bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted Extracellular Vesicles Delivered Verrucarin A to Treat Glioblastoma
Authors: Chen Kai , Si Yingnan , Guan Jia-Shiung , Zhou Zhuoxin , Kim Seulhee , Kim Taehyun , Shan Liang , Willey Christopher D. , Zhou Lufang , Liu Xiaoguang
Published: January 2022

Glioblastomas, accounting for approximately 50% of gliomas, comprise the most aggressive, highly heterogeneous, and malignant brain tumors. The objective of this study was to develop and evaluate a new targeted therapy, i.e., highly potent natural compound verrucarin A (Ver-A), delivered with monoclonal antibody-directed extracellular vesicle (mAb-EV). First, the high surface expression of epidermal growth factor receptor (EGFR) in glioblastoma patient tissue and cell lines was confirmed using immunohistochemistry staining, flow cytometry, and Western blotting. mAb-EV-Ver-A was constructed by packing Ver-A and tagging anti-EGFR mAb to EV generated from HEK293F culture. Confocal microscopy and the In Vivo Imaging System demonstrated that mAb-EV could penetrate the blood–brain barrier, target intracranial glioblastoma xenografts, and deliver drug intracellularly. The in vitro cytotoxicity study showed IC50 values of 2–12 nM of Ver-A. The hematoxylin and eosin staining of major organs in the tolerated dose study indicated minimal systemic toxicity of mAb-EV-Ver-A. Finally, the in vivo anti-tumor efficacy study in intracranial xenograft models demonstrated that EGFR mAb-EV-Ver-A effectively inhibited glioblastoma growth, but the combination with VEGF mAb did not improve the therapeutic efficacy. This study suggested that mAb-EV is an effective drug delivery vehicle and natural Ver-A has great potential to treat glioblastoma.
Postprandial Hyperlipidemia: Association with Inflammation and Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis
Authors: Mena-Vázquez Natalia , Redondo-Rodríguez Rocío , Rioja José , Jimenez-Nuñez Francisco Gabriel , Manrique-Arija Sara , Lisbona-Montañez Jose Manuel , Cano-García Laura , Rojas-Gimenez Marta , Ureña Inmaculada , Valdivielso Pedro , Fernández-Nebro Antonio
Published: January 2022

Objective: To describe postprandial lipidemia in patients with rheumatoid arthritis (RA) and to analyze its association with subclinical atherosclerosis and inflammatory activity. Methods: Observational study of 80 cases of RA and 80 sex- and age-matched controls. We excluded individuals with dyslipidemia. Postprandial hyperlipidemia (PPHL) was defined as postprandial triglycerides >220 mg/dL and/or postprandial ApoB48 levels >75th percentile (>p75). Plasma lipids, cholesterol, triglycerides, ApoB48, and total ApoB were evaluated at baseline and after a meal. Other variables analyzed included subclinical atherosclerosis (defined as presence of carotid atheromatous plaque), inflammatory activity (disease activity score (DAS28-ESR)), cytokines, apolipoproteins, and physical activity. A multivariate analysis was performed to identify factors associated with PPHL in patients with RA. Results: A total of 75 patients with RA and 67 healthy controls fulfilled the inclusion criteria. PPHL was more frequent in patients with RA than controls (No. (%), 29 (38.70) vs. 15 (22.40); p = 0.036), as was subclinical atherosclerosis (No. (%), 22 (30.10) vs. 10 (14.90); p = 0.032). PPHL in patients with RA was associated with subclinical atherosclerosis (OR (95% CI) 4.69 (1.09–12.11); p = 0.037), TNF-α (OR (95% CI) 2.00 (1.00–3.98); p = 0.048), high-sensitivity C-reactive protein (OR (95% CI) 1.10 (1.01–1.19); p = 0.027), and baseline triglycerides (OR (95% CI) 1.02 (1.00–1.04); p = 0.049). Conclusion: PPHL was more frequent in patients with RA than in controls. PPHL in patients with RA was associated with inflammation and subclinical atherosclerosis.
Photodynamic Therapy (PDT) in Prosthodontics: Disinfection of Human Teeth Exposed to Streptococcus mutans and the Effect on the Adhesion of Full Ceramic Veneers, Crowns, and Inlays: An In Vitro Study
Authors: Tisler Corina Elena , Chifor Radu , Badea Mindra Eugenia , Moldovan Marioara , Prodan Doina , Carpa Rahela , Cuc Stanca , Chifor Ioana , Badea Alexandru Florin
Published: January 2022

The use of PDT in prosthodontics as a disinfection protocol can eradicate bacteria from tooth surfaces by causing the death of the microorganisms to which the photosensitizer binds, absorbing the energy of laser light during irradiation. The aim of the study was to investigate the capacity of PDT to increase the bond strength of full ceramic restorations. In this study, 45 extracted human teeth were prepared for veneers, crowns, and inlays and contaminated with Streptococcus mutans. Tooth surfaces decontamination was performed using a diode laser and methylene blue as a photosensitizer. The disinfection effect and the impact on tensile bond strength were evaluated by scanning electron microscopy (SEM) and pull-out tests of the cemented ceramic prosthesis. Results show that the number of bacteria was reduced from colonized prepared tooth surfaces, and the bond strength was increased when PDT was used. In conclusion, the present study indicates that using PDT as a protocol before the final adhesive cementation of ceramic restorations could be a promising approach, with outstanding advantages over conventional methods.
The Effects of HP0044 and HP1275 Knockout Mutations on the Structure and Function of Lipopolysaccharide in Helicobacter pylori Strain 26695
Authors: Liu Ai-Ning , Teng Kai-Wen , Chew Yongyu , Wang Po-Chuan , Nguyen Tram Thi Hong , Kao Mou-Chieh
Published: January 2022

