bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfer of Self-Fruitfulness to Cultivated Almond from Peach and Wild Almond
Authors: Gradziel Thomas M.
Published: October 2022

The almond [Prunus dulcis (Mill.) D.A. Webb] is normally self-sterile, requiring orchard placement of pollinizer cultivars and insect pollinators. Honeybees are the primary insect pollinators utilized, but climate change and the higher frequency of extreme weather events have reduced their availability to levels insufficient to meet the demands of current and anticipated almond acreage. The incorporation of self-fruitfulness may eliminate the need for both pollinizers and pollinators and allow the planting of single cultivar orchards that facilitate orchard management and reduce agrochemical inputs. Self-fruitfulness requires self-compatibility of self-pollen tube growth to fertilization, as well as a high level of consistent self-pollination or autogamy over the range of anticipated bloom environments. The Italian cultivar Tuono has been the sole source of self-compatibility for breeding programs world-wide, leading to high levels of inbreeding in current almond improvement programs. Both self-compatibility and autogamy have been successfully transferred to commercial almonds from cultivated peaches (Prunus persica L.), as well as wild peach and almond species. Self-compatibility was inherited as a novel major gene, but was also influenced by modifiers. Molecular markers developed for one species source often failed to function for other species’ sources. Autogamy was inherited as a quantitative trait. Breeding barriers were more severe in the early stages of trait introgression, but rapidly diminished by the second to third backcross. Increasing kernel size, which was similarly inherited as a quantitative trait, was a major regulator of the introgression rate. Self-fruitfulness, along with good commercial performance of tree and nut traits, was recovered from different species sources, including Prunus mira, Prunus webbii, P. persica, and the P. webbii-derived Italian cultivar Tuono. Differences in expression of self-fruitfulness were observed, particularly during field selection at the early growth stages. Introgression of self-fruitfulness from these diverse sources also enriched overall breeding germplasm, allowing the introduction of useful traits that are not accessible within traditional germplasm.
Yield, Antioxidant Activity and Total Polyphenol Content of Okra Fruits Grown in Slovak Republic
Authors: Fabianová Júlia , Šlosár Miroslav , Kopta Tomáš , Vargová Andrea , Timoracká Mária , Mezeyová Ivana , Andrejiová Alena
Published: October 2022

Climate change, linked with an increase in temperature, contributes to the possibility growing of non-typical and lesser-known vegetable species in the Slovak Republic, including okra. Seven okra cultivars were tested as part of this study, which focused on the basic yield parameters, antioxidant activity and total polyphenol content in okra fruits. The statistical analysis of obtained results revealed significant differences in all monitored parameters of okra. The selection of “plastic” crop cultivars that can produce a steadier yield in each growing year is required due to the significant climate variations between growing seasons. In this regard, the okra cultivar ‘Baby Bubba’ can be recommended. The results also showed the high antioxidant activity and polyphenol content of okra pulp and seeds. Okra has a higher nutritional quality than other vegetable species frequently grown in the Slovak Republic. Okra cultivars ‘Burgundy’, ‘Pure Luck F1′ and ‘Jing Orange’ can be suggested from a nutritional perspective. Finally, it is possible to state that okra cultivars showed good yield potential and nutritional quality compared to the studies realized in countries in which okra is known and commonly used by the human population.
A Gap-Filling Tool: Predicting Daily Sediment Loads Based on Sparse Measurements
Authors: Ouyang Ying
Published: October 2022

Sediment load in streams is known as both a carrier and a potential source of contaminants, while sediment deposition can alter stream flow, stage and morphology, and thereby has broad impacts on stream hydrology, aquatic life, and recreation activity. For vast amounts of watersheds around the world, sparse daily measured sediment data may exist, but continuous and multi-year daily measured sediment data are largely unavailable because of time-consuming and budget constraint for measurements. However, when developing total maximum daily load (TMDL) and calibrating/validating watershed models for sediments, such continuous and multi-year datasets are inevitably required. This study extended the flow-weighted method, developed by Ouyang (Ouyang, Y. Environ. Monit. Assess. 193, 422 (2021)) to predict the continuous and multi-year daily sediment loads based on sparse, limited, and discontinuous measured data. This daily sediment load gap-filling tool was validated using measured data from six different US Geological Survey (USGS) gage stations across US. Results showed that the flow-weighted method well predicted daily sediment loads when a good linear correlation existed between measured seasonal sediment loads and measured seasonal stream discharges, which is a prerequisite to apply the flow-weighted method. Five out of six selected USGS gage stations used in this study met this prerequisite. The flow-weighted method (along with an example R script for implementing the method) is a useful tool for filling the daily sediment load gaps.
From Meadow to Map: Integrating Field Surveys and Interactive Visualizations for Invasive Species Management in a National Park
Authors: Randall Joshua , Inglis Nicole C. , Smart Lindsey , Vukomanovic Jelena
Published: October 2022

