bluuebunny/crossref_metadata_2025 huggingface dataset:
Differentiating Leaf Structures and Physiological Responses to Freezing Stress of Mangrove Kandelia obovata from Different Provenances
Authors: Xin Wenzhen , An Xia , Liu Huizi , Liu Shuangshuang , Yang Sheng , Wei Xin , Zhao Jiali , Lin Renan , Liu Xing , Chen Qiuxia
Published: February 2024

Kandelia obovata (Rhizophoraceae) is the most cold-tolerant mangrove species and has been widely used in coastal wetland ecological restoration due to its specific viviparous phenomenon, beautiful shape, and unique floral pattern. Due to long-term adaptation to their local environment, the phenotypic characteristics and stress resistance of widely distributed plants of the same species often differentiate across different locations. The capacity for cold resistance is closely linked to the physiological and structural characteristics of plants. Herein, we explored the temporal variations in the leaf structure and physiological status of K. obovata under −5.5 °C from different areas such as Jiulongjiang Estuary (JLJ, 24°25′ N), Fujian Province, and Longgang City (LG, 27°34′ N) and Jiaojiang District (JJ, 28°67′ N), Zhejiang Province. The morphological variations implied that the cold resistance of K. obovata obviously strengthened after the northward migration and acclimatization, in the following order: LG > JJ > JLJ. More specifically, after exposure to a sustained low temperature, the relative conductivity (REC), an index widely used to evaluate the degree of plant damage, remarkably increased from 33.62 ± 2.39 to 63.73 ± 3.81, 31.20 ± 1.63 to 49.48 ± 1.12, and 23.75 ± 0.13 to 54.24 ± 1.45 for JLJ, LG, and JJ, respectively (p < 0.05). Additionally, the palisade-to-spongy tissue ratio (P/I) of JLJ and JJ decreased from 0.78 ± 0.05 and 0.75 ± 0.03 to 0.5 ± 0.04 and 0.64 ± 0.02 (p < 0.05), whereas no significant changes were found in LG (p > 0.05). The SOD activity of LG significantly kept increasing, with values increased from 352.49 ± 10.38 to 477.65 ± 1.78 U·g−1, whereas no apparent changes in JLJ and JJ were observed with the sustained low temperature. The results of this study improved our understanding of the response of K. obovata to freezing stress, which could provide a sound theoretical foundation for cultivating cold-resistant varieties, as well as expanding mangrove plantations in higher latitudes.
Duration of Steam Distillation Affects Essential Oil Fractions in Immortelle (Helichrysum italicum)
Authors: Petrović Marinko , Petrović Vesna , Mlinar Zdenko , Babić Sandra , Jukić Jerko , Prebeg Tatjana , Kremer Dario
Published: February 2024

The composition of the essential oil depends on the duration and conditions under which the distillation of the plant material is carried out. In this study, one sample without fractionation and eight fractions (each after 15 min of steam distillation) of the essential oil of cultivated H. italicum were analysed by gas chromatography-mass spectrometry (GC-MS). The steam conditions for all samples were as follows: flow rate 800 L/h, temperature 104 °C, and pressure 0.4 bar. The test of the antimicrobial activity was performed with the modified Kirby–Bauer method (disc diffusion method) on non-selective nutrient media (blood agar) using the reference bacterial and fungal strains. A total of 75 different components were found in the essential oil samples obtained. A shorter distillation time makes the oil richer in monoterpenes and more suitable for the perfume and cosmetics industry. On the other hand, prolonged distillation leads to the essential oil being enriched with sesquiterpene oxides, which can have a negative effect on the fragrance of the essential oil. The essential oil of H. italicum showed antimicrobial activity only against Staphylococcus aureus ATCC 25923, and the best activity was shown by the sixth fraction.
Chemical Composition of Healthy and Raspberry Leaf Blotch Emaravirus-Infected Red Raspberry ‘Willamette’ Fruits
Authors: Miletić Nemanja , Mitić Milan , Popović Branko , Petković Marko , Vasilijević Bojana , Katanić Vera , Jevremović Darko
Published: February 2024

The aim of this study was to determine the changes in chemical composition of fresh red raspberry ‘Willamette’ fruits caused by the presence of raspberry leaf blotch emaravirus (RLBV). In three experimental orchards of ‘Willamette’ raspberry, fruits were harvested from RLBV-free and RLBV-infected plants in 2019 and 2020. Fruits were collected at appropriate maturity stages and further analyzed in terms of total phenolics, total anthocyanins, and selected individual phenolics. In all three experimental orchards, the phenolic profiles of the infected and uninfected fruit samples were considerably different during both studied years. Nonetheless, the intensity of the modifications varied greatly depending on the location and harvest year. Statistical analysis revealed that the influence of RLBV infection on the studied features was undeniable, although the influences of weather conditions and soil composition outweighed the influence of RLBV. Taking into consideration all the experimental and statistical data, it can be concluded that RLBV had an impact on the phenolic profile of raspberry ‘Willamette’ fruits, while sensitivity to environmental conditions and soil composition is emphasized.
Short-Term Storage in a Modified Atmosphere Affects the Chemical Profile of Blueberry (Vaccinium corymbosum L.) Fruit
Authors: Smrke Tina , Cvelbar Weber Nika , Razinger Jaka , Medic Aljaz , Veberic Robert , Hudina Metka , Jakopic Jerneja
Published: February 2024

