bluuebunny/crossref_metadata_2025 huggingface dataset:
Galectin-3, Inflammation, and the Risk of Atrial High-Rate Episodes in Patients with Dual Chamber Pacemakers
Authors: Simu Gelu Radu , Tomoaia Raluca , Rosu Radu Ovidiu , Gusetu Gabriel , Puiu Mihai , Cismaru Gabriel , Caloian Bogdan , Terec Andreea , Buliga Teodor , Boer Armand , Minciuna Ioan Alexandru , Bodizs Gyorgy , Zdrenghea Dumitru , Pop Dana
Published: April 2023

Atrial high-rate episodes (AHREs) are atrial tachyarrhythmias that are exclusively detected by cardiac implantable electronic devices (CIEDs) with an atrial lead. The objective of this study was to investigate the incidence and predictive factors for AHREs, and to evaluate the ability of inflammation biomarkers to predict the occurrence of AHREs. 102 patients undergoing CIED procedure who received a dual chamber pacemaker were included. CIED interrogation was performed 1 year after the implantation procedure. Patients were divided into groups according to the occurrence of AHREs, which was the primary endpoint of the study. The mean age of the patients was of 73 ± 8.6 years and 48% were male. The incidence of AHREs was 67% at 1 year follow-up. Patients with AHREs were older, had higher left atrial indexed volume (LAVi), higher baseline galectin-3 levels (1007.5 ± 447.3 vs. 790 ± 411.7 pg/mL) and received betablockers more often, along with amiodarone and anticoagulants. Interestingly, the CHADSVASC score did not differ significantly between the two groups. A cut-off value of galectin > 990 pg/mL predicted AHREs with moderate accuracy (AUC of 0.63, 95% CI 0.52 to 0.73, p = 0.04), and this association was confirmed in the univariate regression analysis (OR 1.0012, 95% CI 1.0001 to 1.0023, p = 0.0328). However, based on the multivariate regression analysis, galectin lost its prognostic significance under the effect of LAVi, which remained the only independent predictor of AHREs (OR 1.0883, 95% CI 1.0351 to 1.1441, p = 0.0009). AHREs are common in CIEDs patients. Galectin-3 may bring additional data in the prediction of AHREs.
Chemical and Biological Evaluation of Novel 1H-Chromeno[3,2-c]pyridine Derivatives as MAO Inhibitors Endowed with Potential Anticancer Activity
Authors: Kulikova Larisa N. , Purgatorio Rosa , Beloglazkin Andrey A. , Tafeenko Viktor A. , Reza Raesi Gh. , Levickaya Daria D. , Sblano Sabina , Boccarelli Angelina , de Candia Modesto , Catto Marco , Voskressensky Leonid G. , Altomare Cosimo D.
Published: April 2023

About twenty molecules sharing 1H-chromeno[3,2-c]pyridine as the scaffold and differing in the degree of saturation of the pyridine ring, oxidation at C10, 1-phenylethynyl at C1 and 1H-indol-3-yl fragments at C10, as well as a few small substituents at C6 and C8, were synthesized starting from 1,2,3,4-tetrahydro-2-methylchromeno[3,2-c]pyridin-10-ones (1,2,3,4-THCP-10-ones, 1) or 2,3-dihydro-2-methyl-1H-chromeno[3,2-c]pyridines (2,3-DHPCs, 2). The newly synthesized compounds were tested as inhibitors of the human isoforms of monoamine oxidase (MAO A and B) and cholinesterase (AChE and BChE), and the following main SARs were inferred: (i) The 2,3-DHCP derivatives 2 inhibit MAO A (IC50 about 1 μM) preferentially; (ii) the 1,2,3,4-THCP-10-one 3a, bearing the phenylethynyl fragment at C1, returned as a potent MAO B inhibitor (IC50 0.51 μM) and moderate inhibitor of both ChEs (IC50s 7–8 μM); (iii) the 1H-indol-3-yl fragment at C10 slightly increases the MAO B inhibition potency, with the analog 6c achieving MAO B IC50 of 3.51 μM. The MAO B inhibitor 3a deserves further pharmacological studies as a remedy in the symptomatic treatment of Parkinson’s disease and neuroprotectant for Alzheimer’s disease. Besides the established neuroprotective effects of MAO inhibitors, the role of MAOs in tumor insurgence and progression has been recently reported. Herein, antiproliferative assays with breast (MCF-7), colon (HCT116) and cisplatin-resistant ovarian (SK-OV-3) tumor cells revealed that the 10-indolyl-bearing 2,3,4,10-THCP analog 6c exerts anti-tumor activity with IC50s in the range 4.83–11.3 μM.
Secreted Soluble Factors from Tumor-Activated Mesenchymal Stromal Cells Confer Platinum Chemoresistance to Ovarian Cancer Cells
Authors: Koren Carmi Yifat , Khamaisi Hazem , Adawi Rina , Noyman Eden , Gopas Jacob , Mahajna Jamal
Published: April 2023

