bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Attachment Orientations Relate to Coping with Crises? Lessons from a Cross-Sectional Study during the COVID-19 Pandemic
Authors: Egozi Farkash Hadas , Lahad Mooli , Aharonson-Daniel Limor
Published: June 2023

This study was designed to explore whether attachment orientations were related to distress and resilience during the COVID-19 pandemic. The sample included 2000 Israeli Jewish adults who answered an online survey during the first phase of the pandemic. The questions referred to background variables, attachment orientations, distress, and resilience. Responses were analyzed using correlation and regression analyses. A significant positive relationship was found between distress and attachment anxiety, and a significant negative relationship was found between resilience and attachment insecurities (avoidance and anxiety). Women suffered higher distress, as did people with lower income, poor health, secular religious affiliation, a lack of a sense of spacious accommodation, and a dependent family member. The findings indicate that attachment insecurities are associated with the severity of mental health symptoms during the peak period of the COVID-19 pandemic. We recommend strengthening attachment security as a protective factor for psychological distress in therapeutic and educational settings.
The Function of Bed Management in Pandemic Times—A Case Study of Reaction Time and Bed Reconversion
Authors: Barchielli Chiara , Vainieri Milena , Seghieri Chiara , Salutini Eleonora , Zoppi Paolo
Published: June 2023

The last decade was characterized by the reduction in hospital beds throughout Europe. When facing the COVID pandemic, this has been an issue of major importance as hospitals were seriously overloaded with an unexpected growth in demand. The dichotomy formed by the scarcity of beds and the need for acute care was handled by the Bed Management (BM) function. This case study explores how BM was able to help the solidness of the healthcare system, managing hospital beds at best and recruiting others in different settings as intermediate care in a large Local Health Authority (LHA) in central Italy. Administrative data show how the provision of appropriate care was achieved by recruiting approximately 500 beds belonging to private healthcare facilities affiliated with the regional healthcare system and exercising the best BM function. The ability of the system to absorb the extra demand caused by COVID was made possible by using intermediate care beds, which were allowed to stretch the logistic boundaries of the hospitals, and by the promptness of Bed Management in converting beds into COVID beds and reconverting them, and by the timely management of internal patient logistics, thus creating space according to the healthcare demands.
Modeling the Conversation with Digital Health Assistants in Adherence Apps: Some Considerations on the Similarities and Differences with Familiar Medical Encounters
Authors: Spagnolli Anna , Cenzato Giulia , Gamberini Luciano
Published: June 2023

Digital health assistants (DHAs) are conversational agents incorporated into health systems’ interfaces, exploiting an intuitive interaction format appreciated by the users. At the same time, however, their conversational format can evoke interactional practices typical of health encounters with human doctors that might misguide the users. Awareness of the similarities and differences between novel mediated encounters and more familiar ones helps designers avoid unintended expectations and leverage suitable ones. Focusing on adherence apps, we analytically discuss the structure of DHA-patient encounters against the literature on physician-patient encounters and the specific affordances of DHAs. We synthesize our discussion into a design checklist and add some considerations about DHA with unconstrained natural language interfaces.
Development and Validation of the Military Minority Stress Scale
Authors: Goldbach Jeremy T. , Schrager Sheree M. , Mamey Mary Rose , Klemmer Cary , Holloway Ian W. , Castro Carl A.
Published: June 2023

Despite affecting nearly 3% of active-duty service members, little is known about how LGBT-related stress experiences may relate to health outcomes. Thus, the present study sought to create a Military Minority Stress Scale and assess its initial reliability and construct validity in a cross-sectional study of active-duty LGBT service members (N = 248). Associations between 47 candidate items and health outcomes of interest were analyzed to retain those with substantial betas. Item response theory analyzes, reliability testing, invariance testing, and exploratory factor analysis were performed. Construct validity of the final measure was assessed through associations between the sum score of the final measure and the health outcomes. The final 13-item measure demonstrated an excellent reliability (ω = 0.95). Bivariate linear regressions showed significant associations between the sum score of the measure and overall health (β = −0.26, p < 0.001), overall mental health (β = −0.34, p < 0.001), physical health (β = 0.45, p < 0.001), life satisfaction (β = −0.24, p < 0.001), anxiety (β = 0.34, p < 0.001), depressive symptoms (β = 0.37, p < 0.001), suicidality (β = 0.26, p < 0.001), and PTSD (β = 0.42, p < 0.001), respectively. This study provides the first evidence that minority stressors in the military setting can be operationalized and measured. They appear to have a role in the health of LGBT service members and may explain the continued health disparities experienced by this population. Little is known regarding the experiences of LGBT active-duty service members, including experiences of discrimination. Understanding these experiences and their associated health outcomes during military service may therefore help and guide further etiological studies and intervention development.
Correction: Mollinedo-Cardalda et al. Health-Related Functional Fitness within the Elderly Communities of Five European Countries: The in Common Sports Study. Int. J. Environ. Res. Public Health 2021, 18, 12810
Authors: Mollinedo-Cardalda Irimia , Ferreira Manuela , Bezerra Pedro , Cancela-Carral José María
Published: June 2023

There was an error in the original publication [...]
A Bibliometric Analysis of Fintech Trends: An Empirical Investigation
Authors: Garg Girish , Shamshad Mohd , Gauhar Nikita , Tabash Mosab I. , Hamouri Basem , Daniel Linda Nalini
Published: June 2023

