bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Scale Investigation of GARP Family Genes Reveals Their Pivotal Roles in Nutrient Stress Resistance in Allotetraploid Rapeseed
Authors: Hua Ying-Peng , Wu Peng-Jia , Zhang Tian-Yu , Song Hai-Li , Zhang Yi-Fan , Chen Jun-Fan , Yue Cai-Peng , Huang Jin-Yong , Sun Tao , Zhou Ting
Published: November 2022

The GARP genes are plant-specific transcription factors (TFs) and play key roles in regulating plant development and abiotic stress resistance. However, few systematic analyses of GARPs have been reported in allotetraploid rapeseed (Brassica napus L.) yet. In the present study, a total of 146 BnaGARP members were identified from the rapeseed genome based on the sequence signature. The BnaGARP TFs were divided into five subfamilies: ARR, GLK, NIGT1/HRS1/HHO, KAN, and PHL subfamilies, and the members within the same subfamilies shared similar exon-intron structures and conserved motif configuration. Analyses of the Ka/Ks ratios indicated that the GARP family principally underwent purifying selection. Several cis-acting regulatory elements, essential for plant growth and diverse biotic and abiotic stresses, were identified in the promoter regions of BnaGARPs. Further, 29 putative miRNAs were identified to be targeting BnaGARPs. Differential expression of BnaGARPs under low nitrate, ammonium toxicity, limited phosphate, deficient boron, salt stress, and cadmium toxicity conditions indicated their potential involvement in diverse nutrient stress responses. Notably, BnaA9.HHO1 and BnaA1.HHO5 were simultaneously transcriptionally responsive to these nutrient stresses in both hoots and roots, which indicated that BnaA9.HHO1 and BnaA1.HHO5 might play a core role in regulating rapeseed resistance to nutrient stresses. Therefore, this study would enrich our understanding of molecular characteristics of the rapeseed GARPs and will provide valuable candidate genes for further in-depth study of the GARP-mediated nutrient stress resistance in rapeseed.
Hispolon Cyclodextrin Complexes and Their Inclusion in Liposomes for Enhanced Delivery in Melanoma Cell Lines
Authors: Poudel Ishwor , Annaji Manjusha , Wibowo Fajar Setyo , Arnold Robert D. , Fasina Oladiran , Via Brian , Rangari Vijaya , Peresin Maria Soledad , Smith Forrest , Dhanasekaran Muralikrishnan , Tiwari Amit K. , Babu R. Jayachandra
Published: November 2022

Hispolon, a phenolic pigment isolated from the mushroom species Phellinus linteus, has been investigated for anti-inflammatory, antioxidant, and anticancer properties; however, low solubility and poor bioavailability have limited its potential clinical translation. In this study, the inclusion complex of hispolon with Sulfobutylether-β-cyclodextrin (SBEβCD) was characterized, and the Hispolon-SBEβCD Complex (HSC) was included within the sterically stabilized liposomes (SL) to further investigate its anticancer activity against melanoma cell lines. The HSC-trapped-Liposome (HSC-SL) formulation was investigated for its sustained drug delivery and enhanced cytotoxicity. The inclusion complex in the solid=state was confirmed by a Job’s plot analysis, molecular modeling, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Proton nuclear magnetic resonance (NMR) spectroscopy, and scanning electron microscopy (SEM). The HSC-SL showed no appreciable deviation in size (<150 nm) and polydispersity index (<0.2) and improved drug encapsulation efficiency (>90%) as compared to control hispolon liposomes. Individually incorporated hispolon and SBEβCD in the liposomes (H-CD-SL) was not significant in loading the drug in the liposomes, compared to HSC-SL, as a substantial amount of free drug was separated during dialysis. The HSC-SL formulation showed a sustained release compared to hispolon liposomes (H-SLs) and Hispolon-SBEβCD liposomes (H-CD-SLs). The anticancer activity on melanoma cell lines (B16BL6) of HSC and HSC-SL was higher than in H-CD-SL and hispolon solution. These findings suggest that HSC inclusion in the HSC-SL liposomes stands out as a potential formulation approach for enhancing drug loading, encapsulation, and chemotherapeutic efficiency of hispolon and similar water insoluble drug molecules.
Essential Hypertension and Oxidative Stress: Novel Future Perspectives
Authors: Franco Caterina , Sciatti Edoardo , Favero Gaia , Bonomini Francesca , Vizzardi Enrico , Rezzani Rita
Published: November 2022

Among cardiovascular diseases, hypertension is one of the main risk factors predisposing to fatal complications. Oxidative stress and chronic inflammation have been identified as potentially responsible for the development of endothelial damage and vascular stiffness, two of the primum movens of hypertension and cardiovascular diseases. Based on these data, we conducted an open-label randomized study, first, to evaluate the endothelial damage and vascular stiffness in hypertense patients; second, to test the effect of supplementation with a physiological antioxidant (melatonin 1 mg/day for 1 year) in patients with essential hypertension vs. hypertensive controls. Twenty-three patients of either gender were enrolled and randomized 1:1 in two groups (control and supplemented group). The plasmatic total antioxidant capacity (as a marker of oxidative stress), blood pressure, arterial stiffness, and peripheral endothelial function were evaluated at the beginning of the study and after 1 year in both groups. Our results showed that arterial stiffness improved significantly (p = 0.022) in supplemented patients. The endothelial function increased too, even if not significantly (p = 0.688), after 1 year of melatonin administration. Moreover, the supplemented group showed a significative reduction in TAC levels (p = 0.041) correlated with the improvement of arterial stiffness. These data suggest that melatonin may play an important role in reducing the serum levels of TAC and, consequently, in improving arterial stiffness.
Lipid Nanoparticles Delivering Constitutively Active STING mRNA to Stimulate Antitumor Immunity
Authors: Liu Wei , Alameh Mohamad-Gabriel , Yang June F. , Xu Jonathan R. , Lin Paulo J. C. , Tam Ying K. , Weissman Drew , You Jianxin
Published: November 2022

