bluuebunny/crossref_metadata_2025 huggingface dataset:
Mind the Curve: Dose–Response Fitting Biases the Synergy Scores across Software Used for Chemotherapy Combination Studies
Authors: Fuentealba-Manosalva Olga , Mansilla Matías , Buelvas Neudo , Martin-Martin Antonia , Torres Cristian G. , López-Muñoz Rodrigo A.
Published: June 2023

Drug combinations are increasingly studied in the field of anticancer agents. Mathematical models, such as Loewe, Bliss, and HSA, are used to interpret drug combinations, while informatics tools help cancer researchers identify the most effective combinations. However, the different algorithms each software uses lead to results that do not always correlate. This study compared the performance of Combenefit (Ver. 2.021) and SynergyFinder (Ver. 3.6) in analyzing drug synergy by studying combinations involving non-steroidal analgesics (celecoxib and indomethacin) and antitumor drugs (carboplatin, gemcitabine, and vinorelbine) on two canine mammary tumor cell lines. The drugs were characterized, their optimal concentration–response ranges were determined, and nine concentrations of each drug were used to make combination matrices. Viability data were analyzed under the HSA, Loewe, and Bliss models. Celecoxib-based combinations showed the most consistent synergistic effect among software and reference models. Combination heatmaps revealed that Combenefit gave stronger synergy signals, while SynergyFinder produced better concentration–response fitting. When the average values of the combination matrices were compared, some combinations shifted from synergistic to antagonistic due to differences in the curve fitting. We also used a simulated dataset to normalize each software’s synergy scores, finding that Combenefit tends to increase the distance between synergistic and antagonistic combinations. We conclude that concentration–response data fitting biases the direction of the combination (synergistic or antagonistic). In contrast, the scoring from each software increases the differences among synergistic or antagonistic combinations in Combenefit when compared to SynergyFinder. We strongly recommend using multiple reference models and reporting complete data analysis for synergy claiming in combination studies.
Masitinib Inhibits Hepatitis A Virus Replication
Authors: Sasaki-Tanaka Reina , Shibata Toshikatsu , Moriyama Mitsuhiko , Kogure Hirofumi , Hirai-Yuki Asuka , Okamoto Hiroaki , Kanda Tatsuo
Published: June 2023

The hepatitis A virus (HAV) infection causes acute hepatitis. HAV also induces acute liver failure or acute-on-chronic liver failure; however, no potent anti-HAV drugs are currently available in clinical situations. For anti-HAV drug screening, more convenient and useful models that mimic HAV replication are needed. In the present study, we established HuhT7-HAV/Luc cells, which are HuhT7 cells stably expressing the HAV HM175-18f genotype IB subgenomic replicon RNA harboring the firefly luciferase gene. This system was made by using a PiggyBac-based gene transfer system that introduces nonviral transposon DNA into mammalian cells. Then, we investigated whether 1134 US Food and Drug Administration (FDA)-approved drugs exhibited in vitro anti-HAV activity. We further demonstrated that treatment with tyrosine kinase inhibitor masitinib significantly reduced both HAV HM175-18f genotype IB replication and HAV HA11-1299 genotype IIIA replication. Masitinib also significantly inhibited HAV HM175 internal ribosomal entry-site (IRES) activity. In conclusion, HuhT7-HAV/Luc cells are adequate for anti-HAV drug screening, and masitinib may be useful for the treatment of severe HAV infection.
Efficient Secretory Production of Lytic Polysaccharide Monooxygenase BaLPMO10 and Its Application in Plant Biomass Conversion
Authors: Guo Xiao , An Yajing , Lu Fuping , Liu Fufeng , Wang Bo
Published: June 2023

Lytic polysaccharide monooxygenases (LPMOs) can oxidatively break the glycosidic bonds of crystalline cellulose, providing more actionable sites for cellulase to facilitate the conversion of cellulose to cello-oligosaccharides, cellobiose and glucose. In this work, a bioinformatics analysis of BaLPMO10 revealed that it is a hydrophobic, stable and secreted protein. By optimizing the fermentation conditions, the highest protein secretion level was found at a IPTG concentration of 0.5 mM and 20 h of fermentation at 37 °C, with a yield of 20 mg/L and purity > 95%. The effect of metal ions on the enzyme activity of BaLPMO10 was measured, and it was found that 10 mM Ca2+ and Na+ increased the enzyme activity by 47.8% and 98.0%, respectively. However, DTT, EDTA and five organic reagents inhibited the enzyme activity of BaLPMO10. Finally, BaLPMO10 was applied in biomass conversion. The degradation of corn stover pretreated with different steam explosions was performed. BaLPMO10 and cellulase had the best synergistic degradation effect on corn stover pretreated at 200 °C for 12 min, improving reducing sugars by 9.2% compared to cellulase alone. BaLPMO10 was found to be the most efficient for ethylenediamine-pretreated Caragana korshinskii by degrading three different biomasses, increasing the content of reducing sugars by 40.5% compared to cellulase alone following co-degradation with cellulase for 48 h. The results of scanning electron microscopy revealed that BaLPMO10 disrupted the structure of Caragana korshinskii, making its surface coarse and poriferous, which increased the accessibility of other enzymes and thus promoted the process of conversion. These findings provide guidance for improving the efficiency of enzymatic digestion of lignocellulosic biomass.
Dynamic Patterns of Mammalian Mitochondrial DNA Replication Uncovered Using SSiNGLe-5′ES
Authors: Xu Dongyang , Luo Lingcong , Huang Yu , Lu Meng , Tang Lu , Diao Yong , Kapranov Philipp
Published: June 2023