Financial technology, or Fintech, has captured the attention of scholars, students, and institutions across worldwide for over a decade. With a plethora of new financial services, products, and innovative methods to engage with clients, the impact of technology on the financial sector has been extensively studied. This research paper provides a summary of scientific research on FinTech by using bibliometric analysis. Using the Scopus database, the paper analyzed 665 publications and identified research gaps and new study topics through “VOS-Viewer” software and “Biblioshiny” using RStudio. The study focused on FinTech’s functions and research constraints in digital finance by assessing citation links between the most significant articles. The findings provide a starting point for further investigation and offer opportunities for researchers to expand their expertise in exciting and innovative studies. Overall, this study seeks to help researchers discover new avenues for exploration in Fintech while advancing their present understanding. There exists much scope in the area of Digital Lending, Supply Chain Finance, the Internet of Things, and RoboAdvisers.
In Vitro Functional Characterization of Type-I Taste Bud Cells as Monocytes/Macrophages-like Which Secrete Proinflammatory Cytokines
Authors: Hichami Aziz , Saidi Hamza , Khan Amira Sayed , Degbeni Pernelle , Khan Naim Akhtar
Published: June 2023

The sense of taste determines the choice of nutrients and food intake and, consequently, influences feeding behaviors. The taste papillae are primarily composed of three types of taste bud cells (TBC), i.e., type I, type II, and type III. The type I TBC, expressing GLAST (glutamate-–aspartate transporter), have been termed as glial-like cells. We hypothesized that these cells could play a role in taste bud immunity as glial cells do in the brain. We purified type I TBC, expressing F4/80, a specific marker of macrophages, from mouse fungiform taste papillae. The purified cells also express CD11b, CD11c, and CD64, generally expressed by glial cells and macrophages. We further assessed whether mouse type I TBC can be polarized toward M1 or M2 macrophages in inflammatory states like lipopolysaccharide (LPS)-triggered inflammation or obesity, known to be associated with low-grade inflammation. Indeed, LPS-treatment and obesity state increased TNFα, IL-1β, and IL-6 expression, both at mRNA and protein levels, in type I TBC. Conversely, purified type I TBC treated with IL-4 showed a significant increase in arginase 1 and IL-4. These findings provide evidence that type I gustatory cells share many features with macrophages and may be involved in oral inflammation.
Systemic Blood Proteome Patterns Reflect Disease Phenotypes in Neovascular Age-Related Macular Degeneration
Authors: Künzel Steffen E. , Flesch Leonie T. M. , Frentzel Dominik P. , Knecht Vitus A. , Rübsam Anne , Dreher Felix , Schütte Moritz , Dubrac Alexandre , Lange Bodo , Yaspo Marie-Laure , Lehrach Hans , Joussen Antonia M. , Zeitz Oliver
Published: June 2023

There is early evidence of extraocular systemic signals effecting function and morphology in neovascular age-related macular degeneration (nAMD). The prospective, cross-sectional BIOMAC study is an explorative investigation of peripheral blood proteome profiles and matched clinical features to uncover systemic determinacy in nAMD under anti-vascular endothelial growth factor intravitreal therapy (anti-VEGF IVT). It includes 46 nAMD patients stratified by the level of disease control under ongoing anti-VEGF treatment. Proteomic profiles in peripheral blood samples of every patient were detected with LC-MS/MS mass spectrometry. The patients underwent extensive clinical examination with a focus on macular function and morphology. In silico analysis includes unbiased dimensionality reduction and clustering, a subsequent annotation of clinical features, and non-linear models for recognition of underlying patterns. The model assessment was performed using leave-one-out cross validation. The findings provide an exploratory demonstration of the link between systemic proteomic signals and macular disease pattern using and validating non-linear classification models. Three main results were obtained: (1) Proteome-based clustering identifies two distinct patient subclusters with the smaller one (n = 10) exhibiting a strong signature for oxidative stress response. Matching the relevant meta-features on the individual patient’s level identifies pulmonary dysfunction as an underlying health condition in these patients. (2) We identify biomarkers for nAMD disease features with Aldolase C as a putative factor associated with superior disease control under ongoing anti-VEGF treatment. (3) Apart from this, isolated protein markers are only weakly correlated with nAMD disease expression. In contrast, applying a non-linear classification model identifies complex molecular patterns hidden in a high number of proteomic dimensions determining macular disease expression. In conclusion, so far unconsidered systemic signals in the peripheral blood proteome contribute to the clinically observed phenotype of nAMD, which should be examined in future translational research on AMD.
Effects of Moringa oleifera Seed Oil on Cultured Human Sebocytes In Vitro and Comparison with Other Oil Types
Authors: Zouboulis Christos C. , Hossini Amir M. , Hou Xiaoxiao , Wang Chaoxuan , Weylandt Karsten H. , Pietzner Anne
Published: June 2023

