bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyaluronan nanoscale clustering and Hyaluronan synthase 2 expression are linked to the invasion of child fibroblasts and infantile fibrosarcoma in vitro and in vivo
Authors: Tonge Joseph J. , Notley Scott V. , Dunning Mark J. , López-Guajardo Ana , Medcalf Jessica D. , Heldin Paraskevi , Panoutsos George , Gad Annica K. B. 
Published: November 2022

AbstractInfantile fibrosarcoma is a rare childhood tumour that originates in the fibrous connective tissue of the long bones for which there is an urgent need to identify novel therapeutic targets. This study aims to clarify the role of the extracellular matrix component hyaluronan in the invasion of child fibroblasts and Infantile fibrosarcoma into the surrounding environment. Using nanoscale super-resolution STED (Stimulated emission depletion) microscopy followed by computational image analysis, we observed, for the first time, that invasive child fibroblasts showed increased nanoscale clustering of hyaluronan at the cell periphery, as compared to control cells. Hyaluronan was not observed within focal adhesions. Bioinformatic analyses further revealed that the increased nanoscale hyaluronan clustering was accompanied by increased gene expression of Hyaluronan synthase 2, reduced expression of Hyaluronidase 2 and CD44, and no change of Hyaluronan synthase 1 and Hyaluronidases 1, 3, 4 or 5. We further observed that the expression of the Hyaluronan synthase 1, 2 and 3, and the Hyaluronidase 3 and 5 genes was linked to reduced life expectancy of fibrosarcoma patients. The invasive front of infantile fibrosarcoma tumours further showed increased levels of hyaluronan, as compared to the tumour centre. Taken together, our findings are consistent with the possibility that while Hyaluronan synthase 2 increases the levels, the Hyaluronidases 3 and 5 reduce the weight of hyaluronan, resulting in the nanoscale clustering of hyaluronan at the leading edge of cells, cell invasion and the spread of Infantile fibrosarcoma.
Improving hypertension awareness and management in Vietnam through a community-based model
Authors: McGuire Helen , Van Truong Bui , Thi Thu Hien Le , Nguyen Thanh Huyen , Murray Marge , Shellaby Jason , Aerts Ann , George Roshini , Hodges Mary 
Published: November 2022

AbstractHypertension prevalence in Vietnam is high, but few people are aware of their disease status. Detection, diagnosis, and treatment are limited, so new approaches are needed to improve awareness and manage the condition, especially at the primary health care level. The Communities for Healthy Hearts programme operated in four districts of Ho Chi Minh City, with the aim of increasing awareness and ensuring linkage to care. Interventions focused on extending services beyond health facilities to convenient community locations; training cadres of community volunteers to screen, refer, and follow up with clients; training health workers in facilities to diagnose, educate, and manage patients referred from the community; and supporting the process with digital case tracking. Community-based blood pressure screenings took place in client homes, commune health stations, and non-traditional sites such as coffee shops, dentists’ offices, marketplaces, neighbourhood watch/security posts, and tailor shops. In total, 121,273 adults aged 40 and older were screened. Of these, 25.1% had elevated blood pressure or a previous hypertension diagnosis and were referred to health facilities. Of those referred, 56.2% were confirmed to have hypertension, and of those confirmed, 75.2% were treated. Of those treated, 51.0% achieved blood pressure control, a favourable outcome over past programmes.
Diminished neutralization responses towards SARS-CoV-2 Omicron VoC after mRNA or vector-based COVID-19 vaccinations
Authors: Jacobsen Henning , Strengert Monika , Maaß Henrike , Ynga Durand Mario Alberto , Katzmarzyk Maeva , Kessel Barbora , Harries Manuela , Rand Ulfert , Abassi Leila , Kim Yeonsu , Lüddecke Tatjana , Metzdorf Kristin , Hernandez Pilar , Ortmann Julia , Heise Jana-Kristin , Castell Stefanie , Gornyk Daniela , Glöckner Stephan , Melhorn Vanessa , Kemmling Yvonne , Lange Berit , Dulovic Alex , Marsall Patrick , Häring Julia , Junker Daniel , Schneiderhan-Marra Nicole , Hoffmann Markus , Pöhlmann Stefan , Krause Gérard , Cicin-Sain Luka 
Published: November 2022

AbstractSARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection against infection. The novel variant of concern (VoC) Omicron BA.1 and its sub-lineages have the largest number of amino acid alterations in its Spike protein to date. Thus, they may efficiently escape recognition by neutralizing antibodies, allowing breakthrough infections in convalescent and vaccinated individuals in particular in those who have only received a primary immunization scheme. We analyzed neutralization activity of sera from individuals after vaccination with all mRNA-, vector- or heterologous immunization schemes currently available in Europe by in vitro neutralization assay at peak response towards SARS-CoV-2 B.1, Omicron sub-lineages BA.1, BA.2, BA.2.12.1, BA.3, BA.4/5, Beta and Delta pseudotypes and also provide longitudinal follow-up data from BNT162b2 vaccinees. All vaccines apart from Ad26.CoV2.S showed high levels of responder rates (96–100%) towards the SARS-CoV-2 B.1 isolate, and minor to moderate reductions in neutralizing Beta and Delta VoC pseudotypes. The novel Omicron variant and its sub-lineages had the biggest impact, both in terms of response rates and neutralization titers. Only mRNA-1273 showed a 100% response rate to Omicron BA.1 and induced the highest level of neutralizing antibody titers, followed by heterologous prime-boost approaches. Homologous BNT162b2 vaccination, vector-based AZD1222 and Ad26.CoV2.S performed less well with peak responder rates of 48%, 56% and 9%, respectively. However, Omicron responder rates in BNT162b2 recipients were maintained in our six month longitudinal follow-up indicating that individuals with cross-protection against Omicron maintain it over time. Overall, our data strongly argue for booster doses in individuals who were previously vaccinated with BNT162b2, or a vector-based primary immunization scheme.
Significance of seed dispersal by the largest frugivore for large-diaspore trees
Authors: Sato Hiroki 
Published: November 2022

AbstractHow do large-bodied frugivores contribute to seed dispersal of large-diaspore plants? This study examined seed dispersal effectiveness for two large-diaspore tree species, Astrotrichilia asterotricha (AA) and Abrahamia deflexa (AD), in a Madagascan forest. I evaluated fruit removal rates through focal tree observations and factors affecting seedling recruitment up to the 2-year-old seedling stage. I confirmed brown lemur (Eulemur fulvus) as the sole disperser, removing 58.8% and 26.0% of fruits produced by AA and AD. Brown lemurs frequently visited large-crowned AA trees with high density of fallen fruits and more adjacent fruiting trees during seasons with low fruit diversity. Most AA seedlings were removed by predators, although canopy openness slightly improved seedling establishment. Although AD seeds were severely attacked by predators under mother trees, the seedlings survived under dispersal conditions distant from the mother trees, and with low density of diaspores. AD had a higher cumulative probability from fruit removal to seedling recruitment (6.5%) than AA (1.5%) in the first rainy season. This study clarifies the significance of seed dispersal to tree recruitment strategies, which vary among different combinations of tree species and large frugivores, i.e. quantitative dispersal to reach suitable microhabitats, and qualitative dispersal to escape from dangerous zones near mother trees.
Identification of noninvasive diagnostic biomarkers for ectopic pregnancy using data-independent acquisition (DIA)proteomics: a pilot study
Authors: Ma Dan , Yang Ruiqing , Chen Yunlong , Huang Zhengyi , Shen Yuxin , He Chengqi , Zhao Lixing 
Published: November 2022

AbstractAt present, the diagnosis of ectopic pregnancy mainly depends on transvaginal ultrasound and β-hCG. However, these methods may delay diagnosis and treatment time. Therefore, we aimed to screen for serological molecular markers for the early diagnosis of ectopic pregnancy (EP).Using data-independent acquisition (DIA)proteomics, the differential proteins in serum were selected between the intrauterine pregnancy (IP) and EP groups. Then, the expression levels of these differential proteins were measured by enzyme-linked immunosorbent assay. The diagnostic value of the serum biomarkers was evaluated by receiver operating characteristic curve analysis.GSTO1, ECM-1 and β-hCG showed significant differences between the EP and IP groups (P < 0.05). The combination of GSTO1/ECM-1/β-hCG had an area under the curve of 0.93 (95% CI 0.88–0.99), a sensitivity of 88.89% (95% CI 73.94–96.89) and a specificity of 86.11% (95% CI 70.50–95.33) with a likelihood ratio of 6.40.The combination of GSTO1/ECM-1/β-hCG may be developed into a possible approach for the early diagnosis of EP.
Insights into the equilibrium structure and translocation mechanism of TP1, a spontaneous membrane-translocating peptide
Authors: Muñoz-Gacitúa Diego , Guzman Fanny , Weiss-López Boris 
Published: November 2022

