bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Identification, Expression, and Response to Fusarium Infection of the SWEET Gene Family in Garlic (Allium sativum L.)
Authors: Filyushin Mikhail A. , Anisimova Olga K. , Shchennikova Anna V. , Kochieva Elena Z.
Published: April 2023

Proteins of the SWEET (Sugar Will Eventually be Exported Transporters) family play an important role in plant development, adaptation, and stress response by functioning as transmembrane uniporters of soluble sugars. However, the information on the SWEET family in the plants of the Allium genus, which includes many crop species, is lacking. In this study, we performed a genome-wide analysis of garlic (Allium sativum L.) and identified 27 genes putatively encoding clade I–IV SWEET proteins. The promoters of the A. sativum (As) SWEET genes contained hormone- and stress-sensitive elements associated with plant response to phytopathogens. AsSWEET genes had distinct expression patterns in garlic organs. The expression levels and dynamics of clade III AsSWEET3, AsSWEET9, and AsSWEET11 genes significantly differed between Fusarium-resistant and -susceptible garlic cultivars subjected to F. proliferatum infection, suggesting the role of these genes in the garlic defense against the pathogen. Our results provide insights into the role of SWEET sugar uniporters in A. sativum and may be useful for breeding Fusarium-resistant Allium cultivars.
Sickle Cell Hemoglobin Genotypes Affect Malaria Parasite Growth and Correlate with Exosomal miR-451a and let-7i-5p Levels
Authors: Oxendine Harp Keri , Bashi Alaijah , Botchway Felix , Addo-Gyan Daniel , Tetteh-Tsifoanya Mark , Lamptey Amanda , Djameh Georgina , Iqbal Shareen A. , Lekpor Cecilia , Banerjee Saswati , Wilson Michael D. , Dei-Adomakoh Yvonne , Adjei Andrew A. , Stiles Jonathan K. , Driss Adel
Published: April 2023

Malaria affects a significant portion of the global population, with 247 million cases in 2021, primarily in Africa. However, certain hemoglobinopathies, such as sickle cell trait (SCT), have been linked to lower mortality rates in malaria patients. Hemoglobin (Hb) mutations, including HbS and HbC, can cause sickle cell disease (SCD) when both alleles are inherited (HbSS and HbSC). In SCT, one allele is inherited and paired with a normal allele (HbAS, HbAC). The high prevalence of these alleles in Africa may be attributed to their protective effect against malaria. Biomarkers are crucial for SCD and malaria diagnosis and prognosis. Studies indicate that miRNAs, specifically miR-451a and let-7i-5p, are differentially expressed in HbSS and HbAS compared to controls. Our research examined the levels of exosomal miR-451a and let-7i-5p in red blood cells (RBCs) and infected red blood cells (iRBCs) from multiple sickle Hb genotypes and their impact on parasite growth. We assessed exosomal miR-451a and let-7i-5p levels in vitro in RBC and iRBC supernatants. Exosomal miRNAs exhibited distinct expression patterns in iRBCs from individuals with different sickle Hb genotypes. Additionally, we discovered a correlation between let-7i-5p levels and trophozoite count. Exosomal miR-451a and let-7i-5p could modulate SCD and malaria severity and serve as potential biomarkers for malaria vaccines and therapies.
In Silico Design of a Chimeric Humanized L-asparaginase
Authors: Pedroso Alejandro , Herrera Belén Lisandra , Beltrán Jorge F. , Castillo Rodrigo L. , Pessoa Adalberto , Pedroso Enrique , Farías Jorge G.
Published: April 2023

Acute lymphoblastic leukemia (ALL) is the most common cancer among children worldwide, characterized by an overproduction of undifferentiated lymphoblasts in the bone marrow. The treatment of choice for this disease is the enzyme L-asparaginase (ASNase) from bacterial sources. ASNase hydrolyzes circulating L-asparagine in plasma, leading to starvation of leukemic cells. The ASNase formulations of E. coli and E. chrysanthemi present notorious adverse effects, especially the immunogenicity they generate, which undermine both their effectiveness as drugs and patient safety. In this study, we developed a humanized chimeric enzyme from E. coli L-asparaginase which would reduce the immunological problems associated with current L-asparaginase therapy. For these, the immunogenic epitopes of E. coli L-asparaginase (PDB: 3ECA) were determined and replaced with those of the less immunogenic Homo sapiens asparaginase (PDB:4O0H). The structures were modeled using the Pymol software and the chimeric enzyme was modeled using the SWISS-MODEL service. A humanized chimeric enzyme with four subunits similar to the template structure was obtained, and the presence of asparaginase enzymatic activity was predicted by protein–ligand docking.
Composite Hydrogels Based on Poly(Ethylene Glycol) and Cellulose Macromonomers as Fortified Materials for Environmental Cleanup and Clean Water Safeguarding
Authors: Getya Dariya , Lucas Alec , Gitsov Ivan
Published: April 2023