The seeds of Moringa oleifera (horseradish tree) contain about 40% of one of the most stable vegetable oils (Moringa seed oil). Therefore, the effects of Moringa seed oil on human SZ95 sebocytes were investigated and were compared with other vegetable oils. Immortalized human SZ95 sebocytes were treated with Moringa seed oil, olive oil, sunflower oil, linoleic acid and oleic acid. Lipid droplets were visualized by Nile Red fluorescence, cytokine secretion via cytokine antibody array, cell viability with calcein-AM fluorescence, cell proliferation by real-time cell analysis, and fatty acids were determined by gas chromatography. Statistical analysis was performed by the Wilcoxon matched-pairs signed-rank test, the Kruskal–Wallis test and Dunn’s multiple comparison test. The vegetable oils tested stimulated sebaceous lipogenesis in a concentration-dependent manner. The pattern of lipogenesis induced by Moringa seed oil and olive oil was comparable to lipogenesis stimulated by oleic acid with also similar fatty acid secretion and cell proliferation patterns. Sunflower oil induced the strongest lipogenesis among the tested oils and fatty acids. There were also differences in cytokine secretion, induced by treatment with different oils. Moringa seed oil and olive oil, but not sunflower oil, reduced the secretion of pro-inflammatory cytokines, in comparison to untreated cells, and exhibited a low n-6/n-3 index. The anti-inflammatory oleic acid detected in Moringa seed oil probably contributed to its low levels of pro-inflammatory cytokine secretion and induction of cell death. In conclusion, Moringa seed oil seems to concentrate several desired oil properties on sebocytes, such as high content level of the anti-inflammatory fatty acid oleic acid, induction of similar cell proliferation and lipogenesis patterns compared with oleic acid, lipogenesis with a low n-6/n-3 index and inhibition of secretion of pro-inflammatory cytokines. These properties characterize Moringa seed oil as an interesting nutrient and a promising ingredient in skin care products.
Serum Biomarkers of a Pro-Neuroinflammatory State May Define the Pre-Operative Risk for Postoperative Delirium in Spine Surgery
Authors: Ruhnau Johanna , Müller Jonas , Nowak Stephan , Strack Sarah , Sperlich Denise , Pohl Anna , Dilz Jasmin , Saar Angelika , Veser Yannick , Behr Frederik , Rehberg Sebastian , Usichenko Taras , Hahnenkamp Klaus , Ehler Johannes , Flöel Agnes , Schroeder Henry W. S. , Müller Jan-Uwe , Fleischmann Robert , Vogelgesang Antje
Published: June 2023

Advances in spine surgery enable technically safe interventions in older patients with disabling spine disease, yet postoperative delirium (POD) poses a serious risk for postoperative recovery. This study investigates biomarkers of pro-neuroinflammatory states that may help objectively define the pre-operative risk for POD. This study enrolled patients aged ≥60 scheduled for elective spine surgery under general anesthesia. Biomarkers for a pro-neuroinflammatory state included S100 calcium-binding protein β (S100β), brain-derived neurotrophic factor (BDNF), Gasdermin D, and the soluble ectodomain of the triggering receptor expressed on myeloid cells 2 (sTREM2). Postoperative changes of Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and C-reactive protein (CRP) were assessed as markers of systemic inflammation preoperatively, intraoperatively, and early postoperatively (up to 48 h). Patients with POD (n = 19, 75.7 ± 5.8 years) had higher pre-operative levels of sTREM2 (128.2 ± 69.4 pg/mL vs. 97.2 ± 52.0 pg/mL, p = 0.049) and Gasdermin D (2.9 ± 1.6 pg/mL vs. 2.1 ± 1.4 pg/mL, p = 0.29) than those without POD (n = 25, 75.6 ± 5.1 years). STREM2 was additionally a predictor for POD (OR = 1.01/(pg/mL) [1.00–1.03], p = 0.05), moderated by IL-6 (Wald-χ2 = 4.06, p = 0.04). Patients with POD additionally showed a significant increase in IL-6, IL-1β, and S100β levels on the first postoperative day. This study identified higher levels of sTREM2 and Gasdermin D as potential markers of a pro-neuroinflammatory state that predisposes to the development of POD. Future studies should confirm these results in a larger cohort and determine their potential as an objective biomarker to inform delirium prevention strategies.
The Role of Two Heart Biomarkers in IgA Nephropathy
Authors: Sági Balázs , Vas Tibor , Jakabfi-Csepregi Rita , Horváth-Szalai Zoltán , Kőszegi Tamás , Csiky Botond , Nagy Judit , Kovács Tibor József
Published: June 2023

Cardiovascular mortality is a leading cause of death in chronic kidney disease (CKD), as is IgA nephropathy (IgAN). The purpose of this study is to find different biomarkers to estimate the outcome of the disease, which is significantly influenced by the changes in vessels (characterized by arterial stiffness) and the heart. In our cross-sectional study, 90 patients with IgAN were examined. The N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was measured as a heart failure biomarker by an automated immonoassay method, while the carboxy-terminal telopeptide of collagen type I (CITP) as a fibrosis marker was determined using ELISA kits. Arterial stiffness was determined by measuring carotid–femoral pulse wave velocity (cfPWV). Renal function and routine echocardiography examinations were performed as well. Based on eGFR, patients were separated into two categories, CKD 1-2 and CKD 3-5. There were significantly higher NT-proBNP (p = 0.035), cfPWV (p = 0.004), and central aortic systolic pressure (p = 0.037), but not CITP, in the CKD 3-5 group. Both biomarker positivities were significantly higher in the CKD 3-5 group (p = 0.035) compared to the CKD 1-2 group. The central aortic systolic pressure was significantly higher in the diastolic dysfunction group (p = 0.034), while the systolic blood pressure was not. eGFR and hemoglobin levels showed a strong negative correlation, while left ventricular mass index (LVMI), aortic pulse pressure, central aortic systolic pressure, and cfPWV showed a positive correlation with NT-proBNP. cfPWV, aortic pulse pressure, and LVMI showed a strong positive correlation with CITP. Only eGFR was an independent predictor of NT-proBNP by linear regression analysis. NT-proBNP and CITP biomarkers may help to identify IgAN patients at high risk for subclinical heart failure and further atherosclerotic disease.
Effect of Manual Lymphatic Drainage on the Concentrations of Selected Adipokines, Cytokines, C-Reactive Protein and Parameters of Carbohydrate and Lipid Metabolism in Patients with Abnormal Body Mass Index: Focus on Markers of Obesity and Insulin Resistance
Authors: Antoniak-Pietrynczak Klaudia , Zorena Katarzyna , Jaskulak Marta , Hansdorfer-Korzon Rita , Koziński Marek
Published: June 2023

