bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers and Facilitators for the Use of Patient Lifts by Healthcare Workers: A Scoping Review
Authors: Khairallah Ghassan M. , Mowafi Hani , Al-Hajj Samar , Brackett Alexandria , Sakr Carine J.
Published: December 2024

(1) Background: Patient lifts are evidence-based engineering controls used in Safe Patient Handling Programs to assist healthcare workers in moving patients. They have been shown to be beneficial for both healthcare workers and patients. However, these devices are not consistently used. This review aims to determine the scope of the literature and examine the barriers and facilitators for the use of patient lifts by healthcare workers, on a global level. (2) Methods: Electronic databases, including MEDLINE (Ovid), Embase (Ovid), Global Health (Ovid), CINAHL, Scopus, Web of Science—Core Collection, Cochrane CENTRAL, Trials Register of Promoting Health Interventions, PAIS Index (Proquest), and the gray literature were reviewed. Duplicates were removed, titles and abstracts were screened, full texts were assessed, and the quality of the studies were checked. The analysis was carried out qualitatively using thematic analysis. (3) Results: A total of 57 articles were included in this review. Most studies (71.9%) originated in the US alone, and none originated in low- and middle-income countries. The majority were quantitative studies and were conducted in acute care hospitals. The main identified barriers were equipment-related (e.g., time constraints, device unavailability, and inconvenient storage), followed by cultural and behavioral factors (peer pressure, resistance to change, and occupational socialization), followed by organizational factors (staff shortage and workload). The main identified facilitators were mostly organizational factors (leadership support, minimal lift policy, standardized protocols), followed by cultural and behavioral factors (safety culture and worker’s empowerment), then equipment-related factors (device availability and accessibility). Patient- and worker-related factors were the least mentioned. (4) Conclusion: There is a complex interplay of organizational, equipment-related, and cultural factors shaping the use of lifts by healthcare workers. A multifaceted approach that focuses on enhancing organizational support, fostering a robust safety culture, and ensuring equipment availability is warranted.
Assessing Educational Impact of Worldwide Webinar on Management of Myopia Progression in Children
Authors: Gagrani Meghal , Heston Jonathan , Godts Daisy , Granet David , Bremond-Gignac Dominique , Kekunnaya Ramesh , Hertle Richard W. , Leo Seo Wei , Nischal Ken K.
Published: December 2024

Objective: To assess the educational impact of a worldwide webinar approach to myopia progression management in children <8 years and 8–12 years old. Design: Cross-sectional study. Methods: A self-administered survey was conducted for attendees of a 3 h worldwide webinar held in two parts on consecutive days on the management of myopia progression in children. The survey was administered before, immediately after completion of the webinar, and 8 weeks later; responses were recorded on a Likert scale. Questions were posed to assess (a) the confidence of attendees in managing myopia in children <12 years old, (b) attendees’ understanding of latest treatment options, (c) any improvement in attendees’ knowledge after the webinar, and (d) any changes made to practice 8 weeks after the webinar. Pre- and post-responses were analyzed using an unpaired two-tailed t-test. Results: The webinar had 701 and 606 global attendees on the first and second days, respectively. Based on a comparison of contact information, 372 attendees participated on days 1 and 2, meaning 288 and 233 participants attended only day 1 and day 2, respectively. There was a significant increase in the percentage of attendees who were “very confident” in managing myopia after the webinar (p < 0.05). Ninety-nine attendees completed the survey at 8 weeks. Of these, 76% believed that the webinar had “very significantly” or “significantly” improved their ability to manage pediatric myopia and 91% had implemented or intended to implement a change in their practice. The respondents who did not implement a change identified cost and patient compliance as the common barriers. Conclusion: There is a tsunami of research and management options in the field of myopia management at present. We demonstrate that an effective way of disseminating information and education about myopia management is a pre-designed comprehensive webinar held over two consecutive days. There is evidence that such a webinar may also influence a change in clinical practice.
Efficacy of Cystic Fibrosis Transmembrane Regulator Corrector C17 in Beta-Sarcoglycanopathy—Assessment of Patient’s Primary Myotubes
Authors: Scano Martina , Benetollo Alberto , Dalla Barba Francesco , Akyurek Eylem Emek , Carotti Marcello , Sacchetto Roberta , Sandonà Dorianna
Published: December 2024

Limb–girdle muscular dystrophy type 2E/R4 (LGMD2E/R4) is a rare disease that currently has no cure. It is caused by defects in the SGCB gene, mainly missense mutations, which cause the impairment of the sarcoglycan complex, membrane fragility, and progressive muscle degeneration. Here, we studied the fate of some β-sarcoglycan (β-SG) missense mutants, confirming that, like α-SG missense mutants, they are targeted for degradation through the ubiquitin–proteasome system. These data, collected using HEK-293 cells expressing either the I119F- or Y184C mutants of β-SG, were subsequently confirmed in primary myotubes derived from an LGMD2E/R4 patient carrying a homozygous I92T mutation. The knowledge that β-SG with an amino acid substitution shares a pathway of degradation with α-SG mutants, allowed us to explore the pharmacological approach successfully tested in LGMD2D/R3. Several CFTR correctors, particularly corrector C17, preserved β-SG mutants from degradation and promoted localization at the sarcolemma of the entire SG complex. The presence of the complex, despite containing a mutated subunit, improved sarcolemma integrity, as evidenced by the reduced creatine kinase release from myotubes under hypoosmotic stress. These results suggest that β-SG missense mutants undergo proteasomal degradation as α-SG mutants, and that CFTR correctors, particularly C17, may be used as a potential therapeutic option for recovering and stabilizing the SG complex in patients with sarcoglycanopathies.
Study of Photodegradation of Bentazon Herbicide by Using ZnO-Sm2O3 Nanocomposite Under UV Light
Authors: Yasmeen Sadaf , Burratti Luca , Duranti Leonardo , Agresti Antonio , Prosposito Paolo
Published: December 2024

