tilly Hervé , Mihailescu Sorina-Dana , Becker Stéphanie
Published: January 2021

The metabolic tumour volume (MTV) is an independent prognostic indicator in diffuse large B-cell lymphoma (DLBCL). However, its measurement is not standardised and is subject to wide variations depending on the method used. This study aimed to compare the reproducibility of MTV measurement as well as the thresholds obtained for each method and their prognostic values. The baseline MTV was measured in 239 consecutive patients treated at Henri Becquerel Centre by two blinded evaluators. Eight methods were compared: 3 absolute (SUV (standardised uptake value) ≥ 2.5; SUV≥ liver SUVmax; SUV≥ PERCIST SUV), 1 percentage SUV threshold method (SUV ≥ 41% SUVmax) and 4 adaptive methods (Daisne, Nestle, Fitting, Black). The intraclass correlation coefficients were excellent, from 0.91 to 0.96, for the absolute SUV methods, Black and Nestle methods, and good for 41% SUVmax, Fitting and Daisne methods (0.82 to 0.88), with a significantly lower variability with absolute methods compared to 41% SUVmax (p < 0.04). Thresholds were found to be specific to each segmentation method and ranged from 295 to 552 cm3. There was a strong correlation between the MTV and patient prognosis regardless of the segmentation method used (p = 0.001 for PFS and OS). The largest inter-observer cut-off variability was observed in the 41% SUVmax method, which resulted in more inter-observer disagreements in the classification of patients between high and low MTV groups. MTV measurements based on absolute SUV criteria were found to be significantly more reproducible than those based on 41% SUVmax criteria. The threshold was specific for each of eight segmentation methods, but all predicted prognosis.
The Influence of the Different Repair Methods on the Electrical Properties of the Normally off p-GaN HEMT
Authors: Niu Di , Wang Quan , Li Wei , Chen Changxi , Xu Jiankai , Jiang Lijuan , Feng Chun , Xiao Hongling , Wang Qian , Xu Xiangang , Wang Xiaoliang
Published: January 2021

The influence of the repair process on the electrical properties of the normally off p-GaN high-electron-mobility transistor (HEMT) is studied in detail in this paper. We find that the etching process will cause the two-dimensional electron gas (2DEG) and the mobility of the p-GaN HEMT to decrease. However, the repair process will gradually recover the electrical properties. We study different repair methods and different repair conditions, propose the best repair conditions, and further fabricate the p-GaN HEMTs devices. The threshold voltage of the fabricated device is 1.6 V, the maximum gate voltage is 7 V, and the on-resistance is 23 Ω·mm. The device has a good performance, which proves that the repair conditions can be successfully applied to the fabricate of the p-GaN HEMT devices.
Investigation of Fusion between Nanosized Lipid Vesicles and a Lipid Monolayer Toward Formation of Giant Lipid Vesicles with Various Kinds of Biomolecules
Authors: Kamiya Koki , Arisaka Chika , Suzuki Masato
Published: January 2021

We determined the properties of fusion between large unilamellar vesicles (LUVs) and the lipid monolayer by measuring the fluorescence intensity of rhodamine-conjugated phospholipids in cell-sized lipid vesicles. The charge of LUVs (containing cationic lipids) and lipid droplets (containing anionic lipids) promoted lipid membrane fusion. We also investigated the formation of cell-sized lipid vesicles with asymmetric lipid distribution using this fusion method. Moreover, cell-sized asymmetric ganglioside vesicles can be generated from the planar lipid bilayer formed at the interface between the lipid droplets with/without LUVs containing ganglioside. The flip-flop dynamics of ganglioside were observed on the asymmetric ganglioside vesicles. This fusion method can be used to form asymmetric lipid vesicles with poor solubility in n-decane or lipid vesicles containing various types of membrane proteins for the development of complex artificial cell models.
Coupling of a Novel TIMP3 Peptide to Carboxypeptidase G2 for Pro-Drug Activation at the Tumour Site
Authors: Aldughaim Mohammed S. , Alsaffar Fatimah , Barker Michael D.
Published: January 2021