Pollution with organic dyes is one of the most typical environmental problems related to industrial wastewater. The removal of these dyes opens up new prospects for environmental remediation, but the design of sustainable and inexpensive systems for water purification is a fundamental challenge. This paper reports the synthesis of novel fortified hydrogels that can bind and remove organic dyes from aqueous solutions. These hydrophilic conetworks consist of chemically modified poly(ethylene glycol) (PEG-m) and multifunctional cellulose macromonomers (“cellu-mers”). Williamson etherification with 4-vinylbenzyl chloride (4-VBC) is used to modify PEGs of different molecular masses (1, 5, 6, and 10 kDa) and cellobiose, Sigmacell, or Technocell™ T-90 cellulose (products derived from natural renewable resources) with polymerizable/crosslinkable moieties. The networks are formed with good (75%) to excellent (96%) yields. They show good swelling and have good mechanical properties according to rheological tests. Scanning electron microscopy (SEM) reveals that cellulose fibers are visibly embedded into the inner hydrogel structure. The ability to bind and remove organic dyes, such as bromophenol blue (BPB), methylene blue (MB), and crystal violet (CV), from aqueous solutions hints at the potential of the new cellulosic hydrogels for environmental cleanup and clean water safeguarding.
Nanoscale Structural Comparison of Fibrillin-1 Microfibrils Isolated from Marfan and Non-Marfan Syndrome Human Aorta
Authors: Șulea Cristina M. , Mártonfalvi Zsolt , Csányi Csilla , Haluszka Dóra , Pólos Miklós , Ágg Bence , Stengl Roland , Benke Kálmán , Szabolcs Zoltán , Kellermayer Miklós S. Z.
Published: April 2023

Fibrillin-1 microfibrils are essential elements of the extracellular matrix serving as a scaffold for the deposition of elastin and endowing connective tissues with tensile strength and elasticity. Mutations in the fibrillin-1 gene (FBN1) are linked to Marfan syndrome (MFS), a systemic connective tissue disorder that, besides other heterogeneous symptoms, usually manifests in life-threatening aortic complications. The aortic involvement may be explained by a dysregulation of microfibrillar function and, conceivably, alterations in the microfibrils’ supramolecular structure. Here, we present a nanoscale structural characterization of fibrillin-1 microfibrils isolated from two human aortic samples with different FBN1 gene mutations by using atomic force microscopy, and their comparison with microfibrillar assemblies purified from four non-MFS human aortic samples. Fibrillin-1 microfibrils displayed a characteristic “beads-on-a-string” appearance. The microfibrillar assemblies were investigated for bead geometry (height, length, and width), interbead region height, and periodicity. MFS fibrillin-1 microfibrils had a slightly higher mean bead height, but the bead length and width, as well as the interbead height, were significantly smaller in the MFS group. The mean periodicity varied around 50–52 nm among samples. The data suggest an overall thinner and presumably more frail structure for the MFS fibrillin-1 microfibrils, which may play a role in the development of MFS-related aortic symptomatology.
β-Tricalcium Phosphate-Modified Aerogel Containing PVA/Chitosan Hybrid Nanospun Scaffolds for Bone Regeneration
Authors: Boda Róbert , Lázár István , Keczánné-Üveges Andrea , Bakó József , Tóth Ferenc , Trencsényi György , Kálmán-Szabó Ibolya , Béresová Monika , Sajtos Zsófi , D. Tóth Etelka , Deák Ádám , Tóth Adrienn , Horváth Dóra , Gaál Botond , Daróczi Lajos , Dezső Balázs , Ducza László , Hegedűs Csaba
Published: April 2023

Electrospinning has recently been recognized as a potential method for use in biomedical applications such as nanofiber-based drug delivery or tissue engineering scaffolds. The present study aimed to demonstrate the electrospinning preparation and suitability of β-tricalcium phosphate-modified aerogel containing polyvinyl alcohol/chitosan fibrous meshes (BTCP-AE-FMs) for bone regeneration under in vitro and in vivo conditions. The mesh physicochemical properties included a 147 ± 50 nm fibrous structure, in aqueous media the contact angles were 64.1 ± 1.7°, and it released Ca, P, and Si. The viability of dental pulp stem cells on the BTCP-AE-FM was proven by an alamarBlue assay and with a scanning electron microscope. Critical-size calvarial defects in rats were performed as in vivo experiments to investigate the influence of meshes on bone regeneration. PET imaging using 18F-sodium fluoride standardized uptake values (SUVs) detected 7.40 ± 1.03 using polyvinyl alcohol/chitosan fibrous meshes (FMs) while 10.72 ± 1.11 with BTCP-AE-FMs after 6 months. New bone formations were confirmed by histological analysis. Despite a slight change in the morphology of the mesh because of cross-linking, the BTCP-AE-FM basically retained its fibrous, porous structure and hydrophilic and biocompatible character. Our experiments proved that hybrid nanospun scaffold composite mesh could be a new experimental bone substitute bioactive material in future medical practice.
Epigenetic Reprogramming via Synergistic Hypomethylation and Hypoxia Enhances the Therapeutic Efficacy of Mesenchymal Stem Cell Extracellular Vesicles for Bone Repair
Authors: Man Kenny , Brunet Mathieu Y. , Lees Rebecca , Peacock Ben , Cox Sophie C.
Published: April 2023