The removal of organic pollutants from water is significantly important as they have harmful effects on the ecosystem. Heterogeneous photocatalysis is a potential technique for the removal of organic pollutants from the wastewater. In this article, zinc oxide (ZnO) and samarium oxide (Sm2O3) nanoparticles and ZnO-Sm2O3 nanocomposite (ZS) were synthesized by the co-precipitation method. We report the bandgap engineering of zinc oxide (ZnO) by making a composite with samarium oxide (Sm2O3) to enhance the photocatalytic activity. The smaller optical energy bandgap of the ZS nanocomposite as compared to the individual oxide nanoparticles shows that it has a light absorption range from UV to natural light. The photodegradation of bentazon herbicide as a model pollutant has been investigated by using the prepared samples. The photocatalytic activity of the prepared sample against bentazon herbicide was carried out under UV light for 140 min. The degradation efficiency against bentazon of the prepared samples was ZS > ZnO > Sm2O3, respectively. The ZnO-Sm2O3 nanocomposite showed a higher photocatalytic performance against bentazon and achieved a 90% degradation efficiency under a UV light source in 140 min. The pseudo-first-order degradation kinetic was studied under different operational conditions, such as catalyst loading, initial pH and bentazon concentration, showing that the degradation rate of bentazon was strongly influenced by these operational parameters. The obtained optimization conditions for practical application were a catalyst loading of 20 mg, pH of solution equal to 7 and bentazon concentration of 5 ppm for ZS nanocomposite in 60 mL of contaminated water. Furthermore, based on the scavenger study, hydroxyl and superoxide radicals play major role in the degradation experiment. The obtained results show that ZS nanocomposite can be a good potential candidate for wastewater treatment.
Transcriptome-Based Gene Modules and Soluble Sugar Content Analyses Reveal the Defense Response of Cotton Leaves to Verticillium dahliae
Authors: Song Shenglong , Li Yongtai , Zhang Yong , Liu Feng , Zhu Qian-Hao , Zhang Xinyu , Sun Jie , Li Yanjun
Published: December 2024

Verticillium dahliae is a soil-borne phytopathogenic fungus causing destructive Verticillium wilt disease that greatly threats cotton production worldwide. The mechanism of cotton resistance to Verticillium wilt is very complex and requires further research. In this study, RNA-sequencing was used to investigate the defense responses of cotton leaves using varieties resistant (Zhongzhimian 2, or Z2) or susceptible (Xinluzao 7, or X7) to V. dahliae. The leaf samples were collected at 48 and 72 hpi (hours post infection) from the two varieties infected by V. dahliae (strain Vd991) or treated by water. Compared to X7, Z2 had less genes responsive to V. dahliae infection at 72 hpi and had no DEGs (differentially expressed genes) at 48 hpi. WGCNA (Weighted Gene Co-Expression Network Analysis) revealed seven key gene modules which were responsible for the resistance of Z2 and susceptibility of X7. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis of these modules found that several reported disease resistance pathways were found to be up-regulated in Z2, with some of those pathways down-regulated in X7. Unexpectedly, several photosynthesis-related pathways were significantly up-regulated in the leaves of X7 infected by V. dahliae, leading to different profiles of glucose content, which was significantly decreased at 72 hpi and 48 hpi in X7 and Z2, respectively. These results suggest that the leaves of resistant varieties have a slower and different response to V. dahliae compared to those of the susceptible variety, as well as that the translocation of sugars produced by photosynthesis in cotton leaves might vary between the two varieties. Additionally, several HUB genes regulating disease response were identified, including NDR1/HIN1-like protein 12, DELLA protein, cytochrome P450 family protein and LRR receptor-like serine/threonine-protein kinase genes, which have been reported to be related to disease resistance in other plants, which might serve as potential candidates for breeding cotton disease resistance.
Sigma-1 Receptor as a Novel Therapeutic Target in Diabetic Kidney Disease
Authors: Balogh Dora B. , Hodrea Judit , Saeed Adar , Cserhalmi Marcell , Rozsahegyi Alexandra , Lakat Tamas , Lenart Lilla , Szabo Attila J. , Wagner Laszlo J. , Fekete Andrea
Published: December 2024