AbstractCrossing the cellular membrane is one of the main barriers during drug discovery; many potential drugs are rejected for their inability to integrate into the intracell fluid. Although many solutions have been proposed to overcome this barrier, arguably the most promising solution is the use of cell-penetrating peptides. Recently, an array of hydrophobic penetrating peptides was discovered via high throughput screening which proved to be able to cross the membrane passively, and although these peptides proved to be effective at penetrating the cell, the details behind the underlying mechanism of this process remain unknown. In this study, we developed a method to find the equilibrium structure at the transmembrane domain of TP1, a hydrophobic penetrating peptide. In this method, we selectively deuterium-label amino acids in the peptidic chain, and employ results of $$^2$$

2

H-NMR spectroscopy to find a molecular dynamics simulation of the peptide that reproduces the experimental results. Effectively finding the equilibrium orientation and dynamics of the peptide in the membrane. We employed this equilibrium structure to simulate the entire translocation mechanism and found that after the peptide reaches its equilibrium structure, it must undergo a two-step mechanism in order to completely translocate the membrane, each step involving the flip-flop of each arginine residue in the peptide. This leads us to conclude that the RLLR motif is essential for the translocating activity of the peptide.
The utility of the emBODY tool as a novel method of studying complex phenomena-related emotions
Authors: Herman Aleksandra M. , Zaremba Dominika , Kossowski Bartosz , Marchewka Artur 
Published: November 2022

AbstractBodily sensations are one of the major building blocks of emotional experience. However, people differ in their ability to recognise and name their emotions, especially those in response to complex phenomena such as climate change or the COVID-19 pandemic. Therefore, we investigated whether the bodily sensation maps (BSMs) approach can be employed to study emotions related to phenomena that are likely to evoke various, and perhaps even conflicting, emotions in people. Using a unique topographical self-report method—the previously established emBODY tool, 548 participants marked where in the body they feel sensations (activations and deactivations) when they experience distinct emotions (e.g. happiness) and when they think about different phenomena, namely climate change, COVID-19 pandemic, war, nature, friends, and summer holidays. We revealed maps of bodily sensations associated with different emotions and phenomena. Importantly, each phenomenon was related to a statistically unique BSM, suggesting that participants were able to differentiate between feelings associated with distinct phenomena. Yet, we also found that BSMs of phenomena showed some similarity with maps of emotions. Together, these findings indicate that the emBODY tool might be useful in uncovering the range of emotions individuals experience towards complex phenomena.
4D flow MRI in abdominal vessels: prospective comparison of k-t accelerated free breathing acquisition to standard respiratory navigator gated acquisition
Authors: Bane Octavia , Stocker Daniel , Kennedy Paul , Hectors Stefanie J. , Bollache Emilie , Schnell Susanne , Schiano Thomas , Thung Swan , Fischman Aaron , Markl Michael , Taouli Bachir 
Published: November 2022

AbstractVolumetric phase-contrast magnetic resonance imaging with three-dimensional velocity encoding (4D flow MRI) has shown utility as a non-invasive tool to examine altered blood flow in chronic liver disease. Novel 4D flow MRI pulse sequences with spatio-temporal acceleration can mitigate the long acquisition times of standard 4D flow MRI, which are an impediment to clinical adoption. The purpose of our study was to demonstrate feasibility of a free-breathing, spatio-temporal (k−t) accelerated 4D flow MRI acquisition for flow quantification in abdominal vessels and to compare its image quality, flow quantification and inter-observer reproducibility with a standard respiratory navigator-gated 4D flow MRI acquisition. Ten prospectively enrolled patients (M/F: 7/3, mean age = 58y) with suspected portal hypertension underwent both 4D flow MRI acquisitions. The k−t accelerated acquisition was approximately three times faster (3:11 min ± 0:12 min/9:17 min ± 1:41 min, p < 0.001) than the standard respiratory-triggered acquisition. Vessel identification agreement was substantial between acquisitions and observers. Average flow had substantial inter-sequence agreement in the portal vein and aorta (CV < 15%) and poorer agreement in hepatic and splenic arteries (CV = 11–38%). The k−t accelerated acquisition recorded reduced velocities in small arteries and reduced splenic vein flow. Respiratory gating combined with increased acceleration and spatial resolution are needed to improve flow measurements in these vessels.
CaMKII regulates neuromuscular activity and survival of the human blood fluke Schistosoma mansoni
Authors: Hirst Natasha L. , Lawton Scott P. , Walker Anthony J. 
Published: November 2022