The proper replication of mitochondrial DNA is key to the maintenance of this crucial organelle. Multiple studies aimed at understanding the mechanisms of replication of the mitochondrial genome have been conducted in the past several decades; however, while highly informative, they were conducted using relatively low-sensitivity techniques. Here, we established a high-throughput approach based on next-generation sequencing to identify replication start sites with nucleotide-level resolution and applied it to the genome of mitochondria from different human and mouse cell types. We found complex and highly reproducible patterns of mitochondrial initiation sites, both previously annotated and newly discovered in this work, that showed differences among different cell types and species. These results suggest that the patterns of the replication initiation sites are dynamic and might reflect, in some yet unknown ways, the complexities of mitochondrial and cellular physiology. Overall, this work suggests that much remains unknown about the details of mitochondrial DNA replication in different biological states, and the method established here opens up a new avenue in the study of the replication of mitochondrial and potentially other genomes.
Physiology of Red Cell Lineage: From Erythroblast Progenitors to Mature Red Blood Cell
Authors: Ducamp Sarah , Ostuni Mariano A.
Published: June 2023

Red blood cells (RBC) are the most abundant cells in mammals [...]
Comparison of Estetrol Exposure between Women and Mice to Model Preclinical Experiments and Anticipate Human Treatment
Authors: Gallez Anne , Nys Gwenaël , Wuidar Vincent , Dias Da Silva Isabelle , Taziaux Mélanie , Kinet Virginie , Tskitishvili Ekaterine , Noel Agnès , Foidart Jean-Michel , Piel Géraldine , Fillet Marianne , Péqueux Christel
Published: June 2023

Estetrol (E4) is a natural estrogen with promising therapeutic applications in humans. The European Medicines Agency and the Food and Drug Administration have approved the use of 15 mg E4/3 mg drospirenone for contraceptive indication. Phase III clinical trials with 15–20 mg E4 for the relief of climacteric complaints are currently running. Relevant data from preclinical animal models are needed to characterize the molecular mechanisms and the pharmacological effects of E4 and possibly to reveal new therapeutic applications and to anticipate potential adverse effects. Therefore, it is important to design experimental procedures in rodents that closely mimic or anticipate human E4 exposure. In this study, we compared the effects of E4 exposure after acute or chronic administration in women and mice. Women who received chronic E4 treatment per os at a dose of 15 mg once daily reached a steady state within 6 to 8 days, with a mean plasma concentration of 3.20 ng/mL. Importantly, with subcutaneous, intraperitoneal or oral administration of E4 in mice, a stable concentration over time that would mimic human pharmacokinetics could not be achieved. The use of osmotic minipumps continuously releasing E4 for several weeks provided an exposure profile mimicking chronic oral administration in women. Measurements of the circulating concentration of E4 in mice revealed that the mouse equivalent dose necessary to mimic human treatment does not fit with the allometric prediction. In conclusion, this study highlights the importance of precise definition of the most appropriate dose and route of administration to utilize when developing predictive preclinical animal models to mimic or anticipate specific human treatment.
How to Set Up Genetic Counselling for Inherited Macular Dystrophies: Focus on Genetic Characterization
Authors: Raimondi Raffaele , D’Esposito Fabiana , Sorrentino Tania , Tsoutsanis Panos , De Rosa Francesco Paolo , Stradiotto Elisa , Barone Gianmaria , Rizzato Angelica , Allegrini Davide , Costagliola Ciro , Romano Mario R.
Published: June 2023

Inherited macular dystrophies refer to a group of degenerative conditions that predominantly affect the macula in the spectrum of inherited retinal dystrophies. Recent trends indicate a clear need for genetic assessment services in tertiary referral hospitals. However, establishing such a service can be a complex task due to the diverse skills required and multiple professionals involved. This review aims to provide comprehensive guidelines to enhance the genetic characterization of patients and improve counselling efficacy by combining updated literature with our own experiences. Through this review, we hope to contribute to the establishment of state-of-the-art genetic counselling services for inherited macular dystrophies.
Is There a Role for Machine Learning in Liquid Biopsy for Brain Tumors? A Systematic Review
Authors: Menna Grazia , Piaser Guerrato Giacomo , Bilgin Lal , Ceccarelli Giovanni Maria , Olivi Alessandro , Della Pepa Giuseppe Maria
Published: June 2023

The paucity of studies available in the literature on brain tumors demonstrates that liquid biopsy (LB) is not currently applied for central nervous system (CNS) cancers. The purpose of this systematic review focused on the application of machine learning (ML) to LB for brain tumors to provide practical guidance for neurosurgeons to understand the state-of-the-art practices and open challenges. The herein presented study was conducted in accordance with the PRISMA-P (preferred reporting items for systematic review and meta-analysis protocols) guidelines. An online literature search was launched on PubMed/Medline, Scopus, and Web of Science databases using the following query: “((Liquid biopsy) AND (Glioblastoma OR Brain tumor) AND (Machine learning OR Artificial Intelligence))”. The last database search was conducted in April 2023. Upon the full-text review, 14 articles were included in the study. These were then divided into two subgroups: those dealing with applications of machine learning to liquid biopsy in the field of brain tumors, which is the main aim of this review (n = 8); and those dealing with applications of machine learning to liquid biopsy in the diagnosis of other tumors (n = 6). Although studies on the application of ML to LB in the field of brain tumors are still in their infancy, the rapid development of new techniques, as evidenced by the increase in publications on the subject in the past two years, may in the future allow for rapid, accurate, and noninvasive analysis of tumor data. Thus making it possible to identify key features in the LB samples that are associated with the presence of a brain tumor. These features could then be used by doctors for disease monitoring and treatment planning.
Transcriptomic Profiling of Tomato Leaves Identifies Novel Transcription Factors Responding to Dehydration Stress
Authors: Dong Shuchao , Ling Jiayi , Song Liuxia , Zhao Liping , Wang Yinlei , Zhao Tongmin
Published: June 2023