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease. Current treatments for DKD do not halt renal injury progression, highlighting an urgent need for therapies targeting key disease mechanisms. Our previous studies demonstrated that activating the Sigma-1 receptor (S1R) with fluvoxamine (FLU) protects against acute kidney injury by inhibiting inflammation and ameliorating the effect of hypoxia. Based on these, we hypothesized that FLU might exert a similar protective effect in DKD. Diabetes was induced in male Wistar rats using streptozotocin, followed by a seven-week FLU treatment. Metabolic and renal parameters were assessed along with a histological analysis of glomerular damage and fibrosis. The effects of FLU on inflammation, hypoxia, and fibrosis were tested in human proximal tubular cells and normal rat kidney fibroblasts. FLU improved renal function and reduced glomerular damage and tubulointerstitial fibrosis. It also mitigated inflammation by reducing TLR4, IL6, and NFKB1 expressions and moderated the cellular response to tubular hypoxia. Additionally, FLU suppressed TGF-β1-induced fibrotic processes and fibroblast transformation. These findings suggest that S1R activation can slow DKD progression and protect renal function by modulating critical inflammatory, hypoxic, and fibrotic pathways; therefore, it might serve as a promising novel drug target for preventing DKD.
Novel Selectable Marker Sesquiterpenoid Antibiotic Pentalenolactone
Authors: Nikandrova Arina A. , Petriakova Anna D. , Izzi Anton R. , Petrosyan Garegin A. , Tashlitsky Vadim N. , Alferova Vera A. , Panova Tatiana V. , Khrenova Maria G. , Biryukov Mikhail V. , Zakalyukina Yuliya V. , Zvereva Maria I. , Lukianov Dmitrii A. , Sergiev Petr V.
Published: December 2024

Antibiotic resistance has been and remains a major problem in our society. The main solution to this problem is to search and study the mechanisms of antibiotic action. Many groups of secondary metabolites, including antimicrobial ones, are produced by the Actinomycetota phylum. The actinobacterial strains isolated from habitats that have not been well studied are of great interest. Due to high resource competition, antibiotics are now considered a ‘trump card in the game of life’ due to their presence in natural substrates with limited nutrients. Potentially, strains isolated from such habitats can be producers of novel or poorly studied antibiotics. In the current research, we identified the strain Streptomyces sp. AP22 from the soils of the Akhshatyrsky Gorge, which is capable of producing pentalenolactone. This study describes the phenotypic and morphological characteristics of Streptomyces sp. AP22 and its biological activity. Pentalenolactone is a known inhibitor of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an important enzyme involved in glycolysis. We identified a previously unknown mutation in the gapA gene encoding glyceraldehyde-3-phosphate dehydrogenase that confers resistance to this antibiotic compound. This antibiotic is not used in clinical practice, so its application as a selectable marker will not lead to the creation of pathogens resistant to clinically relevant antibiotics. In this case, the selectable marker is based on a genetic construct containing the glyceraldehyde-3-phosphate dehydrogenase gene with a resistance mutation. The use of this selectable marker can be applied to various genetic and molecular techniques, such as cloning and transformation. This can help to facilitate genetic and molecular biology studies of strains resistant to standard selectable markers such as kanamycin or ampicillin.
Purification and Electron Transfer from Soluble c-Type Cytochrome TorC to TorA for Trimethylamine N-Oxide Reduction
Authors: Panwar Alka , Martins Berta M. , Sommer Frederik , Schroda Michael , Dobbek Holger , Iobbi-Nivol Chantal , Jourlin-Castelli Cécile , Leimkühler Silke
Published: December 2024

The enterobacterium Escherichia coli present in the human gut can reduce trimethylamine N-oxide (TMAO) to trimethylamine during anaerobic respiration. The TMAO reductase TorA is a monomeric, bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor-containing enzyme that belongs to the dimethyl sulfoxide reductase family of molybdoenzymes. TorA is anchored to the membrane via TorC, a pentahemic c-type cytochrome which receives the electrons from the menaquinol pool. Here, we designed an expression system for the production of a stable soluble form of multiheme-containing TorC, providing, for the first time, the purification of a soluble pentahemic cytochrome-c from E. coli. Our focus was to investigate the interaction between TorA and soluble TorC to establish the electron transfer pathway. We solved the X-ray structure of E. coli TorA and performed chemical crosslinking of TorA and TorC. Another goal was to establish an activity assay that used the physiological electron transfer pathway instead of the commonly used unphysiological electron donors methylviologen or benzylviologen. An AlphaFold model including the crosslinking sites provided insights into the electron transfer between TorCC and the active site of TorA.
The Emerging Scenario of Ferroptosis in Pancreatic Cancer Tumorigenesis and Treatment
Authors: Lyu Hao , Kong Jinghua , Chen Jiasi , Zhang Rui , Xiao Shuai , Guo Dong , Zhang Qi , Chen Xing-Zhen , Tang Jingfeng , Zhou Cefan
Published: December 2024

Pancreatic cancer remains one of the most lethal forms of cancer. Currently, there is a lack of effective drug treatments for pancreatic cancer. However, as a newly discovered form of non-apoptotic cell death, ferroptosis has garnered increasing attention in relation to pancreatic cancer. Understanding the role of ferroptosis in the tumorigenesis and treatment of pancreatic cancer may enable more effective clinical trials and treatments for pancreatic cancer and may minimize side effects or restrict the emergence of drug resistance. In this review, we summarize the current knowledge regarding the process and underlying mechanisms of ferroptosis, as well as its dual role in both promoting tumorigenesis and facilitating treatment strategies for pancreatic cancer. Additionally, how ferroptosis is implicated in the development of pancreatitis and insulin resistance, indicating that ferroptosis may play an important role in the risk of pancreatitis- and insulin-resistance-related pancreatic cancers, is also addressed.
Comparative Analysis of the Effects of Maternal Hypoxia and Placental Ischemia on HIF1-Dependent Metabolism and the Glucocorticoid System in the Embryonic and Newborn Rat Brain
Authors: Vetrovoy Oleg , Potapova Sofiya , Stratilov Viktor , Tyulkova Ekaterina
Published: December 2024