Treating immunosuppressive tumors represents a major challenge in cancer therapies. Activation of STING signaling has shown remarkable potential to invigorate the immunologically “cold” tumor microenvironment (TME). However, we have shown that STING is silenced in many human cancers, including pancreatic ductal adenocarcinoma (PDAC) and Merkel cell carcinoma (MCC). In this study, we demonstrated that mRNA-lipid nanoparticle (LNP) technology could be used to efficiently deliver naturally occurring constitutively active STING mutant STINGR284S into these cancer cells to reactivate STING antitumor immunity and trigger robust killing of tumor cells. STING agonists are being actively pursued as cancer immunotherapies. However, traditional STING agonists can induce T cell cytotoxicity, counteracting the desired antitumor immune response. In addition, the antitumor efficacy of traditional STING agonists obligatorily depends on STING expression and does not work in STING-silenced cancers. Importantly, we found that STINGR284S mRNA-LNP does not introduce T cell cytotoxicity. Our studies demonstrated that mRNA-LNP delivery of STINGR284S can reactivate the antitumor response without introducing antiproliferative effects in lymphocytic immune cells, overcoming the toxicity and limitations of conventional STING agonists. Our work therefore identifies a novel therapeutic tool for reactivating antitumor immunity in an array of STING-silenced immunologically “cold” tumors that are refractory to current therapies.
Phage-Based Control of Methicillin Resistant Staphylococcus aureus in a Galleria mellonella Model of Implant-Associated Infection
Authors: Materazzi Alessandro , Bottai Daria , Campobasso Claudia , Klatt Ann-Brit , Cesta Novella , De Masi Margherita , Trampuz Andrej , Tavanti Arianna , Di Luca Mariagrazia
Published: November 2022

Staphylococcus aureus implant-associated infections are difficult to treat because of the ability of bacteria to form biofilm on medical devices. Here, the efficacy of Sb-1 to control or prevent S. aureus colonization on medical foreign bodies was investigated in a Galleria mellonella larval infection model. For colonization control assays, sterile K-wires were implanted into larva prolegs. After 2 days, larvae were infected with methicillin-resistant S. aureus ATCC 43300 and incubated at 37 °C for a further 2 days, when treatments with either daptomycin (4 mg/kg), Sb-1 (107 PFUs) or a combination of them (3 x/day) were started. For biofilm prevention assays, larvae were pre-treated with either vancomycin (10 mg/kg) or Sb-1 (107 PFUs) before the S. aureus infection. In both experimental settings, K-wires were explanted for colony counting two days after treatment. In comparison to the untreated control, more than a 4 log10 CFU and 1 log10 CFU reduction was observed on K-wires recovered from larvae treated with the Sb-1/daptomycin combination and with their singular administration, respectively. Moreover, pre-infection treatment with Sb-1 was found to prevent K-wire colonization, similarly to vancomycin. Taken together, the obtained results demonstrated the strong potential of the Sb-1 antibiotic combinatory administration or the Sb-1 pretreatment to control or prevent S. aureus-associated implant infections.
Transcriptome Analysis Reveals Immunomodulatory Effect of Spore-Displayed p75 on Human Intestinal Epithelial Caco-2 Cells
Authors: Kang Soo-Ji , Jun Ji-Su , Hong Kwang-Won
Published: November 2022

Lacticaseibacillus rhamnosus GG (LGG) can promote intestinal health by modulating the immune responses of the gastrointestinal tract. However, knowledge about the immunomodulatory action of LGG-derived soluble factors is limited. In our previous study, we have displayed LGG-derived p75 protein on the spore surface of Bacillus subtilis. The objective of this study was to determine the effect of spore-displayed p75 (CotG-p75) on immune system by investigating transcriptional response of Caco-2 cells stimulated by CotG-p75 through RNA-sequencing (RNA-seq). RNA-seq results showed that CotG-p75 mainly stimulated genes involved in biological processes, such as response to stimulus, immune regulation, and chemotaxis. KEGG pathway analysis suggested that many genes activated by CotG-p75 were involved in NF-ĸB signaling and chemokine signaling pathways. CotG-p75 increased cytokines and chemokines such as CXCL1, CXCL2, CXCL3, CXCL8, CXCL10, CCL20, CCL22, and IL1B essential for the immune system. In particular, CotG-p75 increased the expression levels of NF-ĸB-related genes such as NFKBIA, TNFAIP3, BIRC3, NFKB2, and RELB involved in immune and inflammatory responses. This study provides genes and pathways involved in immune responses influenced by CotG-p75. These comprehensive transcriptome profiling could be used to elucidate the immunomodulatory action of CotG-p75.
Genome-Wide Characterization and Expression Profiling of the GRAS Gene Family in Salt and Alkali Stresses in Miscanthus sinensis
Authors: Zhao Xuhong , Xu Yan , He Guo , He Kang , Xiao Liang , Hu Ruibo , Li Shengjun
Published: November 2022