Drought is among the most challenging environmental restrictions to tomatoes (Solanum lycopersi-cum), which causes dehydration of the tissues and results in massive loss of yield. Breeding for dehydration-tolerant tomatoes is a pressing issue as a result of global climate change that leads to increased duration and frequency of droughts. However, the key genes involved in dehydration response and tolerance in tomato are not widely known, and genes that can be targeted for dehydration-tolerant tomato breeding remains to be discovered. Here, we compared phenotypes and transcriptomic profiles of tomato leaves between control and dehydration conditions. We show that dehydration decreased the relative water content of tomato leaves after 2 h of dehydration treatment; however, it promoted the malondialdehyde (MDA) content and ion leakage ratio after 4 h and 12 h of dehydration, respectively. Moreover, dehydration stress triggered oxidative stress as we detected significant increases in H2O2 and O2− levels. Simultaneously, dehydration enhanced the activities of antioxidant enzymes including peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), and phenylalanine ammonia-lyase (PAL). Genome-wide RNA sequencing of tomato leaves treated with or without dehydration (control) identified 8116 and 5670 differentially expressed genes (DEGs) after 2 h and 4 h of dehydration, respectively. These DEGs included genes involved in translation, photosynthesis, stress response, and cytoplasmic translation. We then focused specifically on DEGs annotated as transcription factors (TFs). RNA-seq analysis identified 742 TFs as DEGs by comparing samples dehydrated for 2 h with 0 h control, while among all the DEGs detected after 4 h of dehydration, only 499 of them were TFs. Furthermore, we performed real-time quantitative PCR analyses and validated expression patterns of 31 differentially expressed TFs of NAC, AP2/ERF, MYB, bHLH, bZIP, WRKY, and HB families. In addition, the transcriptomic data revealed that expression levels of six drought-responsive marker genes were upregulated by de-hydration treatment. Collectively, our findings not only provide a solid foundation for further functional characterization of dehydration-responsive TFs in tomatoes but may also benefit the improvement of dehydration/drought tolerance in tomatoes in the future.
Bacterial Therapy of Cancer: A Way to the Dustbin of History or to the Medicine of the Future?
Authors: Ikryannikova Larisa N. , Gorokhovets Neonila V. , Belykh Darya A. , Kurbatov Leonid K. , Zamyatnin Andrey A.
Published: June 2023

Bacteria are the constant companions of the human body throughout its life and even after its death. The history of a human disease such as cancer and the history of microorganisms, particularly bacteria, are believed to closely intertwined. This review was conceived to highlight the attempts of scientists from ancient times to the present day to discover the relationship between bacteria and the emergence or development of tumors in the human body. Challenges and achievements of 21st century science in forcing bacteria to serve for cancer treatment are considered. The future possibilities of bacterial cancer therapy, including the creation of bacterial microrobots, or “bacteriobots”, are also discussed.
Current State of Knowledge Regarding WHO High Priority Pathogens—Resistance Mechanisms and Proposed Solutions through Candidates Such as Essential Oils: A Systematic Review
Authors: Romanescu Mirabela , Oprean Camelia , Lombrea Adelina , Badescu Bianca , Teodor Ana , Constantin George D. , Andor Minodora , Folescu Roxana , Muntean Delia , Danciu Corina , Dalleur Olivia , Batrina Stefan Laurentiu , Cretu Octavian , Buda Valentina Oana
Published: June 2023

Combating antimicrobial resistance (AMR) is among the 10 global health issues identified by the World Health Organization (WHO) in 2021. While AMR is a naturally occurring process, the inappropriate use of antibiotics in different settings and legislative gaps has led to its rapid progression. As a result, AMR has grown into a serious global menace that impacts not only humans but also animals and, ultimately, the entire environment. Thus, effective prophylactic measures, as well as more potent and non-toxic antimicrobial agents, are pressingly needed. The antimicrobial activity of essential oils (EOs) is supported by consistent research in the field. Although EOs have been used for centuries, they are newcomers when it comes to managing infections in clinical settings; it is mainly because methodological settings are largely non-overlapping and there are insufficient data regarding EOs’ in vivo activity and toxicity. This review considers the concept of AMR and its main determinants, the modality by which the issue has been globally addressed and the potential of EOs as alternative or auxiliary therapy. The focus is shifted towards the pathogenesis, mechanism of resistance and activity of several EOs against the six high priority pathogens listed by WHO in 2017, for which new therapeutic solutions are pressingly required.
Co-Expression of Podoplanin and CD44 in Proliferative Vitreoretinopathy Epiretinal Membranes
Authors: Bonente Denise , Bianchi Laura , De Salvo Rossana , Nicoletti Claudio , De Benedetto Elena , Bacci Tommaso , Bini Luca , Inzalaco Giovanni , Franci Lorenzo , Chiariello Mario , Tosi Gian Marco , Bertelli Eugenio , Barone Virginia
Published: June 2023

