bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticancer Activity of Sunitinib Analogues in Human Pancreatic Cancer Cell Cultures under Normoxia and Hypoxia
Authors: Skaraitė Ieva , Maccioni Elias , Petrikaitė Vilma
Published: March 2023

Pancreatic cancer remains one of the deadliest cancer types. It is usually characterized by high resistance to chemotherapy. However, cancer-targeted drugs, such as sunitinib, recently have shown beneficial effects in pancreatic in vitro and in vivo models. Therefore, we chose to study a series of sunitinib derivatives developed by us, that were proven to be promising compounds for cancer treatment. The aim of our research was to evaluate the anticancer activity of sunitinib derivatives in human pancreatic cancer cell lines MIA PaCa-2 and PANC-1 under normoxia and hypoxia. The effect on cell viability was determined by the MTT assay. The compound effect on cell colony formation and growth was established by clonogenic assay and the activity on cell migration was estimated using a ‘wound healing’ assay. Six out of 17 tested compounds at 1 µM after 72 h of incubation reduced cell viability by 90% and were more active than sunitinib. Compounds for more detailed experiments were chosen based on their activity and selectivity towards cancer cells compared to fibroblasts. The most promising compound EMAC4001 was 24 and 35 times more active than sunitinib against MIA PaCa-2 cells, and 36 to 47 times more active against the PANC-1 cell line in normoxia and hypoxia. It also inhibited MIA PaCa-2 and PANC-1 cell colony formation. Four tested compounds inhibited MIA PaCa-2 and PANC-1 cell migration under hypoxia, but none was more active than sunitinib. In conclusion, sunitinib derivatives possess anticancer activity in human pancreatic adenocarcinoma MIA PaCa-2 and PANC-1 cell lines, and they are promising for further research.
Chemokine Receptors CCR6 and PD1 Blocking scFv E27 Enhances Anti-EGFR CAR-T Therapeutic Efficacy in a Preclinical Model of Human Non-Small Cell Lung Carcinoma
Authors: Wang Jing , Wang Yanan , Pan Hanyu , Zhao Lin , Yang Xinyi , Liang Zhiming , Shen Xiaoting , Zhang Jing , Yang Jinlong , Zhu Yuqi , Xun Jingna , Liang Yue , Lin Qinru , Liang Huitong , Li Min , Zhu Huanzhang
Published: March 2023

Chimeric antigen receptor (CAR)-T cells, a therapeutic agent for solid tumors, are not completely effective due to a lack of infiltration of T cells into the tumor site and immunity caused by Programmed Death Receptor 1(PD1). Here, an epidermal growth factor receptor (EGFR) CAR-T cell was engineered to express the chemokine receptor CCR6 and secrete PD1 blocking Single-chain antibody fragment (scFv) E27 to enhance their anti-tumor effects. The findings showed that CCR6 enhanced the migration of EGFR CAR-E27-CCR6 T cells in vitro by the Transwell migration assay. When incubated with tumor cells, EGFR CAR-E27-CCR6 T cells specifically exerted potent cytotoxicity and produced high levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), and interferon-γ (IFN-γ). A non-small cell lung carcinoma (NSCLC) cell line-derived xenograft model was constructed by implanting modified A549 cell lines into immunodeficient NOD.PrkdcscidIl2rgem1/Smoc (NSG) mice. In comparison with traditional EGFR CAR-T cells, live imaging indicated that EGFR CAR-E27-CCR6 T cells displayed superior anti-tumor function. In addition, the histopathological examination of mouse organs showed no obvious organic damage. Our findings confirmed that PD1 blocking and CCR6 can enhance the anti-tumor function of EGFR CAR-T cells in an NSCLC xenograft model, providing an effective treatment strategy to improve the efficacy of CAR-T in NSCLC.
miRNAs in Uremic Cardiomyopathy: A Comprehensive Review
Authors: D’Agostino Mario , Mauro Davide , Zicarelli Mariateresa , Carullo Nazareno , Greco Marta , Andreucci Michele , Coppolino Giuseppe , Bolignano Davide
Published: March 2023

Uremic Cardiomyopathy (UCM) is an irreversible cardiovascular complication that is highly pervasive among chronic kidney disease (CKD) patients, particularly in End-Stage Kidney Disease (ESKD) individuals undergoing chronic dialysis. Features of UCM are an abnormal myocardial fibrosis, an asymmetric ventricular hypertrophy with subsequent diastolic dysfunction and a complex and multifactorial pathogenesis where underlying biological mechanisms remain partly undefined. In this paper, we reviewed the key evidence available on the biological and clinical significance of micro-RNAs (miRNAs) in UCM. miRNAs are short, noncoding RNA molecules with regulatory functions that play a pivotal role in myriad basic cellular processes, such as cell growth and differentiation. Deranged miRNAs expression has already been observed in various diseases, and their capacity to modulate cardiac remodeling and fibrosis under either physiological or pathological conditions is well acknowledged. In the context of UCM, robust experimental evidence confirms a close involvement of some miRNAs in the key pathways that are known to trigger or worsen ventricular hypertrophy or fibrosis. Moreover, very preliminary findings may set the stage for therapeutic interventions targeting specific miRNAs for ameliorating heart damage. Finally, scant but promising clinical evidence may suggest a potential future application of circulating miRNAs as diagnostic or prognostic biomarkers for improving risk stratification in UCM as well.
Corneal Reconstruction with EGFP-Labelled Limbal Mesenchymal Stem Cells in a Rabbit Model of Limbal Stem Cell Deficiency
Authors: Khorolskaya Julia I. , Perepletchikova Daria A. , Zhurenkov Kirill E. , Kachkin Daniel V. , Rubel Aleksandr A. , Blinova Miralda I. , Mikhailova Natalia A.
Published: March 2023