Ovarian cancer (OC) ranks as the second most common type of gynecological malignancy, has poor survival rates, and is frequently diagnosed at an advanced stage. Platinum-based chemotherapy, such as carboplatin, represents the standard-of-care for OC. However, toxicity and acquired resistance to therapy have proven challenging for the treatment of patients. Chemoresistance, a principal obstacle to durable response in OC patients, is attributed to alterations within the cancer cells, and it can also be mediated by the tumor microenvironment (TME). In this study, we report that conditioned medium (CM) derived from murine and human stromal cells, MS-5 and HS-5, respectively, and tumor-activated HS-5, was active in conferring platinum chemoresistance to OC cells. Moreover, CM derived from differentiated murine pre-adipocyte (3T3-L1), but not undifferentiated pre-adipocyte cells, confers platinum chemoresistance to OC cells. Interestingly, CM derived from tumor-activated HS-5 was more effective in conferring chemoresistance than was CM derived from HS-5 cells. Various OC cells exhibit variable sensitivity to CM activity. Exploring CM content revealed the enrichment of a number of soluble factors in the tumor-activated HS-5, such as soluble uPAR (SuPAR), IL-6, and hepatocyte growth factor (HGF). FDA-approved JAK inhibitors were mildly effective in restoring platinum sensitivity in two of the three OC cell lines in the presence of CM. Moreover, Crizotinib, an ALK and c-MET inhibitor, in combination with platinum, blocked HGF’s ability to promote platinum resistance and to restore platinum sensitivity to OC cells. Finally, exposure to 2-hydroxyestardiol (2HE2) was effective in restoring platinum sensitivity to OC cells exposed to CM. Our results showed the significance of soluble factors found in TME in promoting platinum chemoresistance and the potential of combination therapy to restore chemosensitivity to OC cells.
Plasma Antithrombin III Levels Can Be a Prognostic Factor in Liver Cirrhosis Patients with Portal Vein Thrombosis
Authors: Suda Tsuyoshi , Takatori Hajime , Hayashi Takehiro , Kaji Kiichiro , Nio Kouki , Terashima Takeshi , Shimakami Tetsuro , Arai Kuniaki , Yamashita Tatsuya , Mizukoshi Eishiro , Honda Masao , Okumura Kenichiro , Kozaka Kazuto , Yamashita Taro
Published: April 2023

Liver function influences the plasma antithrombin (AT)-III levels. AT-III is beneficial for patients with portal vein thrombosis (PVT) and low plasma AT-III levels. However, whether these levels affect prognosis in patients with cirrhosis-associated PVT remains unknown. This retrospective study involved 75 patients with cirrhosis and PVT treated with danaparoid sodium with or without AT-III. The plasma AT-III level was significantly lower in patients with liver failure-related death than in those with hepatocellular carcinoma (HCC)-related death (p = 0.005), although the Child–Pugh and albumin-bilirubin (ALBI) scores were not significantly different between these two groups. Receiver operating characteristic curve analysis of the plasma AT-III levels showed cutoff values of 54.0% at 5-year survival. Low plasma AT-III levels (<54.0%) were associated with significantly worse prognosis than high levels in both overall survival (p = 0.0013) and survival excluding HCC-related death (p < 0.0001). Low plasma AT-III (<54.0%) was also associated with a significantly worse prognosis among patients with Child–Pugh A/B or ALBI grade 1/2 (p < 0.0001). Multivariate analyses indicated that low plasma AT-III levels (<54.0%) were an independent prognostic factor for poor survival outcome. Low plasma AT-III levels may be associated with mortality, particularly liver failure-related death, independent of liver function.
Spleen Transcriptome Profiling Reveals Divergent Immune Responses to LPS and Poly (I:C) Challenge in the Yellow Drum (Nibea albiflora)
Authors: Zhao Xiang , Zhang Yuan , Gao Tianxiang , Song Na
Published: April 2023

The yellow drum (Nibea albiflora) is a marine teleost fish with strong disease resistance, yet the understanding of its immune response and key functional genes is fragmented. Here, RNA-Seq was used to investigate the regulation pathways and genes involved in the immune response to infection with lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid (poly (I:C)) on the spleen of the yellow drum. There were fewer differentially expressed genes (DEGs) in the LPS-infected treatment group at either 6 or 48 h. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were mainly significantly enriched in c5-branching dibasic acid metabolic and complement and coagulation cascades pathways. The yellow drum responded more strongly to poly (I:C) infection, with 185 and 521 DEGs obtained under 6 and 48 h treatments, respectively. These DEGs were significantly enriched in the Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway, Jak-STAT signaling pathway, NOD-like signaling pathway, and cytokine–cytokine receptor interaction. The key functional genes in these pathways played important roles in the immune response and maintenance of immune system homeostasis in the yellow drum. Weighted gene co-expression network analysis (WGCNA) revealed several important hub genes. Although the functions of some genes have not been confirmed, our study still provides significant information for further investigation of the immune system of the yellow drum.
Immortalization Reversibility in the Context of Cell Therapy Biosafety
Authors: Sutyagina Oksana I. , Beilin Arkadii K. , Vorotelyak Ekaterina A. , Vasiliev Andrey V.
Published: April 2023

Immortalization (genetically induced prevention of replicative senescence) is a promising approach to obtain cellular material for cell therapy or for bio-artificial organs aimed at overcoming the problem of donor material shortage. Immortalization is reversed before cells are used in vivo to allow cell differentiation into the mature phenotype and avoid tumorigenic effects of unlimited cell proliferation. However, there is no certainty that the process of de-immortalization is 100% effective and that it does not cause unwanted changes in the cell. In this review, we discuss various approaches to reversible immortalization, emphasizing their advantages and disadvantages in terms of biosafety. We describe the most promising approaches in improving the biosafety of reversibly immortalized cells: CRISPR/Cas9-mediated immortogene insertion, tamoxifen-mediated self-recombination, tools for selection of successfully immortalized cells, using a decellularized extracellular matrix, and ensuring post-transplant safety with the use of suicide genes. The last process may be used as an add-on for previously existing reversible immortalized cell lines.
Boesenbergia stenophylla-Derived Stenophyllol B Exerts Antiproliferative and Oxidative Stress Responses in Triple-Negative Breast Cancer Cells with Few Side Effects in Normal Cells
Authors: Lee Min-Yu , Shiau Jun-Ping , Tang Jen-Yang , Hou Ming-Feng , Primus Phoebe Sussana , Kao Chai-Lin , Choo Yeun-Mun , Chang Hsueh-Wei
Published: April 2023