Epiretinal membranes (ERMs) are sheets of tissue that pathologically develop in the vitreoretinal interface leading to progressive vision loss. They are formed by different cell types and by an exuberant deposition of extracellular matrix proteins. Recently, we reviewed ERMs’ extracellular matrix components to better understand molecular dysfunctions that trigger and fuel the onset and development of this disease. The bioinformatics approach we applied delineated a comprehensive overview on this fibrocellular tissue and on critical proteins that could really impact ERM physiopathology. Our interactomic analysis proposed the hyaluronic-acid-receptor cluster of differentiation 44 (CD44) as a central regulator of ERM aberrant dynamics and progression. Interestingly, the interaction between CD44 and podoplanin (PDPN) was shown to promote directional migration in epithelial cells. PDPN is a glycoprotein overexpressed in various cancers and a growing body of evidence indicates its relevant function in several fibrotic and inflammatory pathologies. The binding of PDPN to partner proteins and/or its ligand results in the modulation of signaling pathways regulating proliferation, contractility, migration, epithelial–mesenchymal transition, and extracellular matrix remodeling, all processes that are vital in ERM formation. In this context, the understanding of the PDPN role can help to modulate signaling during fibrosis, hence opening a new line of therapy.
FOXO3 Deficiency in Neutrophils Drives Colonic Inflammation and Tumorigenesis
Authors: Ghimire Jenisha , Iftikhar Rida , Penrose Harrison M. , Snarski Patricia , Ruiz Emmanuelle , Savkovic Suzana D.
Published: June 2023

Inflammatory bowel disease (IBD), characterized by infiltration of polymorphonuclear neutrophils (PMNs), increases the risk of colon cancer. PMN activation corresponds to the accumulation of intracellular Lipid Droplets (LDs). As increased LDs are negatively regulated by transcription factor Forkhead Box O3 (FOXO3), we aim to determine the significance of this regulatory network in PMN-mediated IBD and tumorigenesis. Affected tissue of IBD and colon cancer patients, colonic and infiltrated immune cells, have increased LDs’ coat protein, PLIN2. Mouse peritoneal PMNs with stimulated LDs and FOXO3 deficiency have elevated transmigratory activity. Transcriptomic analysis of these FOXO3-deficient PMNs showed differentially expressed genes (DEGs; FDR < 0.05) involved in metabolism, inflammation, and tumorigenesis. Upstream regulators of these DEGs, similar to colonic inflammation and dysplasia in mice, were linked to IBD and human colon cancer. Additionally, a transcriptional signature representing FOXO3-deficient PMNs (PMN-FOXO3389) separated transcriptomes of affected tissue in IBD (p = 0.00018) and colon cancer (p = 0.0037) from control. Increased PMN-FOXO3389 presence predicted colon cancer invasion (lymphovascular p = 0.015; vascular p = 0.046; perineural p = 0.03) and poor survival. Validated DEGs from PMN-FOXO3389 (P2RX1, MGLL, MCAM, CDKN1A, RALBP1, CCPG1, PLA2G7) are involved in metabolism, inflammation, and tumorigenesis (p < 0.05). These findings highlight the significance of LDs and FOXO3-mediated PMN functions that promote colonic pathobiology.
MicroRNA and lncRNA as the Future of Pulmonary Arterial Hypertension Treatment
Authors: Wołowiec Łukasz , Mędlewska Martyna , Osiak Joanna , Wołowiec Anna , Grześk Elżbieta , Jaśniak Albert , Grześk Grzegorz
Published: June 2023

Pulmonary hypertension (PH) is characterized by a progressive increase in pulmonary arterial pressure and pulmonary vascular resistance. In a short time, it leads to right ventricular failure and, consequently, to death. The most common causes of PH include left heart disease and lung disease. Despite the significant development of medicine and related sciences observed in recent years, we still suffer from a lack of effective treatment that would significantly influence the prognosis and prolong life expectancy of patients with PH. One type of PH is pulmonary arterial hypertension (PAH). The pathophysiology of PAH is based on increased cell proliferation and resistance to apoptosis in the small pulmonary arteries, leading to pulmonary vascular remodeling. However, studies conducted in recent years have shown that epigenetic changes may also lie behind the pathogenesis of PAH. Epigenetics is the study of changes in gene expression that are not related to changes in the sequence of nucleotides in DNA. In addition to DNA methylation or histone modification, epigenetic research focuses on non-coding RNAs, which include microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Preliminary research results give hope that targeting epigenetic regulators may lead to new, potential therapeutic possibilities in the treatment of PAH.
A Targeted Mass Spectrometry Approach to Identify Peripheral Changes in Metabolic Pathways of Patients with Alzheimer’s Disease
Authors: Reveglia Pierluigi , Paolillo Carmela , Angiolillo Antonella , Ferretti Gabriella , Angelico Ruggero , Sirabella Rossana , Corso Gaetano , Matrone Carmela , Di Costanzo Alfonso
Published: June 2023