Prenatal hypoxia, often accompanied by maternal glucocorticoid stress, can predispose offspring to neurological disorders in adulthood. If placental ischemia (PI) primarily reduces fetal oxygen supply, the maternal hypoxia (MH) model also elicits a pronounced fetal glucocorticoid exposure. Here, we compared MH and PI in rats to distinguish their unique and overlapping effects on embryonic and newborn brain development. We analyzed glucocorticoid transport into the developing brain, glucocorticoid receptor (GR) expression, and GR-dependent transcription, along with key enzymes regulating glucocorticoid metabolism in maternal (MP) and fetal placentas (FP) and in the brain. Additionally, we examined hypoxia-inducible factor 1-alpha (HIF1α) and its downstream genes, as well as glycolysis and the pentose phosphate pathway, both associated with the transport of substrates essential for glucocorticoid synthesis and degradation. Both MH and PI induced HIF1-dependent metabolic alterations, enhancing glycolysis and transiently disrupting redox homeostasis. However, only MH caused a maternal glucocorticoid surge that altered early fetal brain glucocorticoid responsiveness. Over time, these differences may lead to distinct long-term outcomes in neuronal structure and function. This work clarifies the individual contributions of hypoxic and glucocorticoid stresses to fetal brain development, suggesting that combining the MH and PI models could provide valuable insights for future investigations into the mechanisms underlying developmental brain pathologies, including non-heritable psychoneurological and neurodegenerative disorders.
Ketoconazole-Fumaric Acid Pharmaceutical Cocrystal: From Formulation Design for Bioavailability Improvement to Biocompatibility Testing and Antifungal Efficacy Evaluation
Authors: Baldea Ioana , Moldovan Remus , Nagy Andras-Laszlo , Bolfa Pompei , Decea Roxana , Miclaus Maria Olimpia , Lung Ildiko , Gherman Ana Maria Raluca , Sevastre-Berghian Alexandra , Martin Flavia Adina , Kacso Irina , Răzniceanu Vlad
Published: December 2024

Development of cocrystals through crystal engineering is a viable strategy to formulate poorly water-soluble active pharmaceutical ingredients as stable crystalline solid forms with enhanced bioavailability. This study presents a controlled cocrystallization process by cooling for the 1:1 cocrystal of Ketoconazole, an antifungal class II drug with the Fumaric acid coformer. This was successfully set up following the meta-stable zone width determination in acetone–water 4:6 (V/V) and pure ethanol. Considering the optimal crystallization data, laboratory scale-up processes were carried out at 1 g batch size, efficiently delivering the cocrystal in high yields up to 90% pure and single phase as revealed by powder X-ray diffraction. Biological assays in vitro showed improved viability and oxidative damage of the cocrystal over Ketoconazole on human dermal fibroblasts and hepatocarcinoma cells; in vivo, on Wistar rats, the cocrystal increased oral Ketoconazole bioavailability with transient minor biochemical transaminases increases and without histological liver alterations. Locally on Balb C mice, it induced no epicutaneuous sensitization. A molecular docking study conducted on sterol 14α-demethylase (CYP51) enzyme from the pathogenic yeast Candida albicans revealed that the cocrystal interacts more efficiently with the enzyme compared to Ketoconazole, indicating that the coformer enhances the binding affinity of the active ingredient.
Gene Variant Related Neurological and Molecular Biomarkers Predict Psychosis Progression, with Potential for Monitoring and Prevention
Authors: Fryar-Williams Stephanie , Tucker Graeme , Clements Peter , Strobel Jörg
Published: December 2024

The (MTHFR) C677T gene polymorphism is associated with neurological disorders and schizophrenia. Patients diagnosed with schizophrenia and schizoaffective disorder and controls (n 134) had data collected for risk factors, molecular and neuro-sensory variables, symptoms, and functional outcomes. Promising gene variant-related predictive biomarkers were identified for diagnosis by Receiver Operating Characteristics and for illness duration by linear regression. These were then analyzed using Spearman’s correlation in relation to the duration of illness. Significant correlations were ranked by strength and plotted on graphs for each MTHFR C677T variant. Homozygous MTHFR 677 TT carriers displayed a mid-illness switch to depression, with suicidality and a late-phase shift from lower to higher methylation, with activated psychosis symptoms. MTHFR 677 CC variant carriers displayed significant premorbid correlates for family history, developmental disorder, learning disorder, and head injury. These findings align with those of low methylation, oxidative stress, multiple neuro-sensory processing deficits, and disability outcomes. Heterozygous MTHFR 677 CT carriers displayed multiple shifts in mood and methylation with multiple adverse outcomes. The graphically presented ranked biomarker correlates for illness duration allow a perspective of psychosis development across gene variants, with the potential for phase of illness monitoring and new therapeutic insights to prevent or delay psychosis and its adverse outcomes.
Synergistic Effects of Photobiomodulation and Differentiation Inducers on Osteogenic Differentiation of Adipose-Derived Stem Cells in Three-Dimensional Culture
Authors: Da Silva Daniella , Crous Anine , Abrahamse Heidi
Published: December 2024