Short-term modified-atmosphere storage with an adjusted CO2 and/or O2 concentration could recover blueberry fruit infested with the larvae of quarantine pests. However, this could significantly affect the fruit quality. In our experiment we investigated the performance of highbush blueberry ‘Bluecrop’ fruit (firmness, peel color, individual phenolics, sugars, and organic acids) under four short-term storage regimes: (1) a regular atmosphere with 0.03% CO2, 21% O2, and 78% N2 at 22 °C, i.e., the control; (2) a regular atmosphere with 0.03% CO2, 21% O2, and 78% N2 at 2 °C; (3) a modified atmosphere with 10% CO2, 5% O2, and 85% N2 at 2 °C; and (4) a modified atmosphere with 100% CO2 at 2 °C. Fruit sampling took place after 24 h, 48 h, and 72 h. Fruit firmness was not significantly altered by storage regime or duration, while some significant, but minor, changes were detected in the color parameters. Regarding the primary metabolites, the sugar/organic acid ratio stagnated in the first 48 h in all storage regimes. The content of the majority of the individual phenolics was significantly higher in the fruit stored under control conditions. From our results, we can conclude that the short-term storage of highbush blueberry ‘Bluecrop’ fruit for 24 h in a cold atmosphere does not affect the phenolic content, and storage for 48 h does not affect the total sugar/organic acid ratio, regardless of the atmosphere composition.
Are We the Problem? A Call to Action for Addressing Institutional Challenges to Engaging Community Partners in Research
Authors: Hippalgaonkar Neha , Nguyen Ryan Huu-Tuan , Cohn Eliza Brumer , Horowitz Joseph , Waite Ana Williams , Mersha Tigist , Sandoval Christen , Khan Sarah , Salum Kauthar , Thomas Paris , Murphy Anne Marie , Brent Beulah , Coleman Lolita , Khosla Paramjeet , Hoskins Kent F. , Henderson Vida , Carnahan Leslie R.
Published: February 2024

Community-engaged research (CEnR) is a potent tool for addressing health inequities and fostering equitable relationships among communities, researchers, and institutions. CEnR involves collaboration throughout the research process, demonstrating improvements in study recruitment and retention, intervention efficacy, program sustainability, capacity building among partners, and enhanced cultural relevance. Despite the increasing demand for CEnR, institutional policies, particularly human participation protection training (HPP), lag behind, creating institutional barriers to community partnerships. Here, we highlight challenges encountered in our ongoing study, Fostering Opportunities in Research through Messaging and Education (FOR ME), focused on promoting shared decision-making around clinical trial participation among Black women diagnosed with breast cancer. Grounded in CEnR methods, FOR ME has a partnership with a community-based organization (CBO) that addresses the needs of Black women with breast cancer. Our CBO partner attempted to obtain HPP training, which was administratively burdensome and time-consuming. As CEnR becomes more prevalent, academic and research institutions, along with researchers, are faced with a call to action to become more responsive to community partner needs. Accordingly, we present a guide to HPP training for community partners, addressing institutional barriers to community partner participation in research. This guide outlines multiple HPP training pathways for community partners, aiming to minimize institutional barriers and enhance their engagement in research with academic partners.
Three-Dimensionally Cultured Jaw Periosteal Cells Attenuate Macrophage Activation of CD4+ T Cells and Inhibit Osteoclastogenesis
Authors: He Fang , Wang Liuran , Umrath Felix , Naros Andreas , Reinert Siegmar , Alexander Dorothea
Published: February 2024

The implementation of a successful therapeutic approach that includes tissue-engineered grafts requires detailed analyses of graft-immune cell interactions in order to predict possible immune reactions after implantation. The phenotypic plasticity of macrophages plays a central role in immune cell chemotaxis, inflammatory regulation and bone regeneration. The present study addresses effects emanating from JPC-seeded β-TCP constructs (3DJPCs) co-cultivated with THP-1 derived M1/M2 macrophages within a horizontal co-culture system. After five days of co-culture, macrophage phenotype and chemokine secretion were analyzed by flow cytometry, quantitative PCR and proteome arrays. The results showed that pro-inflammatory factors in M1 macrophages were inhibited by 3DJPCs, while anti-inflammatory factors were activated, possibly affected by the multiple chemokines secreted by 3D-cultured JPCs. In addition, osteoclast markers of polarized macrophages were inhibited by osteogenically induced 3DJPCs. Functional assays revealed a significantly lower percentage of proliferating CD4+ T cells in the groups treated with secretomes from M1/M2 macrophages previously co-cultured with 3DJPCs compared to controls without secretomes. Quantifications of pit area resorption assays showed evidence that supernatants from 3DJPCs co-cultured with M1/M2 macrophages were able to completely suppress osteoclast maturation, compared to the control group without secretomes. These findings demonstrate the ability of 3D cultured JPCs to modulate macrophage plasticity.
Adipose-Derived Stem Cells: Angiogenetic Potential and Utility in Tissue Engineering
Authors: Biniazan Felor , Stoian Alina , Haykal Siba
Published: February 2024

