bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Neurons Form Axon-Mediated Functional Connections with Human Cardiomyocytes in Compartmentalized Microfluidic Chip
Authors: Häkli Martta , Jäntti Satu , Joki Tiina , Sukki Lassi , Tornberg Kaisa , Aalto-Setälä Katriina , Kallio Pasi , Pekkanen-Mattila Mari , Narkilahti Susanna
Published: March 2022

The cardiac autonomic nervous system (cANS) regulates cardiac function by innervating cardiac tissue with axons, and cardiomyocytes (CMs) and neurons undergo comaturation during the heart innervation in embryogenesis. As cANS is essential for cardiac function, its dysfunctions might be fatal; therefore, cardiac innervation models for studying embryogenesis, cardiac diseases, and drug screening are needed. However, previously reported neuron-cardiomyocyte (CM) coculture chips lack studies of functional neuron–CM interactions with completely human-based cell models. Here, we present a novel completely human cell-based and electrophysiologically functional cardiac innervation on a chip in which a compartmentalized microfluidic device, a 3D3C chip, was used to coculture human induced pluripotent stem cell (hiPSC)-derived neurons and CMs. The 3D3C chip enabled the coculture of both cell types with their respective culture media in their own compartments while allowing the neuronal axons to traverse between the compartments via microtunnels connecting the compartments. Furthermore, the 3D3C chip allowed the use of diverse analysis methods, including immunocytochemistry, RT-qPCR and video microscopy. This system resembled the in vivo axon-mediated neuron–CM interaction. In this study, the evaluation of the CM beating response during chemical stimulation of neurons showed that hiPSC-neurons and hiPSC-CMs formed electrophysiologically functional axon-mediated interactions.
Influence of Substitutions in the Binding Motif of Proline-Rich Antimicrobial Peptide ARV-1502 on 70S Ribosome Binding and Antimicrobial Activity
Authors: Brakel Alexandra , Krizsan Andor , Itzenga Renke , Kraus Carl N. , Otvos Laszlo , Hoffmann Ralf
Published: March 2022

Proline-rich antimicrobial peptides (PrAMPs) are promising candidates to treat bacterial infections. The designer peptide ARV-1502 exhibits strong antimicrobial effects against Enterobacteriaceae both in vitro and in vivo. Since the inhibitory effects of ARV-1502 reported for the 70 kDa heat-shock protein DnaK do not fully explain the antimicrobial activity of its 176 substituted analogs, we further studied their effect on the bacterial 70S ribosome of Escherichia coli, a known target of PrAMPs. ARV-1502 analogues, substituted in positions 3, 4, and 8 to 12 (underlined) of the binding motif D3KPRPYLPRP12 with aspartic acid, lysine, serine, phenylalanine or leucine, were tested in a competitive fluorescence polarization (FP) binding screening assay using 5(6)-carboxyfluorescein-labeled (Cf-) ARV-1502 and the 70S ribosome isolated from E. coli BW25113. While their effect on ribosomal protein expression was studied for green fluorescent protein (GFP) in a cell-free expression system (in vitro translation), the importance of known PrAMP transporters SbmA and MdtM was investigated using E. coli BW25113 and the corresponding knockout mutants. The dissociation constant (Kd) of 201 ± 16 nmol/L obtained for Cf-ARV-1502 suggests strong binding to the E. coli 70S ribosome. An inhibitory binding assay indicated that the binding site overlaps with those of other PrAMPs including Onc112 and pyrrhocoricin as well as the non-peptidic antibiotics erythromycin and chloramphenicol. All these drugs and drug candidates bind to the exit-tunnel of the 70S ribosome. Substitutions of the C-terminal fragment of the binding motif YLPRP reduced binding. At the same time, inhibition of GFP expression increased with net peptide charge. Interestingly, the MIC values of wild-type and ΔsbmA and ΔmdtM knockout mutants indicated that substitutions in the ribosomal binding motif altered also the bacterial uptake, which was generally improved by incorporation of hydrophobic residues. In conclusion, most substituted ARV-1502 analogs bound weaker to the 70S ribosome than ARV-1502 underlining the importance of the YLPRP binding motif. The weaker ribosomal binding correlated well with decreased antimicrobial activity in vitro. Substituted ARV-1502 analogs with a higher level of hydrophobicity or positive net charge improved the ribosome binding, inhibition of translation, and bacterial uptake.
Bee Venom and Its Major Component Melittin Attenuated Cutibacterium acnes- and IGF-1-Induced Acne Vulgaris via Inactivation of Akt/mTOR/SREBP Signaling Pathway
Authors: Gu Hyemin , An Hyun-Jin , Gwon Mi-Gyeong , Bae Seongjae , Leem Jaechan , Lee Sun-Jae , Han Sang-Mi , Zouboulis Christos C. , Park Kwan-Kyu
Published: March 2022