Ocular surface reconstruction is essential for treating corneal epithelial defects and vision recovery. Stem cell-based therapy demonstrates promising results but requires further research to elucidate stem cell survival, growth, and differentiation after transplantation in vivo. This study examined the corneal reconstruction promoted by EGFP-labeled limbal mesenchymal stem cells (L-MSCs-EGFP) and their fate after transplantation. EGFP labeling allowed us to evaluate the migration and survival rates of the transferred cells. L-MSCs-EGFP seeded onto decellularized human amniotic membrane (dHAM) were transplanted into rabbits with a modeled limbal stem cell deficiency. The localization and viability of the transplanted cells in animal tissue were analyzed using histology, immunohistochemistry, and confocal microscopy up to 3 months after transplantation. EGFP-labeled cells remained viable for the first 14 days after transplantation. By the 90th day, epithelialization of the rabbit corneas reached 90%, but the presence of viable labeled cells was not observed within the newly formed epithelium. Although labeled cells demonstrated low survivability in host tissue, the squamous corneal-like epithelium was partially restored by the 30th day after transplantation of the tissue-engineered graft. Overall, this study paves the way for further optimization of transplantation conditions and studying the mechanisms of corneal tissue restoration.
Predicting Key Genes and Therapeutic Molecular Modelling to Explain the Association between Porphyromonas gingivalis (P. gingivalis) and Alzheimer’s Disease (AD)
Authors: Hamarsha Ahmed , Balachandran Kumarendran , Sailan Ahmad Tarmidi , Nasruddin Nurrul Shaqinah
Published: March 2023

The association between Porphyromonas gingivalis (P. gingivalis) and Alzheimer’s disease (AD) remains unclear. The major aim of this study was to elucidate the role of genes and molecular targets in P. gingivalis-associated AD. Two Gene Expression Omnibus (GEO) datasets, GSE5281 for AD (n = 84 Alzheimer’s, n = 74 control) and GSE9723 (n = 4 P. gingivalis, n = 4 control), were downloaded from the GEO database. Differentially expressed genes (DEGs) were obtained, and genes common to both diseases were drawn. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis was performed from the top 100 genes (50 upregulated and 50 downregulated genes). We then proceeded with CMap analysis to screen for possible small drug molecules targeting these genes. Subsequently, we performed molecular dynamics simulations. A total of 10 common genes (CALD1, HES1, ID3, PLK2, PPP2R2D, RASGRF1, SUN1, VPS33B, WTH3DI/RAB6A, and ZFP36L1) were identified with a p-value < 0.05. The PPI network of the top 100 genes showed UCHL1, SST, CHGB, CALY, and INA to be common in the MCC, DMNC, and MNC domains. Out of the 10 common genes identified, only 1 was mapped in CMap. We found three candidate small drug molecules to be a fit for PLK2, namely PubChem ID: 24971422, 11364421, and 49792852. We then performed molecular docking of PLK2 with PubChem ID: 24971422, 11364421, and 49792852. The best target, 11364421, was used to conduct the molecular dynamics simulations. The results of this study unravel novel genes to P. gingivalis-associated AD that warrant further validation.
Drug-Induced Gingival Overgrowth—Molecular Aspects of Drug Actions
Authors: Droździk Agnieszka , Droździk Marek
Published: March 2023

Drug-induced gingival overgrowth (DIGO) is one of the side effects produced by therapeutic agents, most commonly phenytoin, nifedipine and cyclosporin A. However, the precise mechanism of DIGO is not entirely understood. A literature search of the MEDLINE/PubMed databases was conducted to identify the mechanisms involved in DIGO. The available information suggests that the pathogenesis of DIGO is multifactorial, but common pathogenic sequelae of events emerge, i.e., sodium and calcium channel antagonism or disturbed intracellular handling of calcium, which finally lead to reductions in intracellular folic acid levels. Disturbed cellular functions, mainly in keratinocytes and fibroblasts, result in increased collagen and glycosaminoglycans accumulation in the extracellular matrix. Dysregulation of collagenase activity, as well as integrins and membrane receptors, are key mechanisms of reduced degradation or excessive synthesis of connective tissue components. This manuscript describes the cellular and molecular factors involved in the epithelial–mesenchymal transition and extracellular matrix remodeling triggered by agents producing DIGO.
Salicylic Acid Treatment and Its Effect on Seed Yield and Seed Molecular Composition of Pisum sativum under Abiotic Stress
Authors: Berková Veronika , Berka Miroslav , Kameniarová Michaela , Kopecká Romana , Kuzmenko Marharyta , Shejbalová Šarlota , Abramov Dmytro , Čičmanec Petr , Frejlichová Lucie , Jan Novák , Brzobohatý Břetislav , Černý Martin
Published: March 2023