Adipose tissue (AT) is a large and important energy storage organ as well as an endocrine organ with a critical role in many processes. Additionally, AT is an enormous and easily accessible source of multipotent cell types used in our day for all types of tissue regeneration. The ability of adipose-derived stem cells (ADSCs) to differentiate into other types of cells, such as endothelial cells (ECs), vascular smooth muscle cells, or cardiomyocytes, is used in tissue engineering in order to promote/stimulate the process of angiogenesis. Being a key for future successful clinical applications, functional vascular networks in engineered tissue are targeted by numerous in vivo and ex vivo studies. The article reviews the angiogenic potential of ADSCs and explores their capacity in the field of tissue engineering (TE).
Generating Potential RET-Specific Inhibitors Using a Novel LSTM Encoder–Decoder Model
Authors: Liu Lu , Zhao Xi , Huang Xuri
Published: February 2024

The receptor tyrosine kinase RET (rearranged during transfection) plays a vital role in various cell signaling pathways and is a critical factor in the development of the nervous system. Abnormal activation of the RET kinase can lead to several cancers, including thyroid cancer and non-small-cell lung cancer. However, most RET kinase inhibitors are multi-kinase inhibitors. Therefore, the development of an effective RET-specific inhibitor continues to present a significant challenge. To address this issue, we built a molecular generation model based on fragment-based drug design (FBDD) and a long short-term memory (LSTM) encoder–decoder structure to generate receptor-specific molecules with novel scaffolds. Remarkably, our model was trained with a molecular assembly accuracy of 98.4%. Leveraging the pre-trained model, we rapidly generated a RET-specific-candidate active-molecule library by transfer learning. Virtual screening based on our molecular generation model was performed, combined with molecular dynamics simulation and binding energy calculation, to discover specific RET inhibitors, and five novel molecules were selected. Further analyses indicated that two of these molecules have good binding affinities and synthesizability, exhibiting high selectivity. Overall, this investigation demonstrates the capacity of our model to generate novel receptor-specific molecules and provides a rapid method to discover potential drugs.
Cisplatin Toxicity Causes Neutrophil-Mediated Inflammation in Zebrafish Larvae
Authors: Padovani Barbara Nunes , Morales Fénero Camila , Paredes Lais Cavalieri , Amaral Mariana Abrantes do , Domínguez-Amorocho Omar , Cipelli Marcella , Gomes Juliana Moreira Mendonça , da Silva Eloisa Martins , Silva Luísa Menezes , Vieira Raquel de Souza , Pereira Mariana Tominaga , Cruz Mario Costa , Câmara Niels Olsen Saraiva
Published: February 2024

Cisplatin is an antineoplastic agent used to treat various tumors. In mammals, it can cause nephrotoxicity, tissue damage, and inflammation. The release of inflammatory mediators leads to the recruitment and infiltration of immune cells, particularly neutrophils, at the site of inflammation. Cisplatin is often used as an inducer of acute kidney injury (AKI) in experimental models, including zebrafish (Danio rerio), due to its accumulation in kidney cells. Current protocols in larval zebrafish focus on studying its effect as an AKI inducer but ignore other systematic outcomes. In this study, cisplatin was added directly to the embryonic medium to assess its toxicity and impact on systemic inflammation using locomotor activity analysis, qPCR, microscopy, and flow cytometry. Our data showed that larvae exposed to cisplatin at 7 days post-fertilization (dpf) displayed dose-dependent mortality and morphological changes, leading to a decrease in locomotion speed at 9 dpf. The expression of pro-inflammatory cytokines such as interleukin (il)-12, il6, and il8 increased after 48 h of cisplatin exposure. Furthermore, while a decrease in the number of neutrophils was observed in the glomerular region of the pronephros, there was an increase in neutrophils throughout the entire animal after 48 h of cisplatin exposure. We demonstrate that cisplatin can have systemic effects in zebrafish larvae, including morphological and locomotory defects, increased inflammatory cytokines, and migration of neutrophils from the hematopoietic niche to other parts of the body. Therefore, this protocol can be used to induce systemic inflammation in zebrafish larvae for studying new therapies or mechanisms of action involving neutrophils.
HIV Infection Drives Foam Cell Formation via NLRP3 Inflammasome Activation
Authors: Caocci Maurizio , Niu Meng , Fox Howard S. , Burdo Tricia H.
Published: February 2024

Persistent immune activation is linked to an increased risk of cardiovascular disease (CVD) in people with HIV (PWH) on antiretroviral therapy (ART). The NLRP3 inflammasome may contribute to elevated CVD risk in PWH. This study utilized peripheral blood mononuclear cells (PBMCs) from 25 PWH and 25 HIV-negative controls, as well as HIV in vitro infections. Transcriptional changes were analyzed using RNAseq and pathway analysis. Our results showed that in vitro HIV infection of macrophages and PBMCs from PWH had increased foam cell formation and expression of the NLRP3 inflammasome components and downstream cytokines (caspase-1, IL-1β, and IL-18), which was reduced with inhibition of NLRP3 activity using MCC950. Transcriptomic analysis revealed an increased expression of multiple genes involved in lipid metabolism, cholesterol storage, coronary microcirculation disorders, ischemic events, and monocyte/macrophage differentiation and function with HIV infection and oxLDL treatment. HIV infection and NLRP3 activation increased foam cell formation and expression of proinflammatory cytokines, providing insights into the mechanisms underlying HIV-associated atherogenesis. This study suggests that HIV itself may contribute to increased CVD risk in PWH. Understanding the involvement of the inflammasome pathway in HIV atherosclerosis can help identify potential therapeutic targets to mitigate cardiovascular risks in PWH.
Unraveling the Role of the NLRP3 Inflammasome in Lymphoma: Implications in Pathogenesis and Therapeutic Strategies
Authors: Stergiou Ioanna E. , Tsironis Christos , Papadakos Stavros P. , Tsitsilonis Ourania E. , Dimopoulos Meletios Athanasios , Theocharis Stamatios
Published: February 2024