Helicobacter pylori infection is associated with several gastric diseases, including gastritis, peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphatic tissue (MALT) lymphoma. Due to the prevalence and severeness of H. pylori infection, a thorough understanding of this pathogen is necessary. Lipopolysaccharide, one of the major virulence factors of H. pylori, can exert immunomodulating and immunostimulating functions on the host. In this study, the HP0044 and HP1275 genes were under investigation. These two genes potentially encode GDP-D-mannose dehydratase (GMD) and phosphomannomutase (PMM)/phosphoglucomutase (PGM), respectively, and are involved in the biosynthesis of fucose. HP0044 and HP1275 knockout mutants were generated; both mutants displayed a truncated LPS, suggesting that the encoded enzymes are not only involved in fucose production but are also important for LPS construction. In addition, these two gene knockout mutants exhibited retarded growth, increased surface hydrophobicity and autoaggregation as well as being more sensitive to the detergent SDS and the antibiotic novobiocin. Furthermore, the LPS-defective mutants also had significantly reduced bacterial infection, adhesion and internalization in the in vitro cell line model. Moreover, disruptions of the HP0044 and HP1275 genes in H. pylori altered protein sorting into outer membrane vesicles. The critical roles of HP0044 and HP1275 in LPS biosynthesis, bacterial fitness and pathogenesis make them attractive candidates for drug inventions against H. pylori infection.
Status and Perspectives of Commercial Aircraft Morphing
Authors: Giuliani Michelangelo , Dimino Ignazio , Ameduri Salvatore , Pecora Rosario , Concilio Antonio
Published: January 2022

In a previous paper, the authors dealt with the current showstoppers that inhibit commercial applicability of morphing systems. In this work, the authors express a critical vision of the current status of the proposed architectures and the needs that should be accomplished to make them viable for installation onboard of commercial aircraft. The distinction is essential because military and civil issues and necessities are very different, and both the solutions and difficulties to be overcome are widely diverse. Yet, still remaining in the civil segment, there can be other differences, depending on the size of the aircraft, from large jets to commuters or general aviation, which are classifiable in tourism, acrobatic, ultralight, and so on, each with their own peculiarities. Therefore, the paper aims to trace a common technology denominator, if possible, and envisage a future perspective of actual applications.
Claudins and Gastric Cancer: An Overview
Authors: Hashimoto Itaru , Oshima Takashi
Published: January 2022

Despite recent improvements in diagnostic ability and treatment strategies, advanced gastric cancer (GC) has a high frequency of recurrence and metastasis, with poor prognosis. To improve the treatment results of GC, the search for new treatment targets from proteins related to epithelial–mesenchymal transition (EMT) and cell–cell adhesion is currently being conducted. EMT plays an important role in cancer metastasis and is initiated by the loss of cell–cell adhesion, such as tight junctions (TJs), adherens junctions, desmosomes, and gap junctions. Among these, claudins (CLDNs) are highly expressed in some cancers, including GC. Abnormal expression of CLDN1, CLDN2, CLDN3, CLDN4, CLDN6, CLDN7, CLDN10, CLDN11, CLDN14, CLDN17, CLDN18, and CLDN23 have been reported. Among these, CLDN18 is of particular interest. In The Cancer Genome Atlas, GC was classified into four new molecular subtypes, and CLDN18–ARHGAP fusion was observed in the genomically stable type. An anti-CLDN18.2 antibody drug was recently developed as a therapeutic drug for GC, and the results of clinical trials are highly predictable. Thus, CLDNs are highly expressed in GC as TJs and are expected targets for new antibody drugs. Herein, we review the literature on CLDNs, focusing on CLDN18 in GC.
Impact of Lymphadenectomy on the Oncologic Outcome of Patients with Adrenocortical Carcinoma—A Systematic Review and Meta-Analysis
Authors: Hendricks Anne , Müller Sophie , Fassnacht Martin , Germer Christoph-Thomas , Wiegering Verena A. , Wiegering Armin , Reibetanz Joachim
Published: January 2022

(1) Background: Locoregional lymphadenectomy (LND) in adrenocortical carcinoma (ACC) may impact oncological outcome, but the findings from individual studies are conflicting. The aim of this systematic review and meta-analysis was to determine the oncological value of LND in ACC by summarizing the available literature. (2) Methods: A systematic search on studies published until December 2020 was performed according to the PRISMA statement. The primary outcome was the impact of lymphadenectomy on overall survival (OS). Two separate meta-analyses were performed for studies including patients with localized ACC (stage I–III) and those including all tumor stages (I–IV). Secondary endpoints included postoperative mortality and length of hospital stay (LOS). (3) Results: 11 publications were identified for inclusion. All studies were retrospective studies, published between 2001–2020, and 5 were included in the meta-analysis. Three studies (N = 807 patients) reported the impact of LND on disease-specific survival in patients with stage I–III ACC and revealed a survival benefit of LND (hazard ratio (HR) = 0.42, 95% confidence interval (95% CI): 0.26–0.68). Based on results of studies including patients with ACC stage I–IV (2 studies, N = 3934 patients), LND was not associated with a survival benefit (HR = 1.00, 95% CI: 0.70–1.42). None of the included studies showed an association between LND and postoperative mortality or LOS. (4) Conclusion: Locoregional lymphadenectomy seems to offer an oncologic benefit in patients undergoing curative-intended surgery for localized ACC (stage I–III).
Assessment of the Molecular Heterogeneity of E-Cadherin Expression in Invasive Lobular Breast Cancer
Authors: Alexander John , Mariani Odette , Meaudre Celine , Fuhrmann Laetitia , Xiao Hui , Naidoo Kalnisha , Gillespie Andrea , Roxanis Ioannis , Vincent-Salomon Anne , Haider Syed , Natrajan Rachael
Published: January 2022