Mesenchymal stem cells (MSCs) are a promising cell population for regenerative medicine applications, where paracrine signalling through the extracellular vesicles (EVs) regulates bone tissue homeostasis and development. MSCs are known to reside in low oxygen tension, which promotes osteogenic differentiation via hypoxia-inducible factor-1α activation. Epigenetic reprogramming has emerged as a promising bioengineering strategy to enhance MSC differentiation. Particularly, the process of hypomethylation may enhance osteogenesis through gene activation. Therefore, this study aimed to investigate the synergistic effects of inducing hypomethylation and hypoxia on improving the therapeutic efficacy of EVs derived from human bone marrow MSCs (hBMSCs). The effects of the hypoxia mimetic agent deferoxamine (DFO) and the DNA methyltransferase inhibitor 5-azacytidine (AZT) on hBMSC viability was assessed by quantifying the DNA content. The epigenetic functionality was evaluated by assessing histone acetylation and histone methylation. hBMSC mineralisation was determined by quantifying alkaline phosphate activity, collagen production and calcium deposition. EVs were procured from AZT, DFO or AZT/DFO-treated hBMSCs over a two-week period, with EV size and concentration defined using transmission electron microscopy, nanoflow cytometry and dynamic light scattering. The effects of AZT-EVs, DFO-EVs or AZT/DFO-EVs on the epigenetic functionality and mineralisation of hBMSCs were evaluated. Moreover, the effects of hBMSC-EVs on human umbilical cord vein endothelial cells (HUVECs) angiogenesis was assessed by quantifying pro-angiogenic cytokine release. DFO and AZT caused a time–dose dependent reduction in hBMSC viability. Pre-treatment with AZT, DFO or AZT/DFO augmented the epigenetic functionality of the MSCs through increases in histone acetylation and hypomethylation. AZT, DFO and AZT/DFO pre-treatment significantly enhanced extracellular matrix collagen production and mineralisation in hBMSCs. EVs derived from AZT/DFO-preconditioned hBMSCs (AZT/DFO-EVs) enhanced the hBMSC proliferation, histone acetylation and hypomethylation when compared to EVs derived from AZT-treated, DFO-treated and untreated hBMSCs. Importantly, AZT/DFO-EVs significantly increased osteogenic differentiation and mineralisation of a secondary hBMSC population. Furthermore, AZT/DFO-EVs enhanced the pro-angiogenic cytokine release of HUVECs. Taken together, our findings demonstrate the considerable utility of synergistically inducing hypomethylation and hypoxia to improve the therapeutic efficacy of the MSC-EVs as a cell-free approach for bone regeneration.
HIV Promotes Atherosclerosis via Circulating Extracellular Vesicle MicroRNAs
Authors: Da Fonseca Ferreira Andrea , Wei Jianqin , Zhang Lukun , Macon Conrad J. , Degnan Bernard , Jayaweera Dushyantha , Hare Joshua M. , Kolber Michael A. , Bellio Michael , Khan Aisha , Pan Yue , Dykxhoorn Derek M. , Wang Liyong , Dong Chunming
Published: April 2023

People living with HIV (PLHIV) are at a higher risk of having cerebrocardiovascular diseases (CVD) compared to HIV negative (HIVneg) individuals. The mechanisms underlying this elevated risk remains elusive. We hypothesize that HIV infection results in modified microRNA (miR) content in plasma extracellular vesicles (EVs), which modulates the functionality of vascular repairing cells, i.e., endothelial colony-forming cells (ECFCs) in humans or lineage negative bone marrow cells (lin− BMCs) in mice, and vascular wall cells. PLHIV (N = 74) have increased atherosclerosis and fewer ECFCs than HIVneg individuals (N = 23). Plasma from PLHIV was fractionated into EVs (HIVposEVs) and plasma depleted of EVs (HIV PLdepEVs). HIVposEVs, but not HIV PLdepEVs or HIVnegEVs (EVs from HIVneg individuals), increased atherosclerosis in apoE−/− mice, which was accompanied by elevated senescence and impaired functionality of arterial cells and lin− BMCs. Small RNA-seq identified EV-miRs overrepresented in HIVposEVs, including let-7b-5p. MSC (mesenchymal stromal cell)-derived tailored EVs (TEVs) loaded with the antagomir for let-7b-5p (miRZip-let-7b) counteracted, while TEVs loaded with let-7b-5p recapitulated the effects of HIVposEVs in vivo. Lin− BMCs overexpressing Hmga2 (a let-7b-5p target gene) lacking the 3′UTR and as such is resistant to miR-mediated regulation showed protection against HIVposEVs-induced changes in lin− BMCs in vitro. Our data provide a mechanism to explain, at least in part, the increased CVD risk seen in PLHIV.
Recombination of X-ray-Generated Radical Ion Pairs in Alkane Solution Assembles Optically Inaccessible Exciplexes from a Series of Perfluorinated para-Oligophenylenes with N,N-Dimethylaniline
Authors: Nikul’shin Pavel V. , Fedunov Roman G. , Kuibida Leonid V. , Maksimov Alexander M. , Glebov Evgeni M. , Stass Dmitri V.
Published: April 2023

We demonstrate that a series of perfluorinated para-oligophenylenes C6F5-(C6F4)n-C6F5 (n = 1–3) produce exciplexes with N,N-dimethylaniline (DMA) in degassed X-irradiated n-dodecane solutions. The optical characterization of the compounds shows that their short fluorescence lifetimes (ca. 1.2 ns) and UV-Vis absorption spectra, overlapping with the spectrum of DMA with molar absorption coefficients of 2.7–4.6 × 104 M−1cm−1, preclude the standard photochemical exciplex formation pathway via selective optical generation of the local excited state of the donor and its bulk quenching by the acceptor. However, under X-rays, the efficient assembly of such exciplexes proceeds via the recombination of radical ion pairs, which delivers the two partners close to each other and ensures a sufficient energy deposition. The exciplex emission is completely quenched by the equilibration of the solution with air, providing a lower bound of exciplex emission lifetime of ca. 200 ns. The recombination nature of the exciplexes is confirmed by the magnetic field sensitivity of the exciplex emission band inherited from the magnetic field sensitivity from the recombination of spin-correlated radical ion pairs. Exciplex formation in such systems is further supported by DFT calculations. These first exciplexes from fully fluorinated compounds show the largest known red shift of the exciplex emission from the local emission band, suggesting the potential of perfluoro compounds for optimizing optical emitters.
SELENOP rs3877899 Variant Affects the Risk of Developing Advanced Stages of Retinopathy of Prematurity (ROP)
Authors: Strauss Ewa , Januszkiewicz-Lewandowska Danuta , Sobaniec Alicja , Gotz-Więckowska Anna
Published: April 2023