Inflammasomes are multimeric protein complexes, sensors of intracellular danger signals, and crucial components of the innate immune system, with the NLRP3 inflammasome being the best characterized among them. The increasing scientific interest in the mechanisms interconnecting inflammation and tumorigenesis has led to the study of the NLRP3 inflammasome in the setting of various neoplasms. Despite a plethora of data regarding solid tumors, NLRP3 inflammasome’s implication in the pathogenesis of hematological malignancies only recently gained attention. In this review, we investigate its role in normal lymphopoiesis and lymphomagenesis. Considering that lymphomas comprise a heterogeneous group of hematologic neoplasms, both tumor-promoting and tumor-suppressing properties were attributed to the NLRP3 inflammasome, affecting neoplastic cells and immune cells in the tumor microenvironment. NLRP3 inflammasome-related proteins were associated with disease characteristics, response to treatment, and prognosis. Few studies assess the efficacy of NLRP3 inflammasome therapeutic targeting with encouraging results, though most are still at the preclinical level. Further understanding of the mechanisms regulating NLRP3 inflammasome activation during lymphoma development and progression can contribute to the investigation of novel treatment approaches to cover unmet needs in lymphoma therapeutics.
Effects of Nutraceutical Compositions Containing Rhizoma Gastrodiae or Lipoic Acid in an In Vitro Induced Neuropathic Pain Model
Authors: Ferrari Sara , Mulè Simone , Galla Rebecca , Brovero Arianna , Genovese Giulia , Molinari Claudio , Uberti Francesca
Published: February 2024

Background: Peripheral neuropathy is caused by a malfunction in the axons and myelin sheaths of peripheral nerves and motor and sensory neurons. In this context, nonpharmacological treatments with antioxidant potential have attracted much attention due to the issues that some conventional pharmaceutical therapy can generate. Most of these treatments contain lipoic acid, but issues have emerged regarding its use. Considering this, the present study evaluated the beneficial effects of nutraceuticals based on Gastrodiae elata dry extract 10:1 or lipoic acid in combination with other substances (such as citicholine, B vitamins, and acetyl L-carnitine). Method: To assess the combination’s absorption and biodistribution and exclude cytotoxicity, its bioavailability was first examined in a 3D intestinal barrier model that replicated oral ingestion. Subsequently, a 3D model of nerve tissue was constructed to investigate the impacts of the new combination on the significant pathways dysregulated in peripheral neuropathy. Results: Our findings show that the novel combination outperformed in initial pain relief response and in recovering the mechanism of nerve healing following Schwann cell injury by successfully crossing the gut barrier and reaching the target site. Conclusion: This article describes a potential alternative nutraceutical approach supporting the effectiveness of combinations with Gastrodiae elata extract in decreasing neuropathy and regulating pain pathways.
Nanostructured Coatings Based on Graphene Oxide for the Management of Periprosthetic Infections
Authors: Constantinescu Sorin , Niculescu Adelina-Gabriela , Hudiță Ariana , Grumezescu Valentina , Rădulescu Dragoș , Bîrcă Alexandra Cătălina , Dorcioman Gabriela , Gherasim Oana , Holban Alina Maria , Gălățeanu Bianca , Vasile Bogdan Ștefan , Grumezescu Alexandru Mihai , Bolocan Alexandra , Rădulescu Radu
Published: February 2024

To modulate the bioactivity and boost the therapeutic outcome of implantable metallic devices, biodegradable coatings based on polylactide (PLA) and graphene oxide nanosheets (nGOs) loaded with Zinforo™ (Zin) have been proposed in this study as innovative alternatives for the local management of biofilm-associated periprosthetic infections. Using a modified Hummers protocol, high-purity and ultra-thin nGOs have been obtained, as evidenced by X-ray diffraction (XRD) and transmission electron microscopy (TEM) investigations. The matrix-assisted pulsed laser evaporation (MAPLE) technique has been successfully employed to obtain the PLA-nGO-Zin coatings. The stoichiometric and uniform transfer was revealed by infrared microscopy (IRM) and scanning electron microscopy (SEM) studies. In vitro evaluation, performed on fresh blood samples, has shown the excellent hemocompatibility of PLA-nGO-Zin-coated samples (with a hemolytic index of 1.15%), together with their anti-inflammatory ability. Moreover, the PLA-nGO-Zin coatings significantly inhibited the development of mature bacterial biofilms, inducing important anti-biofilm efficiency in the as-coated samples. The herein-reported results evidence the promising potential of PLA-nGO-Zin coatings to be used for the biocompatible and antimicrobial surface modification of metallic implants.
Induced Pluripotent Stem Cells in Drug Discovery and Neurodegenerative Disease Modelling
Authors: Beghini Daniela Gois , Kasai-Brunswick Tais Hanae , Henriques-Pons Andrea
Published: February 2024