The reproductive stage of plant development has the most critical impact on yield. Flowering is highly sensitive to abiotic stress, and increasing temperatures and drought harm crop yields. Salicylic acid is a phytohormone that regulates flowering and promotes stress resilience in plants. However, the exact molecular mechanisms and the level of protection are far from understood and seem to be species-specific. Here, the effect of salicylic acid was tested in a field experiment with Pisum sativum exposed to heat stress. Salicylic acid was administered at two different stages of flowering, and its effect on the yield and composition of the harvested seeds was followed. Plants treated with salicylic acid produced larger seed pods, and a significant increase in dry weight was found for the plants with a delayed application of salicylic acid. The analyses of the seed proteome, lipidome, and metabolome did not show any negative impact of salicylic treatment on seed composition. Identified processes that could be responsible for the observed improvement in seed yields included an increase in polyamine biosynthesis, accumulation of storage lipids and lysophosphatidylcholines, a higher abundance of components of chromatin regulation, calmodulin-like protein, and threonine synthase, and indicated a decrease in sensitivity to abscisic acid signaling.
Pravastatin Improves Colonic and Hepatic Microcirculatory Oxygenation during Sepsis without Affecting Mitochondrial Function and ROS Production in Rats
Authors: Kuebart Anne , Gross Katharina , Ripkens Jan-Joschua , Tenge Theresa , Raupach Annika , Schulz Jan , Truse Richard , Hof Stefan , Marcus Carsten , Vollmer Christian , Bauer Inge , Picker Olaf , Herminghaus Anna
Published: March 2023

Microcirculatory and mitochondrial dysfunction are considered the main mechanisms of septic shock. Studies suggest that statins modulate inflammatory response, microcirculation, and mitochondrial function, possibly through their action on peroxisome proliferator-activated receptor alpha (PPAR-α). The aim of this study was to examine the effects of pravastatin on microcirculation and mitochondrial function in the liver and colon and the role of PPAR-α under septic conditions. This study was performed with the approval of the local animal care and use committee. Forty Wistar rats were randomly divided into 4 groups: sepsis (colon ascendens stent peritonitis, CASP) without treatment as control, sepsis + pravastatin, sepsis + PPAR-α-blocker GW6471, and sepsis + pravastatin + GW6471. Pravastatin (200 µg/kg s.c.) and GW6471 (1 mg/kg) were applied 18 h before CASP-operation. 24 h after initial surgery, a relaparotomy was performed, followed by a 90 min observation period for assessment of microcirculatory oxygenation (μHbO2) of the liver and colon. At the end of the experiments, animals were euthanized, and the colon and liver were harvested. Mitochondrial function was measured in tissue homogenates using oximetry. The ADP/O ratio and respiratory control index (RCI) for complexes I and II were calculated. Reactive oxygen species (ROS) production was assessed using the malondialdehyde (MDA)-Assay. Statistics: two-way analysis of variance (ANOVA) + Tukey’s/Dunnett’s post hoc test for microcirculatory data, Kruskal–Wallis test + Dunn’s post hoc test for all other data. In control septic animals µHbO2 in liver and colon deteriorated over time (µHbO2: −9.8 ± 7.5%* and −7.6 ± 3.3%* vs. baseline, respectively), whereas after pravastatin and pravastatin + GW6471 treatment μHbO2 remained constant (liver: µHbO2 pravastatin: −4.21 ± 11.7%, pravastatin + GW6471: −0.08 ± 10.3%; colon: µHbO2 pravastatin: −0.13 ± 7.6%, pravastatin + GW6471: −3.00 ± 11.24%). In both organs, RCI and ADP/O were similar across all groups. The MDA concentration remained unchanged in all groups. Therefore, we conclude that under septic conditions pravastatin improves microcirculation in the colon and liver, and this seems independent of PPAR-α and without affecting mitochondrial function.
Short-Term Effects of Human versus Bovine Sialylated Milk Oligosaccharide Microinjection on Zebrafish Larvae Survival, Locomotor Behavior and Gene Expression
Authors: Licitra Rosario , Naef Valentina , Marchese Maria , Damiani Devid , Ogi Asahi , Doccini Stefano , Fronte Baldassare , Yan Jingyu , Santorelli Filippo M.
Published: March 2023

Milk oligosaccharides are a complex class of carbohydrates that act as bioactive factors in numerous defensive and physiological functions, including brain development. Early nutrition can modulate nervous system development and can lead to epigenetic imprinting. We attempted to increase the sialylated oligosaccharide content of zebrafish yolk reserves, with the aim of evaluating any short-term effects of the treatment on mortality, locomotor behavior, and gene expression. Wild-type embryos were microinjected with saline solution or solutions containing sialylated milk oligosaccharides extracted from human and bovine milk. The results suggest that burst activity and larval survival rates were unaffected by the treatments. Locomotion parameters were found to be similar during the light phase between control and treated larvae; in the dark, however, milk oligosaccharide-treated larvae showed increased test plate exploration. Thigmotaxis results did not reveal significant differences in either the light or the dark conditions. The RNA-seq analysis indicated that both treatments exert an antioxidant effect in developing fish. Moreover, sialylated human milk oligosaccharides seemed to increase the expression of genes related to cell cycle control and chromosomal replication, while bovine-derived oligosaccharides caused an increase in the expression of genes involved in synaptogenesis and neuronal signaling. These data shed some light on this poorly explored research field, showing that both human and bovine oligosaccharides support brain proliferation and maturation.
Reverse Phase Protein Array Profiling Identifies Recurrent Protein Expression Patterns of DNA Damage-Related Proteins across Acute and Chronic Leukemia: Samples from Adults and the Children’s Oncology Group
Authors: Hoff Fieke W. , Griffen Ti’ara L. , Brown Brandon D. , Horton Terzah M. , Burger Jan , Wierda William , Hubner Stefan E. , Qiu Yihua , Kornblau Steven M.
Published: March 2023