The significance of selenoproteins for the incidence of prematurity and oxidative-damage-related diseases in premature newborns is poorly understood. The latter are at risk for ROP as well as BPD, IVH, PDA, RDS, and NEC, which is particularly high for newborns with extremely low gestational age (ELGA) and extremely low birth weight (ELBW). This study evaluates the hypothesis that variation in the selenoprotein-encoding genes SELENOP, SELENOS, and GPX4 affects the risk of ROP and other comorbidities. The study included infants born ≤ 32 GA, matched for onset and progression of ROP into three groups: no ROP, spontaneously remitting ROP, and ROP requiring treatment. SNPs were determined with predesigned TaqMan SNP genotyping assays. We found the association of the SELENOP rs3877899A allele with ELGA (defined as <28 GA), ROP requiring treatment, and ROP not responsive to treatment. The number of RBC transfusions, ELGA, surfactant treatment, and coexistence of the rs3877899A allele with ELGA were independent predictors of ROP onset and progression, accounting for 43.1% of the risk variation. In conclusion, the SELENOP rs3877899A allele associated with reduced selenium bioavailability may contribute to the risk of ROP and visual impairment in extremely preterm infants.
Local Immune Biomarker Expression Depending on the Uterine Microbiota in Patients with Idiopathic Infertility
Authors: Tapilskaya Natalya I. , Savicheva Alevtina M. , Shalepo Kira V. , Budilovskaya Olga V. , Gzgzyan Aleksandr M. , Bespalova Olesya N. , Khusnutdinova Tatiana A. , Krysanova Anna A. , Obedkova Kseniia V. , Safarian Galina Kh.
Published: April 2023

The endometrium has traditionally been considered sterile. Nowadays, active studies are performed on the female upper genital tract microbiota. Bacteria and/or viruses colonizing the endometrium are known to alter its functional properties, including receptivity and embryo implantation. Uterine cavity inflammation caused by microorganisms leads to disrupted cytokine expression, which, in turn, is mandatory for the successful implantation of the embryo. The present study assessed the vaginal and endometrial microbiota composition and its relation to the levels of cytokines produced by the endometrium in reproductive-aged women complaining of secondary infertility of unknown origin. The multiplex real-time PCR assay was applied for vaginal and endometrial microbiota analysis. The quantitative measurement of endometrial α-defensin (DEFa1), transforming growth factor (TGFβ1), and basic fibroblast growth factor (bFGF2) was carried out using the ELISA (Cloud-Clone Corporation (Katy, TX, USA; manufactured in Wuhan, China). A reliable decline in endometrial TGFβ1 and bFGF2 and an increase in DEFa1 were demonstrated in women with idiopathic infertility when compared to fertile patients. However, TGFβ1, bFGF2, and DEFa1 expression correlated reliably only with the presence of Peptostreptococcus spp. and HPV in the uterine cavity. The obtained results highlight the importance of local immune biomarker determination in the assessment of certain bacteria and viruses’ significance as causative agents of infertility.
The Effect of Sclerostin and Monoclonal Sclerostin Antibody Romosozumab on Osteogenesis and Osteoclastogenesis Mediated by Periodontal Ligament Fibroblasts
Authors: Pigeaud Karina E. , Rietveld Melanie L. , Witvliet Aster F. , Hogervorst Jolanda M. A. , Zhang Chen , Forouzanfar Tim , Bravenboer Nathalie , Schoenmaker Ton , de Vries Teun J.
Published: April 2023

Sclerostin is a bone formation inhibitor produced by osteocytes. Although sclerostin is mainly expressed in osteocytes, it was also reported in periodontal ligament (PDL) fibroblasts, which are cells that play a role in both osteogenesis and osteoclastogenesis. Here, we assess the role of sclerostin and its clinically used inhibitor, romosozumab, in both processes. For osteogenesis assays, human PDL fibroblasts were cultured under control or mineralizing conditions with increasing concentrations of sclerostin or romosozumab. For analyzing osteogenic capacity and alkaline phosphatase (ALP) activity, alizarin red staining for mineral deposition and qPCR of osteogenic markers were performed. Osteoclast formation was investigated in the presence of sclerostin or romosozumab and, in PDLs, in the presence of fibroblasts co-cultured with peripheral blood mononuclear cells (PBMCs). PDL-PBMC co-cultures stimulated with sclerostin did not affect osteoclast formation. In contrast, the addition of romosozumab slightly reduced the osteoclast formation in PDL-PBMC co-cultures at high concentrations. Neither sclerostin nor romosozumab affected the osteogenic capacity of PDL fibroblasts. qPCR analysis showed that the mineralization medium upregulated the relative expression of osteogenic markers, but this expression was barely affected when romosozumab was added to the cultures. In order to account for the limited effects of sclerostin or romosozumab, we finally compared the expression of SOST and its receptors LRP-4, -5, and -6 to the expression in osteocyte rich-bone. The expression of SOST, LRP-4, and LRP-5 was higher in osteocytes compared to in PDL cells. The limited interaction of sclerostin or romosozumab with PDL fibroblasts may relate to the primary biological function of the periodontal ligament: to primarily resist bone formation and bone degradation to the benefit of an intact ligament that is indented by every chew movement.
Circadian Disruption and Mental Health: The Chronotherapeutic Potential of Microbiome-Based and Dietary Strategies
Authors: Codoñer-Franch Pilar , Gombert Marie , Martínez-Raga José , Cenit María Carmen
Published: April 2023