Osteoporosis, a common metabolic bone disorder, leads to increased fracture risk and significant morbidity, particularly in postmenopausal women and the elderly. Traditional treatments often fail to fully restore bone health and may cause side effects, prompting the exploration of regenerative therapies. Adipose-derived stem cells (ADSCs) offer potential for osteoporosis treatment, but their natural inclination toward adipogenic rather than osteogenic differentiation poses a challenge. This study investigates a novel approach combining differentiation inducers (DIs), three-dimensional (3D) hydrogel scaffolds, and photobiomodulation (PBM) to promote osteogenic differentiation of immortalised ADSCs. A dextran-based 3D hydrogel matrix, supplemented with a DI cocktail of dexamethasone, β-glycerophosphate disodium, and ascorbic acid, was used to foster osteogenesis. PBM was applied using near-infrared (825 nm), green (525 nm), and combined wavelengths at fluences of 3 J/cm2, 5 J/cm2, and 7 J/cm2 to enhance osteogenic potential. Flow cytometry identified osteoblast-specific markers, while inverted light microscopy evaluated cellular morphology. Reactive oxygen species assays measured oxidative stress, and quantitative polymerase chain reaction (qPCR) revealed upregulated gene expression linked to osteogenesis. The findings demonstrate that integrating DIs, 3D hydrogels, and PBM effectively drives osteogenic differentiation in immortalised ADSCs. The PBM enhanced osteogenic marker expression, induced morphological changes, and upregulated gene activity, presenting a promising framework for bone regeneration. Future research should assess the stability and functionality of these differentiated cells and explore their applicability in preclinical models of bone injury or degeneration. This integrative approach demonstrated specific efficacy in promoting the osteogenic differentiation of ADSCs, highlighting its potential application in developing targeted treatments for osteoporosis.
Caryophyllene Oxide, a Bicyclic Terpenoid Isolated from Annona macroprophyllata with Antitumor Activity: In Vivo, In Vitro, and In Silico Studies
Authors: Ramírez-Santos Jesica , Calzada Fernando , García-Hernández Normand , Barbosa Elizabeth , Velázquez Claudia , Valdes Miguel
Published: December 2024

The Annona genus contains some species used in Mexican traditional medicine for the treatment cancer, including Annona macroprophyllata (A. macroprophyllata). The present study aimed to investigate the anticancer activity of caryophyllene oxide (CO) isolated from A. macroprophyllata using in vivo, in vitro, and in silico approaches. The identification of CO was performed using gas chromatography-mass spectroscopy and NMR methods. Antilymphoma activity was evaluated in male and female Balb/c mice inoculated with U-937 cells. Cytotoxic activity was evaluated using the WST method and flow cytometry was used to determine the type of cell death. Acute oral toxicity was determined, and a molecular docking study was performed using target proteins associated with cancer, including, HMG-CoA, Bcl-2, Mcl-1, and VEGFR-2. Results showed that CO exhibited significant antilymphoma and cytotoxic activities, and its effects were comparable to MTX. In addition, flow cytometry showed that the anticancer activity of CO could be mediated by the induction of late apoptosis and necrosis. The result for the acute oral toxicity of CO was classified in category 4, suggesting it is low risk. Finally, molecular coupling studies showed that CO had more affinity for the enzymes HMG-CoA reductase and Bcl-2. Our study provides evidences that CO is a potential anticancer agent for the treatment of histiocytic lymphoma.
Branched Linkers for Homogeneous Antibody-Drug Conjugates: How Long Is Long Enough?
Authors: Gulyak Evgeny L. , Komarova Olga A. , Prokopenko Yury A. , Faizullina Elina A. , Malabuiok Diana M. , Ibragimova Aigul R. , Mokrushina Yuliana A. , Serova Oxana V. , Popova Galina P. , Zhitlov Mikhail Y. , Nikitin Timofei D. , Brylev Vladimir A. , Ustinov Alexey V. , Alferova Vera A. , Korshun Vladimir A. , Smirnov Ivan V. , Terekhov Stanislav S. , Sapozhnikova Ksenia A.
Published: December 2024

Homogeneous antibody–drug conjugates (ADCs) exhibit significantly improved pharmacological properties compared to their heterogeneous counterparts. Site-specific conjugation of the payload to the IgG required for homogeneity can be achieved using enzymes. One example is microbial transglutaminase (MTGase), which can selectively perform transamidation on the Q295 residue of human Fc when N297 glycans are removed. As a result, two modifications can be introduced per IgG molecule; however, achieving higher drug-to-antibody ratios (DARs) requires the use of branched linkers. While several such linkers have been reported, little information is available on the relationship between linker structure and ADC properties. To address this gap, we synthesized two branched amino triazide linkers, differing by a PEG4 fragment inserted after the branching point, which were used to prepare two homogeneous trastuzumab-based DAR 6 ADCs (a “short” and a “long” one). This was achieved by a two-step process consisting of enzymatic linker conjugation followed by bioorthogonal coupling with a cleavable linker bearing monomethyl auristatin E (MMAE). Two other trastuzumab–MMAE conjugates were used as controls: a heterogeneous DAR 6 ADC, made using conventional thiol–maleimide chemistry, and a homogeneous DAR 2 ADC. We found that, while the four conjugates had identical affinity for HER2, their cytotoxicity differed significantly: the “long” homogeneous DAR 6 ADC was just as active as its heterogeneous counterpart, but the “short” DAR 6 ADC was an order of magnitude less potent, inferior even to the DAR 2 conjugate. Our findings indicate that the length of the branched linker critically affects the cytotoxic activity of ADCs, possibly due to steric hindrance influencing the rate of linker cleavage by lysosomal enzymes.
Sterol Profile in Leaves of Spring Oats (Avena sativa L.) Under Conditions of the Cryolithozone
Authors: Nokhsorov Vasiliy V. , Sofronova Valentina E. , Sleptsov Igor V. , Senik Svetlana V. , Petrova Lidia V. , Petrov Klim A.
Published: December 2024