The GRAS family genes encode plant-specific transcription factors that play important roles in a diverse range of developmental processes and abiotic stress responses. However, the information of GRAS gene family in the bioenergy crop Miscanthus has not been available. Here, we report the genome-wide identification of GRAS gene family in Micanthus sinensis. A total of 123 MsGRAS genes were identified, which were divided into ten subfamilies based on the phylogenetic analysis. The co-linearity analysis revealed that 59 MsGRAS genes experienced segmental duplication, forming 35 paralogous pairs. The expression of six MsGRAS genes in responding to salt, alkali, and mixed salt-alkali stresses was analyzed by transcriptome and real-time quantitative PCR (RT-qPCR) assays. Furthermore, the role of MsGRAS60 in salt and alkali stress response was characterized in transgenic Arabidopsis. The MsGRAS60 overexpression lines exhibited hyposensitivity to abscisic acid (ABA) treatment and resulted in compromised tolerance to salt and alkali stresses, suggesting that MsGRAS60 is a negative regulator of salt and alkali tolerance via an ABA-dependent signaling pathway. The salt and alkali stress-inducible MsGRAS genes identified serve as candidates for the improvement of abiotic stress tolerance in Miscanthus.
Transcriptome Analysis Revealing the Interaction of Abscisic Acid and Cell Wall Modifications during the Flower Opening and Closing Process of Nymphaea lotus
Authors: Zhou Weijuan , Li Zhaoji , Wu Wentao , Zhao Xia , Wang Enbo , Wang Jian , Song Xiqiang , Zhao Ying
Published: November 2022

As a tropical flower, Nymphaea lotus is a typical night-blooming waterlily used in water gardening. Its petals are rich in aromatic substances that can be used to extract essential oils and as flower tea. However, the short life of the flower seriously affects the development of its cut flowers. At present, neither the mechanism behind the night-opening waterlily flower’s opening and closing nor the difference between day-opening and night-opening waterlily flowers’ opening and closing mechanisms are clear. In this study, endogenous hormone contents of closed (CP) and open (OP) petals were measured, and transcriptome analysis of CP and OP petals was carried out to determine the signal transduction pathway and metabolic pathway that affect flower opening and closing. ABA and cell wall modification were selected as the most significant factors regulating flowering. We used qRT-PCR to identify the genes involved in the regulation of flower opening in waterlilies. Finally, by comparing the related pathways with those of the diurnal type, the obvious difference between them was found to be their hormonal regulation pathways. In conclusion, the endogenous ABA hormone may interact with the cell wall modification pathway to induce the flowering of N. lotus. Our data provide a new direction for the discovery of key factors regulating the flower opening and closing of N. lotus and provide basic theoretical guidance for future horticultural applications.
Pharmacophore Synergism in Diverse Scaffold Clinches in Aurora Kinase B
Authors: Masand Vijay H. , Al-Hussain Sami A. , Rathore Mithilesh M. , Thakur Sumer D. , Akasapu Siddhartha , Samad Abdul , Al-Mutairi Aamal A. , Zaki Magdi E. A.
Published: November 2022

Aurora kinase B (AKB) is a crucial signaling kinase with an important role in cell division. Therefore, inhibition of AKB is an attractive approach to the treatment of cancer. In the present work, extensive quantitative structure–activity relationships (QSAR) analysis has been performed using a set of 561 structurally diverse aurora kinase B inhibitors. The Organization for Economic Cooperation and Development (OECD) guidelines were used to develop a QSAR model that has high statistical performance (R2tr = 0.815, Q2LMO = 0.808, R2ex = 0.814, CCCex = 0.899). The seven-variable-based newly developed QSAR model has an excellent balance of external predictive ability (Predictive QSAR) and mechanistic interpretation (Mechanistic QSAR). The QSAR analysis successfully identifies not only the visible pharmacophoric features but also the hidden features. The analysis indicates that the lipophilic and polar groups—especially the H-bond capable groups—must be present at a specific distance from each other. Moreover, the ring nitrogen and ring carbon atoms play important roles in determining the inhibitory activity for AKB. The analysis effectively captures reported as well as unreported pharmacophoric features. The results of the present analysis are also supported by the reported crystal structures of inhibitors bound to AKB.
On the Role of Seminal Fluid Protein and Nucleic Acid Content in Paternal Epigenetic Inheritance
Authors: Patlar Bahar
Published: November 2022

The evidence supports the occurrence of environmentally-induced paternal epigenetic inheritance that shapes the offspring phenotype in the absence of direct or indirect paternal care and clearly demonstrates that sperm epigenetics is one of the major actors mediating these paternal effects. However, in most animals, while sperm makes up only a small portion of the seminal fluid, males also have a complex mixture of proteins, peptides, different types of small noncoding RNAs, and cell-free DNA fragments in their ejaculate. These seminal fluid contents (Sfcs) are in close contact with the reproductive cells, tissues, organs, and other molecules of both males and females during reproduction. Moreover, their production and use are adjusted in response to environmental conditions, making them potential markers of environmentally- and developmentally-induced paternal effects on the next generation(s). Although there is some intriguing evidence for Sfc-mediated paternal effects, the underlying molecular mechanisms remain poorly defined. In this review, the current evidence regarding the links between seminal fluid and environmental paternal effects and the potential pathways and mechanisms that seminal fluid may follow in mediating paternal epigenetic inheritance are discussed.
Triazavirin—A Novel Effective Antiviral Drug
Authors: Chupakhin Oleg N. , Rusinov Vladimir L. , Varaksin Mikhail V. , Ulomskiy Evgeny N. , Savateev Konstantin V. , Butorin Ilya I. , Du Weijie , Sun Zhiyong , Charushin Valery N.
Published: November 2022