Acne vulgaris is the most common disease of the pilosebaceous unit. The pathogenesis of this disease is complex, involving increased sebum production and perifollicular inflammation. Understanding the factors that regulate sebum production is important in identifying novel therapeutic targets for the treatment of acne. Bee Venom (BV) and melittin have multiple effects including antibacterial, antiviral, and anti-inflammatory activities in various cell types. However, the anti-lipogenic mechanisms of BV and melittin have not been elucidated. We investigated the effects of BV and melittin in models of Insulin-like growth factor-1 (IGF-1) or Cutibacterium acnes (C. acnes)-induced lipogenic skin disease. C. acnes or IGF-1 increased the expression of sterol regulatory element-binding protein-1 (SREBP-1) and proliferator-activated receptor gamma (PPAR-γ), transcription factors that regulate numerous genes involved in lipid biosynthesis through the protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/SREBP signaling pathway. In this study using a C. acnes or IGF-1 stimulated lipogenic disease model, BV and melittin inhibited the increased expression of lipogenic and pro-inflammatory factor through the blockade of the Akt/mTOR/SREBP signaling pathway. This study suggests for the first time that BV and melittin could be developed as potential natural anti-acne agents with anti-lipogenesis, anti-inflammatory, and anti-C. acnes activity.
Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models
Authors: Si Xiaohui , Xiao Lu , Brown Christine E. , Wang Dongrui
Published: March 2022

Immunotherapy using chimeric antigen receptor (CAR) T cells is a rapidly emerging modality that engineers T cells to redirect tumor-specific cytotoxicity. CAR T cells have been well characterized for their efficacy against B cell malignancies, and rigorously studied in other types of tumors. Preclinical evaluation of CAR T cell function, including direct tumor killing, cytokine production, and memory responses, is crucial to the development and optimization of CAR T cell therapies. Such comprehensive examinations are usually performed in different types of models. Model establishment should focus on key challenges in the clinical setting and the capability to generate reliable data to indicate CAR T cell therapeutic potency in the clinic. Further, modeling the interaction between CAR T cells and tumor microenvironment provides additional insight for the future endeavors to enhance efficacy, especially against solid tumors. This review will summarize both in vitro and in vivo models for CAR T cell functional evaluation, including how they have evolved with the needs of CAR T cell research, the information they can provide for preclinical assessment of CAR T cell products, and recent technology advances to test CAR T cells in more clinically relevant models.
Cell Responsiveness to Physical Energies: Paving the Way to Decipher a Morphogenetic Code
Authors: Tassinari Riccardo , Cavallini Claudia , Olivi Elena , Facchin Federica , Taglioli Valentina , Zannini Chiara , Marcuzzi Martina , Ventura Carlo
Published: March 2022

We discuss emerging views on the complexity of signals controlling the onset of biological shapes and functions, from the nanoarchitectonics arising from supramolecular interactions, to the cellular/multicellular tissue level, and up to the unfolding of complex anatomy. We highlight the fundamental role of physical forces in cellular decisions, stressing the intriguing similarities in early morphogenesis, tissue regeneration, and oncogenic drift. Compelling evidence is presented, showing that biological patterns are strongly embedded in the vibrational nature of the physical energies that permeate the entire universe. We describe biological dynamics as informational processes at which physics and chemistry converge, with nanomechanical motions, and electromagnetic waves, including light, forming an ensemble of vibrations, acting as a sort of control software for molecular patterning. Biomolecular recognition is approached within the establishment of coherent synchronizations among signaling players, whose physical nature can be equated to oscillators tending to the coherent synchronization of their vibrational modes. Cytoskeletal elements are now emerging as senders and receivers of physical signals, “shaping” biological identity from the cellular to the tissue/organ levels. We finally discuss the perspective of exploiting the diffusive features of physical energies to afford in situ stem/somatic cell reprogramming, and tissue regeneration, without stem cell transplantation.
The Reconstitution Dynamics of Cultivated Hematopoietic Stem Cells and Progenitors Is Independent of Age
Authors: Gotzhein Frauke , Aranyossy Tim , Thielecke Lars , Sonntag Tanja , Thaden Vanessa , Fehse Boris , Müller Ingo , Glauche Ingmar , Cornils Kerstin
Published: March 2022

Hematopoietic stem cell transplantation (HSCT) represents the only curative treatment option for numerous hematologic malignancies. While the influence of donor age and the composition of the graft have already been examined in clinical and preclinical studies, little information is available on the extent to which different hematological subpopulations contribute to the dynamics of the reconstitution process and on whether and how these contributions are altered with age. In a murine model of HSCT, we therefore simultaneously tracked different cultivated and transduced hematopoietic stem and progenitor cell (HSPC) populations using a multicolor-coded barcode system (BC32). We studied a series of age-matched and age-mismatched transplantations and compared the influence of age on the reconstitution dynamics. We show that reconstitution from these cultured and assembled grafts was substantially driven by hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) independent of age. The reconstitution patterns were polyclonal and stable in all age groups independently of the variability between individual animals, with higher output rates from MPPs than from HSCs. Our experiments suggest that the dynamics of reconstitution and the contribution of cultured and individually transduced HSPC subpopulations are largely independent of age. Our findings support ongoing efforts to expand the application of HSCT in older individuals as a promising strategy to combat hematological diseases, including gene therapy applications.
Cyprinus carpio Skeleton Byproduct as a Source of Collagen for Gelatin Preparation
Authors: Gál Robert , Mokrejš Pavel , Pavlačková Jana , Janáčová Dagmar
Published: March 2022