Mental illness is alarmingly on the rise, and circadian disruptions linked to a modern lifestyle may largely explain this trend. Impaired circadian rhythms are associated with mental disorders. The evening chronotype, which is linked to circadian misalignment, is a risk factor for severe psychiatric symptoms and psychiatric metabolic comorbidities. Resynchronization of circadian rhythms commonly improves psychiatric symptoms. Furthermore, evidence indicates that preventing circadian misalignment may help reduce the risk of psychiatric disorders and the impact of neuro–immuno–metabolic disturbances in psychiatry. The gut microbiota exhibits diurnal rhythmicity, as largely governed by meal timing, which regulates the host’s circadian rhythms. Temporal circadian regulation of feeding has emerged as a promising chronotherapeutic strategy to prevent and/or help with the treatment of mental illnesses, largely through the modulation of gut microbiota. Here, we provide an overview of the link between circadian disruption and mental illness. We summarize the connection between gut microbiota and circadian rhythms, supporting the idea that gut microbiota modulation may aid in preventing circadian misalignment and in the resynchronization of disrupted circadian rhythms. We describe diurnal microbiome rhythmicity and its related factors, highlighting the role of meal timing. Lastly, we emphasize the necessity and rationale for further research to develop effective and safe microbiome and dietary strategies based on chrononutrition to combat mental illness.
Effects of Drought and Flooding on Phytohormones and Abscisic Acid Gene Expression in Kiwifruit
Authors: Wurms Kirstin V. , Reglinski Tony , Buissink Poppy , Ah Chee Annette , Fehlmann Christina , McDonald Stella , Cooney Janine , Jensen Dwayne , Hedderley Duncan , McKenzie Catherine , Rikkerink Erik H. A.
Published: April 2023

Environmental extremes, such as drought and flooding, are becoming more common with global warming, resulting in significant crop losses. Understanding the mechanisms underlying the plant water stress response, regulated by the abscisic acid (ABA) pathway, is crucial to building resilience to climate change. Potted kiwifruit plants (two cultivars) were exposed to contrasting watering regimes (water logging and no water). Root and leaf tissues were sampled during the experiments to measure phytohormone levels and expression of ABA pathway genes. ABA increased significantly under drought conditions compared with the control and waterlogged plants. ABA-related gene responses were significantly greater in roots than leaves. ABA responsive genes, DREB2 and WRKY40, showed the greatest upregulation in roots with flooding, and the ABA biosynthesis gene, NCED3, with drought. Two ABA-catabolic genes, CYP707A i and ii were able to differentiate the water stress responses, with upregulation in flooding and downregulation in drought. This study has identified molecular markers and shown that water stress extremes induced strong phytohormone/ABA gene responses in the roots, which are the key site of water stress perception, supporting the theory kiwifruit plants regulate ABA to combat water stress.
Power Control of Reed–Solomon-Coded OFDM Systems in Rayleigh Fading Channels
Authors: Kim Younggil
Published: April 2023

Power control in an RS-coded orthogonal frequency division multiplex (OFDM) system with error-and-erasure correction decoding in Rayleigh fading channels was investigated. The power of each symbol within a codeword was controlled to reduce the codeword error rate (WER). Several RS-coded OFDM systems with power control are proposed. The WERs of the proposed systems as a function of the signal-to-noise ratio per bit were derived. We found that channel inversion at the transmitter in combination with the erasure generation by ordering fading amplitudes at the receiver provided the lowest WER among the considered systems. Furthermore, the erasure generation by ordering fading amplitudes was found to be better than the erasure generation by comparing fading amplitudes with a threshold.
The Efficacy of Microfracture Combined with Extracorporeal Shock Wave Therapy for Treating Osteochondral Lesion of the Talus and the Quality of Regenerated Cartilage: A Retrospective Cohort Study and MRI Assessment
Authors: Li Jian , Ma Qiaozhi , Hou Jianlei , Liu Yufen , Lu Pengfei , Liu Pengwei , Zhang Zhongwen , Xing Gengyan
Published: April 2023

Background: osteochondral lesion of the talus (OLT) is a common disease in the physically active population, and extracorporeal shock wave therapy (ESWT) is a noninvasive treatment. We hypothesized that microfracture (MF) combined with ESWT may have great potential to become a novel combination treatment of OLT. Methods: the OLT patients who received MF + ESWT or MF + platelet-rich plasma (PRP) injection were retrospectively included, with a minimal follow up of 2y. The daily activating VAS, exercising VAS, and American Orthopedic Foot and Ankle Society Ankle-Hindfoot Score (AOFAS) were used to assess the efficacy and functional outcome, and ankle MRI T2 mapping was used to evaluate the quality of regenerated cartilage in the OLT patients. Results: only transient synovium-stimulated complications were found during the treatment sessions; the complication rate and daily activating VAS did not have differences between groups. MF + ESWT had a higher AOFAS and a lower T2 mapping value than MF + PRP at the 2y follow up. Conclusions: the MF + ESWT had superior efficacy for treating OLT, which resulted in better ankle function and more hyaline-like regenerated cartilage, superior to the traditional MF + PRP.
Lipidomics Reveals Elevated Plasmalogens in Women with Obesity Who Develop Preeclampsia
Authors: Williams Ian M. , Albertolle Matthew E. , Layden Alexander J. , Tao Sunny Y. , Fisher Susan J. , Gandley Robin E. , Roberts James M.
Published: April 2023