AbstractCalcium/calmodulin dependant protein kinase II (CaMKII), an important transducer of Ca2+ signals, orchestrates multiple cellular functions in animals. Here we investigated the importance of CaMKII to Schistosoma mansoni, a blood parasite that causes human schistosomiasis. We demonstrate that phosphorylated (activated) CaMKII is present in cercariae, schistosomula and adult worms, and show that striking activation occurs in the nervous tissue of these parasite life-stages; CaMKII was also activated in the tegument and muscles of adult worms and the vitellaria of females. Exposure of worms to the anti-schistosomal drug praziquantel (PZQ) induced significant CaMKII activation and depletion of CaMKII protein/activation in adult worms resulted in hypokinesia, reduced vitality and death. At medium confidence (global score ≥ 0.40), S. mansoni CaMKII was predicted to interact with 51 proteins, with many containing CaMKII phosphorylation sites and nine mapped to phosphoproteome data including sites within a ryanodine receptor. The CaMKII network was functionally enriched with mitogen-activated protein kinase, Wnt, and notch pathways, and ion-transport and voltage-dependent channel protein domains. Collectively, these data highlight the intricacies of CaMKII signalling in S. mansoni, show CaMKII to be an active player in the PZQ-mediated response of schistosomes and highlight CaMKII as a possible target for the development of novel anti-schistosome therapeutics.
Customizing the mechanical properties of additively manufactured metallic meta grain structure with sheet-based gyroid architecture
Authors: Kim Kibeom , Kim Gun-hee , Kim Hyung Giun , Kim Hoe Joon , Kim Namjung 
Published: November 2022

AbstractThe use of cellular structures has led to unprecedented outcomes in various fields involving optical and mechanical cloaking, negative thermal expansion, and a negative Poisson’s ratio. The unique characteristics of periodic cellular structures primarily originate from the interconnectivity, periodicity, and unique design of the unit cells. However, the periodicity often induces unfavorable mechanical behaviors such as a “post-yielding collapse”, and the mechanical performance is often limited by the design of the unit cells. Therefore, we propose a novel structure called a meta grain structure (MGS), which is inspired by a polycrystalline structure, to enhance flexibility in design and mechanical reliability. A total of 138 different MGSs were built and tested numerically, and the correlations between the design parameters (e.g., the relative density) and mechanical properties of the MGSs were rigorously analyzed. A systematic design methodology was developed to obtain the optimal design of the MGS with the target Young’s modulus. This methodology makes it possible to build a unique structure that offers various design options and overcomes the current limitations of cellular structures. Furthermore, a systematic inverse design methodology makes it possible to produce an MGS that satisfies the required mechanical performance.
Cardiovascular responses to orthostasis during a simulated 3-day heatwave
Authors: Fisher Jason T. , Ciuha Urša , Ioannou Leonidas G. , Simpson Lydia L. , Possnig Carmen , Lawley Justin , Mekjavic Igor B. 
Published: November 2022