Byproducts obtained from fish processing account for up to 70% of their live weight and represent a large amount of unused raw materials rich in proteins, fats, minerals, and vitamins. Recently, the management of the use of predominantly cold-water fish byproducts has become a priority for many processing companies. This paper describes the biotechnological processing of byproducts of warm-water Cyprinus carpio skeletons into gelatins. A Taguchi experimental design with two process factors (HCl concentration during demineralization of the starting material and the amount of enzyme during enzyme conditioning of the collagen) examined at three levels (0.5, 1.0 and 2.0 wt%; 0.0, 0.1 and 0.2 wt% respectively) was used to optimize the processing of fish tissue into gelatin. Depending on the preparation conditions, four gelatin fractions were prepared by multi-stage extraction from the starting material with a total yield of 18.7–55.7%. Extensive characterization of the gel-forming and surface properties of the prepared gelatins was performed. Gelatins belong to the group of zero–low-medium Bloom value (0–170 Bloom) and low–medium viscosity (1.1–4.9 mPa·s) gelatins and are suitable for some food, pharmaceutical, and cosmetic applications. During processing, the pigment can be isolated; the remaining solid product can then be used in agriculture, and H3PO4Ca can be precipitated from the liquid byproduct after demineralization. The carp byproduct processing technology is environmentally friendly and meets the requirements of zero-waste technology.
Effects of a Fully Humanized Type II Anti-CD20 Monoclonal Antibody on Peripheral and CNS B Cells in a Transgenic Mouse Model of Multiple Sclerosis
Authors: Tacke Sabine , Chunder Rittika , Schropp Verena , Urich Eduard , Kuerten Stefanie
Published: March 2022

Successful therapy with anti-CD20 monoclonal antibodies (mAbs) has reinforced the key role of B cells in the immunopathology of multiple sclerosis (MS). This study aimed to determine the effects of a novel class of anti-CD20 mAbs on vascular and extravascular central nervous system (CNS)-infiltrating B cells in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Male hCD20xhIgR3 mice and wild-type C57BL/6 (B6) mice were immunized with human myelin oligodendrocyte glycoprotein (MOG)1–125 to induce EAE. While hCD20xhIgR3 mice were injected intravenously with an anti-human CD20 mAb (5 mg/kg) (rituximab (a type I anti-CD20 mAb) or obinutuzumab (a type II anti-CD20 mAb), B6 mice received the anti-mouse CD20 antibody 18B12. Neither mAb affected clinical disease or serum antibody levels. Obinutuzumab and rituximab had an impact on splenic and CNS-infiltrated B cells with slightly differential depletion efficacy. Additionally, obinutuzumab had beneficial effects on spinal cord myelination. B cell depletion rates in the 18B12/B6 model were comparable with those observed in obinutuzumab-treated hCD20xhIgR3 mice. Our results demonstrate the usefulness of anti-CD20 mAbs for the modulation of B cell-driven peripheral immune response and CNS pathology, with type II antibodies potentially being superior to type I in the depletion of tissue-infiltrating B cells.
The L467F-F508del Complex Allele Hampers Pharmacological Rescue of Mutant CFTR by Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Patients: The Value of the Ex Vivo Nasal Epithelial Model to Address Non-Responders to CFTR-Modulating Drugs
Authors: Sondo Elvira , Cresta Federico , Pastorino Cristina , Tomati Valeria , Capurro Valeria , Pesce Emanuela , Lena Mariateresa , Iacomino Michele , Baffico Ave Maria , Coviello Domenico , Bandiera Tiziano , Zara Federico , Galietta Luis J. V. , Bocciardi Renata , Castellani Carlo , Pedemonte Nicoletta
Published: March 2022

Loss-of-function mutations of the CFTR gene cause cystic fibrosis (CF) through a variety of molecular mechanisms involving altered expression, trafficking, and/or activity of the CFTR chloride channel. The most frequent mutation among CF patients, F508del, causes multiple defects that can be, however, overcome by a combination of three pharmacological agents that improve CFTR channel trafficking and gating, namely, elexacaftor, tezacaftor, and ivacaftor. This study was prompted by the evidence of two CF patients, compound heterozygous for F508del and a minimal function variant, who failed to obtain any beneficial effects following treatment with the triple drug combination. Functional studies on nasal epithelia generated in vitro from these patients confirmed the lack of response to pharmacological treatment. Molecular characterization highlighted the presence of an additional amino acid substitution, L467F, in cis with the F508del variant, demonstrating that both patients were carriers of a complex allele. Functional and biochemical assays in heterologous expression systems demonstrated that the double mutant L467F-F508del has a severely reduced activity, with negligible rescue by CFTR modulators. While further studies are needed to investigate the actual prevalence of the L467F-F508del allele, our results suggest that this complex allele should be taken into consideration as plausible cause in CF patients not responding to CFTR modulators.
Multivariate Genetic Structure of Externalizing Behavior and Structural Brain Development in a Longitudinal Adolescent Twin Sample
Authors: Teeuw Jalmar , Klein Marieke , Mota Nina , Brouwer Rachel , van ‘t Ent Dennis , Al-Hassaan Zyneb , Franke Barbara , Boomsma Dorret , Hulshoff Pol Hilleke
Published: March 2022

Externalizing behavior in its more extreme form is often considered a problem to the individual, their families, teachers, and society as a whole. Several brain structures have been linked to externalizing behavior and such associations may arise if the (co)development of externalizing behavior and brain structures share the same genetic and/or environmental factor(s). We assessed externalizing behavior with the Child Behavior Checklist and Youth Self Report, and the brain volumes and white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]) with magnetic resonance imaging in the BrainSCALE cohort, which consisted of twins and their older siblings from 112 families measured longitudinally at ages 10, 13, and 18 years for the twins. Genetic covariance modeling based on the classical twin design, extended to also include siblings of twins, showed that genes influence externalizing behavior and changes therein (h2 up to 88%). More pronounced externalizing behavior was associated with higher FA (observed correlation rph up to +0.20) and lower MD (rph up to −0.20), with sizeable genetic correlations (FA ra up to +0.42; MD ra up to −0.33). The cortical gray matter (CGM; rph up to −0.20) and cerebral white matter (CWM; rph up to +0.20) volume were phenotypically but not genetically associated with externalizing behavior. These results suggest a potential mediating role for global brain structures in the display of externalizing behavior during adolescence that are both partially explained by the influence of the same genetic factor.
Second Cancer Onset in Myeloproliferative Neoplasms: What, When, Why?
Authors: Cumbo Cosimo , Anelli Luisa , Zagaria Antonella , Coccaro Nicoletta , Tarantini Francesco , Specchia Giorgina , Musto Pellegrino , Albano Francesco
Published: March 2022