This review outlines the data of numerous studies relating to the broad-spectrum antiviral drug Triazavirin that was launched on the Russian pharmaceutical market in 2014 as an anti-influenza drug (the international non-patented name is Riamilovir). The range of antiviral activity of Triazavirin has been significantly expanded during recent years; in particular, it has been shown that Triazavirin exhibits activity against tick-borne encephalitis, Rift Valley fever, West Nile fever, and other infections of viral etiology. This drug has been approved for treatment of influenza and acute respiratory infections by the Russian Ministry of Health on the basis of comprehensive clinical trials involving over 450 patients. Triazavirin was found to be a highly effective and well-tolerated drug, allowing its over-the-counter sale. The recently published data on the use of Triazavirin in clinical practice for the treatment of patients with COVID-19 are discussed, with special attention paid to potential biological targets for this drug.
A Genetic Compensation Phenomenon and Global Gene Expression Changes in Sex-miR-2766-3p Knockout Strain of Spodoptera exigua Hübner (Lepidoptera: Noctuidae)
Authors: Zuo Yayun , Wang Zeyu , Ren Xuan , Pei Yakun , Aioub Ahmed A. A. , Hu Zhaonong
Published: November 2022

MicroRNAs (miRNAs) drive the post-transcriptional repression of target mRNAs and play important roles in a variety of biological processes. miR-2766-3p is conserved and abundant in Lepidopteran species and may be involved in a variety of biological activities. In this study, Sex-miR-2766-3p was predicted to potentially bind to the 3′ untranslated region (UTR) of cap ‘n’ collar isoform C (CncC) in Spodoptera exigua, and Sex-miR-2766-3p was confirmed to regulate the expression of SeCncC through screening with a luciferase reporter system. Although CRISPR/Cas9 has been extensively utilized to examine insect gene function, studies of miRNA function are still relatively uncommon. Thus, we employed CRISPR/Cas9 to knock out Sex-miR-2766-3p from S. exigua. However, the expression of SeCncC was not significantly altered in the knockout strain (2766-KO) compared with that of the WHS strain. This result suggested that a miRNA knockout might lack phenotypes because of genetic robustness. Additionally, we used transcriptome analysis to examine how the global gene expression patterns of the Sex-miR-2766-3p knockout strain varied. RNA-seq data revealed 1746 upregulated and 2183 downregulated differentially expressed genes (DEGs) in the 2766-KO strain, which might be the result of Sex-miR-2766-3p loss or DNA lesions as the trigger for transcriptional adaptation. GO function classification and KEGG pathway analyses showed that these DEGs were enriched for terms related to binding, catalytic activity, metabolic process, and signal transduction. Our findings demonstrated that S. exigua could compensate for the missing Sex-miR-2766-3p by maintaining the expression of SeCncC by other pathways.
Effect of Propofol versus Sevoflurane Anesthesia on Acute Kidney Injury after Lung Transplantation Surgery: A Prospective Randomized Controlled Trial
Authors: Song Young , Paik Hyo-Chae , Kim Namo , Jung Heejae , Lee Jin-Gu , Yoo Young-chul
Published: November 2022

This prospective randomized controlled trial aimed to compare the effects of sevoflurane and propofol anesthesia on the occurrence of acute kidney injury (AKI) following lung transplantation (LTx) surgery. Sixty adult patients undergoing bilateral LTx were randomized to receive either inhalation of sevoflurane or continuous infusion of propofol for general anesthesia. The primary outcomes were AKI incidence according to the Acute Kidney Injury Network (AKIN) criteria and blood biomarker of kidney injury, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C levels within 48 h of surgery. Serum interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and superoxide dismutase were measured before and after surgery. The post-operative 30-day morbidity and long-term mortality were also assessed. Significantly fewer patients in the propofol group developed AKI compared with the sevoflurane group (13% vs. 38%, p = 0.030). NGAL levels were significantly lower in the propofol group at immediately after, 24 h, and 48 h post-operation. IL-6 levels were significantly lower in the propofol group immediately after surgery. AKI occurrence was significantly associated with a lower 5-year survival rate. Total intravenous anesthesia with propofol reduced the AKI incidence in LTx compared with sevoflurane, which is understood to be mediated by the attenuation of inflammatory responses.
Risk Factors and Corresponding Management for Suture Anchor Pullout during Arthroscopic Rotator Cuff Repair
Authors: Li Xiangwei , Xiao Yujia , Shu Han , Sun Xianding , Nie Mao
Published: November 2022