The aim of the study was to assess the impact of manual lymphatic drainage (MLD) on the parameters of carbohydrate metabolism, lipid metabolism and the level of selected adipokines and cytokines in people with abnormal body mass index (BMI). In addition, an attempt was made to assess the optimal cut-off values of serum concentrations of the biochemical parameters studied in identifying the risk of obesity and insulin resistance (IR). The study included 60 subjects who underwent 10 and 30 min long MLD sessions three times a week. The study group included 15 patients with a normal body mass index (group I; n = 15), overweight patients (group II; n = 15) and obese patients (group III; n = 10). The control group was IV; n = 20 subjects not undergoing MLD. Biochemical tests were carried out on all subjects at stage 0′ (before MLD therapy) and at stage 1′ (one month after MLD therapy). In the control group, the time between the sample collection at stage 0′ and stage 1′ was the same as in the study group. Our results showed that 10 MLD sessions may have a positive effect on the selected biochemical parameters, including insulin, 2h-PG, leptin and HOMA-IR values in normal weight and overweight patients. In addition, in the study group, the highest AUCROC values in identifying the risk of obesity were found for leptin (AUCROC = 82.79%; cut-off = 17.7 ng/mL; p = 0.00004), insulin (AUCROC = 81.51%; cut-off = 9.5 µIU/mL; p = 0.00009) and C-peptide (AUCROC = 80.68%; cut-off = 2.3 ng/mL; p = 0.0001) concentrations as well as for HOMA-IR values (AUCROC = 79.97%; cut-off = 1.8; p = 0.0002). When considering the risk of IR, we observed the highest diagnostic value for insulin (AUCROC = 93.05%; cut-off = 1.8 ng/mL; p = 0.053), which was followed by C-peptide (AUCROC = 89.35%; cut-off = 17.7 ng/mL; p = 0.000001), leptin (AUCROC = 79.76%; cut-off = 17.6 ng/mL; p = 0.0002) and total cholesterol (AUCROC = 77.31%; cut-off = 198 mg/dL; p = 0.0008). Our results indicate that MLD may have a positive effect on selected biochemical parameters, including insulin, 2h-PG, leptin and HOMA-IR, in normal weight and overweight patients. In addition, we successfully established optimal cut-off values for leptin in the assessment of obesity and insulin in the assessment of insulin resistance in patients with abnormal body mass index. Based on our findings, we hypothesize that MLD, when combined with caloric restriction and physical activity, may serve as an effective preventive intervention against the development of obesity and insulin resistance.
Harnessing Knowledge from Plant Functional Genomics and Multi-Omics for Genetic Improvement
Authors: Wang Yaqiong , Zeng Jian , Yang Guangxiao , Wan Yongfang , Li Yin
Published: June 2023

Plant biology research has currently entered the post-genomics era with the advances in genomic technologies [...]
Synthesis and Anti-Inflammatory Evaluation of a Library of Chiral Derivatives of Xanthones Conjugated with Proteinogenic Amino Acids
Authors: Vieira Sara F. , Araújo Joana , Gonçalves Virgínia M. F. , Fernandes Carla , Pinto Madalena , Ferreira Helena , Neves Nuno M. , Tiritan Maria Elizabeth
Published: June 2023

In recent decades, the relationship between drug chirality and biological activity has been assuming enormous importance in medicinal chemistry. Particularly, chiral derivatives of xanthones (CDXs) have interesting biological activities, including enantioselective anti-inflammatory activity. Herein, the synthesis of a library of CDXs is described, by coupling a carboxyxanthone (1) with both enantiomers of proteinogenic amino esters as chiral building blocks (2–31), following the chiral pool strategy. The coupling reactions were performed at room temperature with good yields (from 44 to 99.9%) and very high enantiomeric purity, with most of them presenting an enantiomeric ratio close to 100%. To afford the respective amino acid derivatives (32–61), the ester group of the CDXs was hydrolyzed in mild alkaline conditions. Consequently, in this work, sixty new derivatives of CDXs were synthetized. The cytocompatibility and anti-inflammatory activity in the presence of M1 macrophages were studied for forty-four of the new synthesized CDXs. A significant decrease in the levels of a proinflammatory cytokine targeted in the treatment of several inflammatory diseases, namely interleukin 6 (IL-6), was achieved in the presence of many CDXs. The amino ester of L-tyrosine (X1AELT) was the most effective in reducing IL-6 production (52.2 ± 13.2%) by LPS-stimulated macrophages. Moreover, it was ≈1.2 times better than the D-enantiomer. Indeed, enantioselectivity was observed for the majority of the tested compounds. Thus, their evaluation as promising anti-inflammatory drugs should be considered.
Mitochondria in Ageing and Diseases: Partie Deux
Authors: Tobias-Wallingford Hannah , Coppotelli Giuseppe , Ross Jaime M.
Published: June 2023