The risk of developing a solid cancer is a major issue arising in the disease course of a myeloproliferative neoplasm (MPN). Although the connection between the two diseases has been widely described, the backstage of this complex scenario has still to be explored. Several cellular and molecular mechanisms have been suggested to link the two tumors. Sometimes the MPN is considered to trigger a second cancer but at other times both diseases seem to depend on the same source. Increasing knowledge in recent years has revealed emerging pathways, supporting older, more consolidated theories, but there are still many unresolved issues. Our work aims to present the biological face of the complex clinical scenario in MPN patients developing a second cancer, focusing on the main cellular and molecular pathways linking the two diseases.
Inflammatory Response and Secondary White Matter Damage to the Corpus Callosum after Focal Striatal Stroke in Rats
Authors: Lima Rafael Rodrigues , Oliveira Ana Carolina Alves , Fernandes Rafael Monteiro , Nascimento Priscila Cunha , Freire Marco Aurelio M. , Gomes-Leal Walace
Published: March 2022

Stroke is one of the leading causes of death and long-term disabilities worldwide, resulting in a debilitating condition occasioned by disturbances in the cerebral vasculature. Primary damage due to metabolic collapse is a quick outcome following stroke, but a multitude of secondary events, including excitotoxicity, inflammatory response, and oxidative stress cause further cell death and functional impairment. In the present work, we investigated whether a primary ischemic damage into the dorsal striatum may cause secondary damage in the circumjacent corpus callosum (CC). Animals were injected with endothelin-1 and perfused at 3, 7, 14, and 30 post-lesion days (PLD). Sections were stained with Cresyl violet for basic histopathology and immunolabeled by antibodies against astrocytes (anti-GFAP), macrophages/microglia (anti-IBA1/anti MHC-II), oligodendrocytes (anti-TAU) and myelin (anti-MBP), and Anti-Nogo. There were conspicuous microgliosis and astrocytosis in the CC, followed by later oligodendrocyte death and myelin impairment. Our results suggest that secondary white matter damage in the CC follows a primary focal striatal ischemia in adult rats.
Outcomes of Nonagenarians with Acute Myocardial Infarction with or without Coronary Intervention
Authors: Oh Seok , Jeong Myung Ho , Cho Kyung Hoon , Kim Min Chul , Sim Doo Sun , Hong Young Joon , Kim Ju Han , Ahn Youngkeun
Published: March 2022

Percutaneous coronary intervention (PCI) is the mainstay treatment of acute myocardial infarction (AMI); however, many clinicians are reluctant to perform PCI in the elderly population. This study aimed to compare the clinical outcomes of PCI versus medical therapy in nonagenarian Korean patients with AMI. We compared the clinical outcomes of nonagenarian patients with AMI with or without PCI. From the pooled data, based on a series of Korean AMI registries during 2005–2020, 467 consecutive patients were selected and categorized into two groups: the PCI and no-PCI groups. The primary endpoint was 1-year major adverse cardiac event (MACE), a composite of all-cause death, non-fatal myocardial infarction, and any revascularization. Among the 467 participants, 68.5% received PCI. The PCI group had lower proportions of Killip classes III-IV, previous heart failure, and left ventricular ejection fraction <40%, but had higher proportions of all prescribed medications and STEMI diagnosis. The 1-year MACE and all-cause death were higher in the no-PCI group, although partially attenuated post-IPTW. Our study showed that nonagenarian patients with AMI undergoing PCI had better clinical outcomes than those without PCI. Nonetheless, further investigation is needed in the future to elucidate whether PCI is beneficial for this population.
Echocardiography Nomogram for Predicting Survival among Chronic Lung Disease Patients with Severe Pulmonary Hypertension
Authors: Jiang Rong , Wang Lan , Zhao Qin-Hua , Wu Cheng , Yuan Ping , Wang Shang , Zhang Rui , Gong Su-Gang , Wu Wen-Hui , He Jing , Qiu Hong-Ling , Luo Ci-Jun , Liu Jin-Ming , Jing Zhi-Cheng
Published: March 2022