Induced pluripotent stem cells (iPSCs) are derived from reprogrammed adult somatic cells. These adult cells are manipulated in vitro to express genes and factors essential for acquiring and maintaining embryonic stem cell (ESC) properties. This technology is widely applied in many fields, and much attention has been given to developing iPSC-based disease models to validate drug discovery platforms and study the pathophysiological molecular processes underlying disease onset. Especially in neurological diseases, there is a great need for iPSC-based technological research, as these cells can be obtained from each patient and carry the individual’s bulk of genetic mutations and unique properties. Moreover, iPSCs can differentiate into multiple cell types. These are essential characteristics, since the study of neurological diseases is affected by the limited access to injury sites, the need for in vitro models composed of various cell types, the complexity of reproducing the brain’s anatomy, the challenges of postmortem cell culture, and ethical issues. Neurodegenerative diseases strongly impact global health due to their high incidence, symptom severity, and lack of effective therapies. Recently, analyses using disease specific, iPSC-based models confirmed the efficacy of these models for testing multiple drugs. This review summarizes the advances in iPSC technology used in disease modelling and drug testing, with a primary focus on neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases.
The Role of Glucose-6-phosphate Dehydrogenase in the Wine Yeast Hanseniaspora uvarum
Authors: Heinisch Jürgen J. , Murra Andrea , Fernández Murillo Lucía , Schmitz Hans-Peter
Published: February 2024

Hanseniaspora uvarum is the predominant yeast species in the majority of wine fermentations, which has only recently become amenable to directed genetic manipulation. The genetics and metabolism of H. uvarum have been poorly studied as compared to other yeasts of biotechnological importance. This work describes the construction and characterization of homozygous deletion mutants in the HuZWF1 gene, encoding glucose-6-phosphate dehydrogenase (G6PDH), which provides the entrance into the oxidative part of the pentose phosphate pathway (PPP) and serves as a major source of NADPH for anabolic reactions and oxidative stress response. Huzwf1 deletion mutants grow more slowly on glucose medium than wild-type and are hypersensitive both to hydrogen peroxide and potassium bisulfite, indicating that G6PDH activity is required to cope with these stresses. The mutant also requires methionine for growth. Enzyme activity can be restored by the expression of heterologous G6PDH genes from other yeasts and humans under the control of a strong endogenous promoter. These findings provide the basis for a better adaptation of H. uvarum to conditions used in wine fermentations, as well as its use for other biotechnological purposes and as an expression organism for studying G6PDH functions in patients with hemolytic anemia.
The Molecular Mechanism of Body Axis Induction in Lampreys May Differ from That in Amphibians
Authors: Ermakova Galina V. , Kucheryavyy Aleksandr V. , Zaraisky Andrey G. , Bayramov Andrey V.
Published: February 2024

Lamprey homologues of the classic embryonic inducer Noggin are similar in expression pattern and functional properties to Noggin homologues of jawed vertebrates. All noggin genes of vertebrates apparently originated from a single ancestral gene as a result of genome duplications. nogginA, nogginB and nogginC of lampreys, like noggin1 and noggin2 of gnathostomes, demonstrate the ability to induce complete secondary axes with forebrain and eye structures when overexpressed in Xenopus laevis embryos. According to current views, this finding indicates the ability of lamprey Noggin proteins to suppress the activity of the BMP, Nodal/Activin and Wnt/beta-catenin signaling pathways, as shown for Noggin proteins of gnathostomes. In this work, by analogy with experiments in Xenopus embryos, we attempted to induce secondary axes in the European river lamprey Lampetra fluviatilis by injecting noggin mRNAs into lamprey eggs in vivo. Surprisingly, unlike what occurs in amphibians, secondary axis induction in the lampreys either by noggin mRNAs or by chordin and cerberus mRNAs, the inductive properties of which have been described, was not observed. Only wnt8a mRNA demonstrated the ability to induce secondary axes in the lampreys. Such results may indicate that the mechanism of axial specification in lampreys, which represent jawless vertebrates, may differ in detail from that in the jawed clade.
Ex Vivo Optimization of Donor Lungs with Inhaled Sevoflurane during Normothermic Ex Vivo Lung Perfusion (VITALISE): A Pilot and Feasibility Study in Sheep
Authors: Steinkühler Timo , Yang Shuqi , Hu Michiel A. , Jainandunsing Jayant S. , Jager Neeltina M. , Erasmus Michiel E. , Struys Michel M. R. F. , Bosch Dirk J. , van Meurs Matijs , Jabaudon Matthieu , Richard Damien , Timens Wim , Leuvenink Henri G. D. , Nieuwenhuijs-Moeke Gertrude J.
Published: February 2024

Volatile anesthetics have been shown in different studies to reduce ischemia reperfusion injury (IRI). Ex vivo lung perfusion (EVLP) facilitates graft evaluation, extends preservation time and potentially enables injury repair and improvement of lung quality. We hypothesized that ventilating lungs with sevoflurane during EVLP would reduce lung injury and improve lung function. We performed a pilot study to test this hypothesis in a slaughterhouse sheep DCD model. Lungs were harvested, flushed and stored on ice for 3 h, after which EVLP was performed for 4 h. Lungs were ventilated with either an FiO2 of 0.4 (EVLP, n = 5) or FiO2 of 0.4 plus sevoflurane at a 2% end-tidal concentration (Cet) (S-EVLP, n = 5). Perfusate, tissue samples and functional measurements were collected and analyzed. A steady state of the target Cet sevoflurane was reached with measurable concentrations in perfusate. Lungs in the S-EVLP group showed significantly better dynamic lung compliance than those in the EVLP group (p = 0.003). Oxygenation capacity was not different in treated lungs for delta partial oxygen pressure (PO2; +3.8 (−4.9/11.1) vs. −11.7 (−12.0/−3.2) kPa, p = 0.151), but there was a trend of a better PO2/FiO2 ratio (p = 0.054). Perfusate ASAT levels in S-EVLP were significantly reduced compared to the control group (198.1 ± 93.66 vs. 223.9 ± 105.7 IU/L, p = 0.02). We conclude that ventilating lungs with sevoflurane during EVLP is feasible and could be useful to improve graft function.
The Role of the Endocrine System in the Regulation of Acid–Base Balance by the Kidney and the Progression of Chronic Kidney Disease
Authors: Nagami Glenn T. , Kraut Jeffrey A.
Published: February 2024