Mutations and loss of E-cadherin protein expression define the vast majority of invasive lobular carcinomas. In a subset of these cases, the heterogeneous expression of E-cadherin is observed either as wild-type (strong membranous) expression or aberrant expression (cytoplasmic expression). However, it is unclear as to whether the two components would be driven by distinct genetic or epigenetic alterations. Here, we used whole genome DNA sequencing and methylation array profiling of two separately dissected components of nine invasive lobular carcinomas with heterogeneous E-cadherin expression. E-cadherin negative and aberrant/positive components of E-cadherin heterogeneous tumours showed a similar mutational, copy number and promoter methylation repertoire, suggesting they arise from a common ancestor, as opposed to the collision of two independent tumours. We found that the majority of E-cadherin heterogeneous tumours harboured CDH1 mutations in both the E-cadherin negative and aberrant/positive components together with somatic mutations in additional driver genes known to be enriched in both pure invasive carcinomas of no special type and invasive lobular breast cancers, whereas these were less commonly observed in CDH1 wild-type tumours. CDH1 mutant tumours also exhibited a higher mutation burden as well as increased presence of APOBEC-dependent mutational signatures 2 and 13 compared to CDH1 wild-type tumours. Together, our results suggest that regardless of E-cadherin protein expression, tumours showing heterogeneous expression of E-cadherin should be considered as part of the spectrum of invasive lobular breast cancers.
Spatial Metrics of Interaction between CD163-Positive Macrophages and Cancer Cells and Progression-Free Survival in Chemo-Treated Breast Cancer
Authors: Maisel Brenton A. , Yi Misung , Peck Amy R. , Sun Yunguang , Hooke Jeffrey A. , Kovatich Albert J. , Shriver Craig D. , Hu Hai , Nevalainen Marja T. , Tanaka Takemi , Simone Nicole , Wang Li Lily , Rui Hallgeir , Chervoneva Inna
Published: January 2022

Tumor-associated macrophages (TAMs) promote progression of breast cancer and other solid malignancies via immunosuppressive, pro-angiogenic and pro-metastatic effects. Tumor-promoting TAMs tend to express M2-like macrophage markers, including CD163. Histopathological assessments suggest that the density of CD163-positive TAMs within the tumor microenvironment is associated with reduced efficacy of chemotherapy and unfavorable prognosis. However, previous analyses have required research-oriented pathologists to visually enumerate CD163+ TAMs, which is both laborious and subjective and hampers clinical implementation. Objective, operator-independent image analysis methods to quantify TAM-associated information are needed. In addition, since M2-like TAMs exert local effects on cancer cells through direct juxtacrine cell-to-cell interactions, paracrine signaling, and metabolic factors, we hypothesized that spatial metrics of adjacency of M2-like TAMs to breast cancer cells will have further information value. Immunofluorescence histo-cytometry of CD163+ TAMs was performed retrospectively on tumor microarrays of 443 cases of invasive breast cancer from patients who subsequently received adjuvant chemotherapy. An objective and automated algorithm was developed to phenotype CD163+ TAMs and calculate their density within the tumor stroma and derive several spatial metrics of interaction with cancer cells. Shorter progression-free survival was associated with a high density of CD163+ TAMs, shorter median cancer-to-CD163+ nearest neighbor distance, and a high number of either directly adjacent CD163+ TAMs (within juxtacrine proximity <12 μm to cancer cells) or communicating CD163+ TAMs (within paracrine communication distance <250 μm to cancer cells) after multivariable adjustment for clinical and pathological risk factors and correction for optimistic bias due to dichotomization.
Role of ctDNA in Breast Cancer
Authors: Sant Marta , Bernat-Peguera Adrià , Felip Eudald , Margelí Mireia
Published: January 2022

Breast cancer is currently classified by immunohistochemistry. However, technological advances in the detection of circulating tumor DNA (ctDNA) have made new options available for diagnosis, classification, biological knowledge, and treatment selection. Breast cancer is a heterogeneous disease and ctDNA can accurately reflect this heterogeneity, allowing us to detect, monitor, and understand the evolution of the disease. Breast cancer patients have higher levels of circulating DNA than healthy subjects, and ctDNA can be used for different objectives at different timepoints of the disease, ranging from screening and early detection to monitoring for resistance mutations in advanced disease. In early breast cancer, ctDNA clearance has been associated with higher rates of complete pathological response after neoadjuvant treatment and with fewer recurrences after radical treatments. In metastatic disease, ctDNA can help select the optimal sequencing of treatments. In the future, thanks to new bioinformatics tools, the use of ctDNA in breast cancer will become more frequent, enhancing our knowledge of the biology of tumors. Moreover, deep learning algorithms may also be able to predict breast cancer evolution or treatment sensitivity. In the coming years, continued research and the improvement of liquid biopsy techniques will be key to the implementation of ctDNA analysis in routine clinical practice.
Special Issue “Gynaecological Cancers Risk: Breast Cancer, Ovarian Cancer and Endometrial Cancer”
Authors: Manchanda Ranjit
Published: January 2022