Plant sterols (STs) are essential for the regulation of fluidity and permeability of cell membranes, which have a wide structural diversity. The dynamics of changes in sterol molecular species in leaves of a valuable cereal crop, spring oat (Avena sativa L.), as a function of different sowing dates were studied. In particular, 11 molecular species of sterols (STs) and triterpenoids in A. sativa leaves were identified by GC-MS. Triterpenoids Ψ-taraxasterol, cyclolaudenol, and betulin were identified in A. sativa leaves for the first time, which may be related to adaptation to extreme climatic conditions of the cryolithozone. The dynamics of STs and triterpenoids changes were revealed during growth and development of the standard term and late summer sowing term during A. sativa hardening to low ambient temperatures. The ratio of β-sitosterol to campesterol was found to increase in response to low positive air temperatures, while the ratio of stigmasterol to β-sitosterol remained constant from mid-September to the end of October. Overall, leaves of standard-seeded A. sativa plants maintained higher levels of absolute STs and triterpenoids by 1.9-fold than leaves of late-seeded A. sativa plants. It is suggested that the ability of A. sativa plants to synthesize β-sitosterol and stigmasterol may be part of an evolutionary adaptation process to cope with wide temperature fluctuations and to maintain important membrane-bound metabolic processes.
Personality-Aware Course Recommender System Using Deep Learning for Technical and Vocational Education and Training
Authors: Hassan Rana Hammad , Hassan Malik Tahir , Sameem Muhammad Shujah Islam , Rafique Muhammad Aasim
Published: December 2024

Personality represents enduring patterns, providing insights into an individual’s aptitude and behavior. Integrating these insights with learning tendencies shows promise in enhancing learning outcomes, optimizing returns on investment, and reducing dropout rates. This interdisciplinary study integrates techniques in advanced artificial intelligence (AI) with human psychology by analyzing data from the trades of Technical and Vocational Education and Training (TVET) education, by combining them with individual personality traits. This research aims to address dropout rates by providing personalized trade recommendations for TVET, with the goal of optimizing outcome-based personalized learning. The study leverages advanced AI techniques and data from a nationwide TVET program, including information on trades, trainees’ records, and the Big Five personality traits, to develop a Personality-Aware TVET Course Recommendation System (TVET-CRS). The proposed framework demonstrates an accuracy rate of 91%, and a Cohen’s Kappa score of 0.84, with an NMAE at 0.04 and an NDCG at 0.96. TVET-CRS can be effectively integrated into various aspects of the TVET cycle, including dropout prediction, career guidance, on-the-job training assessments, exam evaluations, and personalized course recommendations.
Using Serious Game Techniques with Health Sciences and Biomedical Engineering Students: An Analysis Using Machine Learning Techniques
Authors: Sáiz-Manzanares María Consuelo , Marticorena-Sánchez Raúl , Escolar-Llamazares María Camino , González-Díez Irene , Velasco-Saiz Rut
Published: December 2024

The use of serious games on virtual learning platforms as a learning support resource is increasingly common. They are especially effective in helping students acquire mainly applied curricular content. However, a process is required to monitor the effectiveness and students’ perceived satisfaction. The objectives of this study were to (1) identify the most significant characteristics; (2) determine the most relevant predictors of learning outcomes; (3) identify groupings with respect to the different serious game activities; and (4) to determine students’ perceptions of the usefulness of the simple and complex serious game activities. We worked with a sample of 130 university students studying health sciences and biomedical engineering. The serious game activities were applied in a Moodle environment, UBUVirtual, and monitored using the UBUMonitor tool. The degree type and the type of serious game explained differing percentages of the variance in the learning results in the assessment tests (34.4%—multiple choice tests [individual assessment]; 11.2%—project performance [group assessment]; 25.6%—project presentation [group assessment]). Different clusters were found depending on the group of students and the algorithm applied. The Adjusted Rang Index was applied to determine the most appropriate algorithm in each case. The student satisfaction was high in all the cases. However, they indicated complex serious games as being more useful than simple serious games as learning resources for the practical content in both health sciences and biomedical engineering degrees.
Oviposition Preference and Developmental Performance of Drosophila suzukii on Different Cherry Cultivars
Authors: Yang Fan , Sun Haikuan , Wang Zehua , Xie Jingxia , He Jingyan , Qiao Guanghang , Wang Jing , Wang Yuyu , Wang Shanning
Published: December 2024

Drosophila suzukii is a major pest of sweet cherries. In this study, we evaluated its oviposition preferences across six cherry cultivars and assessed the effects of the fruit traits on its growth and development. Significant differences in the color, firmness, and sugar content were observed among the cultivars and ripeness stages. The highest oviposition rates were recorded for the “Hongdeng” (HD) and “Burlat” (BLT) cultivars in both the non-choice (HD: 31.9 ± 2.0 eggs/cherry; BLT: 31.3 ± 1.9 eggs/cherry) and choice (HD: 32.4 ± 3.2 eggs/cherry; BLT: 27.6 ± 1.9 eggs/cherry) tests, largely influenced by the fruit color. While the developmental parameters showed slight variation across the cultivars, significant differences were observed in the pupation rates (ranging from 0.80 to 0.89) and survival rates (ranging from 0.51 to 0.62), with both parameters being the highest for the “Hongdeng” cultivar. The correlation analysis revealed that a darker fruit color—characterized by lower lightness (L*), lower chromaticity (b*), and a higher color index for red grapes (CIRG)—positively influenced the oviposition and pupation rates. Although the other correlations were not significant, the oviposition and developmental parameters were positively correlated with sweetness and negatively correlated with firmness. These findings enhance our understanding of how cherry traits influence D. suzukii behavior, providing critical insights for pest management strategies in cherry production.
Seasonal Migratory Activity of the Beet Armyworm Spodoptera exigua (Hübner) in the Tropical Area of China
Authors: Wang Xudong , Feng Qing , Zhou Xianyong , Zhang Haowen , Wu Shaoying , Wu Kongming
Published: December 2024