Triple-negative breast cancer (TNBC) is insensitive to target therapy for non-TNBC and needs novel drug discovery. Extracts of the traditional herb Boesenbergia plant in Southern Asia exhibit anticancer effects and contain novel bioactive compounds but merely show cytotoxicity. We recently isolated a new compound from B. stenophylla, stenophyllol B (StenB), but the impact and mechanism of its proliferation-modulating function on TNBC cells remain uninvestigated. This study aimed to assess the antiproliferative responses of StenB in TNBC cells and examine the drug safety in normal cells. StenB effectively suppressed the proliferation of TNBC cells rather than normal cells in terms of an ATP assay. This preferential antiproliferative function was alleviated by pretreating inhibitors for oxidative stress (N-acetylcysteine (NAC)) and apoptosis (Z-VAD-FMK). Accordingly, the oxidative-stress-related mechanisms were further assessed. StenB caused subG1 and G2/M accumulation but reduced the G1 phase in TNBC cells, while normal cells remained unchanged between the control and StenB treatments. The apoptosis behavior of TNBC cells was suppressed by StenB, whereas that of normal cells was not suppressed according to an annexin V assay. StenB-modulated apoptosis signaling, such as for caspases 3, 8, and 9, was more significantly activated in TNBC than in normal cells. StenB also caused oxidative stress in TNBC cells but not in normal cells according to a flow cytometry assay monitoring reactive oxygen species, mitochondrial superoxide, and their membrane potential. StenB induced greater DNA damage responses (γH2AX and 8-hydroxy-2-deoxyguanosine) in TNBC than in normal cells. All these StenB responses were alleviated by NAC pretreatment. Collectively, StenB modulated oxidative stress responses, leading to the antiproliferation of TNBC cells with little cytotoxicity in normal cells.
Molecular Apomorphies in the Secondary and Tertiary Structures of Length-Variable Regions (LVRs) of 18S rRNA Shed Light on the Systematic Position of the Family Thaumastellidae (Hemiptera: Heteroptera: Pentatomoidea)
Authors: Lis Jerzy A.
Published: April 2023

The SSU nrDNA, a small subunit of the nuclear ribosomal DNA (coding 18S rRNA), is one of the most frequently sequenced genes in molecular studies in Hexapoda. In insects, including true bugs (Hemiptera: Heteroptera), only its primary structures (i.e., aligned sequences) are predominantly used in phylogenetic reconstructions. It is known that including RNA secondary structures in the alignment procedure is essential for improving accuracy and robustness in phylogenetic tree reconstruction. Moreover, local plasticity in rRNAs might impact their tertiary structures and corresponding functions. To determine the systematic position of Thaumastellidae within the superfamily Pentatomoidea, the secondary and—for the first time among all Hexapoda—tertiary structures of 18S rRNAs in twelve pentatomoid families were compared and analysed. Results indicate that the shapes of the secondary and tertiary structures of the length-variable regions (LVRs) in the 18S rRNA are phylogenetically highly informative. Based on these results, it is suggested that the Thaumastellidae is maintained as an independent family within the superfamily Pentatomoidea, rather than as a part of the family Cydnidae. Moreover, the analyses indicate a close relationship between Sehirinae and Parastrachiidae, expressed in morpho-molecular synapomorphies in the predicted secondary and tertiary structures of the length-variable region L (LVR L).
Role of G-Protein-Coupled Receptors in Cardiovascular Diseases
Authors: Gencer Selin , van der Vorst Emiel P. C.
Published: April 2023

Cardiovascular diseases (CVDs), such as ischemic heart disease and stroke, are recognized as major causes of deaths worldwide [...]
LC/MS-Based Untargeted Metabolomics Analysis in Women with Morbid Obesity and Associated Type 2 Diabetes Mellitus
Authors: Auguet Teresa , Bertran Laia , Capellades Jordi , Abelló Sonia , Aguilar Carmen , Sabench Fàtima , del Castillo Daniel , Correig Xavier , Yanes Oscar , Richart Cristóbal
Published: April 2023

Obesity is a chronic and complex disease, with an increasing incidence worldwide that is associated with metabolic disorders such as type 2 diabetes mellitus (T2DM). Thus, it is important to determine the differences between metabolically healthy obese individuals and those with metabolic disorders. The aim of this study was to perform an untargeted metabolomics assay in women with morbid obesity (MO) compared to a normal weight group, and to differentiate the metabolome of these women with MO who present with T2DM. We carried out a liquid chromatography-mass spectrometry-based untargeted metabolomics assay using serum samples of 209 Caucasian women: 73 with normal weight and 136 with MO, of which 71 had T2DM. First, we found increased levels of choline and acylglycerols and lower levels of bile acids, steroids, ceramides, glycosphingolipids, lysophosphatidylcholines, and lysophosphatidylethanolamines in MO women than in the control group. Then, in MO women with T2DM, we found increased levels of glutamate, propionyl-carnitine, bile acids, ceramides, lysophosphatidylcholine 14:0, phosphatidylinositols and phosphoethanolamines, and lower levels of Phe-Ile/Leu. Thus, we found metabolites with opposite trends of concentration in the two metabolomic analyses. These metabolites could be considered possible new factors of study in the pathogenesis of MO and associated T2DM in women.
Depletion of Ly6G-Expressing Neutrophilic Cells Leads to Altered Peripheral T-Cell Homeostasis and Thymic Development in Neonatal Mice
Authors: Rühle Jessica , Ginzel Marco , Dietz Stefanie , Schwarz Julian , Lajqi Trim , Beer-Hammer Sandra , Poets Christian F. , Gille Christian , Köstlin-Gille Natascha
Published: April 2023