Severe pulmonary hypertension in chronic lung diseases (severe CLD-PH) differs significantly from other types of PH in physiology and prognosis. We aimed to assess whether echocardiography helps predict long-term survival in patients with severe CLD-PH. This single-centre, observational cohort study enrolled 100 patients with severe CLD-PH (mean pulmonary arterial pressure ≥35 mm Hg or ≥25 mm Hg with cardiac index <2.0 L/min/m2 or pulmonary vascular resistance ≥6 Wood units) between 2009 and 2014. The population was randomly divided into a derivation and validation cohort in a 2:1 ratio. To construct a nomogram, a multivariable logistic regression model was applied, and scores were assigned based on the hazard ratio of independent echocardiographic predictors. Multivariate Cox hazards analysis identified the strongest predictors of mortality as pulmonary arterial systolic pressure (PASP), tricuspid annular plane systolic excursion, and right ventricular end-diastolic transverse dimension. The three independent predictors were entered into the nomogram. Compared with PASP alone, the nomogram resulted in an integrated discrimination improvement of 15.5% (95% confidence interval, 5.52–25.5%, p = 0.002) with a net improvement in model discrimination (C-statistic from 0.591 to 0.746). Using echocardiographic parameters, we established and validated a novel nomogram to predict all-cause death for patients with severe CLD-PH.
Does Far-Infrared Therapy Improve Peritoneal Function and Reduce Recurrent Peritonitis in Peritoneal Dialysis Patients?
Authors: Chang Yuanmay , Chang Jui-Ting , Lee Mei-Yi , Huang Mei-Zen , Chao Yann-Fen C. C. , Shih Yung-Luen , Hwang Yao-Rong
Published: March 2022

The use of peritoneal dialysis in end-stage renal disease is increasing in clinical practice. The main purpose of this study was to evaluate the effect of far-infrared radiation therapy on inflammation and the cellular immunity of patients undergoing peritoneal dialysis. We recruited 56 patients undergoing peritoneal dialysis, and we included 32 patients for the experimental group and 24 patients from the control group in the final analysis. The experimental evaluation in our study was as follows: (1) We used abdominal computed tomography to explore the changes in abdominal blood vessels. (2) We compared the effects of peritoneal dialysis using blood glucose, HbAlC, albumin, urea nitrogen, creatinine, white blood cells, hs-CRP; peritoneal Kt/V of peritoneal function, and eGFR. (3) We compared the cytokines’ concentrations in the two groups while controlling for the other cytokines. Results and Discussion: (1) There was no significant difference in the abdominal blood vessels of the experimental group relative to the control group according to abdominal CT over the 6 months. (2) Our study demonstrates statistically significant effects of FIR therapy on the following parameters: creatinine (p = 0.039 *) and hs-CRP (p < 0.001 **) levels decreased significantly, and eGFR (p = 0.043 *), glucose (p < 0.001 **), and albumin (p = 0.048 *) levels increased significantly. Our study found that in the experimental group, creatinine and hs-CRP levels decreased significantly due to FIR therapy for 6 months. However, our study also found that the glucose level was significantly different after FIR therapy for 6 months. Peritoneal dialysis combined with FIR can reduce the side effects of the glucose in the dialysis buffer, which interferes with peritoneal inflammation and peritoneal mesothelial cell fibrosis. (3) In addition, we also found that no statistically significant difference in any inflammatory cytokine after FIR therapy. IFN-γ (p = 0.124), IL-12p70 (p = 0.093), IL-18 (p = 0.213), and TNF-α (p = 0.254) did not exhibit significant improvements after peritoneal dialysis with FIR treatment over 6 months. Conclusions: We found that the effectiveness of peritoneal dialysis was improved significantly with FIR therapy, and significant improvements in the peritoneal permeability and inflammatory response were observed.
Chest X-ray Does Not Predict the Risk of Endotracheal Intubation and Escalation of Treatment in COVID-19 Patients Requiring Noninvasive Respiratory Support
Authors: Pettenuzzo Tommaso , Giraudo Chiara , Fichera Giulia , Della Paolera Michele , Tocco Martina , Weber Michael , Gorgi Davide , Carlucci Silvia , Lionello Federico , Lococo Sara , Boscolo Annalisa , De Cassai Alessandro , Pasin Laura , Rossato Marco , Vianello Andrea , Vettor Roberto , Sella Nicolò , Navalesi Paolo
Published: March 2022

Forms of noninvasive respiratory support (NIRS) have been widely used to avoid endotracheal intubation in patients with coronavirus disease-19 (COVID-19). However, inappropriate prolongation of NIRS may delay endotracheal intubation and worsen patient outcomes. The aim of this retrospective study was to assess whether the CARE score, a chest X-ray score previously validated in COVID-19 patients, may predict the need for endotracheal intubation and escalation of respiratory support in COVID-19 patients requiring NIRS. From December 2020 to May 2021, we included 142 patients receiving NIRS who had a first chest X-ray available at NIRS initiation and a second one after 48–72 h. In 94 (66%) patients, the level of respiratory support was increased, while endotracheal intubation was required in 83 (58%) patients. The CARE score at NIRS initiation was not predictive of the need for endotracheal intubation (odds ratio (OR) 1.01, 95% confidence interval (CI) 0.96–1.06) or escalation of treatment (OR 1.01, 95% CI 0.96–1.07). In conclusion, chest X-ray severity, as assessed by the CARE score, did not allow predicting endotracheal intubation or escalation of respiratory support in COVID-19 patients undergoing NIRS.
The Serum Profile of Transferrin Isoforms in Pancreatitis
Authors: Mucha Agnieszka , Zaczek Malgorzata , Kralisz Michal , Gruszewska Ewa , Cylwik Bogdan , Panasiuk Anatol , Chrostek Lech
Published: March 2022