Objective: Preeclampsia (PE) is a prevalent pregnancy disorder worldwide with limited preventative treatments available. Obesity triples the risk for PE, yet only 10% of women with obesity develop PE. The factors that distinguish PE from uncomplicated pregnancies in the context of obesity have not been fully established. Methods: We studied a cohort of women with obesity throughout pregnancy to identify lipid mediators and/or biomarkers of PE. Blood samples were collected at each trimester and analyzed by both targeted lipidomics and standard lipid panels. Individual lipid species were compared by PE status at each trimester, as well as by self-identified race (Black vs. White) and fetal sex. Results: Standard lipid panels and clinical measurements revealed few differences between PE and uncomplicated pregnancies. Targeted lipidomics, however, identified plasmalogen, phosphatidylethanolamine, and free fatty acid species that were elevated in the third trimester of women with PE. Furthermore, race and trimester of pregnancy were considerable sources of plasma lipidomic variation in women with obesity. Conclusions: First and second trimester individual plasma lipid species do not predict the development of PE in obese women. In the third trimester, PE patients have elevated levels of plasmalogens—a class of lipoprotein-associated phospholipids that have been implicated in the response to oxidative stress.
Is Continuous Wound Infiltration a Better Option for Postoperative Pain Management after Open Nephrectomy Compared to Thoracic Epidural Analgesia?
Authors: Crettenand François , Assayed-Leonardi Nady , Rohrer Felix , Martinez Carrique Silvia , Roth Beat
Published: April 2023

Background: Despite increasingly advanced minimally invasive percutaneous ablation techniques, surgery remains the only evidence-based therapy in curative intent for larger (>3–4 cm) renal tumors. Although minimally invasive surgery using (robotic-assisted) laparoscopic or retroperitoneoscopic approaches has gained popularity, open nephrectomy (ON) is still performed in 25% of cases, especially in tumors with central localization (partial ON) or large tumors with/without cava thrombus (total ON). As postoperative pain is one of the drawbacks of ON, our study aims to assess recovery and post-operative pain management using continuous wound infiltration (CWI) compared to thoracic epidural analgesia (TEA). Methods: Since 2012, all patients undergoing ON at our tertiary cancer center at CHUV have been included in our prospective ERAS® (enhanced recovery after surgery) registry that is centrally stored in ERAS® Interactive Audit System (EIAS) secured server. This study represents an analysis of all patients operated on with partial or total ON at our center between 2012 and 2022. An additional analysis was performed for the estimations of the total cost of CWI and TEA, based on the diagnosis-related group method. Results: 92 patients were included and analyzed in this analysis (n = 64 (70%) with CWI; n = 28 (30%) with TEA). Adequate oral pain control was earlier achieved in the CWI group compared to the TEA group (median 3 vs. 4 days; p = 0.001), whereas immediate postoperative pain relief was better in the TEA group (p = 0.002). Consequently, opioid use was higher in the CWI group (p = 0.004). Still, reported nausea was lower in the CWI group (p = 0.002). Median time to bowel recovery was similar in both groups (p = 0.03). A shorter LOS (0.5 days) was observed in patients managed with CWI, although this was not statistically significant (p = 0.06). The use of CWI has reduced total hospital costs by nearly 40%. Conclusions: TEA has better results in terms of postoperative pain management compared to CWI following ON. However, CWI is better tolerated, and causes less nausea and earlier recovery, which leads to a shorter length of stay. Given its simplicity and cost-effectiveness, CWI should be encouraged for ON.
A Multi-Centre Randomized Controlled Trial Comparing Connective Tissue Graft with Collagen Matrix to Increase Buccal Soft Tissue Thickness: A Cone-Beam CT Analysis
Authors: Eeckhout Célien , Vuylsteke Fauve , Seyssens Lorenz , Christiaens Véronique , De Bruyckere Thomas , Eghbali Aryan , Vervaeke Stijn , Younes Faris , Cosyn Jan
Published: April 2023

(1) Aim: a cross-linked porcine-derived collagen matrix (CMX) has been developed for soft tissue augmentation. Although this grafting material does not require a second surgical site, recent findings have indicated deeper pockets, more marginal bone loss and more midfacial recession in the short term when compared to connective tissue graft (CTG). Hence, the aim of the present study was to evaluate the safety of CMX based on buccal bone loss over a one-year period. (2) Methods: Patients who were missing a single tooth in the anterior maxilla were included, in whom the failing tooth had been removed at least 3 months prior and who presented a horizontal mucosa defect. All sites had a bucco-palatal bone dimension of at least 6 mm as assessed on Cone-Beam Computed Tomography (CBCT) to ensure complete embedding of an implant by bone. All patients received a single implant and an immediate implant restoration using a full digital workflow. Sites were randomly allocated to the control (CTG) or test group (CMX) to increase buccal soft tissue thickness. All surgeries were performed by means of full thickness mucoperiosteal flap elevation, placing CTG and CMX in contact with the buccal bone wall. Safety was assessed by evaluating the impact of CTG and CMX on buccal bone loss over a one-year period using superimposed CBCT scans. (3) Results: thirty patients were included per group (control: 50% females, mean age 50; test: 53% females, mean age 48) and 51 (control: 25; test: 26) could be analyzed for buccal bone loss. At 1 mm apical to the implant-abutment interface (IAI), most horizontal resorption was found pointing to 0.44 mm in the control group and 0.59 mm in the test group. The difference of 0.14 mm (95% CI: −0.17–0.46) was not statistically significant (p = 0.366). At 3 mm and 5 mm apical to the IAI, the difference between the groups was 0.18 mm (95% CI: −0.05–0.40; p = 0.128) and 0.02 mm (95% CI: −0.24–0.28; p = 0.899), respectively. Vertical buccal bone loss amounted to 1.12 mm in the control group and 1.14 mm in the test group. The difference of 0.02 mm (95% CI: −0.53–0.49) was not statistically significant (p = 0.926). (4) Conclusions: In the short term, soft tissue augmentation with CTG or CMX results in limited buccal bone loss. CMX is a safe alternative to CTG. Longer follow-up is needed to assess the impact of soft tissue augmentation on buccal bone.
Contemporary Treatment and Outcomes of High Surgical Risk Mitral Regurgitation
Authors: Sudo Mitsumasa , Vij Vivian , Wilde Nihal , Tanaka Tetsu , Vogelhuber Johanna , Silaschi Miriam , Weber Marcel , Bakhtiary Farhad , Nickenig Georg , Zimmer Sebastian , Sugiura Atsushi
Published: April 2023