Over the last decade there have been significant advances and developments in our understanding of factors affecting women’s cancer risk, our ability to identify individuals at increased risk and risk stratify populations, as well as implement and evaluate strategies for screening and prevention [...]
Activation of Cobalt Foil Catalysts for CO Hydrogenation
Authors: Rytter Erling , Aaserud Christian , Hilmen Anne-Mette , Bergene Edvard , Holmen Anders
Published: January 2022

CO hydrogenation has been studied on cobalt foils as model catalysts for Fischer–Tropsch (FT) synthesis. The effect of pretreatment (number of calcinations and different reduction times) for cobalt foil catalysts at 220 °C, 1 bar, and H2/CO = 3 has been studied in a microreactor. The foils were examined by scanning electron microscopy (SEM). It was found that the catalytic activity of the cobalt foil increases with the number of pretreatments. The mechanism is likely an increase in the available cobalt surface area from progressively deeper oxidation of the foil, supported by surface roughness detected by SEM. The highest FT activity was obtained using a reduction time of only 5 min (compared to 1 and 30 min). Prolonged reduction caused the sintering of cobalt crystallites, while too short of a reduction time led to incomplete reduction and small crystallites susceptible to low turn-over frequency from structure sensitivity. Larger crystals from longer reduction times gave increased selectivity to heavier components. The paraffin/olefin ratio increased with the increasing number of pretreatments due to olefin hydrogenation favored by enhanced cobalt site density. From the results, it is suggested that olefin hydrogenation is not structure sensitive, and that mass transfer limitations may occur depending on the pretreatment procedure. Produced water did not influence the results for the low conversions experienced in the present study (<6%).
Tandem Reactions Based on the Cyclization of Carbon Dioxide and Propargylic Alcohols: Derivative Applications of α-Alkylidene Carbonates
Authors: Jiang Bowen , Yan Xiangyu , Xu Yong , Likhanova Natalya , Velázquez Heriberto Díaz , Gong Yanyan , Yuan Ye , Verpoort Francis
Published: January 2022

As a well-known greenhouse gas, carbon dioxide (CO2) has attracted increasing levels of attention in areas of energy, environment, climate, etc. Notably, CO2 is an abundant, nonflammable, and renewable C1 feedstock in view of chemistry. Therefore, the transformation of CO2 into organic compounds is an extremely attractive research topic in modern green and sustainable chemistry. Among the numerous CO2 utilization methods, carboxylative cycloaddition of CO2 into propargylic alcohols is an ideal route due to the corresponding products, α-alkylidene cyclic carbonates, which are a series of highly functionalized compounds that supply numerous potential methods for the construction of various synthetically and biologically valuable agents. This cyclization reaction has been intensively studied and systematically summarized, in the past years. Therefore, attention has been gradually transferred to produce more derivative compounds. Herein, the tandem reactions of this cyclization with hydration, amination, alcoholysis, and isomerization to synthesize α-hydroxyl ketones, oxazolidinones, carbamates, unsymmetrical carbonates, tetronic acids, ethylene carbonates, etc. were systematically reviewed.
TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients
Authors: Rubio Miguel A. , Herrando-Grabulosa Mireia , Velasco Roser , Blasco Israel , Povedano Monica , Navarro Xavier
Published: January 2022

Diagnosis of ALS is based on clinical symptoms when motoneuron degeneration is significant. Therefore, new approaches for early diagnosis are needed. We aimed to assess if alterations in appearance and cellular localization of cutaneous TDP-43 may represent a biomarker for ALS. Skin biopsies from 64 subjects were analyzed: 44 ALS patients, 10 healthy controls (HC) and 10 neurological controls (NC) (Parkinson’s disease and multiple sclerosis). TDP-43 immunoreactivity in epidermis and dermis was analyzed, as well as the percentage of cells with TDP-43 cytoplasmic localization. We detected a higher amount of TDP-43 in epidermis (p < 0.001) and in both layers of dermis (p < 0.001), as well as a higher percentage of TDP-43 cytoplasmic positive cells (p < 0.001) in the ALS group compared to HC and NC groups. Dermal cells containing TDP-43 were fibroblasts as identified by co-labeling against vimentin. ROC analyses (AUC 0.867, p < 0.001; CI 95% 0.800–0.935) showed that detection of 24.1% cells with cytoplasmic TDP-43 positivity in the dermis had 85% sensitivity and 80% specificity for detecting ALS. We have identified significantly increased TDP-43 levels in epidermis and in the cytoplasm of dermal cells of ALS patients. Our findings provide support for the use of TDP-43 in skin biopsies as a potential biomarker.
Allergen Immunotherapy: Current and Future Trends
Authors: Pavón-Romero Gandhi F. , Parra-Vargas Maria Itzel , Ramírez-Jiménez Fernando , Melgoza-Ruiz Esmeralda , Serrano-Pérez Nancy H. , Teran Luis M.
Published: January 2022