DNA damage response (DNADR) recognition and repair (DDR) pathways affect carcinogenesis and therapy responsiveness in cancers, including leukemia. We measured protein expression levels of 16 DNADR and DDR proteins using the Reverse Phase Protein Array methodology in acute myeloid (AML) (n = 1310), T-cell acute lymphoblastic leukemia (T-ALL) (n = 361) and chronic lymphocytic leukemia (CLL) (n = 795) cases. Clustering analysis identified five protein expression clusters; three were unique compared to normal CD34+ cells. Individual protein expression differed by disease for 14/16 proteins, with five highest in CLL and nine in T-ALL, and by age in T-ALL and AML (six and eleven proteins, respectively), but not CLL (n = 0). Most (96%) of the CLL cases clustered in one cluster; the other 4% were characterized by higher frequencies of deletion 13q and 17p, and fared poorly (p < 0.001). T-ALL predominated in C1 and AML in C5, but both occurred in all four acute-dominated clusters. Protein clusters showed similar implications for survival and remission duration in pediatric and adult T-ALL and AML populations, with C5 doing best in all. In summary, DNADR and DDR protein expression was abnormal in leukemia and formed recurrent clusters that were shared across the leukemias with shared prognostic implications across diseases, and individual proteins showed age- and disease-related differences.
Neoprzewaquinone A Inhibits Breast Cancer Cell Migration and Promotes Smooth Muscle Relaxation by Targeting PIM1 to Block ROCK2/STAT3 Pathway
Authors: Zhao Guiying , Ren Yali , Yan Jie , Zhang Tingrui , Lu Peng , Lei Jieting , Rao Huanan , Kang Xin , Cao Zhixing , Peng Fu , Peng Cheng , Rao Chaolong , Li Yuzhi
Published: March 2023

Salvia miltiorrhiza Bunge (Danshen) has been widely used to treat cancer and cardiovascular diseases in Chinese traditional medicine. Here, we found that Neoprzewaquinone A (NEO), an active component of S. miltiorrhiza, selectively inhibits PIM1. We showed that NEO potently inhibits PIM1 kinase at nanomolar concentrations and significantly suppresses the growth, migration, and Epithelial-Mesenchymal Transition (EMT) in the triple-negative breast cancer cell line, MDA-MB-231 in vitro. Molecular docking simulations revealed that NEO enters the PIM1 pocket, thereby triggering multiple interaction effects. Western blot analysis revealed that both NEO and SGI-1776 (a specific PIM1 inhibitor), inhibited ROCK2/STAT3 signaling in MDA-MB-231 cells, indicating that PIM1 kinase modulates cell migration and EMT via ROCK2 signaling. Recent studies indicated that ROCK2 plays a key role in smooth muscle contraction, and that ROCK2 inhibitors effectively control the symptoms of high intraocular pressure (IOP) in glaucoma patients. Here, we showed that NEO and SGI-1776 significantly reduce IOP in normal rabbits and relax pre-restrained thoracic aortic rings in rats. Taken together, our findings indicated that NEO inhibits TNBC cell migration and relaxes smooth muscles mainly by targeting PIM1 and inhibiting ROCK2/STAT3 signaling, and that PIM1 may be an effective target for IOP and other circulatory diseases.
Tactics with Prebiotics for the Treatment of Metabolic Dysfunction-Associated Fatty Liver Disease via the Improvement of Mitophagy
Authors: Tsuji Ai , Yoshikawa Sayuri , Ikeda Yuka , Taniguchi Kurumi , Sawamura Haruka , Morikawa Sae , Nakashima Moeka , Asai Tomoko , Matsuda Satoru
Published: March 2023

Mitophagy/autophagy plays a protective role in various forms of liver damage, by renovating cellular metabolism linking to sustain liver homeostasis. A characterized pathway for mitophagy is the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)/Parkin-dependent signaling pathway. In particular, PINK1-mediated mitophagy could play an indispensable role in improving the metabolic dysfunction-associated fatty liver disease (MAFLD) which could precede to steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. In addition, the PI3K/AKT/mTOR pathway might regulate the various characteristics of cellular homeostasis including energy metabolism, cell proliferation, and/or cell protection. Therefore, targeting mitophagy with the alteration of PI3K/AKT/mTOR or PINK1/Parkin-dependent signaling to eliminate impaired mitochondria might be an attractive strategy for the treatment of MAFLD. In particular, the efficacy of prebiotics for the treatment of MAFLD has been suggested to be useful via the modulation of the PI3K/AKT/mTOR/AMPK pathway. Additionally, several edible phytochemicals could activate mitophagy for the improvement of mitochondrial damages, which could also be a promising option to treat MAFLD with providing liver protection. Here, the potential therapeutics with several phytochemicals has been discussed for the treatment of MAFLD. Tactics with a viewpoint of prospective probiotics might contribute to the development of therapeutic interventions.
Whitelist or Leave Our Website! Advances in the Understanding of User Response to Anti-Ad-Blockers
Authors: Redondo Ignacio , Aznar Gloria
Published: March 2023

Website publishers cannot monetize the ad impressions that are prevented by ad-blockers. Publishers can then employ anti-ad-blockers that force users to choose between either accepting ad impressions by whitelisting the website in the ad-blocker, or leaving the website without accessing the content. This study delineates the mechanisms of how willingness to whitelist/leave the website are affected by the request’s sensitivity to recipients as well as the users’ psychological reactance and evaluation of the website advertising. We tested the proposed relationships using an online panel sample of 500 ad-blocker users, who were asked about their willingness to whitelist/leave their favorite online newspaper after receiving a hypothetical anti-ad-blocker request—four alternative requests with different sensitivity levels were created and randomly assigned to the participants. The results confirmed that (a) the request’s sensitivity can improve the recipient’s compliance, (b) users’ psychological reactance plays an important role in explaining the overall phenomenon, and (c) a favorable evaluation of the website advertising can improve willingness to whitelist. These findings help to better understand user response to anti-ad-blockers and may also help publishers increase their whitelist ratios.
Machine-Guided Design of Oxidation-Resistant Superconductors for Quantum Information Applications
Authors: Koppel Carson , Wilfong Brandon , Iwanicki Allana , Hedrick Elizabeth , Berry Tanya , McQueen Tyrel M.
Published: March 2023