Invasive species are an important and growing issue of concern for land managers, and the ability to collect and visualize species coverage data is vital to the management of invasive and native species. This is particularly true of spatial data, which provides invaluable information on location, establishment rates, and spread rates necessary for managing habitats. However, current methods of collection are rarely integrated into a full management tool, making it difficult to quickly collect and visualize multiple years of data for multiple species. We created the Geospatial Meadow Management Tool (GMMT) to provide a complete framework from geospatial data collection to web visualization. We demonstrate the utility of our approach using Valley Forge National Historical Park meadow survey data. The GMMT was created through the ArcGIS suite of software, taking advantage of the modularity of multiple processes, and incorporating an online visualization dashboard that allows for quick and efficient data analysis. Using Valley Forge National Historical Park as a case study, the GMMT provides a wide range of useful species coverage data and visualizations that provide simple yet insightful ways to understand species distribution. This tool highlights the ability of a web-based visualization tool to be modified to incorporate the needs of users, providing powerful visuals for non-GIS experts. Future avenues for this work include highlighted open-data and community engagement, such as citizen science, to address the increasing threat of invasive species both on and off public lands.
Circulating U13 Small Nucleolar RNA as a Potential Biomarker in Huntington’s Disease: A Pilot Study
Authors: Romano Silvia , Romano Carmela , Peconi Martina , Fiore Alessia , Bellucci Gianmarco , Morena Emanuele , Troili Fernanda , Cipollini Virginia , Annibali Viviana , Giglio Simona , Mechelli Rosella , Ferraldeschi Michela , Veneziano Liana , Mantuano Elide , Sani Gabriele , Vecchione Andrea , Umeton Renato , Giubilei Franco , Salvetti Marco , Corbo Rosa Maria , Scarabino Daniela , Ristori Giovanni
Published: October 2022

Plasma small RNAs have been recently explored as biomarkers in Huntington’s disease (HD). We performed an exploratory study on nine HD patients, eight healthy subjects (HS), and five psychiatric patients (PP; to control for iatrogenic confounder effects) through an Affymetrix-Gene-Chip-miRNA-Array. We validated the results in an independent population of 23 HD, 15 pre-HD, 24 PP, 28 Alzheimer’s disease (AD) patients (to control the disease-specificity) and 22 HS through real-time PCR. The microarray results showed higher levels of U13 small nucleolar RNA (SNORD13) in HD patients than controls (fold change 1.54, p = 0.003 HD vs. HS, and 1.44, p = 0.0026 HD vs. PP). In the validation population, a significant increase emerged with respect to both pre-HD and the control groups (p < 0.0001). SNORD13 correlated with the status of the mutant huntingtin carrier (r = 0.73; p < 0.001) and the disease duration (r = 0.59; p = 0.003). The receiver operating characteristic (ROC) curve analysis showed the high accuracy of SNORD13 in discriminating HD patients from other groups (AUC = 0.963). An interactome and pathway analysis on SNORD13 revealed enrichments for factors relevant to HD pathogenesis. We report the unprecedented finding of a potential disease-specific role of SNORD13 in HD. It seems to peripherally report a ‘tipping point’ in the pathogenic cascade at the neuronal level.
Modification of Regulatory T Cell Epitopes Promotes Effector T Cell Responses to Aspartyl/Asparaginyl β-Hydroxylase
Authors: Wirsching Sebastian , Fichter Michael , Cacicedo Maximiliano L. , Landfester Katharina , Gehring Stephan
Published: October 2022

Cancer is a leading cause of death worldwide. The search for innovative therapeutic approaches is a principal focus of medical research. Vaccine strategies targeting a number of tumor-associated antigens are currently being evaluated. To date, none have garnered significant success. Purportedly, an immunosuppressive tumor microenvironment and the accumulation of regulatory T cells contribute to a lack of tumor vaccine efficacy. Aspartyl/asparaginyl β-hydroxylase (ASPH), a promising therapeutic target, is overexpressed in a variety of malignant tumors but is expressed negligibly in normal tissues. Computer analysis predicted that ASPH expresses four peptide sequences (epitopes) capable of stimulating regulatory T cell activity. The abolition of these putative regulatory T cell epitopes increased the CD4+ and CD8+ effector T cell responses to monocyte-derived dendritic cells pulsed with a modified, epitope-depleted version of ASPH in an ex vivo human lymphoid tissue-equivalent coculture system while simultaneously decreasing the overall number of FoxP3+ regulatory T cells. These findings suggest that the efficacy of all new vaccine candidates would profit from screening and eliminating potential tolerogenic regulatory T cell epitopes.
Involvement of the IL-6 Signaling Pathway in the Anti-Anhedonic Effect of the Antidepressant Agomelatine in the Chronic Mild Stress Model of Depression
Authors: Rossetti Andrea C. , Paladini Maria Serena , Brüning Cesar Augusto , Spero Vittoria , Cattaneo Maria Grazia , Racagni Giorgio , Papp Mariusz , Riva Marco A. , Molteni Raffaella
Published: October 2022