The past several decades has seen a huge expansion of the knowledge and research of mitochondrial dysfunction and the role it plays in ageing and age-related diseases [...]
Introducing MdTFL1 Promotes Heading Date and Produces Semi-Draft Phenotype in Rice
Authors: Do Van Giap , Lee Youngsuk , Kim Seonae , Yang Sangjin , Park Juhyeon , Do Gyungran
Published: June 2023

Flowering time (in rice, termed the heading date), plant height, and grain number are crucial agronomic traits for rice productivity. The heading date is controlled via environmental factors (day length and temperature) and genetic factors (floral genes). TERMINAL FLOWER 1 (TFL1) encodes a protein that controls meristem identity and participates in regulating flowering. In this study, a transgenic approach was used to promote the heading date in rice. We isolated and cloned apple MdTFL1 for early flowering in rice. Transgenic rice plants with antisense MdTFL1 showed an early heading date compared with wild-type plants. A gene expression analysis suggested that introducing MdTFL1 upregulated multiple endogenous floral meristem identity genes, including the (early) heading date gene family FLOWERING LOCUS T and MADS-box transcription factors, thereby shortening vegetable development. Antisense MdTFL1 also produced a wide range of phenotypic changes, including a change in overall plant organelles that affected an array of traits, especially grain productivity. The transgenic rice exhibited a semi-draft phenotype, increased leaf inclination angle, restricted flag leaf length, reduced spikelet fertility, and fewer grains per panicle. MdTFL1 plays a central role in regulating flowering and in various physiological aspects. These findings emphasize the role of TFL1 in regulating flowering in shortened breeding and expanding its function to produce plants with semi-draft phenotypes.
Glymphatic System and Mitochondrial Dysfunction as Two Crucial Players in Pathophysiology of Neurodegenerative Disorders
Authors: Kopeć Kamila , Szleszkowski Stanisław , Koziorowski Dariusz , Szlufik Stanislaw
Published: June 2023

Neurodegenerative diseases are a complex problem affecting millions of people around the world. The pathogenesis is not fully understood, but it is known that both insufficiency of the glymphatic system and mitochondrial disorders affect the development of pathology. It appears that these are not just two independent factors that coexist in the processes of neurodegeneration, but that they often interact and drive each other. Bioenergetics disturbances are potentially associated with the accumulation of protein aggregates and impaired glymphatic clearance. Furthermore, sleep disorders characteristic of neurodegeneration may impair the work of both the glymphatic system and the activity of mitochondria. Melatonin may be one of the elements linking sleep disorders with the function of these systems. Moreover, noteworthy in this context is the process of neuroinflammation inextricably linked to mitochondria and its impact not only on neurons, but also on glia cells involved in glymphatic clearance. This review only presents possible direct and indirect connections between the glymphatic system and mitochondria in the process of neurodegeneration. Clarifying the connection between these two areas in relation to neurodegeneration could lead to the development of new multidirectional therapies, which, due to the complexity of pathogenesis, seems to be worth considering.
Immunotherapeutic Development of a Tri-Specific NK Cell Engager Recognizing BCMA
Authors: Oh Felix , Felices Martin , Kodal Behiye , Miller Jeffrey S. , Vallera Daniel A.
Published: June 2023

Chemotherapy-refractive multiple myeloma (MM) is serious and life-threatening, and better treatments are urgently needed. BCMA is a prominent marker on the cell surface of MM cells, rendering it an accepted target for antibody therapy. Considering that MM is a liquid tumor and immunotherapy has enjoyed success against leukemia, we devise an approach designed to enhance NK cell activity against MM. Ordinarily, NK cells function to naturally survey the body and eliminate malignant cells. Our platform approach is designed to enhance NK function. A tri-specific immune-engaging TriKE is manufactured, consisting of a camelid nanobody VHH antibody fragment recognizing CD16 expressed on NK cells and an scFv antibody fragment specifically recognizing BCMA. These two fragments are crosslinked by the human cytokine interleukin-15 (IL-15) known to have prominent activating effects on NK cells. The molecule, when tested by flow cytometry, shows activation of NK cells in their numbers and activity. Additionally, the molecule demonstrates anti-cancer effects in an in vivo xenograft model of human MM. We believe that the drug will have the capability of enhancing NK cells at the site of the immune synapse, i.e., the effector:target cell interface, and this will promote cancer remissions.
The Fast Formation of a Highly Active Homogeneous Catalytic System upon the Soft Leaching of Pd Species from a Heterogeneous Pd/C Precursor
Authors: Galushko Alexey S. , Ilyushenkova Valentina V. , Burykina Julia V. , Shaydullin Ruslan R. , Pentsak Evgeniy O. , Ananikov Valentine P.
Published: June 2023