Decoherence in superconducting qubits has long been attributed to two-level systems arising from the surfaces and interfaces present in real devices. A recent significant step in reducing decoherence was the replacement of superconducting niobium by superconducting tantalum, resulting in a tripling of transmon qubit lifetimes (T1). The identity, thickness, and quality of the native surface oxide, is thought to play a major role, as tantalum only has one oxide whereas niobium has several. Here we report the development of a thermodynamic metric to rank materials based on their potential to form a well-defined, thin, surface oxide. We first computed this metric for known binary and ternary metal alloys using data available from the Materials Project and experimentally validated the strengths and limits of this metric through the preparation and controlled oxidation of eight known metal alloys. Then we trained a convolutional neural network to predict the value of this metric from atomic composition and atomic properties. This allowed us to compute the metric for materials that are not present in the Materials Project, including a large selection of known superconductors, and, when combined with Tc, allowed us to identify new candidate superconductors for quantum information science and engineering (QISE) applications. We tested the oxidation resistance of a pair of these predictions experimentally. Our results are expected to lay the foundation for the tailored and rapid selection of improved superconductors for QISE.
Vanadium Oxide-Based Cathode Materials for Aqueous Zinc-Ion Batteries: Energy Storage Mechanism and Design Strategy
Authors: Qiu Yu , Yan Zhaoqian , Sun Zhihao , Guo Zihao , Liu Hongshou , Du Benli , Tian Shaoyao , Wang Peng , Ding Han , Qian Lei
Published: March 2023

Aqueous zinc ion batteries (AZIBs) are an ideal choice for a new generation of large energy storage devices because of their high safety and low cost. Vanadium oxide-based materials have attracted great attention in the field of AZIB cathode materials due to their high theoretical capacity resulting from their rich oxidation states. However, the serious structural collapse and low intrinsic conductivity of vanadium oxide-based materials cause rapid capacity fading, which hinders their further applications in AZIB cathode materials. Here, the structural characteristics and energy storage mechanisms of vanadium oxide-based materials are reviewed, and the optimization strategies of vanadium oxide-based cathode materials are summarized, including substitutional doping, vacancy engineering, interlayer engineering, and structural composite. Finally, the future research and development direction of vanadium oxide-based AZIBs are prospected in terms of cathode, anode, electrolyte, non-electrode components, and recovery technology.
Effects of Traditional Orchard Abandonment and Landscape Context on the Beneficial Arthropod Community in a Mediterranean Agroecosystem
Authors: de Paz Víctor , Asís Josep D. , Holzschuh Andrea , Baños-Picón Laura
Published: March 2023

Agricultural abandonment is one of the main land-use changes in Europe, and its consequences on biodiversity are context- and taxa-dependent. While several studies have worked on this topic, few have focused on traditional orchards, especially in different landscapes and under a Mediterranean climate. In this context, we aimed to determine the effects of almond orchard abandonment on the communities of three groups of beneficial arthropods and the role of the landscape context in modulating these effects. Between February and September 2019, four samplings were carried out in twelve almond orchards (three abandoned and three traditional (active orchards under traditional agricultural management) located in simple landscapes as well as three abandoned and three traditional in complex landscapes). Abandoned and traditional almond orchards harbor different arthropod communities and diversity metrics that are strongly conditioned by seasonality. Abandoned orchards can favor pollinators and natural enemies, providing alternative resources in simple landscapes. However, the role that abandoned orchards play in simple landscapes disappears as the percentage of semi-natural habitats in the landscape increases. Our results show that landscape simplification, through the loss of semi-natural habitats, has negative consequences on arthropod biodiversity, even in traditional farming landscapes with small fields and high crop diversity.
Detection of Rice Pests Based on Self-Attention Mechanism and Multi-Scale Feature Fusion
Authors: Hu Yuqi , Deng Xiaoling , Lan Yubin , Chen Xin , Long Yongbing , Liu Cunjia
Published: March 2023

In recent years, the occurrence of rice pests has been increasing, which has greatly affected the yield of rice in many parts of the world. The prevention and cure of rice pests is urgent. Aiming at the problems of the small appearance difference and large size change of various pests, a deep neural network named YOLO-GBS is proposed in this paper for detecting and classifying pests from digital images. Based on YOLOv5s, one more detection head is added to expand the detection scale range, the global context (GC) attention mechanism is integrated to find targets in complex backgrounds, PANet is replaced by BiFPN network to improve the feature fusion effect, and Swin Transformer is introduced to take full advantage of the self-attention mechanism of global contextual information. Results from experiments on our insect dataset containing Crambidae, Noctuidae, Ephydridae, and Delphacidae showed that the average mAP of the proposed model is up to 79.8%, which is 5.4% higher than that of YOLOv5s, and the detection effect of various complex scenes is significantly improved. In addition, the paper analyzes and discusses the generalization ability of YOLO-GBS model on a larger-scale pest data set. This research provides a more accurate and efficient intelligent detection method for rice pests and others crop pests.
Potato (Solanum tuberosum) as a New Host for Pentastiridius leporinus (Hemiptera: Cixiidae) and Candidatus Arsenophonus Phytopathogenicus
Authors: Behrmann Sarah Christin , Rinklef André , Lang Christian , Vilcinskas Andreas , Lee Kwang-Zin
Published: March 2023