Neuroinflammation has emerged as an important factor in the molecular underpinnings of major depressive disorder (MDD) pathophysiology and in the mechanism of action of antidepressants. Among the inflammatory mediators dysregulated in depressed patients, interleukin (IL)-6 has recently been proposed to play a crucial role. IL-6 activates a signaling pathway comprising the JAK/STAT proteins and characterized by a specific negative feedback loop exerted by the cytoplasmic protein suppressor of cytokine signalling-3 (SOCS3). On these bases, here, we explored the potential involvement of IL-6 signaling in the ability of the antidepressant drug agomelatine to normalize the anhedonic-like phenotype induced in the rat by chronic stress exposure. To this aim, adult male Wistar rats were subjected to the chronic mild stress (CMS) paradigm and chronically treated with vehicle or agomelatine. The behavioral evaluation was assessed by the sucrose consumption test, whereas molecular analyses were performed in the prefrontal cortex. We found that CMS was able to stimulate IL-6 production and signaling, including SOCS3 gene and protein expression, but the SOCS3-mediated feedback-loop inhibition failed to suppress the IL-6 cascade in stressed animals. Conversely, agomelatine treatment normalized the stress-induced decrease in sucrose consumption and restored the negative modulation of the IL-6 signaling via SOCS3 expression and activity. Our results provide additional information about the pleiotropic mechanisms that contribute to agomelatine’s therapeutic effects.
Mutation Hotspot for Changing the Substrate Specificity of β-N-Acetylhexosaminidase: A Library of GlcNAcases
Authors: Nekvasilová Pavlína , Kulik Natalia , Kotik Michael , Petrásková Lucie , Slámová Kristýna , Křen Vladimír , Bojarová Pavla
Published: October 2022

β-N-Acetylhexosaminidase from Talaromyces flavus (TfHex; EC 3.2.1.52) is an exo-glycosidase with dual activity for cleaving N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc) units from carbohydrates. By targeting a mutation hotspot of the active site residue Glu332, we prepared a library of ten mutant variants with their substrate specificity significantly shifted towards GlcNAcase activity. Suitable mutations were identified by in silico methods. We optimized a microtiter plate screening method in the yeast Pichia pastoris expression system, which is required for the correct folding of tetrameric fungal β-N-acetylhexosaminidases. While the wild-type TfHex is promiscuous with its GalNAcase/GlcNAcase activity ratio of 1.2, the best single mutant variant Glu332His featured an 8-fold increase in selectivity toward GlcNAc compared with the wild-type. Several prepared variants, in particular Glu332Thr TfHex, had significantly stronger transglycosylation capabilities than the wild-type, affording longer chitooligomers – they behaved like transglycosidases. This study demonstrates the potential of mutagenesis to alter the substrate specificity of glycosidases.
The Potential of Using an Autogenous Tendon Graft by Injecting Bone Marrow Aspirate in a Rabbit Meniscectomy Model
Authors: Iida Ken , Hashimoto Yusuke , Orita Kumi , Nishino Kazuya , Kinoshita Takuya , Nakamura Hiroaki
Published: October 2022

Bone marrow aspirate (BMA) is an excellent source of cells and growth factors and has been used successfully for bone, cartilage, and soft-tissue healing. This study aimed to investigate the histological and biomechanical properties of autogenous tendon graft by injecting BMA and its protective effect against degenerative changes in a rabbit model of meniscal defects. Adult white rabbits were divided into untreated, tendon, and tendon + BMA groups, and meniscal defects were created in the knees. The tendon graft and articular cartilage status were evaluated by macroscopic and histological analysis at 4, 12, and 24 weeks postoperatively among the three groups. The tendon graft in the tendon and tendon + BMA groups were used for biomechanical evaluation at 4, 12, and 24 weeks postoperatively. The meniscal covering ratio in the tendon + BMA group was better than that in the tendon and untreated groups at 12 and 24 weeks postoperatively. The matrix around the central portion of cells in the tendon + BMA group was positively stained by safranin O and toluidine blue staining with metachromasia at 24 weeks. The histological score of the tendon graft in the tendon + BMA group was significantly higher than that in the untreated and tendon groups at 12 and 24 weeks postoperatively. In the tendon + BMA group, cartilage erosion was not shown at 4 weeks, developed slowly, and was better preserved at 12 and 24 weeks compared to the untreated and tendon groups. Histological scores for the articular cartilage were significantly better in the tendon + BMA group at 24 weeks. The compressive stress on the tendon graft in the tendon + BMA group was significantly higher than that in the tendon group at 12 weeks postoperatively. Transplantation of autogenous tendon grafts by injecting BMA improved the histologic score of the regenerated meniscal tissue and was more effective than the tendon and untreated group for preventing cartilage degeneration in a rabbit model of massive meniscal defects.
KDF1 Novel Variant Causes Unique Dental and Oral Epithelial Defects
Authors: Yu Miao , Liu Hangbo , Liu Yang , Zheng Jinglei , Wu Junyi , Sun Kai , Feng Hailan , Liu Haochen , Han Dong
Published: October 2022

Keratinocyte differentiation factor 1 (KDF1) is a recently identified and rare candidate gene for human tooth agenesis; however, KDF1-related morphological characteristics and pathological changes in dental tissue and the oral epithelium remain largely unknown. Here, we employed whole-exome sequencing (WES) and Sanger sequencing to screen for the suspected variants in a cohort of 151 tooth agenesis patients, and we segregated a novel KDF1 heterozygous missense variation, c.920G>C (p.R307P), in a non-syndromic tooth agenesis family. Essential bioinformatics analyses and tertiary structural predictions were performed to analyze the structural changes and functional impacts of the novel KDF1 variant. The subsequent functional assessment using a TOP-flash/FOP-flash luciferase reporter system demonstrated that KDF1 variants suppressed the activation of canonical Wnt signaling in 293T cells. To comprehensively investigate the KDF1-related oral morphological anomalies, we performed scanning electron microscopy and ground section of the lower right lateral deciduous incisor extracted from #285 proband, and histopathological assessment of the gingiva. The phenotypic analyses revealed a series of tooth morphological anomalies related to the KDF1 variant R307P, including a shovel-shaped lingual surface of incisors and cornicione-shaped marginal ridges with anomalous morphological occlusal grooves of premolars and molars. Notably, keratinized gingival epithelium abnormalities were revealed in the proband and characterized by epithelial dyskeratosis with residual nuclei, indistinct stratum granulosum, epithelial hyperproliferation, and impaired epithelial differentiation. Our findings revealed new developmental anomalies in the tooth and gingival epithelium of a non-syndromic tooth agenesis individual with a novel pathogenic KDF1 variant, broadening the phenotypic spectrum of KDF1-related disorders and providing new evidence for the crucial role of KDF1 in regulating human dental and oral epithelial development.
RhFGF21 Protects Epidermal Cells against UVB-Induced Apoptosis through Activating AMPK-Mediated Autophagy
Authors: Zhao Yeli , Lin Jingjing , Li Jiana , Bwalya Canol , Xu Yuyun , Niu Yue , Zhang Yujie , Wu Junyi , Xu Yifan , Chen Jun , Ye Shasha , Lin Li
Published: October 2022