AbstractGlobal warming has caused an increase in the frequency, duration, and intensity of summer heatwaves (HWs). Prolonged exposure to hot environments and orthostasis may cause conflicting demands of thermoregulation and blood pressure regulation on the vasomotor system, potentially contributing to cardiovascular complications and occupational heat strain. This study assessed cardiovascular and skin blood flow (SkBF) responses to orthostasis before, during and after a 3-day simulated HW. Seven male participants maintained a standard work/rest schedule for nine consecutive days split into three 3-day parts; thermoneutral pre-HW (25.4 °C), simulated HW (35.4 °C), thermoneutral post-HW. Gastrointestinal (Tgi) and skin (Tsk) temperatures, cardiovascular responses, and SkBF were monitored during 10-min supine and 10-min 60° head-up tilt (HUT). SkBF, indexed using proximal–distal skin temperature gradient (∆TskP-D), was validated using Laser-Doppler Flowmetry (LDF). The HW significantly increased heart rate, cardiac output and SkBF of the leg in supine; HUT increased SkBF of the arm and leg, and significantly affected all cardiovascular variables besides cardiac output. Significant regional differences in SkBF presented between the arm and leg in all conditions; the arm displaying vasodilation throughout, while the leg vasoconstricted in non-HW before shifting to vasodilation in the HW. Additionally, ∆TskP-D strongly correlated with LDF (r = −.78, p < 0.001). Prolonged HW exposure and orthostasis, individually, elicited significant changes in cardiovascular and SkBF variables. Additionally, varying regional blood flow responses were observed, suggesting the upper and lower vasculature receives differing vasomotor control. Combined cardiovascular alterations and shifts towards vasodilation indicate an increased challenge to industrial workers during HWs.
Comparative study of the cytotoxicity, apoptotic, and epigenetic effects of Boswellic acid derivatives on breast cancer
Authors: Jamshidi-adegani Fatemeh , Ghaemi Shokoofeh , Al-Hashmi Sulaiman , Vakilian Saeid , Al-kindi Juhaina , Rehman Najeeb Ur , Alam Khurshid , Al-Riyami Khamis , Csuk Rene , Arefian Ehsan , Al-Harrasi Ahmed 
Published: November 2022

AbstractThis study aimed to compare the effect of Boswellic acid derivatives on the viability, apoptosis, and epigenomic profiling of breast cancer. According to the viability assays, 3-O-acetyl-11-keto-β-Boswellic acid (AKBA) showed more toxicity against MDA-MB-231 cells when compared with the 3-O-acetyl-β-Boswellic acid (ABA). In contrast, ABA revealed less toxicity against MCF-10A. Cell cycle and apoptosis assays determined the maximum apoptotic effect of AKBA on MCF-7, and MDA-MB-231 cells. Interestingly, β-Boswellic acid (BA) and ABA did not promote the apoptosis in MCF-10A cells. Transwell migration assay indicated the greatest normalized inhibition (around 160%) in the migration of MDA-MB-231 cells induced by AKBA. The expression of P53, BAX, and BCL2 genes in cancerous cell lines has affirmed that both AKBA and ABA could induce the maximal apoptosis. Western-blot investigation demonstrated that the maximum over-expression of P53 protein (1.96 times) was caused by AKBA in MDA-MB-231 cells, followed by ABA in MCF-7 cells. The BCL2 protein expression was in agreement with the previously reported results. The global DNA methylation in both cancerous cells was reduced by ABA. These results suggest that ABA represented more epigenetic modulatory effect while AKBA shows more cytotoxic and apoptotic effect against breast cancer cell lines.
Beneficial effects of SS-31 peptide on cardiac mitochondrial dysfunction in tafazzin knockdown mice
Authors: Russo Silvia , De Rasmo Domenico , Signorile Anna , Corcelli Angela , Lobasso Simona 
Published: November 2022

AbstractBarth Syndrome (BTHS), a genetic disease associated with early-onset cardioskeletal myopathy, is caused by loss-of-function mutations of the TAFAZZIN gene, which is responsible for remodeling the mitochondrial phospholipid cardiolipin (CL). Deregulation of CL biosynthesis and maturation in BTHS mitochondria result in a dramatically increased monolysocardiolipin (MLCL)/CL ratio associated with bioenergetic dysfunction. One of the most promising therapeutic approaches for BTHS includes the mitochondria-targeted tetrapeptide SS-31, which interacts with CL. Here, we used TAFAZZIN knockdown (TazKD) mice to investigate for the first time whether in vivo administration of SS-31 could affect phospholipid profiles and mitochondrial dysfunction. The CL fingerprinting of TazKD cardiac mitochondria obtained by MALDI-TOF/MS revealed the typical lipid changes associated with BTHS. TazKD mitochondria showed lower respiratory rates in state 3 and 4 together with a decreased in maximal respiratory rates. Treatment of TazKD mice with SS-31 improved mitochondrial respiratory capacity and promoted supercomplex organization, without affecting the MLCL/CL ratio. We hypothesize that SS-31 exerts its effect by influencing the function of the respiratory chain rather than affecting CL directly. In conclusion, our results indicate that SS-31 have beneficial effects on improving cardiac mitochondrial dysfunction in a BTHS animal model, suggesting the peptide as future pharmacologic agent for therapy.