The beet armyworm Spodoptera exigua (Hübner), a global pest, feeds on and affects a wide range of crops. Its long-distance migration with the East Asian monsoon frequently causes large-scale outbreaks in East and Southeast Asia. This pest mainly breeds in tropical regions in the winter season every year; however, few studies have investigated associations with its population movements in this region. From 2017 to 2023, we monitored its population dynamics in a tropical site, located in Hainan Province of China, using a searchlight trap. Dissection of the ovaries of female S. exigua moths captured from the air revealed that most of them were reproductively mature and could be classified as a transit migratory population. Migration occurred most often in summer and least often in winter, with an increasing trend over the years. According to a trajectory model analysis based on the Weather Research and Forecasting (WRF) model, S. exigua migrated from Hainan Island to mainland China in the spring, primarily moved from the areas of Southeast Asia to Hainan and mainland China during the summer, and returned from China to Southeast Asia in the autumn and winter. Overall, our research defines the movement paths of S. exigua in the tropical area of China, establishing a theoretical foundation for its regional monitoring, early warning, and management in China and Southeast Asian countries.
Campylobacter jejuni-Related Myocarditis: A Case Report and Review of the Literature
Authors: Zouganeli Virginia , Kourek Christos , Bistola Vasiliki , Mademli Maria , Grigoropoulos Ioannis , Thomas Konstantinos , Tsiodras Sotirios , Filippatos Gerasimos , Farmakis Dimitrios
Published: December 2024

Campylobacter jejuni, a common cause of gastroenteritis worldwide, has also been associated with rare extraintestinal infections, including myocarditis. We report a unique case of a 24-year-old male who presented with febrile diarrhea and acute chest pain. Diagnostic investigations revealed elevated cardiac troponin levels, normal electrocardiography findings, and myocardial inflammation on cardiac magnetic resonance imaging, confirming the diagnosis of acute myocarditis. Stool cultures identified Campylobacter jejuni as the causative agent. The patient was managed with supportive care, including hydration and electrolyte replacement, and a three-day course of azithromycin (500 mg daily). He achieved a full recovery and was discharged after eight days, with subsequent follow-up demonstrating the complete resolution of myocardial dysfunction. This case emphasizes the need to consider Campylobacter jejuni-related myocarditis in the differential diagnosis of young patients presenting with chest pain and diarrhea, along with an overview of its diagnostic and therapeutic challenges.
Learnability of Ultrasound-Guided Locoregional Anesthesia for Carotid Endarterectomy
Authors: Seybold Benjamin , Gaier Nils , Ofenloch Andreas , Boeckler Dittmar , Kalenka Armin , Fiedler-Kalenka Mascha O.
Published: December 2024

Background/Objectives: There is an ongoing debate about the most advantageous anesthesia technique for carotid endarterectomy (CEA). From an anesthesiologic perspective, locoregional anesthesia (LRA) appears to offer significant benefits. However, the learning curve and complication rates for anesthesiologists newly performing ultrasound-guided LRA for CEA remain unclear and are to be examined in greater detail in this study. Methods: This retrospective, single-center study included all consecutive LRA administrations for CEA following the introduction of this procedure at a district hospital in Germany from November 2013 to November 2017. Nine board-certified anesthesiologists, initially inexperienced in LRA for CEA but with prior experience in other ultrasound-guided peripheral nerve blocks (PNBs), received theoretical training and supervision during their first six combined deep and superficial cervical plexus blocks under ultrasound guidance. The primary endpoint was the incidence of insufficient block quality, indicated by pain and restlessness or the additional need for analgesics. Secondary endpoints included LRA-associated complications. Patients were divided into four groups based on the number of previously performed LRA procedures by the attending anesthesiologist. Results: In 83 patients, LRA was performed by initially inexperienced anesthesiologists. Group A (patients managed by anesthesiologists performing their 1st to 3rd cervical plexus blockades) included 21 patients, Group B (blockades 4–6) included 12 patients, Group C (blockades 7–9) included 9 patients, and Group D (≥10 blockades) included 41 patients, respectively. The overall complication rate was 22% (18/83). Insufficient block quality occurred in 18.1% of patients (15/83), resulting in three conversions to general anesthesia (3.6%). Additional complications included dysphagia (n = 2) and Horner’s syndrome (n = 1). The incidence of insufficient block quality was significantly reduced (p = 0.008) after performing the first three blockades. Conclusions: Ultrasound-guided cervical plexus block for CEA appears to be a rapidly learnable anesthesia technique for anesthesiologists experienced in other ultrasound-guided PNBs, with a low risk of complications. After three supervised blockades, the failure rate of LRA decreases significantly.
Abstracts of the 16th European Congress of Paediatric and Adolescent Gynaecology †
Authors: Christopoulos Panagiotis , Vatopoulou Anastasia , Michala Lina , Nižňanská Zuzana , Stankovic Zoran , Roos Evelien , Theodoridis Theodoros , Tsimaris Pandelis , Lathe Pallavi , Daniilidis Angelos , Vlahos Nikos F. , Bumbulienė Žana
Published: December 2024