Total transferrin concentration changes in acute-phase reactions. Additionally, the alteration of transferrin glycosylation in inflammations can occur. The aim of this study is to evaluate the effect of pancreatitis on the serum profile of transferrin isoforms. The tested groups consisted of 84 patients with acute pancreatitis and 42 patients with chronic hepatitis. Transferrin isoforms were analyzed by capillary electrophoresis on a MINICAP electrophoretic system (Sebia, France). There was a significant decrease in the concentration of pentasialotransferrin in both acute and chronic pancreatitis, and a significant increase in tetrasialotransferrin in the acute pancreatitis group when compared to the control group. There were no significant changes in transferrin isoforms between the acute and chronic pancreatitis groups, and between the edematous and necrotizing forms of the disease. Considering the etiology of acute pancreatitis, we noticed higher values of bile acids and γ-glutamyltransferase in acute pancreatitis of alcoholic etiology than that in pancreatitis of other etiologies. In conclusion, the alterations in transferrin isoform profile in acute and chronic pancreatitis are not organ specific. Because similar changes were observed in hepatitis, we can conclude that the serum profile of transferrin isoforms is involved in the pathogenesis of the disease.
Fabrication of a Human Skin Mockup with a Multilayered Concentration Map of Pigment Components Using a UV Printer
Authors: Nagasawa Kazuki , Yamamoto Shoji , Arai Wataru , Hakkaku Kunio , Koopipat Chawan , Hirai Keita , Tsumura Norimichi
Published: March 2022

In this paper, we propose a pipeline that reproduces human skin mockups using a UV printer by obtaining the spatial concentration map of pigments from an RGB image of human skin. The pigment concentration distributions were obtained by a separating method of skin pigment components with independent component analysis from the skin image. This method can extract the concentration of melanin and hemoglobin components, which are the main pigments that make up skin tone. Based on this concentration, we developed a procedure to reproduce a skin mockup with a multi-layered structure that is determined by mapping the absorbance of melanin and hemoglobin to CMYK (Cyan, Magenta, Yellow, Black) subtractive color mixing. In our proposed method, the multi-layered structure with different pigments in each layer contributes greatly to the accurate reproduction of skin tones. We use a UV printer because the printer is capable of layered fabrication by using UV-curable inks. As the result, subjective evaluation showed that the artificial skin reproduced by our method has a more skin-like appearance than that produced using conventional printing.
Antioxidant and Anti-Colorectal Cancer Properties in Methanolic Extract of Mangrove-Derived Schizochytrium sp.
Authors: Kalidasan Kaliyamoorthy , Dufossé Laurent , Manivel Gunasekaran , Senthilraja Poomalai , Kathiresan Kandasamy
Published: March 2022

This work studied the antioxidant and anti-colorectal cancer properties of a potential strain of thraustochytrids, Schizochytrium sp. (SMKK1), isolated from mangrove leaf litter. The biomass was extracted with methanol and screened for antioxidant activity using six different assays. The extract exhibited the highest total antioxidant activity (87.37 ± 1.22%) and the lowest nitric oxide radical (75.12 ± 2.22%), and the activity increased with the concentration of the extract. The methanolic extract was further tested for in vitro cytotoxicity on the colon cancer cell line (HT29). The extract was also analyzed for polyunsaturated fatty acids using GC-MS. The five predominant HTVS-based compounds, viz., arachidonic acid, linolenic acid (alpha-linolenic acid and gamma-linolenic acid), eicosapentaenoic acid, and docosahexaenoic acid, were identified in the extract, and these were tested against the colon cancer protein IGF binding (IGF-1) using the in silico docking method. The results revealed that all the five compounds were capable of destroying the colon oncoprotein responsible for anti-colon carcinogen, based on activation energy and also good hydrogen bond interaction against IGF binding proteins. Of the compounds, docosahexaenoic acid was the most effective, having a docking score of −10.8 Kcal/mol. All the five fatty acids passed the ADMET test and were hence accepted for further clinical trials towards the development of anticancer drugs.
Insecticidal Efficacy of Metarhizium anisopliae Derived Chemical Constituents against Disease-Vector Mosquitoes
Authors: Vivekanandhan Perumal , Swathy Kannan , Murugan Amarchand Chordia , Krutmuang Patcharin
Published: March 2022

Insecticides can cause significant harm to both terrestrial and aquatic environments. The new insecticides derived from microbial sources are a good option with no environmental consequences. Metarhizium anisopliae (mycelia) ethyl acetate extracts were tested on larvae, pupae, and adult of Anopheles stephensi (Liston, 1901), Aedes aegypti (Meigen, 1818), and Culex quinquefasciatus (Say, 1823), as well as non-target species Eudrilus eugeniae (Kinberg, 1867) and Artemia nauplii (Linnaeus, 1758) at 24 h post treatment under laboratory condition. In bioassays, Metarhizium anisopliae extracts had remarkable toxicity on all mosquito species with LC50 values, 29.631 in Ae. aegypti, 32.578 in An. stephensi and 48.003 in Cx. quinquefasciatus disease-causing mosquitoes, in A. nauplii shows (5.33–18.33 %) mortality were produced by the M. anisopliae derived crude extract. The LC50 and LC90 values were, 620.481; 6893.990 μg/mL. No behavioral changes were observed. A low lethal effect was observed in E. eugeniae treated with the fungi metabolites shows a 14.0 % mortality. The earthworm E. eugeniae mid-gut histology revealed that M. anisopliae extracts had no more harmful effects on the epidermis, circular muscle, setae, mitochondrion, and intestinal lumen tissues than chemical pesticides. By Liquid chromatography mass spectrometry (LC-MS) analysis, camphor (25.4 %), caprolactam (20.68 %), and monobutyl phthalate (19.0 %) were identified as significant components of M. anisopliae metabolites. Fourier transform infrared (FT-IR) spectral investigations revealed the presence of carboxylic acid, amides, and phenol groups, all of which could be involved in mosquito toxicity. The M. anisopliae derived chemical constituents are effective on targeted pests, pollution-free, target-specific, and are an alternative chemical insecticide.
Vitamin D and Histological Features of Breast Cancer: Preliminary Data from an Observational Retrospective Italian Study
Authors: Lello Stefano , Capozzi Anna , Scardina Lorenzo , Ionta Lucia , Sorge Roberto , Scambia Giovanni , Franceschini Gianluca
Published: March 2022