Pentastiridius leporinus is a planthopper (Hemiptera: Cixiidae) that vectors two phloem-restricted bacterial pathogens to sugar beet (Beta vulgaris (L.)): the γ-proteobacterium Candidatus Arsenophonus phytopathogenicus and the stolbur phytoplasma Candidatus Phytoplasma solani. These bacteria cause an economically important disease known as syndrome basses richesses (SBR), characterized by yellowing, deformed leaves and low beet yields. Having observed potato fields in Germany infested with cixiid planthoppers and showing signs of leaf yellowing, we used morphological criteria and COI and COII as molecular markers, to identify the planthoppers (adults and nymphs) primarily as P. leporinus. We analyzed planthoppers, potato tubers, and sugar beet roots and detected both pathogens in all sample types, confirming that P. leporinus adults and nymphs can transmit the bacteria. This is the first time that P. leporinus has been shown to transmit Arsenophonus to potato plants. We also found that two generations of P. leporinus were produced in the warm summer of 2022, which will probably increase the pest population size (and thus the prevalence of SBR) in 2023. We conclude that P. leporinus has expanded its host range to potato, and can now utilize both host plants during its developmental cycle, a finding that will facilitate the development of more efficient control strategies.
Effects of Intravenous Iron Replacement Therapy on Cardiovascular Outcomes in Patients with Heart Failure: A Systematic Review and Meta-Analysis
Authors: Reinhold Johannes , Burra Vyas , Corballis Natasha , Tsampasian Vasiliki , Matthews Gareth , Papadopoulou Charikleia , Vassiliou Vassilios S.
Published: March 2023

(1) Background: Iron deficiency (ID) is an important adverse prognostic marker in patients with heart failure (HF); however, it is unclear whether intravenous iron replacement reduces cardiovascular mortality in this patient group. Here, we estimate the effect of intravenous iron replacement therapy on hard clinical outcomes following the publication of IRONMAN, the largest trial in this field. (2) Methods: In this systematic review and meta-analysis, prospectively registered with PROSPERO and reported according to PRISMA guidelines, we searched PubMed and Embase for randomized controlled trials investigating intravenous iron replacement in patients with HF and co-existing ID. The primary outcome was cardiovascular mortality and secondary outcomes were all-cause mortality, hospitalizations for HF and a combination of the primary outcome and hospitalizations for HF. (3) Results: A total of 1671 items were identified and after removal of duplicates we screened titles and abstracts of 1202 records. Some 31 studies were identified for full-text review and 12 studies were included in the final review. The odds ratio (OR) for cardiovascular death using a random effects model was 0.85 (95% CI 0.69 to 1.04) and for all-cause mortality it was 0.83 (95% CI 0.59 to 1.15). There was a significant reduction in hospitalizations for HF (OR 0.49, 95% CI 0.35 to 0.69) and the combination of hospitalizations for HF and cardiovascular death (OR 0.65, 95% CI 0.5 to 0.85). (4) Conclusions: This review supports the use of IV iron replacement reducing hospitalization rates for HF, however more research is required to determine the effect on cardiovascular mortality and to identify the patient population most likely to benefit.
Minimal Access Tricuspid Valve Surgery
Authors: Sauvé Jean-Alexandre , Wu Yung-Szu , Ghatanatti Ravi , Zacharias Joseph
Published: March 2023

Tricuspid valve diseases are a heterogeneous group of pathologies that typically have poor prognoses when treated medically and are associated with significant morbidity and mortality with traditional surgical techniques. Minimal access tricuspid valve surgery may mitigate some of the surgical risks associated with the standard sternotomy approach by limiting pain, reducing blood loss, lowering the risk of wound infections, and shortening hospital stays. In certain patient populations, this may allow for a prompt intervention that could limit the pathologic effects of these diseases. Herein, we review the literature on minimal access tricuspid valve surgery focusing on perioperative planning, technique, and outcomes of minimal access endoscopic and robotic surgery for isolated tricuspid valve disease.
Monitoring Systems in Home Ventilation
Authors: Arnal Jean-Michel , Oranger Mathilde , Gonzalez-Bermejo Jésus
Published: March 2023

Non-invasive ventilation (NIV) is commonly used at home for patient with nocturnal hypoventilation caused by a chronic respiratory failure. Monitoring NIV is required to optimize the ventilator settings when the lung condition changes over time, and to detect common problems such as unintentional leaks, upper airway obstructions, and patient–ventilator asynchronies. This review describes the accuracy and limitations of the data recorded by the ventilator. To efficiently interpret this huge amount of data, clinician assess the daily use and regularity of NIV utilization, the unintentional leaks and their repartition along the NIV session, the apnea–hypopnea index and the flow waveform, and the patient–ventilator synchrony. Nocturnal recordings of gas exchanges are also required to detect nocturnal alveolar hypoventilation. This review describes the indication, validity criteria, and interpretation of nocturnal oximetry and transcutaneous capnography. Polygraphy and polysomnography are indicated in specific cases to characterize upper airway obstruction. Telemonitoring of the ventilator is a useful tool that should be integrated in the monitoring strategy. The technical solution, information, and limitations are discussed. In conclusion, a basic monitoring package is recommended for all patients complemented by advanced monitoring for specific cases.
Narcotic Requirements before and after Implementation of Buccal Nerve Blocks for Buccal Mucosa Graft Harvest: Technique and Retrospective Review
Authors: Nolte Adam , Perez Alejandra , Mallory Chase , Demus Timothy , Boyer Jessica , Jamieson Scott , Jivanji Dhaval , Cordon Billy
Published: March 2023