Objectives of Paediatric and Adolescent Gynaecology (PAG): PAG aims to foster a collaborative environment that bridges knowledge from various disciplines to ensure the highest quality of care for children and adolescents with gynaecological issues. The European Association of PAG and HellenicPAG, like all National PAG Societies, support research and education to advance new insights, improve health outcomes, enhance quality of life, and protect future fertility. Additionally, PAG promotes international cooperation by proposing guidelines for good clinical practice in terms of prevention, diagnosis, procedures, and treatment. Scientific Program and Highlights: The scientific committee curated a comprehensive program featuring renowned experts and researchers from across Europe. Over four days, participants explored a wide range of topics through lectures, panel discussions, case studies, debates, video presentations, and workshops. The conference attracted professionals from various disciplines, including gynaecology, paediatrics, paediatric endocrinology, psychology, plastic surgery, and paediatric surgery. The collaboration between the European Association of Paediatric and Adolescent Gynaecology and the Hellenic Society of Paediatric and Adolescent Gynaecology resulted in a cutting-edge scientific program. World-renowned experts (Appendix A) presented on all aspects of paediatric and adolescent gynaecology, with a particular focus on emerging topics such as abortion, global rights, transgender care, teenage pregnancy, and more. Theme—Individualized Care in an Evolving World: The congress theme aligned perfectly with the evolving landscape of PAG. By presenting high-quality, evidence-based topics, the program aimed to equip the next generation of specialists with the knowledge and skills needed to provide individualized care in a rapidly changing world.
Obsessive–Compulsive Disorder with a Religious Focus: An Observational Study
Authors: Ayoub Wissam Al Rida , Dib El Jalbout Jana , Maalouf Nancy , Ayache Samar S. , Chalah Moussa A. , Abdel Rassoul Ronza
Published: December 2024

Background: Obsessive–compulsive disorder (OCD) is a psychiatric disorder with poorly detailed subtypes/dimensions, such as religious OCD (ROCD). To date, little is known about ROCD characteristics. This work aimed to describe the sociodemographic and clinical characteristics, along with the religiosity and spirituality, of Lebanese Muslim citizens diagnosed with OCD and exhibiting religious symptoms. Methods: Participants were Lebanese Muslims, outpatients with OCD and religious symptoms, aged 18 or above, who could complete a questionnaire. Exclusion criteria were as follows: other psychiatric disorders and cognitive or physical impairments preventing participation. They completed a questionnaire including the 25-item Arabic Scale of Obsessions and Compulsions (10 questions addressing obsessions, 10 questions addressing compulsions, and 5 filler items, all of which were rated on a 4–point Likert scale, with higher total scores indicating increasing severity), the 26-item Spiritual Involvement and Beliefs Scale (rated on a 5-point Likert scale, with higher scores indicating higher spirituality), and questions assessing sociodemographic, clinical, and religiosity variables. Results: Fifty adults (62% females, 52% aged between 18 and 29 years) completed the study. They had mild (26%), moderate (48%), and severe (26%) OCD symptoms. The majority attended religious school at least at one point in their life and described a moderate to very high degree of self-religiosity and parental religiosity. Group comparisons (patients with mild vs. moderate vs. severe OCD symptoms) showed significant differences with regard to a family history of psychiatric disorders (p = 0.043), the frequency of self-questioning if they prayed correctly (p = 0.005), a higher rating of partial ablution repetition (p = 0.006), and the frequency of partial ablution repetitions (p = 0.041). No significant group differences were noted with regard to sociodemographic or spirituality outcomes. The prevalence of religious doubts (i.e., self-questioning if praying correctly) and specific rituals (partial ablution repetition) among severe OCD patients were 100% (13/13) and 77% (10/13), respectively. Conclusions: The results suggest a link between specific religious practices and OCD severity, underscoring the need for culturally sensitive approaches in diagnosing and treating ROCD.
Vocal Outcome Following Thyroidectomy for Differentiated Thyroid Carcinoma
Authors: Rosa Maria Silvia , Dell’Era Valeria , Campagnoli Massimo , Campini Silvia , Barozza Ottavia , Borello Giovanni , Garzaro Massimiliano , Aluffi Valletti Paolo
Published: December 2024

Background: Voice alteration is a recognized complication of thyroid surgery, impacting the quality of life and communication for affected individuals. In this prospective observational study, the Acoustic Voice Quality Index (AVQI) was employed to assess vocal outcomes after thyroidectomy. Method: Between February 2018 and August 2022, 224 patients underwent Thyroid surgery in our department, of which 74 with differentiated thyroid carcinoma (DTC) were enrolled in accordance with the inclusion criteria. Endoscopic findings and AVQI scores were evaluated before and after surgery (voice analysis was conducted using the Praat software program version 6.0.33). Results: Vocal fold impairment was present in 6.76% of patients after surgery (T1), with full recovery within 3 months. During preadmission evaluation, an AVQI score > 2.35 indicating hoarseness was present in 37 patients (despite normal vocal cord motility). Of these, 25 (67.57%), 26 (70.27%), and 24 (17.76%) maintained this trend at T1, T2, and T3, respectively. No significant variation in mean AVQI values was observed based on gender, age, and central neck dissection. Conclusion: AVQI values did not show significant variations comparing pre- and postoperative values. Thyroid surgery for DTC performed by experienced surgeons does not seem to impact significantly on patients’ voice quality.