Ultraviolet irradiation, especially ultraviolet B (UVB) irradiation, increases the risks of various skin diseases, such as sunburn, photo-aging and cancer. However, few drugs are available to treat skin lesions. Therefore, the discovery of drugs to improve the health of irradiated skin is urgently needed. Fibroblast growth factor 21 (FGF21) is a metabolic factor that plays an important role in the protection and repair of various types of pathological damage. The effects of FGF21 on skin injury caused by UVB-irradiation were the focus of this study. We found that UVB irradiation promoted the expression of FGF21 protein in mouse epidermal cells, and exogenous recombinant human FGF21 (rhFGF21) protected mouse skin tissue against UVB-induced injury. RhFGF21 inhibited the inflammatory responses and epidermal cell apoptosis as well as promotion of autophagy in UVB-irradiated mice. Moreover, we found that rhFGF21 protected HaCaT cells against UVB-induced apoptosis, and the protective effect was enhanced by treatment with an autophagy activator (rapamycin) but was inhibited by treatment with an autophagy inhibitor (3-methyladenine, 3MA). AMP-activated protein kinase (AMPK), as a cellular energy sensor, regulates autophagy. RhFGF21 increased the expression of p-AMPK protein in epidermal cells irradiated with UVB in vivo and in vitro. Moreover, rhFGF21 increased autophagy levels and the viability were diminished by treatment with an AMPK inhibitor (compound C). RhFGF21 protects epidermal cells against UVB-induced apoptosis by inducing AMPK-mediated autophagy.
Aphid BCR4 Structure and Activity Uncover a New Defensin Peptide Superfamily
Authors: Loth Karine , Parisot Nicolas , Paquet Françoise , Terrasson Hugo , Sivignon Catherine , Rahioui Isabelle , Ribeiro Lopes Mélanie , Gaget Karen , Duport Gabrielle , Delmas Agnès F. , Aucagne Vincent , Heddi Abdelaziz , Calevro Federica , da Silva Pedro
Published: October 2022

Aphids (Hemiptera: Aphidoidea) are among the most detrimental insects for agricultural plants, and their management is a great challenge in agronomical research. A new class of proteins, called Bacteriocyte-specific Cysteine-Rich (BCR) peptides, provides an alternative to chemical insecticides for pest control. BCRs were initially identified in the pea aphid Acyrthosiphon pisum. They are small disulfide bond-rich proteins expressed exclusively in aphid bacteriocytes, the insect cells that host intracellular symbiotic bacteria. Here, we show that one of the A. pisum BCRs, BCR4, displays prominent insecticidal activity against the pea aphid, impairing insect survival and nymphal growth, providing evidence for its potential use as a new biopesticide. Our comparative genomics and phylogenetic analyses indicate that BCRs are restricted to the aphid lineage. The 3D structure of BCR4 reveals that this peptide belongs to an as-yet-unknown structural class of peptides and defines a new superfamily of defensins.
Response of the Urothelial Carcinoma Cell Lines to Cisplatin
Authors: Holíčková Andrea , Roška Jan , Órásová Eveline , Bruderová Vladimíra , Palacka Patrik , Jurkovičová Dana , Chovanec Miroslav
Published: October 2022

Cisplatin (CDDP)-based chemotherapy is the standard of care in patients with muscle-invasive bladder cancer. However, in a large number of cases, the disease becomes resistant or does not respond to CDDP, and thus progresses and disseminates. In such cases, prognosis of patients is very poor. CDDP manifests its cytotoxic effects mainly through DNA damage induction. Hence, response to CDDP is mainly dependent on DNA damage repair and tolerance mechanisms. Herein, we have examined CDDP response in a panel of the urothelial carcinoma cell (UCC) lines. We characterized these cell lines with regard to viability after CDDP treatment, as well as kinetics of induction and repair of CDDP-induced DNA damage. We demonstrate that repair of CDDP-induced DNA lesions correlates, at least to some extent, with CDDP sensitivity. Furthermore, we monitored expression of the key genes involved in selected DNA repair and tolerance mechanisms, nucleotide excision repair, homologous recombination and translesion DNA synthesis, and show that it differs in the UCC lines and positively correlates with CDDP resistance. Our data indicate that CDDP response in the UCC lines is dependent on DNA damage repair and tolerance factors, which may, therefore, represent valuable therapeutic targets in this malignancy.
Iron–Sulfur Clusters toward Stresses: Implication for Understanding and Fighting Tuberculosis
Authors: Elchennawi Ingie , Ollagnier de Choudens Sandrine
Published: October 2022