The reduction in opioid use has become a public health priority. We aimed to assess if performing buccal nerve blocks (BNB) at the time of buccal mucosa graft (BMG) harvest impacts post-operative narcotic usage in the inpatient setting. We retrospectively reviewed clinical characteristics and morphine milligram equivalents (MMEs) received for all patients that underwent a BMG urethroplasty at our institution. The primary outcome measure was post-operative MMEs for patients before and after implementing the BNB. We identified 74 patients that underwent BMG urethroplasty, 37 of which were before the implementation of the BNB and 37 of which were after. No other changes were made to the peri-operative pathway between these time points. The mean total MMEs per day, needed post-operatively, was lower in the BNB group (8.8 vs. 5.0, p = 0.12). A histogram distribution of the two groups, categorized by number of MMEs received, showed no significant differences between the two groups. In this retrospective analysis, we report our experience using BNBs at the time of buccal mucosa graft harvest. While there were no significant differences between the number of MMEs received before and after implementation, further research is needed to assess the blocks’ impact on pain scores.
Advances in CAR-T Cell Therapy in Head and Neck Squamous Cell Carcinoma
Authors: Wang Han-Qi , Fu Ruxing , Man Qi-Wen , Yang Guang , Liu Bing , Bu Lin-Lin
Published: March 2023

Surgery with the assistance of conventional radiotherapy, chemotherapy and immunotherapy is the basis for head and neck squamous cell carcinoma (HNSCC) treatment. However, with these treatment modalities, the recurrence and metastasis of tumors remain at a high level. Increasingly, the evidence indicates an excellent anti-tumor effect of chimeric antigen receptor T (CAR-T) cells in hematological malignancy treatment, and this novel immunotherapy has attracted researchers’ attention in HNSCC treatment. Although several clinical trials have been conducted, the weak anti-tumor effect and the side effects of CAR-T cell therapy against HNSCC are barriers to clinical translation. The limited choices of targeting proteins, the barriers of CAR-T cell infiltration into targeted tumors and short survival time in vivo should be solved. In this review, we introduce barriers of CAR-T cell therapy in HNSCC. The limitations and current promising strategies to overcome barriers in solid tumors, as well as the applications for HNSCC treatment, are covered. The perspectives of CAR-T cell therapy in future HNSCC treatment are also discussed.
The Influence of Family Milieu on Dental Anxiety in Adolescents—A Cross-Sectional Study
Authors: Uziel Nir , Meyerson Joseph , Kuskasy Moataz , Gilon Efrat , Eli Ilana
Published: March 2023

Parents play a significant role in the development of dental anxiety in their adolescent children. This cross-sectional study aimed to evaluate the influence of family milieu on adolescents’ dental anxiety. The level of dental anxiety (Dental Anxiety Scale—DAS) was evaluated in 100 adolescent dental patients (ages 13–18 years) and their parents. Parents supplied information about family demographics and their personal experiences of dental treatment. Concomitantly, the family’s behavior was observed during the dental encounter. The adolescents’ mean DAS score was 9.83 ± 2.05. Adolescents’ DAS was higher when their parents’ memories from their own dental encounters were negative. A positive correlation was found between adolescents’ dental anxiety and that of their father (r = 0.52, p < 0.001) and mother (r = 0.79, p < 0.001). The following variables showed a significant ability to predict adolescents’ dental anxiety (stepwise regression): mother’s DAS (B = 0.57), adolescent’s behavior at the dental visit (B = 0.87), being the firstborn child (B = −0.44), father’s DAS (B = 0.13), and mother’s level of education (B = −0.10). The results showed that intra-family relationships and behavior, parents’ education, dental fear, and memories from previous treatments play an important role in defining the level of dental anxiety in their adolescent children.
Perinatal Psychoactive Substances Use: A Rising Perinatal Mental Health Concern
Authors: ELNahas Gihan , Thibaut Florence
Published: March 2023

Introduction: A significant increase in psychoactive drugs use was observed in women of childbearing age and during the perinatal period worldwide. Yet, the use of illicit drugs, alcohol and tobacco during pregnancy is a serious health risk for the mother, developing fetus and newborn. Methods: This review of current trends and consequences of psychoactive substance use in the general population and in pregnant women was conducted using the English and French literature published during the years 2000 to 2022, supplemented by guidelines, meta-analyses and reviews. Results: According to current rates of prenatal substances use, it was calculated that 380,000 offspring were exposed to illicit substances, more than 500,000 to alcohol and over one million to tobacco during uterine life. Alarmingly, drug-related pregnancy-associated mortality has shown a staggering 190% rise between 2010 and 2019 in the USA. Different drugs of abuse, when used during pregnancy, increase the risk of stillbirth, neonatal abstinence syndrome and sudden infant death. Adverse effects on pregnancy include premature rupture of membranes, placental abruption, preterm birth, low birth space? weight and small-for-gestational-age infants. There is also an increased risk of morbidity and mortality for the pregnant women. Long-term negative adverse effects of perinatal exposure to substances also include a number of neurocognitive, behavioral and emotional dysfunctions in infants. Each type of substance has its own specificities, which will be briefly summarized. Conclusion: All childbearing age women must be informed about the potential harm of the prenatal use of psychoactive substances and should be encouraged to stop their use when pregnancy is planned and, at least, when pregnancy is known. Questioning women about their alcohol consumption should be systematic at the first prenatal visit and then at every prenatal visit until delivery. Multidisciplinary prevention approaches as well as intervention measures targeted to each type of psychoactive substance can save mothers’ lives and mitigate serious adversities to the offspring.
Cardiac Surgery in Nonagenarians Following the TAVI/TMVI Era: A Multicenter 23-Year Comparative Analysis
Authors: Nasso Giuseppe , Santarpino Giuseppe , Di Bari Nicola , Fattouch Khalil , Condello Ignazio , Moscarelli Marco , Del Giglio Mauro , Paparella Domenico , Lamarra Mauro , Savini Carlo , Coppola Roberto , Fiorani Vinicio , Speziale Giuseppe
Published: March 2023