Background: Vitamin D (vitD) may be involved in different extraskeletal conditions as well as skeletal muscle diseases. It has been hypothesized that, at least in part, a low level of vitD could contribute to facilitating cancer development. Breast cancer (BC) seems to be associated with low levels of vitD. Materials and methods: This was an observational retrospective evaluation of 87 women (mean age: 54 ± 12 years old) who underwent surgery for the treatment of BC. Our main purpose was to correlate the types of BC and the levels of vitD. Results: A positive significant correlation (R > 0.7) was found between non-invasive carcinoma in situ and 25(OH)D levels and age (R = 0.82, p < 0.05). A positive, but nonsignificant, correlation was reported between invasive ductal carcinoma and 25(OH)D and age (R = 0.45, p > 0.05). A negative but nonsignificant correlation was found between invasive lobular carcinoma and 25(OH)D and age (R = 0.24, p > 0.05). Discussion and Conclusions: We did not find a significant relationship between vitD and BC subtypes. Considering the positive significant correlation between vitD levels and age for in situ BC, although preliminary, our results seem to suggest a possible role of vitD in in situ BC. However, these findings need to be confirmed in larger studies.
eHealth and mHealth in Chronic Diseases—Identification of Barriers, Existing Solutions, and Promoters Based on a Survey of EU Stakeholders Involved in Regions4PerMed (H2020)
Authors: Stefanicka-Wojtas Dorota , Kurpas Donata
Published: March 2022

Background: In recent years, rapid population ageing has become a worldwide phenomenon. Both electronic health services (eHealth) and mobile health services (mHealth) are becoming important components of healthcare delivery. The market for mHealth is growing extremely fast. However, despite the increasing investment and interest in eHealth, several challenges still need to be overcome to enable broader and more systematic implementation of ICT in healthcare. Methods: This study presents data from the survey “Barriers and facilitators of Personalised Medicine implementation- qualitative study under Regions4PerMed (H2020) project”. In addition, this paper discusses the results of the conference, Health Technology in Connected & Integrated Care, held under the Horizon 2020 project and interregional coordination for a fast and deep uptake of personalised health (Regions4Permed) (July 2020—online conference). The above sections were preceded by an analysis of existing articles. Results: The data obtained from the surveys show that the main barriers to the adoption of eHealth and mHealth are the lack of skills of seniors, but also the lack of user-friendly technology and a simple user interface. Access to individual data while ensuring its security and the lack of digitisation of medical data are also serious issues. In addition, medical digital solutions are overly fragmented due to national legislations that deviate from the General Data Protection Regulation. Conclusions: By using technological solutions, it is possible to improve diagnosis and treatment decisions, and better adapt treatment and reduce its duration and cost. However, there are still barriers to the development of eHealth. Clear recommendations for implementation are needed to enable further development of personalised eHealth and mHealth solutions
Further Tests of the ZCAPM Asset Pricing Model
Authors: Kolari James W. , Huang Jianhua Z. , Liu Wei , Liao Huiling
Published: March 2022

In a recent book, Kolari et al. developed a new theoretical capital asset pricing model dubbed the ZCAPM. Based on out-of-sample cross-sectional tests using U.S. stocks, the ZCAPM consistently outperformed well-known multifactor models popular in the finance literature. This paper presents further evidence that expands their sample period from 1927 to 2020. Results are provided for the subperiods 1927 to 1964 and 1965 to 2020. Our results corroborate those of KLH. In cross-sectional tests, the ZCAPM outperforms the CAPM as well as the Fama and French three-factor model and Carhart four-factor model. Outperformance is found in terms of both higher goodness of fit and the statistical significance of factor loadings. Interestingly, the earlier subperiod results highlight problems with the endogeneity of test assets in cross-sectional tests of multifactor models.
The Effects of Tidal Flat Reclamation on the Stability of the Coastal Area in the Jiangsu Province, China, from the Perspective of Landscape Structure
Authors: Chen Yanhui , Li Guosheng , Cui Linlin , Li Lijuan , He Lei , Ma Peipei
Published: March 2022

As one of the most important wetland systems, coastal wetlands play an important role in conserving water, regulating the climate and protecting biodiversity. However, due to large-scale and long-term tidal flat reclamations, the landscape structure and function of the coastal wetlands have been greatly affected. Therefore, it is necessary to understand the spatio-temporal characteristics of the impact of tidal flat reclamation on regional ecology and to quantitatively assess the relationships between them. In this study based on long-term, multiperiod remote sensing data, the main spatio-temporal variation characteristics of stability, and the relationship between stability and tidal flat reclamation were analyzed with regard to the influence scope of tidal flat reclamation. The results showed that a substantial decrease in natural wetlands in 1980, mainly caused by tidal flat reclamation, was discovered in the Jiangsu coastal area, and the influence scope of tidal flat reclamation on regional landscape ecology was roughly 30 km. In the affected area, the overall stability had a tendency to improve, but the stability change characteristics between reclamation area and non-reclamation area varied greatly. Especially in the reclamation area, the stability of construction wetlands and non-wetlands deteriorated. Spatially, the stability outside the reclamation area had the characteristics of first deteriorating and then improving as the distance from the reclamation area increased. Under the influence of tidal flat reclamation, the influence of different use types of TFR on stability was not completely consistent, and the influence of the same uses type of tidal flat reclamation on different landscapes was also different.
Effect of Cropland Abandonment on Soil Carbon Stock in an Agroforestry System in Southwestern Spain
Authors: Alías Juan Carlos , Mejías José Antonio , Chaves Natividad
Published: March 2022