Introduction: Due to the aging of the population, the incidence of rotator cuff tears is growing. For rotator cuff repair, arthroscopic suture-anchor repair has gradually replaced open transosseous repair, so suture anchors are now considered increasingly important in rotator cuff tear reconstruction. There are some but limited studies of suture anchor pullout after arthroscopic rotator cuff repair. However, there is no body of knowledge in this area, which makes it difficult for clinicians to predict the risk of anchor pullout comprehensively and manage it accordingly. Methods: The literature search included rotator cuff repair as well as anchor pullout strength. A review of the literature was performed including all articles published in PubMed until September 2021. Articles of all in vitro biomechanical and clinical trial levels in English were included. After assessing all abstracts (n = 275), the full text and the bibliographies of the relevant articles were analyzed for the questions posed (n = 80). Articles including outcomes without the area of interest were excluded (n = 22). The final literature research revealed 58 relevant articles. Narrative synthesis was undertaken to bring together the findings from studies included in this review. Result: Based on the presented studies, the overall incidence of anchor pullout is not low, and the incidence of intraoperative anchor pullout is slightly higher than in the early postoperative period. The risk factors for anchor pullout are mainly related to bone quality, insertion depth, insertion angle, size of rotator cuff tear, preoperative corticosteroid injections, anchor design, the materials used to produce anchors, etc. In response to the above issues, we have introduced and evaluated management techniques. They include changing the implant site of anchors, cement augmentation for suture anchors, increasing the number of suture limbs, using all-suture anchors, using an arthroscopic transosseous knotless anchor, the Buddy anchor technique, Steinmann pin anchoring, and transosseous suture repair technology. Discussion: However, not many of the management techniques have been widely used in clinical practice. Most of them come from in vitro biomechanical studies, so in vivo randomized controlled trials with larger sample sizes are needed to see if they can help patients in the long run.
Evolving Role of Catheter Ablation for Atrial Fibrillation: Early and Effective Rhythm Control
Authors: Chen Shaojie , Yin Yuehui , Ling Zhiyu , Meyer Christian , Pürerfellner Helmut , Martinek Martin , Kiuchi Márcio Galindo , Futyma Piotr , Zhu Lin , Schratter Alexandra , Wang Jiazhi , Acou Willem-Jan , Sommer Philipp , Ouyang Feifan , Liu Shaowen , Chun Julian K. R. , Schmidt Boris
Published: November 2022

Catheter Ablation (CA) is an effective therapeutic option in treating atrial fibrillation (AF). Importantly, recent data show that CA as a rhythm control strategy not only significantly reduces AF burden, but also substantially improves clinical hard endpoints. Since AF is a progressive disease, the time of Diagnosis-to-Intervention appears crucial. Recent evidence shows that earlier rhythm control is associated with a lower risk of adverse cardiovascular outcomes in patients with early AF. Particularly, CA as an initial first line rhythm control strategy is associated with significant reduction of arrhythmia recurrence and rehospitalization in patients with paroxysmal AF. CA is shown to significantly lower the risk of progression from paroxysmal AF to persistent AF. When treating persistent AF, the overall clinical success after ablation remains unsatisfactory, however the ablation outcome in patients with “early” persistent AF appears better than those with “late” persistent AF. “Adjunctive” ablation on top of pulmonary vein isolation (PVI), e.g., ablation of atrial low voltage area, left atrial posterior wall, vein of Marshall, left atrial appendage, etc., may further reduce arrhythmia recurrence in selected patient group. New ablation concepts or new ablation technologies have been developing to optimize therapeutic effects or safety profile and may ultimately improve the clinical outcome.
A Natural History Study of RP2-Related Retinopathy
Authors: Cheloni Riccardo , Jackson Daniel , Moosajee Mariya
Published: November 2022

X-linked retinitis pigmentosa (RP) is a severe form of RP, often with early macular involvement. This study aimed to characterise the natural history of patients with a diagnosis of X-linked RP due to RP2 mutations. Clinical details, best-corrected visual acuity (BCVA) and multimodal retinal imaging were retrospectively collected from patients with RP2 variants from Moorfields Eye Hospital (London, UK). Measures of the ellipsoid-zone (EZ) width, central retinal thickness (CRT), and thickness of the photoreceptor and retinal pigment epithelium complex (PR+RPE, taken between the external limiting membrane and RPE) were extracted from spectral-domain optical coherence tomography (SD-OCT) scans. A total of 47 affected males (median baseline age: 20 years, IQR: 12.5–36.5) were included, and 41 had two or more visits (median follow-up: 8.0 years, IQR: 3.2–14.5). A total of 24 RP2 variants were identified, 13 of which were novel. BCVA dropped from 0.66 LogMAR at baseline (IQR, 0.35–1.4) to 1.3 LogMAR at the most recent visit (IQR: 0.6–1.4). SD-OCT revealed a prevalent outer retinal atrophy (n = 23/35, 65.7%), and measurable EZ width at baseline in 34.3% of patients (n = 12). Age significantly affected all quantitative measures (p < 0.001) except EZ width (p = 0.58), with exponential decays of 46–49% and 12.6–33.9% per decade for BCVA and SD-OCT measures, respectively. RP2 patients exhibited rapid progression to outer retina atrophy and early macular involvement with substantial vision loss by age 30–40.
COVID-19 Vaccination Is Associated with a Better Outcome in Acute Ischemic Stroke Patients: A Retrospective Observational Study
Authors: Rizzo Pier Andrea , Bellavia Simone , Scala Irene , Colò Francesca , Broccolini Aldobrando , Antonica Riccardo , Vitali Francesca , Angeloni Benedetta Maria , Brunetti Valerio , Di Iorio Riccardo , Monforte Mauro , Della Marca Giacomo , Calabresi Paolo , Luigetti Marco , Frisullo Giovanni
Published: November 2022