Systemic acid–base status is primarily determined by the interplay of net acid production (NEAP) arising from metabolism of ingested food stuffs, buffering of NEAP in tissues, generation of bicarbonate by the kidney, and capture of any bicarbonate filtered by the kidney. In chronic kidney disease (CKD), acid retention may occur when dietary acid production is not balanced by bicarbonate generation by the diseased kidney. Hormones including aldosterone, angiotensin II, endothelin, PTH, glucocorticoids, insulin, thyroid hormone, and growth hormone can affect acid–base balance in different ways. The levels of some hormones such as aldosterone, angiotensin II and endothelin are increased with acid accumulation and contribute to an adaptive increase in renal acid excretion and bicarbonate generation. However, the persistent elevated levels of these hormones can damage the kidney and accelerate progression of CKD. Measures to slow the progression of CKD have included administration of medications which inhibit the production or action of deleterious hormones. However, since metabolic acidosis accompanying CKD stimulates the secretion of several of these hormones, treatment of CKD should also include administration of base to correct the metabolic acidosis.
Formal Security Analysis of ISA100.11a Standard Protocol Based on Colored Petri Net Tool
Authors: Feng Tao , Chen Taining , Gong Xiang
Published: February 2024

This paper presents a formal security analysis of the ISA100.11a standard protocol using the Colored Petri Net (CPN) modeling approach. Firstly, we establish a security threat model for the ISA100.11a protocol and provide a detailed description and analysis of the identified security threats. Secondly, we use the CPN tool to model the protocol formally and conduct model checking and security analysis. Finally, we analyze and discuss the results of the model checking, which demonstrate that the ISA100.11a standard protocol may have vulnerabilities when certain security threats exist, and provide some suggestions to enhance the security of the protocol. This research provides a certain level of security assurance for the ISA100.11a standard protocol and serves as a reference for similar security research on protocols.
Shape Matters: Detecting Vertebral Fractures Using Differentiable Point-Based Shape Decoding
Authors: Hempe Hellena , Bigalke Alexander , Heinrich Mattias Paul
Published: February 2024

Background: Degenerative spinal pathologies are highly prevalent among the elderly population. Timely diagnosis of osteoporotic fractures and other degenerative deformities enables proactive measures to mitigate the risk of severe back pain and disability. Methods: We explore the use of shape auto-encoders for vertebrae, advancing the state of the art through robust automatic segmentation models trained without fracture labels and recent geometric deep learning techniques. Our shape auto-encoders are pre-trained on a large set of vertebrae surface patches. This pre-training step addresses the label scarcity problem faced when learning the shape information of vertebrae for fracture detection from image intensities directly. We further propose a novel shape decoder architecture: the point-based shape decoder. Results: Employing segmentation masks that were generated using the TotalSegmentator, our proposed method achieves an AUC of 0.901 on the VerSe19 testset. This outperforms image-based and surface-based end-to-end trained models. Our results demonstrate that pre-training the models in an unsupervised manner enhances geometric methods like PointNet and DGCNN. Conclusion: Our findings emphasize the advantages of explicitly learning shape features for diagnosing osteoporotic vertebrae fractures. This approach improves the reliability of classification results and reduces the need for annotated labels.
De Novo Genome Assembly at Chromosome-Scale of Hermetia illucens (Diptera Stratiomyidae) via PacBio and Omni-C Proximity Ligation Technology
Authors: Costagli Simone , Abenaim Linda , Rosini Giulia , Conti Barbara , Giovannoni Roberto
Published: February 2024

Hermetia illucens is a species of great interest for numerous industrial applications. A high-quality reference genome is already available for H. illucens. However, the worldwide maintenance of numerous captive populations of H. illucens, each with its own genotypic and phenotypic characteristics, made it of interest to perform a de novo genome assembly on one population of H. illucens to define a chromosome-scale genome assembly. By combining the PacBio and the Omni-C proximity ligation technologies, a new H. illucens chromosome-scale genome of 888.59 Mb, with a scaffold N50 value of 162.19 Mb, was assembled. The final chromosome-scale assembly obtained a BUSCO completeness of 89.1%. By exploiting the Omni-C proximity ligation technology, topologically associated domains and other topological features that play a key role in the regulation of gene expression were identified. Further, 65.62% of genomic sequences were masked as repeated sequences, and 32,516 genes were annotated using the MAKER pipeline. The H. illucens Lsp-2 genes that were annotated were further characterized, and the three-dimensional organization of the encoded proteins was predicted. A new chromosome-scale genome assembly of good quality for H. illucens was assembled, and the genomic annotation phase was initiated. The availability of this new chromosome-scale genome assembly enables the further characterization, both genotypically and phenotypically, of a species of interest for several biotechnological applications.
Transcriptomics Provide Insights into the Photoperiodic Regulation of Reproductive Diapause in the Green Lacewing, Chrysoperla nipponensis (Okamoto) (Neuroptera: Chrysopidae)
Authors: Liu Shaoye , Gao Yuqing , Shi Rangjun , Huang Haiyi , Xu Yongyu , Chen Zhenzhen
Published: February 2024