Understanding the interface between soluble metal complexes and supported metal particles is important in order to reveal reaction mechanisms in a new generation of highly active homogeneous transition metal catalysts. In this study, we show that, in the case of palladium forming on a carbon (Pd/C) catalyst from a soluble Pd(0) complex Pd2dba3, the nature of deposited particles on a carbon surface turns out to be much richer than previously assumed, even if a very simple experimental procedure is utilized without the use of additional reagents and procedures. In the process of obtaining a heterogeneous Pd/C catalyst, highly active “hidden” metal centers are formed on the carbon surface, which are leached out by the solvent and demonstrate diverse reactivity in the solution phase. The results indicate that heterogeneous catalysts may naturally contain trace amounts of molecular monometallic centers of a different nature by easily transforming them to the homogeneous catalytic system. In line with a modern concept, a heterogenized homogeneous catalyst precursor was found to leach first, leaving metal nanoparticles mostly intact on the surface. In this study, we point out that the previously neglected soft leaching process contributes to high catalyst activity. The results we obtained demand for leaching to be reconsidered as a flexible tool for catalyst construction and for the rational design of highly active and selective homogeneous catalytic systems, starting from easily available heterogeneous catalyst precursors.
Screening of Fungal Strains and Formulations of Metarhizium anisopliae to Control Phyllotreta striolata in Chinese Flowering Cabbage
Authors: Chen Wei , Yuan Wenjing , He Renkun , Pu Xinhua , Hu Qiongbo , Weng Qunfang
Published: June 2023

(1) Background: The cabbage flea beetle (CFB; Phyllotreta striolata) seriously damages the production of Chinese flowering cabbage (CFC; Brassica campestris L. ssp. chinensis var. utilis), which is a key leafy vegetable in South China. A large number of chemical insecticides have been sprayed to control this pest; as a result, residues and resistances are becoming an issue. It is necessary to develop biocontrol technologies to address this issue. (2) Methods: Fungal strains were selected based on bioactivity against CFB, and CFC seed pelletization with fungal conidia was subject to evaluation of control efficacy against CFB. The effective mixture of fungus and chemical insecticide was determined based on safety and joint toxicology tests. (3) Results: The screening of 103 strains from 14 genera identified the Metarhizium anisopliae strain MaGX19S02 (Ma) as the one with the highest virulence. The LC50s of Ma to CFB adult and second instar larvae on day 9 post-treatment were 3.04 × 106 and 27.2 × 106 spores/mL, respectively. In the pot test, the pelletization of CFC seeds with Ma conidia (50/25/12.5 mg in 1 g seed with 4 g fillers) demonstrated significant CFB mortalities (45–82%) 20 days after the larvae were introduced. In the field test, the seed pelletization achieved 57–81% control efficacy 14 days after sowing. Furthermore, the combination of Ma with chlorfenapyr (Chl) demonstrated a synergistic effect against CFB; based on this result, we prepared the mixture formulation of 20% Ma-Chl wettable powder (WP). The assessment of the effects of 20% Ma-Chl WP (500× diluent) against CFB revealed 93.33% mortality in the pot test and 61.3% control efficacy in the field test on day 7 post-treatment. (4) Conclusions: The findings demonstrate the potential of Ma to control CFB in the field. Seed pelletization with Ma conidia effectively controlled CFB larvae and protected CFC seedlings, wherein a mixture formulation of 20% Ma-Chl WP had substantial efficacy in controlling CFB adults. Our research provides new methods for CFB biocontrol.
Applying Satyrization to Insect Pest Control: The Case of the Spotted Wing Drosophila, Drosophila suzukii Matsumura
Authors: Cerasti Flavia , Mastrantonio Valentina , Dallai Romano , Cristofaro Massimo , Porretta Daniele
Published: June 2023

Drosophila suzukii represents one of the major agricultural pests worldwide. The identification of safety and long-lasting tools to suppress its populations is therefore crucial to mitigate the environmental and economic damages due to its occurrence. Here, we explore the possibility of using satyrization as a tool to control the abundance of D. suzukii. By using males of D. melanogaster, we realized courtship tests, spermathecae analysis, and multiple-choice experiments to assess the occurrence and extent of pre- and post-zygotic isolation between the two species, as well as the occurrence of fitness costs in D. suzukii females due to satyrization. Our results showed that: (i) D. melanogaster males successfully courted D. suzukii females; (ii) D. melanogaster males significantly affected the total courtship time of D. suzukii males, which reduced from 22.6% to 6.4%; (iii) D. melanogaster males were able to inseminate D. suzukii and reduce their offspring, inducing a high fitness cost. Reproductive interference occurs at different steps between D. melanogaster and D. suzukii, both alone and in combination with other area-wide control approaches.
Effects of Electrical Stimulation on Facial Paralysis Recovery after Facial Nerve Injury: A Review on Preclinical and Clinical Studies
Authors: Yoo Myung Chul , Kim Jeong Hee , Kim Yong Jun , Jung Junyang , Kim Sung Soo , Kim Sang Hoon , Yeo Seung Geun
Published: June 2023

Various methods have been used to improve function and manage facial nerve injury. Although electrical stimulation therapy is frequently used to treat facial paralysis, its effects have been found to vary and no clear standards have been developed. The current review describes the results of preclinical and clinical studies evaluating the effectiveness of electrical stimulation therapy in promoting the recovery of a peripheral facial nerve injury. Evidence is presented showing the efficacy of electrical stimulation in promoting nerve regeneration after peripheral nerve injuries in both animal models and human patients. The ability of electrical stimulation to promote the recovery of facial paralysis was found to depend on the type of injury (compression or transection), the species of animal tested, the type of disease, the frequency and method of electrical stimulation, and the duration of the follow-up. Electrical stimulation, however, can also have potential negative outcomes, such as reinforcing synkinesis, including mistargeted axonal regrowth via inappropriate routes; excessive collateral axonal branching at the lesion site; and multiple innervations at neuromuscular junctions. Because of the inconsistencies among studies and the low quality of evidence, electrical stimulation therapy is not currently regarded as a primary treatment of facial paralysis in patients. However, understanding the effects of electrical stimulation, as determined in preclinical and clinical studies, is important for the potential validity of future research on electrical stimulation.
Lactate to Albumin Ratio for Predicting Clinical Outcomes after In-Hospital Cardiac Arrest
Authors: Haschemi Jafer , Müller Charlotte Theresia , Haurand Jean Marc , Oehler Daniel , Spieker Maximilian , Polzin Amin , Kelm Malte , Horn Patrick
Published: June 2023