Newborns and especially preterm infants are much more susceptible to infections than adults. Due to immature adaptive immunity, especially innate immune cells play an important role in a newborn’s infection defense. Neonatal neutrophils exhibit profound differences in their functionality compared to neutrophils of adults. In particular, neonates possess a relevant population of suppressive neutrophils, which not only inhibit but also specifically modulate the function of T-cells. In this study, we investigated whether neonatal neutrophils are already involved in T-cell development in the thymus. For this purpose, we used a newly developed model of antibody-mediated immune cell depletion in which we administered a depleting antibody to pregnant and then lactating dams. Using this method, we were able to sufficiently deplete Ly6G-positive neutrophils in offspring. We demonstrated that the depletion of neutrophils in newborn mice resulted in altered peripheral T-cell homeostasis with a decreased CD4+/CD8+ T-cell ratio and decreased expression of CD62L. Neutrophil depletion even affected T-cell development in the thymus, with increased double positive thymocytes and a decreased CD4+/CD8+ single positive thymocyte ratio. Altogether, we demonstrated a previously unknown mechanism mediating neutrophils’ immunomodulatory effects in newborns.
The Impact of Light Wavelength and Darkness on Metabolite Profiling of Korean Ginseng: Evaluating Its Anti-Cancer Potential against MCF-7 and BV-2 Cell Lines
Authors: Sadiq Nooruddin , Kwon Hyukjoon , Park Nam , Hamayun Muhammad , Jung Je-Hyeong , Yang Seung-Hoon , Jang Soo-Won , Kabadayı Seda , Kim Ho-Youn , Kim Young-Joo
Published: April 2023

Korean ginseng is a source of functional foods and medicines; however, its productivity is hindered by abiotic stress factors, such as light. This study investigated the impacts of darkness and different light wavelengths on the metabolomics and anti-cancer activity of ginseng extracts. Hydroponically-grown Korean ginseng was shifted to a light-emitting diodes (LEDs) chamber for blue-LED and darkness treatments, while white fluorescent (FL) light treatment was the control. MCF-7 breast cancer and lipopolysaccharide (LPS)-induced BV-2 microglial cells were used to determine chemo-preventive and neuroprotective potential. Overall, 53 significant primary metabolites were detected in the treated samples. The levels of ginsenosides Rb1, Rb2, Rc, Rd, and Re, as well as organic and amino acids, were significantly higher in the dark treatment, followed by blue-LED treatment and the FL control. The dark-treated ginseng extract significantly induced apoptotic signaling in MCF-7 cells and dose-dependently inhibited the NF-κB and MAP kinase pathways in LPS-induced BV-2 cells. Short-term dark treatment increased the content of Rd, Rc, Rb1, Rb2, and Re ginsenosides in ginseng extracts, which promoted apoptosis of MCF-7 cells and inhibition of the MAP kinase pathway in BV-2 microglial cells. These results indicate that the dark treatment might be effective in improving the pharmacological potential of ginseng.
Foetal Haemoglobin as a Marker of Bone Marrow Suppression Secondary to Anti-Kell Alloimmunisation
Authors: Morales Painamil Rodrigo Alfredo , de Aledo-Castillo José Manuel González , Teresa-Palacio Marta , Argudo-Ramírez Ana , López-Galera Rosa M. , Paredes-Fuentes Abraham J. , Aldecoa-Bilbao Victoria , Alsina-Casanova Miguel
Published: April 2023

Anti-Kell alloimmunisation is a potentially severe minor blood group type incompatibility, not only as a cause of haemolytic disease of the foetus and newborn, but also due to the destruction of red blood cells (RBC) and mature form in the bone marrow with the subsequent hyporegenerative anaemia. In severe cases and when the foetus shows signs of anaemia, an intrauterine transfusion (IUT) may be necessary. When repeated, this treatment can suppress erythropoiesis and worsen the anaemia. We report the case of a newborn who required four IUTs plus an additional RBC transfusion at one month of life due to late onset anaemia. The identification of an adult haemoglobin profile with a complete absence of foetal haemoglobin in the patient’s newborn screening samples at 2 and 10 days of life warned us of a possible late anaemia. The newborn was successfully treated with transfusion, oral supplements and subcutaneous erythropoietin. A blood sample taken at 4 months of life showed the expected haemoglobin profile for that age with a foetal haemoglobin of 17.7%. This case illustrates the importance of a close follow-up of these patients, as well as the usefulness of the haemoglobin profile screening as a tool for anaemia assessment.
Fruit Structure in Amphicarpic Annual Gymnarrhena micrantha (Asteraceae, Gymnarrheneae) in Relation to the Species Biology
Authors: Kravtsova Tatyana
Published: April 2023