Allergen immunotherapy (AIT) is the sole disease-modifying treatment for allergic rhinitis; it prevents rhinitis from progressing to asthma and lowers medication use. AIT against mites, insect venom, and certain kinds of pollen is effective. The mechanism of action of AIT is based on inducing immunological tolerance characterized by increased IL-10, TGF-β, and IgG4 levels and Treg cell counts. However, AIT requires prolonged schemes of administration and is sometimes associated with adverse reactions. Over the last decade, novel forms of AIT have been developed, focused on better allergen identification, structural modifications to preserve epitopes for B or T cells, post-traductional alteration through chemical processes, and the addition of adjuvants. These modified allergens induce clinical-immunological effects similar to those mentioned above, increasing the tolerance to other related allergens but with fewer side effects. Clinical studies have shown that molecular AIT is efficient in treating grass and birch allergies. This article reviews the possibility of a new AIT to improve the treatment of allergic illness.
HMGB1-Mediated Activation of the Inflammatory-Reparative Response Following Myocardial Infarction
Authors: Foglio Eleonora , Pellegrini Laura , Russo Matteo Antonio , Limana Federica
Published: January 2022

Different cell types belonging to the innate and adaptive immune system play mutually non-exclusive roles during the different phases of the inflammatory-reparative response that occurs following myocardial infarction. A timely and finely regulation of their action is fundamental for the process to properly proceed. The high-mobility group box 1 (HMGB1), a highly conserved nuclear protein that in the extracellular space can act as a damage-associated molecular pattern (DAMP) involved in a large variety of different processes, such as inflammation, migration, invasion, proliferation, differentiation, and tissue regeneration, has recently emerged as a possible regulator of the activity of different immune cell types in the distinct phases of the inflammatory reparative process. Moreover, by activating endogenous stem cells, inducing endothelial cells, and by modulating cardiac fibroblast activity, HMGB1 could represent a master regulator of the inflammatory and reparative responses following MI. In this review, we will provide an overview of cellular effectors involved in these processes and how HMGB1 intervenes in regulating each of them. Moreover, we will summarize HMGB1 roles in regulating other cell types that are involved in the different phases of the inflammatory-reparative response, discussing how its redox status could affect its activity.
The Multiple Faces of the GH/IGF Axis
Authors: Chesnokova Vera
Published: January 2022

Over the past two decades, interest in the role of the somatotroph growth hormone/insulin-like growth factor (GH/IGF1) axis in multiple aspects of physiology and pathology has grown exponentially [...]
Development of Magnetically Soft Amorphous Microwires for Technological Applications
Authors: Zhukova Valentina , Corte-Leon Paula , Blanco Juan Maria , Ipatov Mihail , Gonzalez-Legarreta Lorena , Gonzalez Alvaro , Zhukov Arcady
Published: January 2022

Amorphous magnetic microwires can be suitable for a variety of technological applications due to their excellent magnetic softness and giant magnetoimpedance (GMI) effect. Several approaches for optimization of soft magnetic properties and GMI effect of magnetic microwires covered with an insulating, flexible, and biocompatible glass coating with tunable magnetic properties are overviewed. The high GMI effect and soft magnetic properties, achieved even in as-prepared Co-rich microwires with a vanishing magnetostriction coefficient, can be further improved by appropriate heat treatment (including stress-annealing and Joule heating). Although as-prepared Fe-rich amorphous microwires exhibit low GMI ratio and rectangular hysteresis loops, stress-annealing, Joule heating, and combined stress-annealed followed by conventional furnace annealing can substantially improve the GMI effect (by more than an order of magnitude).
Platelet Count and Volume and Pharmacological Closure with Paracetamol of Ductus Arteriosus in Preterm Infants
Authors: Dani Carlo , Ciarcià Martina , Miselli Francesca , Luzzati Michele , Coviello Caterina , Paladini Angela , Bottoni Anthea , D’Andrea Vito , Vento Giovanni
Published: January 2022

Background: Low platelet count might promote resistance to pharmacological closure with indomethacin and ibuprofen of a hemodynamically significant patent ductus arteriosus (hsPDA). However, no studies have investigated if this occurs with paracetamol. Methods: We retrospectively assessed the correlation between platelet count, mean platelet volume (MPV), and plateletcrit (PCT), as well as the effectiveness of paracetamol in closing hsPDA in infants born at 23+0–31+6 weeks of gestation who were treated with 15 mg/kg/6 h of i.v. paracetamol for 3 days. Results: We studied 79 infants: 37 (47%) Had closure after a course of paracetamol and 42 (53%) did not. Platelet count and PCT did not correlate with paracetamol success or failure in closing hsPDA, while MPV was lower at birth (10.7 ± 1.4 vs. 9.5 ± 1.1; p < 0.001) and prior to starting therapy (11.7 ± 1.9 vs. 11.0 ± 1.6; p = 0.079) in refractory infants. Regression analysis confirmed that the low MVP measured prior to starting the treatment increased the risk of hsPDA paracetamol closure failure (OR 1.664, 95% CI 1.153–2.401). Conclusions: The greater MPV correlated positively with the effectiveness of paracetamol in closing hsPDA, while platelet count and PCT did not influence closure rates. Additional studies are needed to confirm our results.
Cognitive Behavioural Therapy for an Adolescent with Anorexia Nervosa
Authors: Baile José I. , Rabito-Alcón María F.
Published: January 2022