Broad-spectrum cytotoxic drugs have been used in cancer therapy for decades. However, their lack of specificity to cancer cells often results in serious side-effects, limiting efficacy. For this reason, antibodies have been used to attempt to specifically target cytotoxic drugs to tumours. One such approach is antibody-directed enzyme prodrug therapy (ADEPT) which uses a tumour-directed monoclonal antibody, coupled to an enzyme, to convert a systemically administered non-toxic prodrug into a toxic one only at the tumour site. Among the main drawbacks of ADEPT is the immunogenicity of the antibody-enzyme complex, which is exacerbated by slow clearance due to size, hence limiting repeated administration. Additionally, the mono-specificity of the antibody could potentially result in drug resistance with repeated administration. We have identified a novel short peptide sequence, p700, derived from a human tissue inhibitor of metalloproteinases-3 (TIMP-3), which binds to and inhibits a number of tyrosine kinase growth factor receptors (VEGFRs1-3, FGFRs 1-4 and PDGFRα) which are known to be upregulated in many tumours and tumour vasculature. In this report, we fused p700 to His-tagged, codon-optimised, carboxypeptidase G2 (CPG2). CPG2 is a bacterial enzyme used in ADEPT, which activates potent nitrogen-mustard pro-drugs by removal of an inhibitory glutamic acid residue. Recombinant CPG2-p700 was highly expressed in Escherichia coli and successfully purified by nickel affinity chromatography. Biolayer interferometry showed that CPG2-p700 had a 100-fold increase in binding affinity for VEGFR2 compared with CPG2 alone and retained its catalytic activity, as determined by methotrexate cleavage. In the presence of CPG2-p700, the ZD2676P pro-drug showed significant cytotoxicity for 4T1 cells compared with prodrug alone or CPG2 alone. p700 is, therefore, a potentially useful alternative to monoclonal antibodies for enzyme pro-drug therapy and could equally be used for effective delivery of other cytotoxic drugs to tumour tissue.
The Structures, Molecular Orbital Properties and Vibrational Spectra of the Homo- and Heterodimers of Sulphur Dioxide and Ozone. An Ab Initio Study
Authors: Ford Thomas A.
Published: January 2021

The structures of a number of dimers of sulphur dioxide and ozone were optimized by means of a series of ab initio calculations. The dimer species were classified as either genuine energy minima or transition states of first or higher order, and the most probable structures consistent with the experimental data were confirmed. The molecular orbitals engaged in the interactions resulting in adduct formation were identified and relations between the orbitals of the dimers of the valence isoelectronic monomer species were examined. The vibrational spectra of the most probable structures were computed and compared with those reported in the literature, particularly with spectra observed in cryogenic matrices. The calculations were extended to predict the properties of a number of possible heterodimers formed between sulphur dioxide and ozone.
Surface Permeability of Membrane and Catalytic Performance Based on Redox-Responsive of Hybrid Hollow Polymeric Microcapsules
Authors: Wu Guangyu , Wang Jingyi , Liu Qi , Lu Ran , Wei Yuhan , Cheng Feng , Han Jiangang , Xing Weinan , Huang Yudong
Published: January 2021

“Smart” polymeric microcapsules with excellent permeability of membranes have drawn considerable attention in scientific and industrial research such as drug delivery carriers, microreactors, and artificial organelles. In this work, hybrid hollow polymeric microcapsules (HPs) containing redox-active gold-sulfide bond were prepared with bovine serum albumin, inorganic metal cluster (AuNCs), and poly(N-isopropylacrylamide) conjugates by using Pickering emulsion method. HPs were transferred from water-in-oil to water-in-water by adding PEGbis(N-succinimidylsuccinate). To achieve redox-responsive membrane, the Au-S bond units incorporated into the microcapsules’ membranes, allowed us to explore the effects of a new stimuli, that is, the redox Au-S bond breaking on the microcapsules’ membranes. The permeability of these hybrid hollow polymeric microcapsules could be sensitively tuned via adding environment-friendly hydrogen peroxide (H2O2), resulting from a fast fracture of Au-S bond. Meanwhile, AuNCs and conjugates could depart from the microcapsules, and enhance the permeability of the membrane. Based on the excellent permeability of the membrane, phosphatase was encapsuled into HPs and p-nitrophenyl phosphate as a substrate. After adding 1 × 10−2 and 1 × 10−4 M H2O2, the catalytic efficiency was nearly 4.06 and 2.22 times higher than that of HPs in the absence of H2O2, respectively. Hence, the unique redox-responsive HPs have potential applications in biocatalytic reaction, drug delivery, and materials as well as in bioscience.
Recent Advances in Nanosystems and Strategies for Vaginal Delivery of Antimicrobials
Authors: Chindamo Giulia , Sapino Simona , Peira Elena , Chirio Daniela , Gallarate Marina
Published: January 2021