Background: It is unclear whether and how COVID-19 vaccination may affect the outcome of patients with acute ischemic stroke (AIS). We investigated this potential association in a retrospective study by comparing previously vaccinated (VAX) versus unvaccinated (NoVAX) stroke patients. Methods: We collected clinical reports for all consecutive AIS patients admitted to our hospital and evaluated the outcome predictors in VAX and NoVAX groups. Adjustments were made for possible confounders in multivariable logistic regression analysis, and adjusted hazard ratios were calculated. Results: A total of 466 AIS patients (287 VAX and 179 NoVAX) were included in this study. The NIHSS score at discharge and mRS score at a 3-month follow-up visit were significantly lower in VAX patients compared to NoVAX patients (p < 0.001). Good outcomes (mRS 0–2) were significantly associated with COVID-19 vaccination before AIS (adjusted hazard ratio, 0.400 [95% CI = 0.216–0.741]). Conclusions: The observation that COVID-19 vaccination can influence the outcome of AIS provides support for further studies investigating the role of immunity in ischemic brain damage.
The Effect of Anti-Tumor Necrosis Factor-Alpha Therapy within 12 Weeks Prior to Surgery on Postoperative Complications in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis
Authors: Cira Kamacay , Weber Marie-Christin , Wilhelm Dirk , Friess Helmut , Reischl Stefan , Neumann Philipp-Alexander
Published: November 2022

The rate of abdominal surgical interventions and associated postoperative complications in inflammatory bowel disease (IBD) patients is still substantially high. There is an ongoing debate as to whether or not patients who undergo treatment with anti-tumor necrosis factor-alpha (TNF-α) agents may have an increased risk for general and surgical postoperative complications. Therefore, a systematic review and meta-analysis was conducted in order to assess the effect of anti-TNF-α treatment within 12 weeks (washout period) prior to abdominal surgery on 30-day postoperative complications in patients with IBD. The results of previously published meta-analyses examining the effect of preoperative anti-TNF-α treatment on postoperative complications reported conflicting findings which is why we specifically focus on the effect of anti-TNF-α treatment within 12 weeks prior to surgery. PubMed, Cochrane, Scopus, Web of Science, World Health Organization Trial Registry, ClinicalTrials.gov and reference lists were searched (June 1995–February 2022) to identify studies, investigating effects of anti-TNF-α treatment prior to abdominal surgery on postoperative complications in IBD patients. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated and subgroup analyses were performed. In this case, 55 cohort studies (22,714 patients) were included. Overall, postoperative complications (OR, 1.23; 95% CI, 1.04–1.45; p = 0.02), readmission (OR, 1.39; 95% CI, 1.11–1.73; p = 0.004), and intra-abdominal septic complications (OR, 1.89; 95% CI, 1.44–2.49; p < 0.00001) were significantly higher for anti-TNF-α-treated patients. Significantly higher intra-abdominal abscesses and readmission were found for anti-TNF-α-treated CD patients (p = 0.05; p = 0.002). Concomitant treatment with immunosuppressives in <50% of anti-TNF-α-treated patients was associated with significantly lower mortality rates (OR, 0.32; 95% CI, 0.12–0.83; p = 0.02). Anti-TNF-α treatment within 12 weeks prior to surgery is associated with higher short-term postoperative complication rates (general and surgical) for patients with IBD, especially CD.
Efficacy and Safety of Tranexamic Acid in Shoulder Arthroscopic Surgery: A Systematic Review and Meta-Analysis
Authors: Sun Yiyuan , Xiao Dan , Fu Weili , Cai Wufeng , Huang Xihao , Li Qi , Li Jian
Published: November 2022

Background: Visual clarity during shoulder arthroscopy can ensure an efficient and effective performance of the procedure, and it is highly related to bleeding without a tourniquet. Tranexamic acid (TXA) is widely used in adult reconstruction procedures; however, its use in shoulder arthroscopic operations is a relatively novel topic. Purpose: To analyze the available literature on visual clarity, blood loss, pain control, functional outcomes, and complications after the administration of tranexamic acid in shoulder arthroscopic surgery. Methods: A literature search was performed to retrieve randomized controlled trials examining the use of tranexamic acid at the time of shoulder arthroscopic surgery. The literature search included the MEDLINE, Embase, Web of Science, and Cochrane Library databases. The primary outcomes included visual clarity, blood loss, and visual analog scale scores for pain. Secondary outcomes were operative time, irrigation amount used, postoperative shoulder swelling, the need for pressure increase, mean arterial pressure (MAP), functional outcomes, postoperative adverse effects such as deep venous thrombosis, and pulmonary embolism. The outcomes were pooled to perform a meta-analysis. Results: Seven prospective randomized controlled trials met the inclusion criteria for analysis. All of the included studies performed arthroscopic rotator cuff repair. No significant difference in visual clarity was observed (SMD (standardized mean difference), 0.45 [95% CI(confidence interval), −0.68, 1.59]; p = 0.44) nor in pain score (MD (mean difference), −0.46 [95% CI, −0.97, 0.05]; p = 0.08) between the TXA group and the control group. Two studies found no significant difference in blood loss between the TXA group and the control group. The meta-analysis from five studies demonstrated no significant difference between the TXA and control groups in operative time (MD, −3.51 [95% CI, −15.82, 8.80]; p = 0.58) or irrigation amount used (MD, −2.53 [95% CI, −5.93, 0.87]; p = 0.14). Two trials reported different statistical results in postoperative shoulder swelling. No significant differences regarding the need for pressure increase and MAP were reported between groups. No wound complications or infections or cardiac, thrombotic, or thromboembolic complications were recorded in either group. Conclusion: The use of intravenous or local TXA in shoulder arthroscopic surgery did not increase complications or thromboembolic events, but TXA had no obviously effect of reducing bleeding to obtain a clear visual field or pain release in patients undergoing shoulder arthroscopic surgery.
Predicting Adult Hospital Admission from Emergency Department Using Machine Learning: An Inclusive Gradient Boosting Model
Authors: Patel Dhavalkumar , Cheetirala Satya Narayan , Raut Ganesh , Tamegue Jules , Kia Arash , Glicksberg Benjamin , Freeman Robert , Levin Matthew A. , Timsina Prem , Klang Eyal
Published: November 2022