In the amphicarpic annual Gymnarrhena micrantha Desf. (Asteraceae), aerial and subterranean fruits differ in morphology, dispersal ability and germination behavior. The aim of our work was to study their structural features in relation to the eco-physiological properties, using light and scanning electron microscopes. Five fruit morphs were found, three of aerial achenes: ebracteate, bracteate and double bracteate ones, and two subterranean fruits with achenes, enveloped in involucral bracts, developed from (I) sessile or (II) not sessile different heads. This species shows divergent fruit differentiation, an increase in their diversity along several lines of morphological differentiation, which corresponds to a multiple seed dispersal and germination strategy. In addition to the already known distinctive features of subterranean achenes (larger size, undeveloped pappus, poor pubescence), they also differ in the simplified structure of the apical and basal achene regions, the absence of the corolla expanded base (cupula) and nectary, other cells parameters in the exotesta and endosperm, another form of the disproportionately developed embryo. The peculiarities of probably subterranean fruit II (seemingly originated through apomixis) extend to various color, pappus structure, sparse pubescence, and the ability of the fruit wall to delaminate. The lack of dense pubescence in the subterranean achenes is a key trait that could lead to increased water permeability of the fruit wall and affect germination rate. Possible adaptive significance of aerial achene structural features is discussed, including specialized corolla cupula, which may be an adaptation to dissemination by rainwater and ants.
Assessing the Credit Risk of Crypto-Assets Using Daily Range Volatility Models
Authors: Fantazzini Dean
Published: April 2023

In this paper, we analyzed a dataset of over 2000 crypto-assets to assess their credit risk by computing their probability of death using the daily range. Unlike conventional low-frequency volatility models that only utilize close-to-close prices, the daily range incorporates all the information provided in traditional daily datasets, including the open-high-low-close (OHLC) prices for each asset. We evaluated the accuracy of the probability of death estimated with the daily range against various forecasting models, including credit scoring models, machine learning models, and time-series-based models. Our study considered different definitions of “dead coins” and various forecasting horizons. Our results indicate that credit scoring models and machine learning methods incorporating lagged trading volumes and online searches were the best models for short-term horizons up to 30 days. Conversely, time-series models using the daily range were more appropriate for longer term forecasts, up to one year. Additionally, our analysis revealed that the models using the daily range signaled, far in advance, the weakened credit position of the crypto derivatives trading platform FTX, which filed for Chapter 11 bankruptcy protection in the United States on 11 November 2022.
Molten Salt Synthesis of Micro-Sized Hexagonally Shaped REMnO3 (RE = Y, Er, Tm, Yb)
Authors: Karoblis Dovydas , Zarkov Aleksej , Murauskas Tomas , Kareiva Aivaras
Published: April 2023

Yttrium manganite (YMnO3) is a compound belonging to the hexagonal rare earth manganites family, which demonstrates multiferroic properties. This material can be prepared by several synthetic approaches, with the most common one being the solid-state synthesis. In this work, we show a possibility of preparing this material via molten salt synthesis using the NaCl-KCl mixture as the reaction medium and yttrium and manganese nitrates as the starting materials. We demonstrate that, by varying the reaction temperature and the nitrates-to-chlorides ratio, it is feasible to synthesize hexagonally shaped particles of microscopic dimensions. A similar synthesis procedure can be successfully applied for the preparation of other hexagonal manganites—ErMnO3, TmMnO3, and YbMnO3.
Evaluation of Membrane Permeability of Copper-Based Drugs
Authors: Umba-Tsumbu Evariste , Hammouda Ahmed N. , Jackson Graham Ellis
Published: April 2023

Membrane permeability of copper complexes with potential anti-inflammatory activity were measured using an artificial membrane in a modified Franz cell. Using CuCl2 as the control, all the ligands tested enhanced the diffusion of copper, with enhancement factors ranging from 2 to 7. Octanol/water partition coefficients (log Ko/w) were measured and correlated with the permeability coefficients (Kp). In addition, chemical speciation was used to determine the predominant complex in solution at physiological pH. No correlation was found between the measured permeability coefficients and either molecular weight (MW) or log Ko/w.
Mosquito Blood Feeding Prevention Using an Extra-Low DC Voltage Charged Cloth
Authors: Luan Kun , McCord Marian G. , West Andre J. , Cave Grayson , Travanty Nicholas V. , Apperson Charles S. , Roe R. Michael
Published: April 2023

Mosquito vector-borne diseases such as malaria and dengue pose a major threat to human health. Personal protection from mosquito blood feeding is mostly by treating clothing with insecticides and the use of repellents on clothing and skin. Here, we developed a low-voltage, mosquito-resistant cloth (MRC) that blocked all blood feeding across the textile and was flexible and breathable. The design was based on mosquito head and proboscis morphometrics, the development of a novel 3-D textile with the outer conductive layers insulated from each other with an inner, non-conductive woven mesh, and the use of a DC (direct current; extra-low-voltage) resistor-capacitor. Blockage of blood feeding was measured using host-seeking Aedes aegypti adult female mosquitoes and whether they could blood feed across the MRC and an artificial membrane. Mosquito blood feeding decreased as voltage increased from 0 to 15 volts. Blood feeding inhibition was 97.8% at 10 volts and 100% inhibition at 15 volts, demonstrating proof of concept. Current flow is minimal since conductance only occurs when the mosquito proboscis simultaneously touches the outside layers of the MRC and is then quickly repelled. Our results demonstrated for the first time the use of a biomimetic, mosquito-repelling technology to prevent blood feeding using extra-low energy consumption.
High-Sucrose Diet Exposure on Larvae Contributes to Adult Fecundity and Insecticide Tolerance in the Oriental Fruit Fly, Bactrocera dorsalis (Hendel)
Authors: Wang Lei , Wei Dan-Dan , Wang Gui-Qiang , Huang Han-Qin , Wang Jin-Jun
Published: April 2023

Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) is one of the broad host ranges and economically-important insect pests in tropical and subtropical areas. A wide range of hosts means they have strong adaptation ability to changes in dietary macronutrients (e.g., sucrose and protein). However, the effects of dietary conditions on the phenotypes and genotypes of B. dorsalis are still unclear. In this study, we aimed to investigate the effects of larval dietary sucrose on the life history traits and stress tolerance of B. dorsalis, and its defense response at the molecular level. The results showed that low-sucrose (LS) induced decreased body size, shortened developmental duration, and enhanced sensitivity to beta-cypermethrin. Otherwise, high-sucrose (HS) diet increased developmental duration, adult fecundity, and tolerance to malathion. Based on transcriptome data, 258 and 904 differentially expressed genes (DEGs) were identified in the NS (control) versus LS groups, and NS versus HS groups, respectively. These yielded DEGs were relevant to multiple specific metabolisms, hormone synthesis and signaling, and immune-related pathways. Our study will provide biological and molecular perspective to understand phenotypic adjustments to diets and the strong host adaptability in oriental fruit flies.
UV-Spectrophotometric Determination of the Active Pharmaceutical Ingredients Meloxicam and Nimesulide in Cleaning Validation Samples with Sodium Carbonate
Authors: Nikolaychuk Pavel Anatolyevich
Published: April 2023

The spectrophotometric methods of determination of the active pharmaceutical ingredients meloxicam and nimesulide were reviewed and a simple UV-spectrophotometric method for the determination of these active pharmaceutical ingredients in industrial equipment cleaning validation samples was proposed. The methods were based on extraction of the residual quantities of meloxicam and nimesulide from the manufacturing equipment surface by the concentrated sodium carbonate solution and the subsequent UV-spectrophotometric determination of the basic forms of the drugs at the wavelength of 362 nm for meloxicam and at 397 nm for nimesulide. The calibration graphs were linear in the range from 5 to 25 mg/L of both nimesulide and meloxicam, the molar attenuation coefficients were 6100 m2/mol for nimesulide and 9100 m2/mol for meloxicam, the limit of detection was 0.8 mg/L for nimesulide and 1.9 mg/L for meloxicam and the limit of quantification was 2.5 mg/L for nimesulide and 5.8 mg/L for meloxicam. The methods were selective with respect to the common excipients, showed a good accuracy (the relative uncertainty did not exceed 7%) and precision (the relative standard deviation did not exceed 4%), did not require lengthy sample preparation or sophisticated laboratory equipment and were suitable for the routine analysis of cleaning validation samples.
Malignant Bone and Soft Tissue Lesions of the Foot
Authors: Angelini Andrea , Biz Carlo , Cerchiaro Mariachiara , Longhi Valentina , Ruggieri Pietro
Published: April 2023

Malignant tumors of the foot are rare pathologies that can involve the skin, soft tissue, or bone. Due to their rarity, they are often misdiagnosed, resulting in inadequate excision and poor outcomes. A correct approach with a careful examination and radiological study, followed by a properly performed biopsy, is thus mandatory to avoid these pitfalls. The present article reviews the most common malignant bone and soft tissue lesions of the foot region, discussing their clinicopathological presentation, imaging features, and current concepts in treatment.
Potential Role of Innate Lymphoid Cells in the Pathogenesis and Treatment of Skin Diseases
Authors: Borgia Francesco , Li Pomi Federica , Alessandrello Clara , Vaccaro Mario , Gangemi Sebastiano
Published: April 2023

Group 2 innate lymphoid cells (ILC2s) are lymphoid cells that are resident in mucosal tissues, especially the skin, which, once stimulated by epithelial cell-derived cytokines, release IL-5, IL-13, and IL-4, as the effectors of type 2 immune responses. This research aims to evaluate the role of ILC2s in the pathogenesis of skin diseases, with a particular focus on inflammatory cutaneous disorders, in order to also elucidate potential therapeutic perspectives. The research has been conducted in articles, excluding reviews and meta-analyses, on both animals and humans. The results showed that ILC2s play a crucial role in the pathogenesis of systemic skin manifestations, prognosis, and severity, while a potential antimelanoma role is emerging from the new research. Future perspectives could include the development of new antibodies targeting or stimulating ILC2 release. This evidence could add a new therapeutic approach to inflammatory cutaneous conditions, including allergic ones.
Intraoperative OCT for Lamellar Corneal Surgery: A User Guide
Authors: Moramarco Antonio , di Geronimo Natalie , Airaldi Matteo , Gardini Lorenzo , Semeraro Francesco , Iannetta Danilo , Romano Vito , Fontana Luigi
Published: April 2023

Intraoperative OCT is an innovative and promising technology which allows anterior and posterior segment ocular surgeons to obtain a near-histologic cross-sectional and tomographic image of the tissues. Intraoperative OCT has several applications in ocular surgery which are particularly interesting in the context of corneal transplantation. Indeed, iOCT images provide a direct and meticulous visualization of the anatomy, which could guide surgical decisions. In particular, during both big-bubble and manual DALK, the visualization of the relationship between the corneal layers and instruments allows the surgeon to obtain a more desirable depth of the trephination, thus achieving more type 1 bubbles, better regularity of the plane, and a reduced risk of DM perforation. During EK procedures, iOCT supplies information about proper descemetorhexis, graft orientation, and interface quality in order to optimize the postoperative adhesion and reduce the need for re-bubbling. Finally, mushroom PK, a challenging technique for many surgeons, can be aided through the use of iOCT since it guides the correct apposition of the lamellae and their centration. The technology of iOCT is still evolving: a larger field of view could allow for the visualization of all surgical fields, and automated tracking and iOCT autofocusing guarantee the continued centration of the image.
Prognostic Optical Coherence Tomography Biomarkers in Neovascular Age-Related Macular Degeneration
Authors: Nawash Baraa , Ong Joshua , Driban Matthew , Hwang Jonathan , Chen Jeffrey , Selvam Amrish , Mohan Sashwanthi , Chhablani Jay
Published: April 2023