Introduction: The treatment of anorexia nervosa remains a matter of much debate. Though cognitive behavioural therapy would seem to offer good results, there is still no resounding evidence pointing to a single treatment of choice. The case presented in this paper examines the treatment with CBT of a patient presenting anorexia nervosa. Evaluation/diagnosis: An adolescent girl, 17 years of age, voluntarily attends psychological therapy to address eating behaviour problems. After administering the EAT-26, EDI-2, and BSQ standardised screening tests, as well as a clinical interview for assessment, a psychopathological profile is obtained, providing a diagnosis of anorexia nervosa, restricting subtype. Therapeutic goals: The therapeutic goals set were to reach a healthy weight for the patient’s age and height (specified as a minimum BMI of 18.5) and change the structure of thoughts, feelings, and behaviour that was justifying and maintaining the disorder. Treatment: Treatment lasted for 33 sessions and used cognitive behavioural techniques, such as cognitive restructuring, response cost, and positive reinforcement, in addition to family intervention techniques. Nutrition therapy was also carried out in parallel to the treatment sessions. Results: Following eight months of weekly sessions, the patient reached the target weight and changed attitudes towards food and body image, replacing them with healthy thoughts and behaviours. Follow-up made one and two years after the end of the treatment saw that these results were maintained. Discussion and conclusions: In this case, CBT proved effective in achieving the patient’s physical and psychological recovery. Therefore, this case contributes to the evidence of the efficacy of this therapeutic approach in certain cases of ED.
Soluble Expression of a Neo2/15-Conjugated Single Chain Fv against PD-L1 in Escherichia coli
Authors: Kim Sun-Hee , Jeong Hee-Jin
Published: January 2022

Immunocytokines, antibody-cytokine fusion proteins, have the potential to improve the therapeutic index of cytokines by delivering the cytokine to the site of localized tumor cells using antibodies. In this study, we produced a recombinant anti-programmed death-ligand 1 (PD-L1) scFv, an antibody fragment against PD-L1 combined with a Neo2/15, which is an engineered interleukin with superior function using an E. coli expression system. We expressed the fusion protein in a soluble form and purified it, resulting in high yield and purity. The high PD-L1-binding efficiency of the fusion protein was confirmed via enzyme-linked immunosorbent assay, suggesting the application of this immunocytokine as a cancer-related therapeutic agent.
Catalytic Production of Levulinic and Formic Acids from Fructose over Superacid ZrO2–SiO2–SnO2 Catalyst
Authors: Hes Nataliia , Mylin Artur , Prudius Svitlana
Published: January 2022

Catalytic conversion of fructose to levulinic and formic acids over tin-containing superacid (H0 = −14.52) mixed oxide was studied. Mesoporous ZrO2–SiO2–SnO2 (Zr:Si:Sn = 1:2:0.4) was synthesized by the sol–gel method. The fructose transformation was carried out in a rotated autoclave at 160–190 °C for 1–5 h using a 20 wt.% aqueous solution. The results showed that doping ZrO2–SiO2 samples with Sn4+ ions improved both fructose conversion and selectivity toward levulinic and formic acids. Under optimal conditions of 180 °C, 3.5 h and fructose to catalyst weight ratio 20:1, levulinic and formic acids yields were 80% and 90%, respectively, at complete fructose conversion. At this, humic substances formed in the quantity of 10 wt.% based on the target products.
A Simulation Study on Spread of Disease and Control Measures in Closed Population Using ABM
Authors: Kim Youngmin , Cho Namsuk
Published: January 2022

An infectious disease can cause a detrimental effect on national security. A group such as the military called a “closed population”, which is a subset of the general population but has many distinct characteristics, must survive even in the event of a pandemic. Hence, it requires its own distinct solution during a pandemic. In this study, we investigate a simulation analysis for implementing an agent-based model that reflects the characteristics of agents and the environment in a closed population and finds effective control measures for making the closed population functional in the course of disease spreading.
Brain Tumour Classification Using Noble Deep Learning Approach with Parametric Optimization through Metaheuristics Approaches
Authors: Nayak Dillip Ranjan , Padhy Neelamadhab , Mallick Pradeep Kumar , Bagal Dilip Kumar , Kumar Sachin
Published: January 2022

Deep learning has surged in popularity in recent years, notably in the domains of medical image processing, medical image analysis, and bioinformatics. In this study, we offer a completely autonomous brain tumour segmentation approach based on deep neural networks (DNNs). We describe a unique CNN architecture which varies from those usually used in computer vision. The classification of tumour cells is very difficult due to their heterogeneous nature. From a visual learning and brain tumour recognition point of view, a convolutional neural network (CNN) is the most extensively used machine learning algorithm. This paper presents a CNN model along with parametric optimization approaches for analysing brain tumour magnetic resonance images. The accuracy percentage in the simulation of the above-mentioned model is exactly 100% throughout the nine runs, i.e., Taguchi’s L9 design of experiment. This comparative analysis of all three algorithms will pique the interest of readers who are interested in applying these techniques to a variety of technical and medical challenges. In this work, the authors have tuned the parameters of the convolutional neural network approach, which is applied to the dataset of Brain MRIs to detect any portion of a tumour, through new advanced optimization techniques, i.e., SFOA, FBIA and MGA.
Meta-Governance Framework to Guide the Establishment of Mass Collaborative Learning Communities
Authors: Zamiri Majid , Camarinha-Matos Luis M. , Sarraipa João
Published: January 2022