Tuberculosis (TB) remains the leading cause of death due to a single pathogen, accounting for 1.5 million deaths annually on the global level. Mycobacterium tuberculosis, the causative agent of TB, is persistently exposed to stresses such as reactive oxygen species (ROS), reactive nitrogen species (RNS), acidic conditions, starvation, and hypoxic conditions, all contributing toward inhibiting bacterial proliferation and survival. Iron–sulfur (Fe-S) clusters, which are among the most ancient protein prosthetic groups, are good targets for ROS and RNS, and are susceptible to Fe starvation. Mtb holds Fe-S containing proteins involved in essential biological process for Mtb. Fe-S cluster assembly is achieved via complex protein machineries. Many organisms contain several Fe-S assembly systems, while the SUF system is the only one in some pathogens such as Mtb. The essentiality of the SUF machinery and its functionality under the stress conditions encountered by Mtb underlines how it constitutes an attractive target for the development of novel anti-TB.
Delaying the Stall of A Low-Wing Aircraft Using A Novel Powerful Vortex Generator
Authors: Goharshadi Mostafa , Mirzaei Masoud
Published: October 2022

In this study, a new aerodynamic surface concept is introduced, which is a powerful vortex generator (PVG). It can delay the stall point in a low-wing aircraft. This delay leads to a significant increase in the CLmax of an aircraft. The results of this research show that the use of PVG, due to its longitudinal position, does not affect the aerodynamic center of the aircraft as well as its static stability. This is an advantage for this method compared to the method based on LEX, in which the aerodynamic center moves forward and the static stability of the aircraft reduces. As a case study, this research focused on a low-wing advanced training jet. Additionally, the aerodynamic characteristics of the aircraft were investigated in three points, including takeoff /landing condition, one maneuvering point, and one MMO condition. To evaluate the concept of PVG in more realistic situations, the wing airfoil was optimized at the same three points using the adjoint method. Then, the effect of PVG on various configurations of the aircraft, including the clean configuration and the different types of flap, was investigated. Since all the analyses were performed using computational fluid dynamics, at first, the validation of numerical methods was conducted on two test cases in low-speed and high-speed flows. The results of the case study show that the PVG greatly delays the separation and increases the value of CLmax. For example, in the case of a hinged leading-edge flap and single slotted trailing-edge flap, more than 12 degrees of delay in the stall was achieved, and the value of CLmax increased from 1.4 to 2.05 (46% increase).
Research of Static and Dynamic Properties of Power Semiconductor Diodes at Low and Cryogenic Temperatures
Authors: Ostapchuk Mikhail , Shishov Dmitry , Shevtsov Daniil , Zanegin Sergey
Published: October 2022

Systems with high-temperature superconductors (HTSC) impose new requirements on power conversions, since the main part of the losses in such systems is induced in the semiconductors of the converters. Within the framework of this study, the possibility of improving the static and dynamic characteristics of power semiconductor diodes using cryogenic cooling was confirmed; in some cases, a loss reduction of up to 30% was achieved.
Pulmonary Embolism Response Teams: Theory, Implementation, and Unanswered Questions
Authors: Bejjani Antoine , Khairani Candrika D. , Campia Umberto , Piazza Gregory
Published: October 2022

Pulmonary embolism (PE) continues to represent a significant health care burden and its incidence is steadily increasing worldwide. Constantly evolving therapeutic options and the rarity of randomized controlled trial data to drive clinical guidelines impose challenges on physicians caring for patients with PE. Recently, PE response teams have been developed and recommended to help address these issues by facilitating a consensus among local experts while advocating the management of acute PE according to each individual patient profile. In this review, we focus on the clinical challenges supporting the need for a PE response team, report the current evidence for their implementation, assess their impact on PE management and outcomes, and address unanswered questions and future directions.
The Effect of Stimulation Protocols (GnRH Agonist vs. Antagonist) on the Activity of mTOR and Hippo Pathways of Ovarian Granulosa Cells and Its Potential Correlation with the Outcomes of In Vitro Fertilization: A Hypothesis
Authors: Papapanou Michail , Syristatidi Kalliopi , Gazouli Maria , Eleftheriades Makarios , Vlahos Nikolaos , Siristatidis Charalampos
Published: October 2022