In-hospital cardiac arrest (IHCA) is associated with high mortality and poor neurological outcomes. Our objective was to assess whether the lactate-to-albumin ratio (LAR) can predict the outcomes in patients after IHCA. We retrospectively screened 75,987 hospitalised patients at a university hospital between 2015 and 2019. The primary endpoint was survival at 30-days. Neurological outcomes were assessed at 30 days using the cerebral performance category scale. 244 patients with IHCA and return of spontaneous circulation (ROSC) were included in this study and divided into quartiles of LAR. Overall, there were no differences in key baseline characteristics or rates of pre-existing comorbidities among the LAR quartiles. Patients with higher LAR had poorer survival after IHCA compared to patients with lower LAR: Q1, 70.4% of the patients; Q2, 50.8% of the patients; Q3, 26.2% of the patients; Q4, 6.6% of the patients (p = 0.001). Across increasing quartiles, the probability of a favourable neurological outcome in patients with ROSC after IHCA decreased: Q1: 49.2% of the patients; Q2: 32.8% of the patients; Q3: 14.7% of the patients; Q4: 3.2% of the patients (p = 0.001). The AUCs for predicting 30-days survival using the LAR were higher as compared to using a single measurement of lactate or albumin. The prognostic performance of LAR was superior to that of a single measurement of lactate or albumin for predicting survival after IHCA.
Are Local Drug Delivery Systems a Challenge in Clinical Periodontology?
Authors: Budală Dana Gabriela , Luchian Ionut , Tatarciuc Monica , Butnaru Oana , Armencia Adina Oana , Virvescu Dragoș Ioan , Scutariu Monica Mihaela , Rusu Darian
Published: June 2023

Placing antimicrobial treatments directly in periodontal pockets is an example of the local administration of antimicrobial drugs to treat periodontitis. This method of therapy is advantageous since the drug concentration after application far surpasses the minimum inhibitory concentration (MIC) and lasts for a number of weeks. As a result, numerous local drug delivery systems (LDDSs) utilizing various antibiotics or antiseptics have been created. There is constant effort to develop novel formulations for the localized administration of periodontitis treatments, some of which have failed to show any efficacy while others show promise. Thus, future research should focus on the way LDDSs can be personalized in order to optimize future clinical protocols in periodontal therapy.
Cardiac Resynchronization Therapy beyond Nominal Settings: An IEGM-Based Approach for Paced and Sensed Atrioventricular Delay Offset Optimization in Daily Clinical Practice
Authors: Kloosterman Mariëlle , Daniëls Fenna , Roseboom Eva , Rienstra Michiel , Maass Alexander H.
Published: June 2023

Optimization of the atrioventricular (AV) delay has been performed in several landmark trials in cardiac resynchronization therapy (CRT), although it is often not performed in daily practice. Our aim was to study optimal AV delays and investigate a simple intracardiac electrogram (IEGM)-based optimization approach. 328 CRT patients with paired IEGM and echocardiography optimization data were included in our single-center observational study. Sensed (sAV) and paced (pAV) AV delays were optimized using an iterative echocardiography method. The offset between sAV and pAV delays was calculated using the IEGM method. The mean age of the patients was 69 ± 12 years; 64% were men, 48% had ischemic etiology of heart failure. During echocardiographic optimization, an offset of 73 ± 18 ms was found, differing from nominal AV settings (p < 0.001). Based on the IEGM method, the optimal offset was 75 ± 25 ms. The echocardiographic and IEGM-generated AV offset delays showed good correlation (R2 = 0.62, p < 0.001) and good agreement according to Bland-Altman plot analysis. CRT responders had a near zero offset difference between IEGM and echo optimization (−0.2 ± 17 ms), while non-responders had an offset difference of 6 ± 17 ms, p = 0.006. In conclusion, optimal AV delays are patient-specific and differ from nominal settings. pAV delay can easily be calculated from IEGM after sAV delay optimization.
A Narrative Review of the Association of Obstructive Sleep Apnea with Hypertension: How to Treat Both When They Coexist?
Authors: Altay Servet , Fırat Selma , Peker Yüksel ,   The TURCOSACT Collaborators
Published: June 2023

Hypertension (HT) is a worldwide public health issue and an essential risk factor for cardiovascular and cerebrovascular diseases. Obstructive sleep apnea (OSA) is a condition characterized by recurrent episodes of apnea and hypopnea as a consequence of partial or complete obstruction of the upper airways due to anatomic and/or functional disturbances. There is mounting evidence of a relationship between OSA and HT. In patients with OSA, HT is predominantly nocturnal and characterized by high diastolic blood pressure and usually by a nondipping pattern. Optimizing the blood pressure control is recommended in the current guidelines as the first treatment option in hypertensive patients with OSA. Continuous positive airway pressure (CPAP) therapy may reduce blood pressure, albeit only slightly as a stand-alone treatment. CPAP, as an add-on treatment to antihypertensive medication, appears to be an efficient treatment modality when both conditions coexist. This narrative review aims to summarize the current perspectives on the association of OSA with HT and the treatment options available for adults with OSA-related HT.
Exploring the Validity of an Optoelectronic Integrated Cone Beam Computed Tomography Jaw Tracking System
Authors: van der Helm Hayo C. , Dieters Arjan J. A. , Dijkstra Pieter U. , van der Meer Wicher J. , Kuijpers-Jagtman Anne Marie
Published: June 2023