Background: Studies reporting on the outcome of 90-year-old patients undergoing cardiac surgery are scant in literature; and currently, those regarding the implementation of trans-catheter techniques number even fewer. Methods: We compared patients aged >89 years operated on between 1998 and 2008 at 8 Italian cardiac surgery centers, with patients of the same age operated on between 2009 and 2021. All of the patients were operated on with “open” surgery, with the exclusion of percutaneous valve repair/implantation procedures. Results: The patients of the two groups (group 98-08—127 patients, and group 09-21—101 patients) had comparable preoperative risk factors in terms of the LogEuroSCORE (98-08: 21.3 ± 6.1 vs. 09-21: 20.9 ± 11.1, p = 0.12). There was a considerable difference in the type of surgery (isolated valve, isolated coronary, and combined surgery, 46.5, 38.5, and 15% vs. 52, 13, and 35% in 98-08 and 09-21, respectively, p = 0.01). Analogous operating durations were recorded (cross-clamp time: 98-08: 46 ± 28 min vs. 09-21: 51 ± 28 min, p = 0.06). The number of packed bypasses was lower in 09-21 (1.3 ± 0.6 vs. 2.4 ± 1.2, p = 0.001). In the postoperative period, there was a statistically significant difference in the 30-day survival in favor of the “more recent” patients (98-08: 17 deaths (13.4%) versus 09-21: 6(5.9%); p = 0.001), also confirmed in the subgroups (12.2% vs. 0% in isolated coronary surgery, p < 0.001; and 12.3% vs. 0% in isolated valve surgery, p < 0.001). Conclusions: Accurate pre-, intra-, and post-operative evaluation/management to reduce biological impacts facilitate significant improvements in the outcomes in nonagenarian patients when compared to the results recorded in previous years.
The Global Burden of Valvular Heart Disease: From Clinical Epidemiology to Management
Authors: Santangelo Gloria , Bursi Francesca , Faggiano Andrea , Moscardelli Silvia , Simeoli Pasquale , Guazzi Marco , Lorusso Roberto , Carugo Stefano , Faggiano Pompilio
Published: March 2023

Valvular heart disease is a leading cause of cardiovascular morbidity and mortality and a major contributor of symptoms and functional disability. Knowledge of valvular heart disease epidemiology and a deep comprehension of the geographical and temporal trends are crucial for clinical advances and the formulation of effective health policy for primary and secondary prevention. This review mainly focuses on the epidemiology of primary (organic, related to the valve itself) valvular disease and its management, especially emphasizing the importance of heart valve centers in ensuring the best care of patients through a multidisciplinary team.
The Imprint of Exposome on the Development of Atopic Dermatitis across the Lifespan: A Narrative Review
Authors: Grafanaki Katerina , Bania Angelina , Kaliatsi Eleni G. , Vryzaki Eleftheria , Vasilopoulos Yiannis , Georgiou Sophia
Published: March 2023

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects more than 200 million people worldwide, including up to 20% of children and 10% of the adult population. Although AD appears frequently in childhood and often continues into adulthood, about 1 in 4 adults develop the adult-onset disease. The prenatal period, early childhood, and adolescence are considered critical timepoints for the development of AD when the exposome results in long-lasting effects on the immune system. The exposome can be defined as the measure of all the exposures of an individual during their lifetime and how these exposures relate to well-being. While genetic factors could partially explain AD onset, multiple external environmental exposures (external exposome) in early life are implicated and are equally important for understanding AD manifestation. In this review, we describe the conceptual framework of the exposome and its relevance to AD from conception and across the lifespan. Through a spatiotemporal lens that focuses on the multi-level phenotyping of the environment, we highlight a framework that embraces the dynamic complex nature of exposome and recognizes the influence of additive and interactive environmental exposures. Moreover, we highlight the need to understand the developmental origins of AD from an age-related perspective when studying the effects of the exposome on AD, shifting the research paradigm away from the per se categorized exposome factors and beyond clinical contexts to explore the trajectory of age-related exposome risks and hence future preventive interventions.
Contemporary Management of Cardiogenic Shock Complicating Acute Myocardial Infarction
Authors: De Luca Leonardo , Mistrulli Raffaella , Scirpa Riccardo , Thiele Holger , De Luca Giuseppe
Published: March 2023

Despite an improvement in pharmacological therapies and mechanical reperfusion, the outcome of patients with acute myocardial infarction (AMI) is still suboptimal, especially in patients with cardiogenic shock (CS). The incidence of CS accounts for 3–15% of AMI cases, with mortality rates of 40% to 50%. In contrast to a large number of trials conducted in patients with AMI without CS, there is limited evidence-based scientific knowledge in the CS setting. Therefore, recommendations and actual treatments are often based on registry data. Similarly, knowledge of the available options in terms of temporary mechanical circulatory support (MCS) devices is not equally widespread, leading to an underutilisation or even overutilisation in different regions/countries of these treatment options and nonuniformity in the management of CS. The aim of this article is to provide a critical overview of the available literature on the management of CS as a complication of AMI, summarising the most recent evidence on revascularisation strategies, pharmacological treatments and MCS use.