Before the development of transcatheter interventions, patients with mitral regurgitation (MR) and high surgical risk were often conservatively treated and subject to poor prognoses. We aimed to assess the therapeutic approaches and outcomes in the contemporary era. The study participants were consecutive high-risk MR patients from April 2019 to October 2021. Among the 305 patients analyzed, 274 (89.8%) underwent mitral valve interventions, whereas 31 (10.2%) received medical therapy alone. Of the interventions, transcatheter edge-to-edge mitral repair (TEER) was the most frequent (82.0% of overall), followed by transcatheter mitral valve replacement (TMVR) (4.6%). In patients treated with medical therapy alone, non-optimal morphologies for TEER and TMVR were shown in 87.1% and 65.0%, respectively. Patients undergoing mitral valve interventions experienced less frequent heart failure (HF) rehospitalization compared to those with medical therapy alone (18.2% vs. 42.0%, p < 0.01). Mitral valve intervention was associated with a lower risk of HF rehospitalization (HR 0.36 [0.18–0.74]) and an improved New York Heart Association class (p < 0.01). Most high-risk MR patients can be treated with mitral valve interventions. However, approximately 10% remained on medical therapy alone and were considered as unsuitable for current transcatheter technologies. Mitral valve intervention was associated with a lower risk of HF rehospitalization and improved functional status.
Re-Irradiation for Recurrent Head and Neck Cancer: Freedom from Cancer Recurrence Rate
Authors: Mohamad Issa , Abu Hejleh Taher , Abdelqader Sania , Wahbeh Lina , Taqash Ayat , Almousa Abdelatif , Mayta Ebrahim , Al-Ibraheem Akram , Abuhijla Fawzi , Abu-Hijlih Ramiz , Hussein Tariq , Al-Gargaz Wisam , Ghatasheh Hamza , Hosni Ali
Published: April 2023

Salvage re-irradiation (rRT) for patients with locoregionally recurrent head and neck cancer (rHNC) remains challenging. A retrospective analysis was performed on 49 patients who received rRT between 2011 and 2018. The co-primary endpoint of the study was 2-year freedom from cancer recurrence rate (FCRR) and overall survival (OS), and secondary endpoints were 2-year disease-free survival (DFS), local failure (LF), regional failure (RF), distant metastases (DM), and RTOG grade 3 ≥ late toxicities. Adjuvant and definitive rRT were delivered to 22 and 27 patients, respectively. A total of 91% of patients were managed with conventional re-RT and 71% of patients received concurrent chemotherapy. The median follow-up after rRT was 30 months. The 2-year FCRR, OS, DFS, LF, RF, and DM were 64%, 51%, 28%, 32%, 9%, and 39% respectively. MVA showed that poor performance status (PS: 1–2 vs. 0) and age > 52 years were predictive of worse OS. In comparison, poor PS (1–2 vs. 0) and total dose of rRT < 60 Gy were predictive of worse DFS. Late RTOG toxicity of grade 3 ≥ was reported in nine (18.3%) patients. FCRR at 2 years after salvage rRT for rHNC was higher than other traditional endpoints and could be an important endpoint to be included in future rRT studies. rRT for rHNC at our cohort was relatively successful, with a manageable level of late severe toxicity. Replacing this approach in other developing countries is a viable option.
Moving from Inpatient to Outpatient or Home Initiation of Non-Invasive Home Mechanical Ventilation
Authors: Kampelmacher Mike J.
Published: April 2023

Home mechanical ventilation (HMV) is an effective treatment for patients with chronic hypercapnic respiratory failure caused by restrictive or obstructive pulmonary disorders. Traditionally, HMV is initiated in the hospital, nowadays usually on a pulmonary ward. The success of HMV, and especially non-invasive home mechanical ventilation (NIV), has led to a steep and ongoing increase in the incidence and prevalence of HMV, in particular for patients with COPD or obesity hypoventilation syndrome. Consequently, the number of available hospital beds to accommodate these patients has become insufficient, and models of care that minimize the use of (acute) hospital beds need to be developed. At present, the practices for initiation of NIV vary widely, reflecting the limited research on which to base model-of-care decisions, local health system features, funding models, and historical practices. Hence, the opportunity to establish outpatient and home initiation may differ between countries, regions, and even HMV centres. In this narrative review, we will describe the evidence regarding the feasibility, effectiveness, safety, and cost savings of outpatient and home initiation of NIV. In addition, the benefits and challenges of both initiation strategies will be discussed. Finally, patient selection and execution of both approaches will be examined.
Novel Time-Lapse Parameters Correlate with Embryo Ploidy and Suggest an Improvement in Non-Invasive Embryo Selection
Authors: Serrano-Novillo Clara , Uroz Laia , Márquez Carmen
Published: April 2023