Optical coherence tomography has revolutionized the diagnosis and management of neovascular age-related macular degeneration. OCT-derived biomarkers have the potential to further guide therapeutic advancements with anti-vascular endothelial growth factor; however, the clinical convergence between these two tools remains suboptimal. Therefore, the aim of this review of literature was to examine the current data on OCT biomarkers and their prognostic value. Thirteen biomarkers were analyzed, and retinal fluid had the strongest-reported impact on clinical outcomes, including visual acuity, clinic visits, and anti-VEGF treatment regimens. In particular, intra-retinal fluid was shown to be associated with poor visual outcomes. Consistencies in the literature with regard to these OCT prognostic biomarkers can lead to patient-specific clinical decision making, such as early-initiated treatment and proactive monitoring. An integrated analysis of all OCT components in combination with new efforts toward automated analysis with artificial intelligence has the potential to further improve the role of OCT in nAMD therapy.
Effect of Neoadjuvant Hormonal Therapy on the Postoperative Course for Patients Undergoing Robot-Assisted Radical Prostatectomy
Authors: Farzat Mahmoud , Weib Peter , Sukhanov Iurii , Rosenbauer Josef , Tanislav Christian , Wagenlehner Florian M.
Published: April 2023

Objectives: Neoadjuvant hormonal therapy (NHT) preceding robot-assisted radical prostatectomy (RARP) may be beneficial in high-risk cases to facilitate surgical resection. Yet, its improvement in local tumor control is not obvious. Its benefit regarding overall cancer survival is also not evident, and it may worsen sexual and hormonal functions. This study explores the effect of NHT on the perioperative course after RARP. Methods: In this study, 500 patients from a tertiary referral center who underwent RARP by a specialized surgeon were retrospectively included. Patients were divided into two groups: the NHT (n = 55, 11%) group, which included patients who received NHT (median: 1 month prior to RARP), and the standard non-NHT (NNHT) group (n = 445, 89%). Demographic and perioperative data were analyzed. Postoperative results, complications, and readmission rates were compared between the groups. Results: NHT patients were heterogeneous from the rest regarding cancer parameters such as PSA (25 vs. 7.8 ng/mL) and tumor risk stratification, and they were more comorbid (p = 0.006 for the ASA score). They also received fewer nerve-sparing procedures (14.5% vs. 80.4%), while the operation time was similar. Positive surgical margins (PSM) (21.8% vs. 5.4%) and positive lymph nodes (PLN) (56.4% vs. 12.7%) were significantly higher in the NHT group compared to the non-NHT (NNHT) group. Hospital stay was equal, whereas catheter days were 3 days longer in the NHT group. NHT patients also suffered more minor vesicourethral-anastomosis-related complications. Major complications (p = 0.825) and readmissions (p = 0.070) did not differ between groups. Conclusion: Patients receiving NHT before RARP did not experience more major complications or readmissions within 90 days after surgery. Patients with unfavorable, high-risk tumors may benefit from NHT since it facilitates surgical resection. Randomized controlled trials are necessary to measure the advantages and disadvantages of NHT.
Maternal Bariatric Surgery and Offspring Health: A Sibling Matched Analysis Comparing Offspring Born before and after the Surgery
Authors: Gothelf Itamar , Sheiner Eyal , Wainstock Tamar
Published: April 2023

(1) Background: Due to the global escalation in the prevalence of obesity, bariatric surgeries have become a popular solution in many western countries. The aim of the current study was to compare offspring health and the obesity of women before and after undergoing bariatric surgeries. (2) Methods: A retrospective population-based study was performed, including all singleton deliveries which occurred at a tertiary medical center between the years 1991–2021. Among women who had bariatric surgeries, the health of the offspring born before and after the surgery were compared. The offspring were followed up until the age of 18 years, and their hospitalization records were summarized. The incidence of hospitalization with either endocrine, cardiac, respiratory, neurologic, or infectious diagnoses were compared between the groups, as well as offspring obesity. Multivariable Cox proportional models were used to match between siblings and to address confounding variables, including maternal age, gestational age at delivery, fertility treatment, smoking and pregnancy hypertensive disorders. (3) Results: The study population included 3074 deliveries of women who underwent bariatric surgeries (1586 were before and 1488 after the surgery). Offspring born after maternal bariatric surgeries were at a comparable risk for most morbidities, besides endocrine-related morbidities (3.1% vs. 5.0%, OR = 1.61; 1.1–2.35) and obesity (2.5% vs. 4.1%, OR = 1.63; 1.08–2.48). The risk for these morbidities was higher among the offspring of mothers after, vs. before, the surgery, despite adjustment for maternal age and other confounding variables. (4) Conclusions: While bariatric surgeries are considered an effective treatment for obesity, it seems to have less of an effect on the offspring of women who underwent such surgeries. Other persistent factors are most likely associated with the offspring’s risk for morbidities, especially endocrine morbidities and obesity, which remain even though the mother underwent bariatric surgeries.
Impact of Noisy Labels on Dental Deep Learning—Calculus Detection on Bitewing Radiographs
Authors: Büttner Martha , Schneider Lisa , Krasowski Aleksander , Krois Joachim , Feldberg Ben , Schwendicke Falk
Published: April 2023