Vaginal infections such as bacterial vaginosis (BV), chlamydia, gonorrhea, genital herpes, candidiasis, and trichomoniasis affect millions of women each year. They are caused by an overgrowth of microorganisms, generally sexually transmitted, which in turn can be favored by alterations in the vaginal flora. Conventional treatments of these infections consist in systemic or local antimicrobial therapies. However, in the attempt to reduce adverse effects and to contrast microbial resistance and infection recurrences, many efforts have been devoted to the development of vaginal systems for the local delivery of antimicrobials. Several topical dosage forms such as aerosols, lotions, suppositories, tablets, gels, and creams have been proposed, although they are sometimes ineffective due to their poor penetration and rapid removal from the vaginal canal. For these reasons, the development of innovative drug delivery systems, able to remain in situ and release active agents for a prolonged period, is becoming more and more important. Among all, nanosystems such as liposomes, nanoparticles (NPs), and micelles with tunable surface properties, but also thermogelling nanocomposites, could be exploited to improve local drug delivery, biodistribution, retention, and uptake in vulvovaginal tissues. The aim of this review is to provide a survey of the variety of nanoplatforms developed for the vaginal delivery of antimicrobial agents. A concise summary of the most common vaginal infections and of the conventional therapies is also provided.
Gold Nanoparticles: Can They Be the Next Magic Bullet for Multidrug-Resistant Bacteria?
Authors: Okkeh Mohammad , Bloise Nora , Restivo Elisa , De Vita Lorenzo , Pallavicini Piersandro , Visai Livia
Published: January 2021

In 2017 the World Health Organization (WHO) announced a list of the 12 multidrug-resistant (MDR) families of bacteria that pose the greatest threat to human health, and recommended that new measures should be taken to promote the development of new therapies against these superbugs. Few antibiotics have been developed in the last two decades. Part of this slow progression can be attributed to the surge in the resistance acquired by bacteria, which is holding back pharma companies from taking the risk to invest in new antibiotic entities. With limited antibiotic options and an escalating bacterial resistance there is an urgent need to explore alternative ways of meeting this global challenge. The field of medical nanotechnology has emerged as an innovative and a powerful tool for treating some of the most complicated health conditions. Different inorganic nanomaterials including gold, silver, and others have showed potential antibacterial efficacies. Interestingly, gold nanoparticles (AuNPs) have gained specific attention, due to their biocompatibility, ease of surface functionalization, and their optical properties. In this review, we will focus on the latest research, done in the field of antibacterial gold nanoparticles; by discussing the mechanisms of action, antibacterial efficacies, and future implementations of these innovative antibacterial systems.
Microbiome as Mediator of Diet on Colorectal Cancer Risk: The Role of Vitamin D, Markers of Inflammation and Adipokines
Authors: Serrano Davide , Pozzi Chiara , Guglietta Silvia , Fosso Bruno , Suppa Mariano , Gnagnarella Patrizia , Corso Federica , Bellerba Federica , Macis Debora , Aristarco Valentina , Manghi Paolo , Segata Nicola , Trovato Cristina , Zampino Maria Giulia , Marzano Marinella , Bonanni Bernardo , Rescigno Maria , Gandini Sara
Published: January 2021