Controlled ovarian hyperstimulation (COH) is essential for the success of in vitro fertilization (IVF). Evidence showing the comparison of different COH protocols remains predominantly of low certainty and derives from unspecified infertile and highly heterogeneous populations. Thus, personalized approaches to examine the response of patients to the various COH protocols need to be investigated. Data from in vitro and animal studies have identified the mechanistic target of rapamycin (mTOR) and Hippo signaling pathways play a key role in follicular homeostasis and oocyte quality. To be specific, current data indicate the controlled activation of mTOR and the controlled inhibition of the Hippo pathway within the ovarian granulosa cells (GC). Both are reported to lead to a nurturing follicular microenvironment, increase oocyte quality, and potentially improve reproductive outcomes. As intracellular markers, phosphorylated/unphosphorylated levels of the pathways’ main downstream mediators could be included among the candidate “personalized” predictors of patients’ response to COH protocols and final IVF outcomes. Based on these hypotheses, we make a preliminary attempt to investigate their validity: We propose a prospective cohort study to compare the levels of certain phosphorylated/unphosphorylated components of the investigated pathways (mTOR, ribosomal protein S6 kinase beta-1 (p70S6K-1), yes-associated protein-1 (YAP-1), and transcriptional coactivator with PDZ-binding motif (TAZ)) within the follicular fluid-isolated GC between women undergoing gonadotropin-releasing hormone (GnRH) antagonist/“short” protocols and those receiving GnRH agonist/“long 21” protocols. A case-control design comparing these levels between women achieving pregnancy and those who did not is further planned. Additional analyses addressing the population’s expected heterogeneity are planned after the completion of the pilot phase, during which 100 participants undergoing IVF are intended to be recruited. At this stage, these hypotheses are solely based on in vitro/animal data, and thus, similar studies on humans in this respect are necessary for the investigation of their potential validity.
Improvement of Post-Operative Quality of Life in Patients 2 Years after Minimally Invasive Surgery for Pain and Deep Infiltrating Endometriosis
Authors: Legendri Sophie , Carbonnel Marie , Feki Anis , Moawad Gaby , Aubry Gabrielle , Vallée Alexandre , Ayoubi Jean-Marc
Published: October 2022

This study addressed the improvement in the quality of life of patients 2 years after minimally invasive surgery for painful deep infiltrating endometriosis (DIE), evaluated with EHP-5 (Endometriosis Health Profile-5) scores and the intensity of dysmenorrhea and dyspareunia. This was a retrospective study, performed in a referral centre for endometriosis, between January 2010 and January 2019. EHP-5 scores were complete for 54 patients, and two subgroups were analysed: classic laparoscopy (CL) vs. robotic laparoscopy (RL), and conservative surgery (ConservS) vs. total surgery (TS). There was an important decrease in 2-year post-operative EHP-5 scores in the global population (pre-op: 61.36 (42.18–68.75) and 2-year post-op: 20.45 (0–38.06); p < 0.001). The Visual Analogic Scale (VAS) was also lower for dysmenorrhea (pre-op: 8 (7–9.75) vs. 2-year post-op: 3 (2–5.25); p < 0.001) and dyspareunia (pre-op: 6 (3.1–8.9) vs. 2-year post-op: 3 (0–6); p < 0.001). In the subgroup analysis, EHP-5 scores were improved in the RL group (pre-op: 65.9 (59.09–71.02) vs. 2-year post-op: 11.4 (0–38.06); p < 0.001) and the CL group (pre-op: 50 (34.65–68.18) vs. 2-year post-op: 27.27 (14.20–40.90); p < 0.001), with a slight advantage for RL (p = 0.04), and the same improvements were found for ConservS (pre-op: 61.4 (38.06–71.59) vs. 2-year post-op: 22.7 (11.93–38.07); p < 0.001) and TS groups (pre-op: 61.59 (51.70–68.75) vs. 2-year post-op: 13.63 (0–44.30); p < 0.001). Minimally invasive surgery improved the quality of life for DIE patients 2 years after surgery, and conservative surgery showed comparable results to total surgery.
A Clot Waveform Analysis of Thrombin Time Using a Small Amount of Thrombin Is Useful for Evaluating the Clotting Activity of Plasma Independent of the Presence of Emicizumab
Authors: Wada Hideo , Shiraki Katsuya , Matsumoto Takeshi , Suzuki Kei , Yamashita Yoshiki , Tawara Isao , Shimpo Hideto , Shimaoka Motomu
Published: October 2022

Objective: Although emicizumab is a bispecific, monoclonal antibody that has led to a significant improvement of treatment for hemophilia A patients with inhibitors, the routine monitoring of patients treated with emicizumab is difficult. Thrombin time (TT) reflects thrombin burst, which mainly depends on activation of factor V (FV) and FVIII. Methods: We, therefore, developed a method for evaluating clotting activity independent of the presence of emicizumab. Normal plasma (NP) or FVIII-deficient plasma (FVIIIDP) with and without emicizumab was measured using clot waveform analysis (CWA)-activated partial thromboplastin time (APTT) and TT. Results: Emicizumab caused clot formation in FVIIIDP using the CWA-APTT; however, the coagulation peaks of plasma with and without emicizumab measured by the CWA-TT did not differ to a statistically significant extent. Regarding the mixing tests with NP and FVIIIDP, CWA-APTT showed large differences between each mixing test in plasma with and without emicizumab, whereas the CWA-TT showed similar patterns in mixing plasma with and without emicizumab. Regarding the standard curve of FVIII activity, the CWA-APTT showed an FVIII-concentration-dependent increase; however, the values with each concentration of FVIII differed between samples with and without emicizumab, whereas CWA-TT showed FVIII-concentration-dependent fluctuations independent of the presence of emicizumab, and the values with each concentration of FVIII were similar in samples with and without emicizumab. Conclusions: As CWA-TT using a small amount of thrombin (0.5 IU/mL) can reflect thrombin burst and be useful for evaluating FVIII activity, independent of the presence of emicizumab, it is useful for monitoring clotting activity in patients with an anti-FVIII inhibitor treated with emicizumab.
Multivessel versus Culprit-Only Percutaneous Coronary Intervention in Patients with Non-ST-Elevation Acute Coronary Syndrome
Authors: Pustjens Tobias F. S. , Timmermans Marijke J. C. , Rasoul Saman , van ‘t Hof Arnoud W. J. ,   on behalf of the PCI Registration Committee,   the Cardiothoracic Surgery Registration Committee of The Netherlands Heart Registration
Published: October 2022