The low profitability of agricultural products in a globalized market context is causing the abandonment of less profitable agroforestry systems in Spain. This fact is implicated in a change in land use, increasing the forest area, which could alter the carbon stock in the soil. Thus, the objective of this study was to determine if the abandonment of rural areas and the change in land use has an impact on the soil organic carbon stock in agroforestry systems in southwestern Spain. Through historical aerial photographs and current satellite images, sites were identified where samples of abandoned agricultural soils in the 1950s were collected. They were compared with soil samples from adjacent locations whose agricultural activities continue to this day. After more than 60 years, the abandonment of agricultural activity is associated with a 54% increase in C concentration and 34.8% in soil organic carbon in the upper 30 cm of soil profiles. Therefore, the abandonment of agricultural land has influenced the carbon stock of this territory, becoming a carbon sink.
Comparison of Three Ten Meter Land Cover Products in a Drought Region: A Case Study in Northwestern China
Authors: Kang Junmei , Yang Xiaomei , Wang Zhihua , Cheng Hongbin , Wang Jun , Tang Hongtao , Li Yan , Bian Zongpan , Bai Zhuoli
Published: March 2022

The ecological and natural conditions in drought regions are harsh. Water shortages and land desertification are prominent features of these regions. The land cover in these regions has a large impact on global climate change, as well as on ecological protection and construction. To make rational and sustainable use of land resources, it is crucial to quickly grasp the accuracy and spatial distribution differences of multi-source remote sensing land cover products in drought regions. Therefore, taking northwestern China as the study area, in this study, the accuracy and spatial pattern distribution differences of three high-resolution (10 m) land cover products, namely, the Finer Resolution Observation and Monitoring of Global Land Cover (FROM-GLC), European Space Agency (ESA), and Environmental Systems Research Institute (ESRI) products, were compared and analyzed via area composition similarity, spatial pattern consistency, and absolute accuracy assessment for three validation samples. The results show that the FROM-GLC product had the highest overall accuracy, ranging from 53.81% to 73.45%. The ESRI product had the lowest overall accuracy, ranging from 35.90% to 64.16%. The spatial consistencies of the three products were low, accounting for 46.26% of the total area, and they were mostly distributed in a single area (mainly bare land and forest). The low accuracy for grassland, bare land, shrubland, and other vegetation types was the primary reason for the large differences between the three products. Future research should focus on improving the mapping accuracy for these vegetation types. Accuracies for water and cropland of the three products were consistent, and, thus, the FROM-GLC, ESA, and ESRI products can be used as auxiliary data in research related to water resources and cropland resources in drought regions.
The Maternal–Fetal Gut Microbiota Axis: Physiological Changes, Dietary Influence, and Modulation Possibilities
Authors: Miko Eva , Csaszar Andras , Bodis Jozsef , Kovacs Kalman
Published: March 2022

The prenatal period and the first years of life have a significant impact on the health issues and life quality of an individual. The appropriate development of the immune system and the central nervous system are thought to be major critical determining events. In parallel to these, establishing an early intestinal microbiota community is another important factor for future well-being interfering with prenatal and postnatal developmental processes. This review aims at summarizing the main characteristics of maternal gut microbiota and its possible transmission to the offspring, thereby affecting fetal and/or neonatal development and health. Since maternal dietary factors are potential modulators of the maternal–fetal microbiota axis, we will outline current knowledge on the impact of certain diets, nutritional factors, and nutritional modulators during pregnancy on offspring’s microbiota and health.
Deep Learning Approaches for Prognosis of Automated Skin Disease
Authors: Kshirsagar Pravin R. , Manoharan Hariprasath , Shitharth S. , Alshareef Abdulrhman M. , Albishry Nabeel , Balachandran Praveen Kumar
Published: March 2022

Skin problems are among the most common ailments on Earth. Despite its popularity, assessing it is not easy because of the complexities in skin tones, hair colors, and hairstyles. Skin disorders provide a significant public health risk across the globe. They become dangerous when they enter the invasive phase. Dermatological illnesses are a significant concern for the medical community. Because of increased pollution and poor diet, the number of individuals with skin disorders is on the rise at an alarming rate. People often overlook the early signs of skin illness. The current approach for diagnosing and treating skin conditions relies on a biopsy process examined and administered by physicians. Human assessment can be avoided with a hybrid technique, thus providing hopeful findings on time. Approaches to a thorough investigation indicate that deep learning methods might be used to construct frameworks capable of identifying diverse skin conditions. Skin and non-skin tissue must be distinguished to detect skin diseases. This research developed a skin disease classification system using MobileNetV2 and LSTM. For this system, accuracy in skin disease forecasting is the primary aim while ensuring excellent efficiency in storing complete state information for exact forecasts.