Selecting the best embryo for transfer is key to success in assisted reproduction. The use of algorithms or artificial intelligence can already predict blastulation or implantation with good results. However, ploidy predictions still rely on invasive techniques. Embryologists are still essential, and improving their evaluation tools can enhance clinical outcomes. This study analyzed 374 blastocysts from preimplantation genetic testing cycles. Embryos were cultured in time-lapse incubators and tested for aneuploidies; images were then studied for morphokinetic parameters. We present a new parameter, “st2, start of t2”, detected at the beginning of the first cell cleavage, as strongly implicated in ploidy status. We describe specific cytoplasmic movement patterns associated with ploidy status. Aneuploid embryos also present slower developmental rates (t3, t5, tSB, tB, cc3, and t5-t2). Our analysis demonstrates a positive correlation among them for euploid embryos, while aneuploids present non-sequential behaviors. A logistic regression study confirmed the implications of the described parameters, showing a ROC value of 0.69 for ploidy prediction (95% confidence interval (CI), 0.62 to 0.76). Our results show that optimizing the relevant indicators to select the most suitable blastocyst, such as by including st2, could reduce the time until the pregnancy of a euploid baby while avoiding invasive and expensive methods.
More Prevalent and Severe Low Bone-Mineral Density in Boys with Severe Adolescent Idiopathic Scoliosis Than Girls: A Retrospective Study of 798 Surgical Patients
Authors: Wu Zhichong , Zhu Xiufen , Xu Leilei , Liu Zhen , Feng Zhenhua , Hung Vivian Wing Yin , Cheng Jack Chun Yiu , Qiu Yong , Lee Wayne Y. W. , Lam Tsz Ping , Zhu Zezhang
Published: April 2023

Introduction: A total of 0.1–0.8% of AIS patients progress to severe stages without clear mechanisms, and AIS girls are more prone to curve progression than boys. Recent studies suggest that AIS girls have systemic and persistent low bone-mineral density (BMD), which has been shown to be a significant prognostic factor of curve progression in AIS. The present study aimed to (a) investigate the prevalence of low BMD in patients with severe AIS and (b) assess the sexual dimorphism and independent risk factors of low BMD in severe AIS patients. Materials and Methods: A total of 798 patients (140 boys vs. 658 girls) with AIS who reached surgical threshold (Cobb ≥ 40°) were recruited. BMD were assessed using BMD Z-scores from dual-energy X-ray absorptiometry (DXA). Demographic, clinical, and laboratory values of the subjects were collected from their medical records. Logistic regression analysis was performed to identify independent risk factors of low BMD. Results: The overall prevalence of BMD Z-score ≤ −2 and ≤ −1 were 8.1% and 37.5%, respectively. AIS boys had significantly lower BMD Z-scores (−1.2 ± 0.96 vs. −0.57 ± 0.92) and higher prevalence of low BMD (Z-score ≤ −2: 22.1% vs. 5.2%, p < 0.001; Z-score ≤ −1: 59.3% vs. 32.8%, p < 0.001) than girls. Sex, BMI, serum alkaline phosphatase, and potassium were independent factors of low BMD in the severe AIS patients. Conclusions: The present large cohort of surgical AIS patients revealed that low BMD is more prevalent and severe in boys than in girls with severe curves. Low BMD may serve as a more valuable predictive factor for curve progression to the surgical threshold in boys than girls with AIS.
Use of First-Line Oral Analgesics during and after COVID-19: Results from a Survey on a Sample of Italian 696 COVID-19 Survivors with Post-Acute Symptoms
Authors: Galluzzo Vincenzo , Zazzara Maria Beatrice , Ciciarello Francesca , Tosato Matteo , Bizzarro Alessandra , Paglionico Annamaria , Varriano Valentina , Gremese Elisa , Calvani Riccardo , Landi Francesco
Published: April 2023

Background—Analgesics could be used to manage painful symptoms during and after COVID-19. Materials and methods—Persistence of painful symptoms was assessed during and after COVID-19 in a sample of patients admitted to a post-acute COVID-19 outpatient service in Rome, Italy. Data on type and frequency of use of first-line analgesics were collected. Pain severity was evaluated with a numeric rating scale (NRS) from 0 to 10. Results—Mean age of 696 participants was 57.1 ± 20.3 years and 61.7% were women. During COVID-19, the most prevalent symptoms were fever, fatigue, arthralgia, myalgia and headache. Acetaminophen was used by 40% of the sample. Only 6.7% needed to continue analgesic therapy after COVID-19. Frequent causes of analgesics consumption were persistent arthralgia and myalgia. The most common analgesics used amongst those who continued taking analgesics in the post-acute phase of COVID-19 were the following: acetaminophen (31%), ibuprofen (31%) and other non-steroidal anti-inflammatory drug (NSAID) (29.5%); in older subjects the most common analgesic used was acetaminophen (54%). Most of the subjects in this group said there was an improvement in pain perception after taking analgesic therapy (84%). Conclusions—Use of analgesics in the post-acute COVID-19 is common in subjects with persistent arthralgia and myalgia, and common analgesics were acetaminophen and ibuprofen. Further research on the safety and efficacy of those medications in COVID-19 is warranted.
Hardness Measurements and Interface Behavior of SiC-B4C-Si Multiple Phase Particulate Composites Made with Melt Infiltration and Additive Manufacturing
Authors: Cramer Corson L. , Cakmak Ercan , Unocic Kinga A.
Published: April 2023

Reaction-bonded SiC-B4C-Si ceramic composites were binder jet 3D-printed and subsequently pressureless-melt-infiltrated with molten Si. The addition of B4C aided the Si infiltration to produce a highly dense composite. The microstructures and phases of these composites were examined. The measured hardness values of each constituent with Vickers and nanoindentation matched the bulk values, and the macro-hardness values with Knoop and spherical indentation represented the bulk, composite hardness values of all three phases together, which was close to a rule of mixtures value. For particulate-based composites, this is a significant finding. The interfacial bonds of SiC and Si were imaged using scanning transmission electron microscopy to view intimacy, whereas the crack propagation was examined with carefully placed indents. This work demonstrated that pressureless melt infiltration with a reactive particle provides a method to shape non-wetting reaction-bonded ceramic composites with limited shrinkage and high density and provides insights into the mechanical behavior with numerous indentation techniques.