Alzheimer’s disease (AD), a neurodegenerative disorder, is the most common cause of dementia in the elderly population. Since its original description, there has been intense debate regarding the factors that trigger its pathology. It is becoming apparent that AD is more than a brain disease and harms the whole-body metabolism. We analyzed 630 polar and apolar metabolites in the blood of 20 patients with AD and 20 healthy individuals, to determine whether the composition of plasma metabolites could offer additional indicators to evaluate any alterations in the metabolic pathways related to the illness. Multivariate statistical analysis showed that there were at least 25 significantly dysregulated metabolites in patients with AD compared with the controls. Two membrane lipid components, glycerophospholipids and ceramide, were upregulated, whereas glutamic acid, other phospholipids, and sphingolipids were downregulated. The data were analyzed using metabolite set enrichment analysis and pathway analysis using the KEGG library. The results showed that at least five pathways involved in the metabolism of polar compounds were dysregulated in patients with AD. Conversely, the lipid pathways did not show significant alterations. These results support the possibility of using metabolome analysis to understand alterations in the metabolic pathways related to AD pathophysiology.
Comparison of the Antibacterial Effect of Silver Nanoparticles and a Multifunctional Antimicrobial Peptide on Titanium Surface
Authors: Moreno Daniel , Buxadera-Palomero Judit , Ginebra Maria-Pau , Manero José-María , Martin-Gómez Helena , Mas-Moruno Carlos , Rodríguez Daniel
Published: June 2023

Titanium implantation success may be compromised by Staphylococcus aureus surface colonization and posterior infection. To avoid this issue, different strategies have been investigated to promote an antibacterial character to titanium. In this work, two antibacterial agents (silver nanoparticles and a multifunctional antimicrobial peptide) were used to coat titanium surfaces. The modulation of the nanoparticle (≈32.1 ± 9.4 nm) density on titanium could be optimized, and a sequential functionalization with both agents was achieved through a two-step functionalization method by means of surface silanization. The antibacterial character of the coating agents was assessed individually as well as combined. The results have shown that a reduction in bacteria after 4 h of incubation can be achieved on all the coated surfaces. After 24 h of incubation, however, the individual antimicrobial peptide coating was more effective than the silver nanoparticles or their combination against Staphylococcus aureus. All tested coatings were non-cytotoxic for eukaryotic cells.
Elaboration of the Effective Multi-Target Therapeutic Platform for the Treatment of Alzheimer’s Disease Based on Novel Monoterpene-Derived Hydroxamic Acids
Authors: Aleksandrova Yulia , Munkuev Aldar , Mozhaitsev Evgenii , Suslov Evgenii , Tsypyshev Dmitry , Chaprov Kirill , Begunov Roman , Volcho Konstantin , Salakhutdinov Nariman , Neganova Margarita
Published: June 2023

Novel monoterpene-based hydroxamic acids of two structural types were synthesized for the first time. The first type consisted of compounds with a hydroxamate group directly bound to acyclic, monocyclic and bicyclic monoterpene scaffolds. The second type included hydroxamic acids connected with the monoterpene moiety through aliphatic (hexa/heptamethylene) or aromatic linkers. An in vitro analysis of biological activity demonstrated that some of these molecules had powerful HDAC6 inhibitory activity, with the presence of a linker area in the structure of compounds playing a key role. In particular, it was found that hydroxamic acids containing a hexa- and heptamethylene linker and (-)-perill fragment in the Cap group exhibit excellent inhibitory activity against HDAC6 with IC50 in the submicromolar range from 0.56 ± 0.01 µM to 0.74 ± 0.02 µM. The results of the study of antiradical activity demonstrated the presence of moderate ability for some hydroxamic acids to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2ROO• radicals. The correlation coefficient between the DPPH radical scavenging activity and oxygen radical absorbance capacity (ORAC) value was R2 = 0.8400. In addition, compounds with an aromatic linker based on para-substituted cinnamic acids, having a monocyclic para-menthene skeleton as a Cap group, 35a, 38a, 35b and 38b, demonstrated a significant ability to suppress the aggregation of the pathological β-amyloid peptide 1-42. The 35a lead compound with a promising profile of biological activity, discovered in the in vitro experiments, demonstrated neuroprotective effects on in vivo models of Alzheimer’s disease using 5xFAD transgenic mice. Together, the results obtained demonstrate a potential strategy for the use of monoterpene-derived hydroxamic acids for treatment of various aspects of Alzheimer’s disease.
Influence of Occlusal Hypofunction on Alveolar Bone Healing in Rats
Authors: Damanaki Anna , Beisel-Memmert Svenja , Nokhbehsaim Marjan , Abedi Ali , Rath-Deschner Birgit , Nogueira Andressa V. B. , Deschner James
Published: June 2023

The aim of this in vivo study was to investigate the effect of occlusal hypofunction on alveolar bone healing in the absence or presence of an enamel matrix derivative (EMD). A standardized fenestration defect over the root of the mandibular first molar in 15 Wistar rats was created. Occlusal hypofunction was induced by extraction of the antagonist. Regenerative therapy was performed by applying EMD to the fenestration defect. The following three groups were established: (a) normal occlusion without EMD treatment, (b) occlusal hypofunction without EMD treatment, and (c) occlusal hypofunction with EMD treatment. After four weeks, all animals were sacrificed, and histological (hematoxylin and eosin, tartrate-resistant acid phosphatase) as well as immunohistochemical analyses (periostin, osteopontin, osteocalcin) were performed. The occlusal hypofunction group showed delayed bone regeneration compared to the group with normal occlusion. The application of EMD could partially, but not completely, compensate for the inhibitory effects of occlusal hypofunction on bone healing, as evidenced by hematoxylin and eosin and immunohistochemistry for the aforementioned molecules. Our results suggest that normal occlusal loading, but not occlusal hypofunction, is beneficial to alveolar bone healing. Adequate occlusal loading appears to be as advantageous for alveolar bone healing as the regenerative potential of EMD.
Peritoneal Fluid Analysis of Advanced Ovarian Cancers after Hyperthermic Intraperitoneal Chemotherapy
Authors: Chen Wei-Chun , Chang Ting-Chang , Chou Hung-Hsueh , Cheng Mei-Hsiu , Hong Jun-Jie , Hsieh Yi-Shan , Cheng Chao-Min
Published: June 2023