Supervised deep learning requires labelled data. On medical images, data is often labelled inconsistently (e.g., too large) with varying accuracies. We aimed to assess the impact of such label noise on dental calculus detection on bitewing radiographs. On 2584 bitewings calculus was accurately labeled using bounding boxes (BBs) and artificially increased and decreased stepwise, resulting in 30 consistently and 9 inconsistently noisy datasets. An object detection network (YOLOv5) was trained on each dataset and evaluated on noisy and accurate test data. Training on accurately labeled data yielded an mAP50: 0.77 (SD: 0.01). When trained on consistently too small BBs model performance significantly decreased on accurate and noisy test data. Model performance trained on consistently too large BBs decreased immediately on accurate test data (e.g., 200% BBs: mAP50: 0.24; SD: 0.05; p < 0.05), but only after drastically increasing BBs on noisy test data (e.g., 70,000%: mAP50: 0.75; SD: 0.01; p < 0.05). Models trained on inconsistent BB sizes showed a significant decrease of performance when deviating 20% or more from the original when tested on noisy data (mAP50: 0.74; SD: 0.02; p < 0.05), or 30% or more when tested on accurate data (mAP50: 0.76; SD: 0.01; p < 0.05). In conclusion, accurate predictions need accurate labeled data in the training process. Testing on noisy data may disguise the effects of noisy training data. Researchers should be aware of the relevance of accurately annotated data, especially when testing model performances.
Myocardial Work Index in Professional Football Players: A Novel Method for Assessment of Cardiac Adaptation
Authors: Refoyo Elena , Troya Jesús , de la Fuente Ana , Beltrán Almudena , Celada Oscar Luis , Díaz-González Leonel , Pedrero-Tomé Roberto , García-Yébenes Manuel , Villalón Jose María
Published: April 2023

Background: The global myocardial work index (GWI), a novel, valid, and non-invasive method based on speckle-tracking echocardiography, could provide value for calculating left ventricular (LV) function and energy consumption in athletes. Materials and Methods: We prospectively analyzed a single-center cohort of Spanish First-Division football players who attended a pre-participation screening program from June 2020 to June 2021, compared to a control group. All the individuals underwent an electrocardiogram and echocardiography, including two-dimensional speckle tracking and 4D-echo. The study aimed to evaluate the feasibility of myocardial work in professional football players and its correlations with other echocardiographic parameters. Results: The study population comprised 97 individuals (49 professional players and 48 controls). The mean age was 30.48 ± 7.20 years old. The professional football players had significantly higher values of LVEDV (p < 0.001), LVESV (p < 0.001), LV-mass index (p = 0.011), PWTd (p = 0.023), and EA (p < 0.001) compared with the control group. In addition, the professional players had lower GCW (p = 0.003) and a tendency to show lower GWI values (p < 0.001). These findings could suggest that professional football players have more remodeling and less MW, related to their adaptation to intensive training. Significant differences in GLS (p = 0.01) and GWE (p = 0.04) were observed as a function of the septal thickness of the athletes. Irrespective of the MW variable, the parameters with better correlations across all the populations were SBP, DBP, and GLS. Conclusions: The GWI is a novel index to assess cardiac performance, with less load dependency than strain measurements. Future GWI analyses are warranted to understand myocardial deformation and other pathological differential diagnoses.
Airway Complications after Lung Transplantation—A Contemporary Series of 400 Bronchial Anastomoses from a Single Center
Authors: Muñoz-Fos Anna , Moreno Paula , González Francisco Javier , Ruiz Eloisa , Vaquero Jose Manuel , Baamonde Carlos , Cerezo Francisco , Algar Javier , Ramos-Izquierdo Ricard , Salvatierra Ángel , Alvarez Antonio
Published: April 2023

(1) Objective: To determine whether recent advances in lung transplantation (LT) have reduced the incidence and changed the risk factors for airway complications (AC). (2) Methods: Retrospective analysis of patients receiving a lung transplant between January 2007 and January 2019. An AC was defined as a bronchoscopic abnormality in the airway, either requiring or not requiring an endoscopic or surgical intervention. Both univariable and multivariable analyses were performed to identify risk factors for AC. (3) Results: 285 lung transplants (170 single and 115 bilateral lung transplants) were analysed, comprising 400 anastomoses at risk. A total of 50 anastomoses resulted in AC (12%). There were 14 anastomotic and 11 non-anastomotic stenoses, 4 dehiscences, and 3 malacias. Independent predictors for AC were: gender male (OR: 4.18; p = 0.002), cardiac comorbidities (OR: 2.74; p = 0.009), prolonged postoperative mechanical ventilation (OR: 2.5; p = 0.02), PaO2/FiO2 < 300 mmHg at 24 h post-LT (OR: 2.48; p = 0.01), graft infection (OR: 2.16; p = 0.05), and post-LT isolation of Aspergillus spp. (OR: 2.63; p = 0.03). (4) Conclusions: In spite of advances in lung transplantation practice, the risk factors, incidence, and lethality of AC after LT remains unchanged. Graft dysfunction, an infected environment, and the need of prolonged mechanical ventilation remain an Achilles heel for AC.