Background and aim: We analyzed an inclusive gradient boosting model to predict hospital admission from the emergency department (ED) at different time points. We compared its results to multiple models built exclusively at each time point. Methods: This retrospective multisite study utilized ED data from the Mount Sinai Health System, NY, during 2015–2019. Data included tabular clinical features and free-text triage notes represented using bag-of-words. A full gradient boosting model, trained on data available at different time points (30, 60, 90, 120, and 150 min), was compared to single models trained exclusively at data available at each time point. This was conducted by concatenating the rows of data available at each time point to one data matrix for the full model, where each row is considered a separate case. Results: The cohort included 1,043,345 ED visits. The full model showed comparable results to the single models at all time points (AUCs 0.84–0.88 for different time points for both the full and single models). Conclusion: A full model trained on data concatenated from different time points showed similar results to single models trained at each time point. An ML-based prediction model can use used for identifying hospital admission.
Impact of a Weight-Loss Rehabilitation Program on Sleep Apnea Risk and Subjective Sleepiness in Patients with Overweight/Obesity: The DietSleep Study
Authors: Bailly Sébastien , Fabre Odile , Cals-Maurette Mallory , Pantagis Laurent , Terrail Robin , Legrand Rémy , Astrup Arne , Pépin Jean-Louis
Published: November 2022

Obstructive sleep apnea (OSA) is one of the most frequent chronic diseases, and comorbid obesity occurs in more than 60% of cases. Variations in body weight influence both OSA severity and OSA-related symptoms. We prospectively assessed the impact of a weight-loss program using the Berlin score to reflect OSA risk, and we also used the Epworth Sleepiness Scale (ESS) to assess daytime sleepiness. DietSleep was a prospective multicentric cohort study investigating OSA risk and daytime sleepiness before and after weight-loss intervention. One hundred and twenty-seven patients were included (initial OSA risk 36%), most of whom were women (85.8%) with a median body mass index (BMI) of 29.7 kg/m2, and the interquartile range was (27.6; 34). The diet-based weight-loss program induced a median decrease in BMI of 3.7 kg/m2 (−5; −2.9) (body weight~12.1% (−16.0; −8.8)) over a period of 171 days (114; 269). Changes in anthropometric values were similar regarding OSA risk after adjusting for initial values. Berlin scores significantly improved from 3 (1; 5) to 1 (0; 2), p < 0.01; the proportion of patients with a Berlin score ≥2 decreased from 36% to 7% after the intervention. The proportion of patients with ESS ≥11 decreased from 13% to 2%. These results confirm that a weight-loss program produces clinically relevant weight loss and a significant improvement in both OSA and subjective daytime sleepiness.
Influence of Spatially Distributed Out-of-Plane CFRP Fiber Waviness on the Estimation of Knock-Down Factors Based on Stochastic Numerical Analysis
Authors: Schuster Andreas , Degenhardt Richard , Willberg Christian , Wille Tobias
Published: November 2022

The presence of waviness defects in CFRP materials due to fiber undulation affects the structural performance of composite structures. Hence, without a reliable assessment of the resulting material properties, the full weight-saving potential cannot be exploited. Within the paper, a probabilistic numerical approach for improved estimation of material properties based on spatially distributed fiber waviness is presented. It makes use of a homogenization approach to derive viable knock-down factors for the different plies on the laminate level for reference material and is demonstrated for a representative tension loadcase. For the stochastic analysis, a random field is selected which describes the complex inner geometry of the plies in the laminate model and is numerically discretized by the Karhunen–Loeve expansion methods to fit into an FE model for the strength analysis. Conducted analysis studies reveal a substantial influence of randomly distributed waviness defects on the derived knock-down factors. Based on a topological analysis of the waviness fields, the reduction of the material properties was found to be weakly negatively correlated related to simple geometrical properties such as maximum amplitudes of the waviness field, which justifies the need for further subsequent sensitivity studies.
Multifunctional Medical Grade Resin with Enhanced Mechanical and Antibacterial Properties: The Effect of Copper Nano-Inclusions in Vat Polymerization (VPP) Additive Manufacturing
Authors: Vidakis Nectarios , Petousis Markos , Papadakis Vassilis M. , Mountakis Nikolaos
Published: November 2022

Vat photopolymerization (VPP) is an additive manufacturing process commonly used in medical applications. This work aims, for the first time in the literature, to extend and enhance the performance of a commercial medical-grade resin for the VPP process, with the development of nanocomposites, using Copper (Cu) nanoparticles as the additive at two different concentrations. The addition of the Cu nanoparticles was expected to enhance the mechanical properties of the resin and to enable biocidal properties on the nanocomposites since Cu is known for its antibacterial performance. The effect of the Cu concentration was investigated. The nanocomposites were prepared with high-shear stirring. Specimens were 3D printed following international standards for mechanical testing. Their thermal and spectroscopic response was also investigated. The morphological characteristics were examined. The antibacterial performance was evaluated with an agar well diffusion screening process. The experimental results were analyzed with statistical modeling tools with two control parameters (three levels each) and eleven response parameters. Cu enhanced the mechanical properties in all cases studied. 0.5 wt.% Cu nanocomposite showed the highest improvement (approximately 11% in tensile and 10% in flexural strength). The antibacterial performance was sufficient against S. aureus and marginal against E. coli.
Effect of Cooling and Annealing Conditions on the Microstructure, Mechanical and Superelastic Behavior of a Rotary Forged Ti–18Zr–15Nb (at. %) Bar Stock for Spinal Implants
Authors: Lukashevich Konstantin , Sheremetyev Vadim , Komissarov Alexander , Cheverikin Vladimir , Andreev Vladimir , Prokoshkin Sergey , Brailovski Vladimir
Published: November 2022