Obesity and diet are associated with colorectal cancer (CRC) risk, and microbiome could mediate this risk factor. To investigate this interaction, we performed a case–control study (34 CRC cases and 32 controls) and analyzed fecal microbiota composition using 16S rRNA metabarcoding and sub-sequential shotgun analyses of genomic bacterial DNA to evaluate the role of microbiome and diet in CRC etiology, taking into account vitamin D and other risk biomarkers. Dietary habits were evaluated using a short questionnaire. Multivariate methods for data integration and mediation analysis models were used to investigate causal relationships. CRC cases were significantly more often deficient in vitamin D than controls (p = 0.04); FokI and CYP24A1 polymorphism frequency were different between cases and controls (p = 0.03 and p = 0.02, respectively). A diet poor in fatty fish and rich in carbohydrates was found to be significantly associated with CRC risk (p = 0.011). The mediation analysis confirmed the significant role of the microbiome in mediating CRC risk—increasing levels of Bifidobacteria/Escherichia genera ratio, an indicator of “healthy” intestinal microbiome, can overcome the effect of diet on CRC risk (p = 0.03). This study suggests that microbiome mediates the diet effect on CRC risk, and that vitamin D, markers of inflammation, and adipokines are other factors to consider in order to achieve a better knowledge of the whole carcinogenic process.
Malnutrition According to GLIM Criteria Is Associated with Mortality and Hospitalizations in Rehabilitation Patients with Stable Chronic Obstructive Pulmonary Disease
Authors: Dávalos-Yerovi Vanesa , Marco Ester , Sánchez-Rodríguez Dolores , Duran Xavier , Meza-Valderrama Delky , Rodríguez Diego A. , Muñoz Elena , Tejero-Sánchez Marta , Muns Maria Dolors , Guillén-Solà Anna , Duarte Esther
Published: January 2021

Malnutrition has a negative impact on patients with chronic pulmonary obstructive disease (COPD). The purpose of this study was to assess the prevalence of malnutrition, defined by the Global Leadership Initiative for Malnutrition (GLIM), in stable COPD patients referred to pulmonary rehabilitation, and to explore potential associations of malnutrition according to GLIM, and its components, with increased risk of mortality and hospitalizations in 2 years. In a post-hoc analysis of a prospective cohort of 200 rehabilitation patients with stable COPD, main outcome variables were hospital admissions, length of stay, and mortality during a 2-year follow-up. Covariates were malnutrition according to GLIM and its phenotypic criteria: unintentional weight loss, low body mass index (BMI), and low fat-free mass (FFM). Univariate and multivariate analysis were performed using logistic and proportional hazard Cox regression. Malnutrition according to GLIM showed 45% prevalence and was associated with increased mortality risk. Low age-related BMI and FFM were independently associated with mortality, which persisted after adjustment for age and lung function. Malnutrition and low BMI were also associated with increased risk of hospitalization. Malnutrition according to GLIM criteria was highly prevalent in rehabilitation patients with COPD and was associated with nearly 3 times greater mortality and hospitalization risk.
A Comprehensive Review Evaluating the Impact of Protein Source (Vegetarian vs. Meat Based) in Hepatic Encephalopathy
Authors: Iqbal Umair , Jadeja Ravirajsinh N. , Khara Harshit S. , Khurana Sandeep
Published: January 2021

Hepatic encephalopathy (HE) is a common neurological consequence in patients with cirrhosis and has a healthcare burden of USD 5370 to 50,120 per patient annually. HE significantly hampers the quality of life and is a major cause of morbidity and mortality. Patients with cirrhosis are at a high risk for protein-calorie malnutrition due to altered metabolism. Current evidence has changed the old belief of protein restriction in patients with cirrhosis and now 1.2 to 1.5 g/kg/day protein intake is recommended. Case series and studies with small numbers of participants showed that a vegetarian protein diet decreases the symptoms of HE when compared to a meat-based diet, but the evidence is limited and requires further larger randomized controlled trials. However, vegetable or milk-based protein diets are good substitutes for patients averse to meat intake. Branch chain amino acids (BCAA) (leucine, isoleucine and valine) have also been shown to be effective in alleviating symptoms of HE and are recommended as an alternative therapy in patients with cirrhosis for the treatment of HE. In this review, we provide an overview of current literature evaluating the role of protein intake in the management of HE in cirrhosis.