Chrysoperla nipponensis (Okamoto) displays typical adult reproductive diapause under short photoperiods; however, our understanding of the molecular mechanism underlying photoperiod-sensitive reproduction remains limited. In this study, we performed transcriptome profiling of four treatments (the diapause-sensitive stage and pre-diapause phase under long and short photoperiods) of C. nipponensis using RNA sequencing (RNA-seq). A total of 71,654 unigenes were obtained from the samples. Enrichment analysis showed that fatty acid metabolism-related pathways were altered under a short photoperiod. Moreover, β-oxidation-related gene expression was active during the diapause-sensitive period under a short photoperiod. The knockdown of juvenile hormone acid methyltransferase 1 (Jhamt1) prolonged the pre-oviposition period but did not affect the reproductive ability of female individuals in C. nipponensis. These findings provided us with a more comprehensive understanding of the molecular mechanisms of photoperiod-sensitive diapause and show that groundwork is crucial for bolstering the long-term storage and biocontrol potential of C. nipponensis.
Comparative Transcriptomics Analysis Reveals Rusty Grain Beetle’s Aggregation Pheromone Biosynthesis Mechanism in Response to Starvation
Authors: Zeng Fangfang , Jiang Haixin , Xu Haoqi , Shen Ruotong , Wang Dianxuan
Published: February 2024

Pheromones are the basis of insect aggregation, mating, and other behaviors. Cucujoid grain beetles produce macrocyclic lactones as aggregation pheromones, yet research on their biosynthesis at the molecular level remains limited. The rusty grain beetle, C. ferrugineus, is an important economic species in China. Although two aggregation pheromone components have been identified, their suspected biosynthesis via the MVA pathway and the FAS pathway lacks molecular elucidation. Previous evidence supports that starvation affects the production of aggregation pheromones. Therefore, we constructed comparative transcriptome libraries of pheromone production sites in C. ferrugineus under starvation stress and identified genes related to pheromone biosynthesis and hormone regulation. A total of 2665 genes were significantly differentially expressed, of which 2029 genes were down-regulated in starved beetles. Putative C. ferrugineus genes directly involved in pheromone biosynthesis were identified, as well as some genes related to the juvenile hormone (JH) pathway and the insulin pathway, both of which were depressed in the starved beetles, suggesting possible functions in pheromone biosynthesis and regulation. The identification of genes involved in macrolide lactone biosynthesis in vivo holds great significance, aiding in the elucidation of the synthesis and regulatory mechanisms of cucujoid grain beetle pheromones.
Continuous Erector Spinae Plane Block for Pain Management in a Pediatric Kidney Transplant Recipient: A Case Report and Review of the Current Literature
Authors: Capuano Paolo , Burgio Gaetano , Abbate Serena , Ranucci Giusy , Bici Kejd , Cintorino Davide , Arcadipane Antonio , Martucci Gennaro
Published: February 2024

Pain management in patients undergoing kidney transplantation requires careful consideration due to their altered physiology, and potential risks associated with certain analgesic options. In recent years, personalized and multimodal approaches have proven to be pivotal in perioperative pain management, as well as in children. Implementing regional analgesia methods offers a valuable solution in many pediatric surgical settings and the erector spinae plane block (ESPB) could represent a possible analgesic strategy in pediatric patients undergoing renal transplantation. Here, we report the case of a 13-year-old child who underwent living-donor kidney transplantation (LDKx) and received continuous erector spinae plane block (ESPB) for perioperative pain management. This multimodal approach with continuous ESPB resulted in optimal pain control without the need for opioids, allowing for early mobilization and for an optimal postoperative course.
Weight Regain after Metabolic Surgery: Beyond the Surgical Failure
Authors: Salazar Juan , Duran Pablo , Garrido Bermary , Parra Heliana , Hernández Marlon , Cano Clímaco , Añez Roberto , García-Pacheco Henry , Cubillos Gabriel , Vasquez Neidalis , Chacin Maricarmen , Bermúdez Valmore
Published: February 2024

Patients undergoing metabolic surgery have factors ranging from anatomo-surgical, endocrine metabolic, eating patterns and physical activity, mental health and psychological factors. Some of the latter can explain the possible pathophysiological neuroendocrine, metabolic, and adaptive mechanisms that cause the high prevalence of weight regain in postbariatric patients. Even metabolic surgery has proven to be effective in reducing excess weight in patients with obesity; some of them regain weight after this intervention. In this vein, several studies have been conducted to search factors and mechanisms involved in weight regain, to stablish strategies to manage this complication by combining metabolic surgery with either lifestyle changes, behavioral therapies, pharmacotherapy, endoscopic interventions, or finally, surgical revision. The aim of this revision is to describe certain aspects and mechanisms behind weight regain after metabolic surgery, along with preventive and therapeutic strategies for this complication.
Navigating the Spectrum of Two Pediatric COVID-19 Complications: Multi-System Inflammatory Syndrome in Children and Post-Acute Sequelae of SARS-CoV-2 Infection
Authors: Parzen-Johnson Simon , Katz Ben Z
Published: February 2024