In this work, the microstructure, phase state, texture, superelastic and mechanical properties of a Ti–18Zr–15Nb (at. %) shape memory alloy subjected to a combined thermomechanical treatment, including hot rotary forging with either air cooling or water quenching and post-deformation annealing are studied. It was revealed that the main structural component of the deformed and annealed alloy is BCC β-phase. With an increase in the forging temperature from 600 to 700 °C, the average grain size increases from 5.4 to 17.8 µm for the air-cooled specimens and from 3.4 to 14.7 µm for the water-quenched specimens. Annealing at 525 °C after forging at 700 °C with water quenching leads to the formation of a mixed statically and dynamically polygonized substructure of β-phase. In this state, the alloy demonstrates the best combination of functional properties in this study: a Young’s modulus of ~33 GPa, an ultimate tensile strength of ~600 MPa and a superelastic recovery strain of ~3.4%.
Green Synthesis of Platinum Nanoparticles for Biomedical Applications
Authors: Mikhailova Ekaterina O.
Published: November 2022

The diverse biological properties of platinum nanoparticles (PtNPs) make them ideal for use in the development of new tools in therapy, diagnostics, and other biomedical purposes. “Green” PtNPs synthesis is of great interest as it is eco-friendly, less energy-consuming and minimizes the amount of toxic by-products. This review is devoted to the biosynthesis properties of platinum nanoparticles based on living organisms (bacteria, fungi, algae, and plants) use. The participation of various biological compounds in PtNPs synthesis is highlighted. The biological activities of “green” platinum nanoparticles (antimicrobial, anticancer, antioxidant, etc.), the proposed mechanisms of influence on target cells and the potential for their further biomedical application are discussed.
Seismic Waveform Inversion Capability on Resource-Constrained Edge Devices
Authors: Manu Daniel , Tshakwanda Petro Mushidi , Lin Youzuo , Jiang Weiwen , Yang Lei
Published: November 2022

Seismic full wave inversion (FWI) is a widely used non-linear seismic imaging method used to reconstruct subsurface velocity images, however it is time consuming, has high computational cost and depend heavily on human interaction. Recently, deep learning has accelerated it’s use in several data-driven techniques, however most deep learning techniques suffer from overfitting and stability issues. In this work, we propose an edge computing-based data-driven inversion technique based on supervised deep convolutional neural network to accurately reconstruct the subsurface velocities. Deep learning based data-driven technique depends mostly on bulk data training. In this work, we train our deep convolutional neural network (DCN) (UNet and InversionNet) on the raw seismic data and their corresponding velocity models during the training phase to learn the non-linear mapping between the seismic data and velocity models. The trained network is then used to estimate the velocity models from new input seismic data during the prediction phase. The prediction phase is performed on a resource-constrained edge device such as Raspberry Pi. Raspberry Pi provides real-time and on-device computational power to execute the inference process. In addition, we demonstrate robustness of our models to perform inversion in the presence on noise by performing both noise-aware and no-noise training and feeding the resulting trained models with noise at different signal-to-noise (SNR) ratio values. We make great efforts to achieve very feasible inference times on the Raspberry Pi for both models. Specifically, the inference times per prediction for UNet and InversionNet models on Raspberry Pi were 22 and 4 s respectively whilst inference times for both models on the GPU were 2 and 18 s which are very comparable. Finally, we have designed a user-friendly interactive graphical user interface (GUI) to automate the model execution and inversion process on the Raspberry Pi.
Dietary Curcumin Supplementation Enhanced Ammonia Nitrogen Stress Tolerance in Greater Amberjack (Seriola dumerili): Growth, Serum Biochemistry and Expression of Stress-Related Genes
Authors: Hong Jiawei , Fu Zhengyi , Hu Jing , Zhou Shengjie , Yu Gang , Ma Zhenhua
Published: November 2022

This study was conducted to determine whether curcumin has a positive effect in greater amberjack (Seriola dumerili), especially the ammonia nitrogen stress tolerance ability. The results showed that the stress recovery process of digestive enzymes amylase and trypsin, as well as absorptive enzymes Na+/K+-ATPase, γ-GT and CK, was accelerated. Lysozyme activity increased in the fish fortified with both curcumin diets. Aspartate aminotransferase activity restriction was activated at a low curcumin level. However, alanine aminotransferase activity restriction happened only at 0.02% dietary curcumin. Facilitation of lipid metabolism by curcumin was very clear, as triglyceride and total cholesterol content was basically maintained at the original level or even showed a slight decrease after recovery. HSP70 and HSP90 genes were not evidently stimulated to express in liver, kidney and spleen tissues. In addition, curcumin showed its inhibition capacity on IL1β and IFN-γ and a promoting effect on TGF-β1. The expression of NF-κB1 decreased in a higher degree in fish fed with 0.02% dietary curcumin, while 0.01% dietary curcumin accelerated the recovery pace of C3 and lgT after stress. This study showed that dietary curcumin supplementation can enhance ammonia nitrogen stress tolerance in greater amberjack, and its application prospect can be confirmed.