This study investigated miRNA and cytokine expression changes in peritoneal fluid samples of patients with advanced ovarian cancer (OVCA) after receiving hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreduction surgery (CRS). We collected samples prior to HIPEC, immediately after HIPEC, and 24/48/72 h after CRS from a total of 6 patients. Cytokine levels were assessed using a multiplex cytokine array, and a miRNA PanelChip Analysis System was used for miRNA detection. Following HIPEC, miR-320a-3p, and miR-663-a were found to be immediately down-regulated but increased after 24 h. Further, significant upregulation post-HIPEC and sustained increases in expression were detected in six other miRNAs, including miR-1290, miR-1972, miR-1254, miR-483-5p, miR-574-3p, and miR-574-5p. We also found significantly increased expression of cytokines, including MCP-1, IL-6, IL-6sR, TIMP-1, RANTES, and G-CSF. The changing expression pattern throughout the study duration included a negative correlation in miR-320a-3p and miR-663-a to cytokines including RANTES, TIMP-1, and IL-6 but a positive correlation in miRNAs to cytokines including MCP-1, IL-6sR, and G-CSF. Our study found miRNAs and cytokines in the peritoneal fluid of OVCA patients demonstrated different expression characteristics following CRS and HIPEC. Both changes in expression demonstrated correlations, but the role of HIPEC remains unknown, prompting the need for research in the future.
Effect of Nitrogen on Stored-Product Insect Control at Industrial Scale
Authors: Rumbos Christos I. , Sakka Maria K. , Vassilakos Thomas N. , Athanassiou Christos G.
Published: June 2023

In this study, we evaluated the insecticidal effect of nitrogen against Sitophilus granarius (L.), Sitophilus oryzae (L.), Rhyzopertha dominica (F.), Prostephanus truncatus (Horn), Tribolium confusum Jacquelin du Val, and Oryzaephilus surinamensis (L.). Four trials were conducted in chambers containing flour in bags or sacks with >99% nitrogen level. Adults of all the above species, as well as immature life stages (eggs, larvae, and pupae) of T. confusum were used in the trials. Our results showed that nitrogen caused high mortality for all species and life stages tested. Some survival was recorded for R. dominica and T. confusum pupae. Low progeny production was recorded for S. granarius, S. oryzae, and R. dominica. In conclusion, our trials indicated that a high nitrogen environment can provide satisfactory control of various primary and secondary stored-product insect species.
Effects of Different Diets on Biological Characteristics of Predatory Mite Amblyseius Eharai (Acari: Phytoseiidae)
Authors: Thao Nguyen T. P. , Thuy Nguyen T. , Quyen Ho L.
Published: June 2023

In this study, we investigated the effects of different diets on the development and reproduction of the predatory mite Amblyseius eharai. The results show that feeding on citrus red mite (Panonychus citri) led to the fastest life cycle completion (6.9 ± 0.22 days), the longest oviposition period (26.19 ± 0.46 days), the greatest female longevity (42.03 ± 0.43 days), and the highest total number of eggs per female (45.63 ± 0.94 eggs). Feeding on Artemia fanciscana cysts resulted in the highest oviposition rate (1.98 ± 0.04 eggs), a high total number of eggs per female (33.93 ± 0.36 eggs), and the highest intrinsic rate of increase (rm = 0.242). The hatching rate did not differ significantly among the five types of food, and the proportion of females ranged from 60% to 65% across all diets.
Movement of Striacosta albicosta (Smith) (Lepidoptera: Noctuidae) Larvae on Transgenic Bt and Non-Bt Maize
Authors: Montezano Débora G. , Hunt Thomas E. , Colombo da Luz Priscila M. , Karnik Kelsey , Kachman Stephen D. , Vélez Ana M. , Peterson Julie A.
Published: June 2023