Background: There is uncertainty whether multivessel (MV-PCI) or culprit-only percutaneous coronary intervention (CO-PCI) should be the treatment of choice in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) and multivessel disease (MVD). Aims: To evaluate clinical characteristics and outcomes in these patients undergoing MV-PCI or CO-PCI at the index procedure. Methods: Data were retrieved from the nationwide Netherlands Heart Registration. All NSTE-ACS patients with MVD undergoing PCI between 1 January 2017 and 1 October 2019 were grouped into a MV-PCI or CO-PCI group. The primary endpoint was all-cause mortality at long-term follow-up (median 756 days (593–996)). Secondary endpoints were reinterventions, urgent CABG, myocardial infarction (MI) < 30 days, target vessel revascularisation (TVR) and mortality at 1 year. Propensity score matching analyses were performed. Results: In total, 10,507 NSTE-ACS patients with MVD were included into the MV-PCI (N = 4235) and CO-PCI group (N = 6272). Analysing crude data, mortality rates at long-term follow-up (10.7% vs. 10.2%; p = 0.383), mortality at 1 year (6.0% vs. 5.6%; p = 0.412) and MI <30 days (0.8% vs. 0.9%; p = 0.513) were similar between both groups. Reinterventions (11.1% vs. 20.0%; p < 0.001), urgent CABG (0.1% vs. 0.4%; p = 0.001) and TVR (5.2% vs. 6.7%; p = 0.003) occurred less often in the MV-PCI group. Survival analysis after multiple imputation and propensity score matching showed similar mortality rates at long-term follow-up (log-rank p = 0.289), but a significant reduction for reinterventions in the MV-PCI group (log-rank p < 0.001). Conclusion: NSTE-ACS patients with MVD undergoing MV-PCI have similar mortality rates at long-term follow-up compared to CO-PCI. However, improved event-free survival in terms of fewer coronary reinterventions was observed.
TECAR Therapy Associated with High-Intensity Laser Therapy (Hilt) and Manual Therapy in the Treatment of Muscle Disorders: A Literature Review on the Theorised Effects Supporting Their Use
Authors: Szabo Dan Alexandru , Neagu Nicolae , Teodorescu Silvia , Predescu Corina , Sopa Ioan Sabin , Panait Loredana
Published: October 2022

Background: It has been estimated that between 30 and 50 per cent of all injuries that take place throughout participation in a sport are the consequence of soft tissue injuries, and muscle injuries are the primary cause of physical disability. Methods: The current literature review was designed between October 2021 and April 2022, according to the PRISMA standards, using the PubMed, Scopus, and Web of Science databases. At the screening stage, we eliminated articles that did not fit into the themes developed in all subchapters of the study (n = 70), articles that dealt exclusively with orthopaedics (n = 34), 29 articles because the articles had only the abstract visible, and 17 articles that dealt exclusively with other techniques for the treatment of musculoskeletal disorders. The initial search revealed 343 titles in the databases, from which 56 duplicate articles were automatically removed, and 2 were added from other sources. Results: The combination of these three techniques results in the following advantages: It increases joint mobility, especially in stiff joints, it increases the range of motion, accelerates tissue repair, improves tissue stability, and extensibility, and it reduces soft tissue inflammation (manual therapy). In addition, it decreases the concentration of pro-inflammatory mediators and improves capillary permeability, resulting in the total eradication of inflammation (HILT). It warms the deep tissues, stimulates vascularity, promotes the repose of tissues (particularly muscle tissue), and stimulates drainage (TECAR). Conclusions: TECAR therapy, combined with manual therapy and High-Intensity Laser therapy in treating muscle diseases, presented optimal collaboration in the recovery process of all muscle diseases.
Is ROTEM Diagnostic in Trauma Care Associated with Lower Mortality Rates in Bleeding Patients?—A Retrospective Analysis of 7461 Patients Derived from the TraumaRegister DGU®
Authors: Riehl Katrin , Lefering Rolf , Maegele Marc , Caspers Michael , Migliorini Filippo , Schenker Hanno , Hildebrand Frank , Fröhlich Matthias , Driessen Arne
Published: October 2022

Introduction: Death from uncontrolled trauma haemorrhage and subsequent trauma-induced coagulopathy (TIC) is potentially preventable. Point-of-care devices such as rotational thromboelastometry (ROTEM®) are advocated to detect haemostatic derangements more rapidly than conventional laboratory diagnostics. Regarding reductions in RBC transfusion, the use of ROTEM has been described as being efficient and associated with positive outcomes in several studies. Objective: The effect of ROTEM use was assessed on three different outcome variables: (i) administration of haemostatics, (ii) rate of RBC transfusions and (iii) mortality in severely injured patients. Methods and Material: A retrospective analysis of a large data set of severely injured patients collected into the TraumaRegister DGU® between 2009 and 2016 was conducted. The data of 7461 patients corresponded to the inclusion criteria and were subdivided into ROTEM-using and ROTEM-non-using groups. Both groups were analysed regarding (i) administration of haemostatics, (ii) rate of RBC transfusions and (iii) mortality. Results: A lower mortality rate in ROTEM-using groups was observed (p = 0.043). Furthermore, more patients received haemostatic medication when ROTEM was used. In ROTEM-using groups, there was a statistically relevant higher application of massive transfusion. Conclusions: In this retrospective study, the use of ROTEM was associated with reduced mortality and an increased application of haemostatics and RBC transfusions. Prospective evidence is needed for further evidence-based recommendations.
FTO and Anthropometrics: The Role of Modifiable Factors
Authors: Evans Cassandra , Curtis Jason , Antonio Jose
Published: October 2022