Purpose: This review summarizes the current scope of understanding associated with two common post-infectious complications associated with COVID-19 infection: Multi-System Inflammatory Syndrome in Children (MIS-C) and Post-Acute Sequelae of SARS-CoV-2 infection (PASC). It identifies current gaps in the knowledge and issues that may limit the ability to fill these gaps. This review provides a framework to drive continued research. Methods: A comprehensive review of the current literature was performed, identifying seminal articles describing the emergence of MIS-C and PASC, and works from the literature focused on the clinical implications and pathophysiologic understanding of these disorders. Findings: Although pediatric patients experienced few severe cases of acute COVID-19 infection, the burden of disease from post-infectious sequelae is substantial. Mortality is low, but morbidity is significant. There are still numerous unknowns about the pathophysiology of both MIS-C and PASC; however, with widespread immunity developing after increased vaccination and prior infection, it may be difficult to perform adequate prospective studies to answer pathophysiologic questions. Long-term sequalae of MIS-C seem to be minimal whereas, by definition, PASC is an ongoing problem and may be severe. Implications: The rapid sharing of information regarding novel conditions such as MIS-C and PASC are key to interventions related to future post-infectious sequelae outside of those stemming from COVID-19. Although MIS-C seems unlikely to return as a clinical condition in substantial numbers, there is still significant learning that can be gleaned from existing patients about general aspects of epidemiology, equity, and pathophysiology. There is significant morbidity associated with PASC and additional resources need to be dedicated to determining appropriate and effective therapies moving forward.
Immuno-Diagnostic Interest in Monitoring CD16+CD56+ (Natural Killer) Cells and CD19+CD45+ (B Lymphocytes) in Individuals Newly Diagnosed with HIV in a Tertiary Care Center
Authors: Al-Mughales Jamil
Published: February 2024

Background/Objective: Monitoring multiple cellular markers of immune cells may provide a more accurate evaluation of the immune status of people living with human immunodeficiency virus (PLHIV). This study assessed the value of CD16+CD56+ cells (NK cells) and CD19+ lymphocytes (B cells) phenotyping in indicating viral load, AIDS status, and treatment efficacy. Method: A retrospective, laboratory-based study was conducted at the Diagnostic immunology division of a referral tertiary hospital. It involved 82 newly diagnosed HIV patients treated between 2009–2016. We explored three objectives: (1) the paired change in CD16+CD56+ and CD19+CD45+ cells counts and percentages from baseline to 2-to-6 months after treatment; (2) the association of these phenotypes with 5 gradual categories of viral load; and (3) the accuracy of CD16+CD56+ and CD19+CD45+ cells counts in indicating AIDS stage defined as CD4+ < 200 cells/mm3. The second and third objectives were tested using a pooled analysis (N = 300–373). Result: The median CD19+CD45+ and CD16+CD56+ counts increased by 1.9-fold and 1.3-fold after treatment respectively (p < 0.001). A negative correlation of viral load with both CD16+CD56+ (ρ = −0.29, p < 0.001) and CD19+CD45+ (ρ = −0.34, p < 0.001) counts was observed. CD16+CD56+ count < 73 cells/mm3 and CD19+CD45+ count < 166.5 were indicative for AIDS with 95.5% and 63.6% sensitivity respectively. Conclusions: Findings advocate for the usefulness of CD16+CD56+ and CD19+CD45+ phenotyping in characterizing the severity of HIV infection and its impact on both the humoral and cellular immunity, as well as monitoring the effectiveness of treatment.
Correction: Akbarpour et al. Dyslipidemia Treatment and Lipid Control in US Adults with Diabetes by Sociodemographic and Cardiovascular Risk Groups in the NIH Precision Medicine Initiative All of Us Research Program. J. Clin. Med. 2023, 12, 1668
Authors: Akbarpour Meleeka , Devineni Divya , Gong Yufan , Wong Nathan D.
Published: February 2024

In the original publication [...]
Linear IgA Bullous Dermatosis in Korea Using the Nationwide Health Insurance Database
Authors: Kim Yu Rim , Kim Ji Hyeon , Kim Sang Won , Lee Jae Min , Bae Jacob S.
Published: February 2024

(1) Background: Linear immunoglobulin A bullous dermatosis (LABD) is a rare autoimmune, subepidermal blistering disease, characterized by linear IgA deposits along the epidermal basement membrane. LABD is idiopathic and is associated with medication and systemic autoimmune diseases. (2) Methods: We investigated the demographic characteristics, disease course, causative agents, and associated diseases in Korean patients with LABD. The Korean Health Insurance Review and Assessment Service database was used to obtain data. We identified 670 LABD cases between 2010 and 2022. (3) Results: The annual incidence of LABD was 1.3 per 100,000 persons, with a higher prevalence in individuals ≥60 years old. The patients were treated with dapsone for 30.7 ± 56.7 days, had 1.3 ± 0.7 hospital visits, and were hospitalized for 19.8 ± 19.7 days. Risk factors, including malignancy, commonly preceded LABD. Antibiotic use, specifically vancomycin and third-generation cephalosporins, was a risk factor. The mean age of LABD diagnosis was 55.9 ± 21.7 years. (4) Conclusion: This is the first published study to assess a nationwide cohort for LABD. The incidence of LABD was higher than that in other studies. Most case reports have linked LABD with the administration of specific antibiotics; however, this study shows there were more associations with other conditions.