Exposure of lepidopteran pests to Bacillus thuringiensis (Bt) proteins has been shown to affect the behavior of larvae, including increased movement and avoidance of Bt-expressing plants or diet. Therefore, we hypothesized that the behavior of western bean cutworm, Striacosta albicosta (Smith) (Lepidoptera: Noctuidae), an important pest of maize, could be affected when exposed to Bt plants. To test this hypothesis, we conducted a series of artificial arena and on-plant experiments to determine S. albicosta neonate behavior when exposed to Bt and non-Bt plant tissue. Video tracking experiments presented neonate larvae with the choice of Bt or non-Bt pollen in a Petri dish for 15 min while being video recorded for analysis with EthoVision software. This study showed an increase in mean velocity and total time spent moving for larvae in the presence of Cry1F vs. non-Bt when compared with Vip3A vs. non-Bt or Cry1F vs. Vip3A. However, there was no difference in total distance moved or time spent in the food zone for all scenarios. Maize tissue choice experiments allowed neonatal larvae the choice of feeding on Bt or non-Bt tassel or leaves for 9 h in Petri dish arenas. This experiment showed that larvae preferred tassel tissue over leaves but did not indicate that larvae could distinguish between Bt and non-Bt tissue. In contrast, on-plant experiments (including a whole plant neonate dispersal study under controlled conditions and an in-field silking behavior experiment) indicated that the presence of Cry1F and Vip3A Bt toxins increased plant abandonment, suggesting that larvae are able to detect and avoid Bt toxins. The discrepancy of these results is likely due to the on-plant studies providing more field-realistic environmental conditions and a longer duration of exposure to Bt toxins for the behavioral experiments. Our results represent the first steps in understanding the complex behavior of S. albicosta when exposed to Bt plants. A better understanding of the response of larvae when exposed to Bt traits can aid in the management of this pest, particularly for the design of resistance management strategies and refuge design.
Economic Assessment of the Impact of the Sugarcane Industry: An Empirical Approach with Two Focuses for San Luis Potosí, México
Authors: Pérez Medina Pedro , Galindo Mendoza María Guadalupe , Álvarez Fuentes Gregorio , Tenorio Martínez Leonardo David , Barrera López Valter Armando
Published: June 2023

The sugarcane industry has a high environmental impact. In countries such as Mexico, cultivation and harvesting practices consume and pollute many ecological resources. However, quantifying these impacts is difficult due to their diverse nature and different units of measurement. In this study, an approach with two focuses was taken to assess the environmental costs of the sugarcane industry in San Luis Potosí, México. The first focus is human health costs related to air pollution (black carbon) and the second one is a lifecycle assessment applied to the production phase. In the first case, four scenarios, with different concentrations and populations, were projected. Costs of 516.8 thousand USD were estimated for a scenario in which black carbon concentrations exceeded the WHO reference by one unit for the total population. In the second case, costs of 642 million USD were estimated for the impairment of seven ecosystem-based services. These estimates may vary due to the source and specificity of the information provided, but nevertheless are considered an appropriate approximation of the cost of environmental damage. It is recommended that first-hand information be collected and systematized to improve the certainty of the estimates and that changes to sugarcane agrifood systems be considered to reduce environmental costs.
Evaluation of Ocular Perfusion in Patients with End-Stage Renal Disease Receiving Hemodialysis Using Optical Coherence Tomography Angiography
Authors: Lahme Larissa , Storp Jens Julian , Marchiori Elena , Esser Eliane , Eter Nicole , Mihailovic Natasa , Alnawaiseh Maged
Published: June 2023

Hemodialysis (HD) is known to affect ocular blood flow. This case-control study aims to evaluate macular and peripapillary vasculature in patients with end-stage renal disease (ESRD) receiving HD in comparison to matched controls. A total of 24 eyes of 24 ESRD patients receiving HD and 24 eyes of 24 healthy, age- and gender-matched control subjects were prospectively included in this study. Optical coherence tomography angiography was used to image the superficial (SCP), deep (DCP), and choriocapillary (CC) macular vascular plexus, as well as the radial peripapillary capillaries (RPC) of the optic disc. In addition, retinal thickness (RT) and retinal volume (RV) were compared between both groups. Flow density (FD) values of each retinal layer and data of parameters related to the foveal avascular zone (FAZ), as well as RT and RV, were analyzed using Mann–Whitney U tests. There was no significant difference in FAZ parameters between the two groups. Whole en face FD of the SCP and CC was noticeably reduced in the HD group in comparison to the control group. FD was negatively correlated with the duration of HD treatment. RT and RV were significantly smaller in the study group than in controls. Retinal microcirculation appears altered in patients with ESRD undergoing HD. Concurrently, the DCP appears more resilient towards hemodynamic changes in comparison to the other microvascular retinal layers. OCTA is a useful, non-invasive tool to investigate retinal microcirculation in ESRD patients.
Anterior Quadratus Lumborum Block and Quadriceps Strength: A Prospective Cohort Study
Authors: Kadoya Yuma , Tanaka Nobuhiro , Suzuka Takanori , Yamanaka Takayuki , Iwata Masato , Ozu Naoki , Kawaguchi Masahiko
Published: June 2023

The decrease in quadriceps strength after anterior quadratus lumborum block (AQLB) has not been quantified. This prospective cohort study investigated the incidence of quadriceps weakness after AQLB. We enrolled patients undergoing robot-assisted partial nephrectomy, and AQLB was performed at the L2 level with 30 mL of 0.375% ropivacaine. We evaluated each quadriceps’ maximal voluntary isometric contraction using a handheld dynamometer preoperatively and postoperatively at 1 and 4 days. The incidence of muscle weakness was defined as a 25% reduction in muscle strength compared with the preoperative baseline, and “muscle weakness possibly caused by nerve block” was defined as a 25% reduction compared with the non-block side. We also assessed the numerical rating scale and quality of recovery-15 scores. Thirty participants were analyzed. The incidence of muscle weakness compared with preoperative baseline and the non-block side was 13.3% and 30.0%, respectively. Patients with a numerical rating scale ≥ 4 or quality of recovery-15 score < 122, which was classified as moderate or poor, had decreased muscle strength with relative risks of 1.75 and 2.33, respectively. All patients ambulated within 24 h after surgery. The incidence of quadriceps weakness possibly caused by nerve block was 13.3%; however, all patients could ambulate after 1 day.
Microcirculatory Disease in Patients after Heart Transplantation
Authors: Iwańczyk Sylwia , Woźniak Patrycja , Smukowska-Gorynia Anna , Araszkiewicz Aleksander , Nowak Alicja , Jankowski Maurycy , Konwerska Aneta , Urbanowicz Tomasz , Lesiak Maciej
Published: June 2023