Numerous gene variants are linked to an individual’s propensity to become overweight or obese. The most commonly studied gene variant is the FTO single nucleotide polymorphism. The FTO risk allele is linked with increased body mass, BMI and other lifestyle factors that may perpetuate an individual’s risk for obesity. Studies assessing eating behaviors, eating preferences, nutrition interventions and other lifestyle factors were reviewed. These studies demonstrated a clear difference in eating behaviors and preferences. Lifestyle modifications including physical activity and diet were effective in weight management even in those with the risk allele.
Shear Modulus of a Carbonate Sand–Silt Mixture with THF Hydrate
Authors: Ren Yuzhe , Chiu C. F. , Ma Lu , Cheng Y. P. , Ji Litong , Jiang Chao
Published: October 2022

The maximum shear modulus (Gmax) is an important factor determining soil deformation, and it is closely related to engineering safety and seafloor stability. In this study, a series of bender element tests was carried out to investigate the Gmax of a hydrate-bearing carbonate sand (CS)–silt mixture. The soil mixture adopted a CS:silt ratio of 1:4 by weight to mimic the fine-grained deposit of the South China Sea (SCS). Tetrahydrofuran (THF) was used to form the hydrate. Special specimen preparation procedures were adopted to form THF hydrate inside the intraparticle voids of the CS. The test results indicate that hydrate contributed to a significant part of the skeletal stiffness of the hydrate-bearing CS–silt mixture, and its Gmax at 5% hydrate saturation (Sh) was 4–6 times that of the host soil mixture. Such stiffness enhancement at a low Sh may be related to the cementation hydrate morphology. However, the Gmax of the hydrate-bearing CS–silt mixture was also sensitive to the effective stress for an Sh ranging between 5% and 31%, implying that the frame-supporting hydrate morphology also plays a key role in the skeletal stiffness of the soil mixture. Neither the existing cementation models nor the theoretical frame-supporting (i.e., Biot–Gassmann theory by Lee (BGTL)), could alone provide a satisfactory prediction of the test results. Thus, further theoretical study involving a combination of cementation and frame-supporting models is essential to understand the effects of complicated hydrate morphologies on the stiffness of soil with a substantial amount of intraparticle voids.
CFD Study on Hydrodynamic Performances of a Planing Hull
Authors: Pacuraru Florin , Mandru Andreea , Bekhit Adham
Published: October 2022

The scope of the present study is to investigate the effects of various geometrical hull features, such as tunnels, spray rails and whiskers on the hydrodynamic performance of a high-speed planing hull. The criteria being tested to emphasize the boat performance are the total drag, sinkage and trim angle. In addition, the decomposition of the resistance into viscous and wave-making resistance are taken into consideration. The study starts with a validation test against experimental data in order to accentuate the capability of the Computational Fluid Dynamics CFD simulation to accurately predict the total drag and trim angle of the initial form. This is later followed by a verification study based on the Richardson Extrapolation method with a grid- and time-step-convergence test in order to predict the numerical errors during the simulation. After establishing the simulation parameters regarding the proper grid size and time step, the comparative study takes place for five hull shapes and two whisker configurations while the boat is sailing at eight different speeds. The assessment of the hydrodynamic flow parameters is evaluated compared to the initial form in order to investigate the influence of the geometry change on the hydrodynamic performances of the boat. Validation of the numerical results showed the reliability of the CFD simulation to accurately predict the drag and trim angle of the boat, while the comparative study revealed that the total drag can be reduced by up to 9%, especially at higher speeds.
Experimental Study on Wave Current Characteristics and Stability of the Junction of Artificial Island and Subsea Tunnel
Authors: Ge Longzai , Chen Hanbao , Chen Songgui , Liu Haiyuan
Published: October 2022

In order to ensure the safety and reliability of the submerged tunnel covering layer at the junction of an artificial island and tunnel under extremely bad conditions, the wave current characteristics and the stability of the protective structure in the variable slope section were studied. By conducting model tests, the coupling effect of wave and current is revealed in this study. The hydrodynamic field, including the varying angles between waves and currents, is simulated in the model test. The ratio (Hs′/Hs) of the wave height and the ratio (U′/U) of the velocity with and without the existence of a current, the relative velocity (U/C), the wave steepness (Hs/L), the relative water depth (d/L) and the angle (α) between wave and current are obtained, and the corresponding calculation expression is derived, by checking the test results, the empirical formula can better predict the changes of wave height and water flow after wave current coupling. The stable weight of the surface protection rock is obtained through an optimization test. Based on the relationship between the stable weight of the protection rock and the wave height under the wave–current coupling effect, a modified expression for calculating the stable weight of the armor block is derived. The modified calculation method can support estimating the stable weight of the armor rocks of an overburden structure of a similar immersed tunnel under the wave–current coupling effect. This study can not only solve the practical problems of major projects of the Shenzhen–Zhongshan channel but also provide valuable basic data and technical support for the construction of overburden of subsea-immersed tube tunnels in the future.