Jaw motion tracking functionalities of cone beam computed tomography (CBCT)-scanners can visualize, record, and analyze movements of the mandible. In this explorative study, the validity of the 4D-Jaw Motion module (4D-JM) of the ProMax 3D Mid CBCT scanner (Planmeca, Helsinki, Finland) was tested in vitro. The validity of the 4D-JM was accepted if values differed less than 0.6 mm (three voxels sizes) from the gold standard. Three dry human skulls were used. CBCT scans, the gold standard, were taken in eight jaw positions and exported as three-dimensional (3D) models. Individualized 3D-printed dental wafers ensured the correct positioning of the mandible. Jaw positions were recorded with the 4D-JM tracking device and exported as 3D models. The coordinates of six reference points for both superimposed 3D models were obtained. The differences in the x, y and z-axis and the corresponding vector differences between gold standard 3D models and 4D-JM models were calculated. For the mandible 10% and for the maxilla 90% of the vector differences fell within 0.6 mm of the gold standard. With an increasing vertical jaw opening, larger differences between the gold standard and the 4D-JM 3D models were found. The smallest differences of the mandible were observed on the x axis. In this study, the 4D-JM validity was not acceptable by the authors’ predefined standards.
CABG Patients Develop Global DNA Hypermethylation, That Negatively Affect the Mitochondrial Function and Promote Post-Surgical Cognitive Decline: A Proof of Concept in Small Cohort
Authors: Boovarahan Sri Rahavi , Kale Suresh Babu , Prem Priyanka N. , Ravindran Sriram , Arthanarisami Akshayakeerthi , Rengaraju Jeyashri , Ali Nemat , Ramalingam Senthilkumar , Mohany Mohamed , AlAsmari Abdullah F. , Al-Rejaie Salim S. , Waseem Mohammad , Kurian Gino A.
Published: June 2023

Global DNA hypermethylation and mitochondrial dysfunction are reported to be associated with the development of mild cognitive decline (MCI). The present study aims to generate preliminary data that connect the above association with post-surgical coronary artery bypass grafting (CABG) cognitive decline in patients. Data were collected from 70 CABG patients and 25 age-matched controls. Cognitive function was assessed using the Montreal Cognitive Assessment (MOCA) test on day 1 (before surgery) and on the day of discharge. Similarly, blood was collected before and one day after the CABG procedure for mitochondrial functional analysis and expression of DNA methylation genes. Test analysis score suggested 31 (44%) patients had MCI before discharge. These patients showed a significant decrease in complex I activity and an increase in malondialdehyde levels (p < 0.001) from the control blood samples. Post-surgical samples showed a significant reduction in blood MT-ND1 mRNA expression from control and from pre-surgical samples (p < 0.005), along with elevated DNMT1 gene expression (p < 0.047), with an insignificant increase in TET1 and TET3 gene expression. Correlation analysis showed a significant positive relation between cognitive decline and elevated blood DNMT1 and declined blood complex I activity, signifying that cognitive decline experienced by post-surgical CABG patients is associated with increased DNMT1 expression and declined complex I activity. Based on the data, we conclude that both DNA hypermethylation and mitochondrial dysfunction are associated with post-CABG MCI, where the former is negatively correlated, and the latter is positively correlated with post-surgical MCI in CABG cases. Additionally, a multimarker approach that comprises MOCA, DNA methylation, DNMT, and NQR activities can be utilized to stratify the population that is sensitive to developing post-CABG MCI.
Trabecular Bone Score Significantly Influences Treatment Decisions in Secondary Osteoporosis
Authors: Al-Hashimi Leith , Klotsche Jens , Ohrndorf Sarah , Gaber Timo , Hoff Paula
Published: June 2023

The trabecular bone score (TBS) can be determined in addition to the Dual Energy X-ray Absorptiometry (DXA) for bone mineral density (BMD) measurement to diagnose, evaluate, and stratify bone loss and decide on appropriate treatment in patients at risk. Especially in patients with secondary osteoporosis, TBS detects restricted bone quality. To investigate the influence of an additional evaluation of TBS on patients’ treatment strategy decisions, we enrolled 292 patients, with a high proportion of patients with secondary osteoporosis, from one outpatient unit over one year. Patients eligible for BMD measurement had the option to opt-in for TBS measurement. We analyzed demographic data, leading diagnoses, bone metabolism parameters, and results of BMD and TBS measurements. More than 90% of patients consented to TBS measurement. TBS measurement influenced the decision in approximately 40% of patients with a treatment indication for anti-osteoporotic drugs. We demonstrate that depending on the underlying disease/risk spectrum, 21–25.5% of patients had an unremarkable BMD measurement with poor bone quality shown in the TBS measurement. In patients with secondary osteoporosis, the use of TBS supplementary to DXA seems useful to better assess fracture risk and, thus, to initiate therapy for osteoporosis in these patients in time.