The application of mass collaboration in different areas of study and work has been increasing over the last few decades. For example, in the education context, this emerging paradigm has opened new opportunities for participatory learning, namely, “mass collaborative learning (MCL)”. The development of such an innovative and complementary method of learning, which can lead to the creation of knowledge-based communities, has helped to reap the benefits of diversity and inclusion in the creation and development of knowledge. In other words, MCL allows for enhanced connectivity among the people involved, providing them with the opportunity to practice learning collectively. Despite recent advances, this area still faces many challenges, such as a lack of common agreement about the main concepts, components, applicable structures, relationships among the participants, as well as applicable assessment systems. From this perspective, this study proposes a meta-governance framework that benefits from various other related ideas, models, and methods that together can better support the implementation, execution, and development of mass collaborative learning communities. The proposed framework was applied to two case-study projects in which vocational education and training respond to the needs of collaborative education–enterprise approaches. It was also further used in an illustration of the MCL community called the “community of cooks”. Results from these application cases are discussed.
Microalgae as a Sustainable, Natural-Oriented and Vegan Dermocosmetic Bioactive Ingredient: The Case of Neochloris oleoabundans
Authors: Morocho-Jácome Ana Lucía , Santos Bruna Bertoloni dos , Carvalho João Carlos Monteiro de , Almeida Tânia Santos de , Rijo Patrícia , Velasco Maria Valéria Robles , Rosado Catarina , Baby André Rolim
Published: January 2022

“Vegan” and “sustainable” characteristics are strong claim trends behind the development of innovative skincare, fragrances, and makeup products. This created a need in the market for compliant ingredients. To date, there have been no records evidencing the use of the microalgae Neochloris oleoabundans (NA) in dermocosmetics. Therefore, we studied the applicability of such a natural compound in this context. NA was cultivated, and the scavenging activity (SA) of the NA extracts was evaluated. The highest SA was from the aqueous extract (54.8% ± 2.1%), being higher than that of the positive control. Two hydrogels were prepared with 1.0% ammonium acryloyldimethyltaurate/VP copolymer: (1) control gel; and (2) gel with a 1.0% NA aqueous extract. In vivo experiments were performed in healthy male and female volunteers with skin phototypes of II–IV. The stratum corneum (SC) hydration and the transepidermal water loss (TEWL) were measured in the forearm of participants to determine their biocompatibility. This parameter was determined by skin bioengineering measurements, confirming that SC hydration and TEWL were not affected by the samples. The laser Doppler measurements results showed a delayed erythema onset in the sites, where the NA hydrogel was applied. The results confirmed the biocompatibility and the anti-inflammatory activity of an innovative ingredient derived from microalgae suitable for a natural and vegan lifestyle.
Phase Properties of Different HfO2 Polymorphs: A DFT-Based Study
Authors: Laudadio Emiliano , Stipa Pierluigi , Pierantoni Luca , Mencarelli Davide
Published: January 2022

Background: Hafnium Dioxide (HfO2) represents a hopeful material for gate dielectric thin films in the field of semiconductor integrated circuits. For HfO2, several crystal structures are possible, with different properties which can be difficult to describe in detail from an experimental point of view. In this study, a detailed computational approach has been shown to present a complete analysis of four HfO2 polymorphs, outlining the intrinsic properties of each phase on the basis of atomistic displacements. Methods: Density functional theory (DFT) based methods have been used to accurately describe the chemical physical properties of the polymorphs. Corrective Hubbard (U) semi-empirical terms have been added to exchange correlation energy in order to better reproduce the excited-state properties of HfO2 polymorphs. Results: the monoclinic phase resulted in the lowest cohesive energy, while the orthorhombic showed peculiar properties due to its intrinsic ferroelectric behavior. DFT + U methods showed the different responses of the four polymorphs to an applied field, and the orthorhombic phase was the least likely to undergo point defects as oxygen vacancies. Conclusions: The obtained results give a deeper insight into the differences in excited states phenomena in relation to each specific HfO2 polymorph.
microRNA Profile Associated with Positive Lymph Node Metastasis in Early-Stage Cervical Cancer
Authors: Barquet-Muñoz Salim Abraham , Pedroza-Torres Abraham , Perez-Plasencia Carlos , Montaño Sarita , Gallardo-Alvarado Lenny , Pérez-Montiel Delia , Herrera-Montalvo Luis Alonso , Cantú-de León David
Published: January 2022

Lymph node metastasis (LNM) is an important prognostic factor in cervical cancer (CC). In early stages, the risk of LNM is approximately 3.7 to 21.7%, and the 5-year overall survival decreases from 80% to 53% when metastatic disease is identified in the lymph nodes. Few reports have analyzed the relationship between miRNA expression and the presence of LNM. The aim of this study was to identify a subset of miRNAs related to LNM in early-stage CC patients. Formalin-fixed paraffin-embedded tissue blocks were collected from patients with early-stage CC treated by radical hysterectomy with lymphadenectomy. We analyzed samples from two groups of patients—one group with LNM and the other without LNM. Global miRNA expression was identified by microarray analysis, and cluster analysis was used to determine a subset of miRNAs associated with LNM. Microarray expression profiling identified a subset of 36 differentially expressed miRNAs in the two groups (fold change (FC) ≥ 1.5 and p < 0.01). We validated the expression of seven miRNAs; miR-487b, miR-29b-2-5p, and miR-195 were underexpressed, and miR-92b-5p, miR-483-5p, miR-4534, and miR-548ac were overexpressed according to the microarray experiments. This signature exhibited prognostic value for identifying early-stage CC patients with LNM. These findings may help detect LNM that cannot be observed in imaging studies.
Immune-Related Pneumonitis Was Decreased by Addition of Chemotherapy with PD-1/L1 Inhibitors: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials (RCTs)
Authors: Long Yi-Xiu , Sun Yue , Liu Rui-Zhi , Zhang Ming-Yi , Zhao Jing , Wang Yu-Qing , Zhou Yu-Wen , Cheng Ke , Chen Ye , Zhu Cai-Rong , Liu Ji-Yan
Published: January 2022