Although the treatment and prognosis of patients after heart transplantation have significantly improved, late graft dysfunction remains a critical problem. Two main subtypes of late graft dysfunction are currently described: acute allograft rejection and cardiac allograft vasculopathy, and microvascular dysfunction appears to be the first stage of both. Studies revealed that coronary microcirculation dysfunction, assessed by invasive methods in the early post-transplant period, correlates with a higher risk of late graft dysfunction and death during long-term follow-up. The index of microcirculatory resistance, measured early after heart transplantation, might identify the patients at higher risk of acute cellular rejection and major adverse cardiovascular events. It may also allow optimization and enhancement of post-transplantation management. Moreover, cardiac allograft vasculopathy is an independent prognostic factor for transplant rejection and survival rate. The studies showed that the index of microcirculatory resistance correlates with anatomic changes and reflects the deteriorating physiology of the epicardial arteries. In conclusion, invasive assessment of the coronary microcirculation, including the measurement of the microcirculatory resistance index, is a promising approach to predict graft dysfunction, especially the acute allograft rejection subtype, during the first year after heart transplantation. However, further advanced studies are needed to fully grasp the importance of microcirculatory dysfunction in patients after heart transplantation.
Complete Pathologic Response to PARP Inhibitor Olaparib in a Patient with Stage IVB Recurrent Endometrioid Endometrial Adenocarcinoma
Authors: Senguttuvan Rosemary Noel , Wei Christina , Raoof Mustafa , Dellinger Thanh H. , Wang Edward Wenge
Published: June 2023

Treatment for endometrial cancer is rapidly evolving with the increased use and integration of somatic tumor RNA sequencing in clinical practice. There is a paucity of data regarding PARP inhibition in endometrial cancer given that mutations in homologous recombination genes are rare, and currently no FDA approval exists. A 50-year-old gravida 1 para 1 woman with a diagnosis of stage IVB poorly differentiated endometrioid endometrial adenocarcinoma presented to our comprehensive cancer center. Following surgical staging, she was placed on adjuvant chemotherapy with carboplatin/paclitaxel which was held multiple times due to poor performance status and complications. CT scan of the abdomen and pelvis following cycles 3 of adjuvant chemotherapy showed recurrent progressive disease. She received one cycle of liposomal doxorubicin but discontinued it due to severe cutaneous toxicity. Based on the BRIP1 mutation identified, the patient was placed on compassionate use of Olaparib in January 2020. Imaging during this surveillance period showed a significant decrease in hepatic, peritoneal, and extraperitoneal metastases, and eventually the patient had a clinical complete response in a year. The most recent CT A/P in December 2022 showed no sites of active recurrent or metastatic disease in the abdomen or pelvis. We present a unique case of a patient with recurrent stage IVB poorly differentiated endometrioid endometrial adenocarcinoma with multiple somatic gene mutations including BRIP1, who had a pathologic complete response following compassionate use of Olaparib for 3 years. To our knowledge, this is the first reported case of high grade endometrioid endometrial cancer that has shown a pathologic complete response to a PARP inhibitor.
Referrals, Symptoms and Treatment of Patients Referred to a Secondary Spine Centre—How Can We Help?
Authors: Droeghaag Ruud , Nabben Daphne , Smeets Anouk , van Hemert Wouter , van Orshoven Narender , van Santbrink Henk , Most Jasper , Curfs Inez
Published: June 2023

Introduction: Spinal disorders are amongst the conditions with the highest burden of disease. To limit the increase of healthcare-related costs in the ageing population, the selection of different types of care for patients with spinal disorders should be optimized. The first step is to investigate the characteristics of these patients and the relationship with treatment. Research Question: The primary aim of this study was to provide insights in the characteristics, symptoms, diagnosis and treatment of patients referred to a specialized spinal health care centre. The secondary aim was to perform an in-depth analysis of resource utilization for a representative subgroup of patients. Methods: This study describes the characteristics of 4855 patients referred to a secondary spine centre. Moreover, an extensive analysis of a representative subgroup of patients (~20%) is performed. Results: The mean age was 58.1, 56% of patients were female, and the mean BMI was 28. In addition, 28% of patients used opioids. Mean self-reported health status was 53.3 (EuroQol 5D Visual Analogue Scale), and pain ranged from 5.8 to 6.7 (Visual Analogue Scale neck/back/arm/leg). Additional imaging was received by 67.7% of patients. Surgical treatment was indicated for 4.9% of patients. The majority (83%) of non-surgically treated patients received out-of-hospital treatment; 25% of patients received no additional imaging or in-hospital treatment. Conclusion: The vast majority of patients received non-surgical treatments. We observed that ~10% of patients did not receive in-hospital imaging or treatment and had acceptable or good questionnaire scores at the time of referral. These findings suggest that there is potential for improvement in efficacy of referral, diagnosis, and treatment. Future studies should aim to develop an evidence base for improved patient selection for clinical pathways. The efficacy of chosen treatments requires investigation of large cohorts.