Purpose: Immune-related pneumonitis (IRP) has attracted extensive attention, owing to its increased mortality rate. Conventional chemotherapy (C) has been considered as an immunosuppressive agent and may thus reduce IRP’s risk when used in combination with PD-1/L1 inhibitors. This study aimed to assess the risk of IRP with PD-1/L1 inhibitors plus chemotherapy (I+C) versus PD-1/L1 inhibitors alone (I) in solid cancer treatment. Method: Multiple databases were searched for RCTs before January 2021. This NMA was performed among I+C, I, and C to investigate IRP’s risk. Subgroup analysis was carried out on the basis of different PD-1/L1 inhibitors and cancer types. Results: Thirty-one RCTs (19,624 patients) were included. The I+C group exhibited a lower risk of IRP in any grade (RR, 0.60; 95% CI, 0.38–0.95) and in grade 3–5 (RR, 0.44; 95% CI, 0.21–0.92) as opposed to the I group. The risk of any grade IRP with PD-1 plus chemotherapy was lower than that with PD-1 monotherapy (RR, 0.50; 95% CI, 0.28–0.89), although grade 3–5 IRP was similar. There was no statistically meaningful difference in the risk of any grade IRP between PD-L1 plus chemotherapy and PD-L1 inhibitors monotherapy (RR, 0.95; 95% CI, 0.43–2.09) or grade 3–5 IRP (RR, 0.71;95% CI, 0.24–2.07). In addition, compared with the I group, the I+C group was correlated with a decreased risk in IRP regardless of cancer type, while a substantial difference was only observed in NSCLC patients for grade 3–5 IRP (RR, 0.39; 95% CI, 0.15–0.98). Conclusion: In comparison to PD-1/L1 inhibitor treatment alone, combining chemotherapy with PD-1/L1 inhibitors might reduce the risk of IRP in the general population. Furthermore, PD-1 inhibitors in combination with chemotherapy were correlated with a decreased risk of IRP compared to PD-1 inhibitor treatment alone. In contrast to the I group, the I+C group exhibited a lower risk of IRP, especially for NSCLC patients.
Lymph Node Dissection Is a Risk Factor for Short-Term Cough after Pulmonary Resection
Authors: Wu Xiaoli , Xing Hanyang , Chen Ping , Ma Jihua , Wang Xintian , Mao Chengyi , Zhao Xiaoying , Dai Fuqiang
Published: January 2022

Cough is a common complication after pulmonary resection. However, the factors associated with cough that develop after pulmonary resection are still controversial. In this study, we used the Simplified Cough Score (SCS) and the Leicester Cough Questionnaire (LCQ) score to investigate potential risk factors for postoperative cough. Between January 2017 and June 2021, we collected the clinical data of 517 patients, the SCS at three days after surgery and the LCQ at two weeks and six weeks after surgery. Then, univariate and multivariate analyses were used to identify the independent risk factors for postoperative cough. The clinical baseline data of the cough group and the non-cough group were similar. However, the cough group had longer operation time and more blood loss. The patients who underwent lobectomy were more likely to develop postoperative cough than the patients who underwent segmentectomy and wedge resection, while the patients who underwent systematic lymph node dissection were more likely to develop postoperative cough than the patients who underwent lymph node sampling and those who did not undergo lymph node resection. When the same lymph node management method was applied, there was no difference in the LCQ scores between the patients who underwent wedge resection, lobectomy and segmentectomy. The lymph node resection method was an independent risk factor for postoperative cough (p < 0.001). Conclusions: Lymph node resection is an independent risk factor for short-term cough after pulmonary resection with video-assisted thoracoscopic surgery, and damage to the vagus nerve and its branches (particularly the pulmonary branches) is a possible cause of short-term cough. The mechanism of postoperative cough remains to be further studied.
Ain’t Nothing like Family—Female Brown Bears Share Their Home Range with Relatives
Authors: Olejarz Astrid , Aspi Jouni , Kojola Ilpo , Nivala Vesa , Niskanen Alina K. , Harmoinen Jenni
Published: January 2022

Sociality in animal populations is a continuum, and interactions between conspecifics are meaningful for all vertebrates. Ignorance of social structures can lead to misunderstanding their ecology and, consequently, to unsuccessful species management. Here, we combined genetic and spatial data on radio-collared brown bears (Ursus arctos) to investigate kin-related home range overlap and kin-related centroid distance within central and eastern Finland. We found that the extent of home range overlap was positively correlated with relatedness among adult females. In addition, home range centroid distance decreased as relatedness increased. Moreover, there were significant differences between the two studied regions: female brown bears in central Finland were more closely related to each other, and the sizes of their home ranges were larger than those in eastern Finland. The smaller home ranges and lower degree of relatedness among bears in eastern Finland might be a result of the substantially higher hunting pressure in the area, combined with immigration of new unrelated individuals from Russia.