bluuebunny/crossref_metadata_2025 huggingface dataset:
Histone Marks-Dependent Effect on Alternative Splicing: New Perspectives for Targeted Splicing Modulation in Cancer?
Authors: Imbriano Carol , Belluti Silvia
Published: July 2022

Alternative splicing (AS) is a tightly regulated mechanism that generates the complex human proteome from a small number of genes. Cis-regulatory RNA motifs in exons and introns control AS, recruiting positive and negative trans-acting splicing regulators. At a higher level, chromatin affects splicing events. Growing evidence indicates that the popular histone code hypothesis can be extended to RNA-level processes, such as AS. In addition to nucleosome positioning, which can generate transcriptional barriers to shape the final splicing outcome, histone post-translational modifications can contribute to the detailed regulation of single exon inclusion/exclusion. A histone-based system can identify alternatively spliced chromatin stretches, affecting RNAPII elongation locally or recruiting splicing components via adaptor complexes. In tumor cells, several mechanisms trigger misregulated AS events and produce cancer-associated transcripts. On a genome-wide level, aberrant AS can be the consequence of dysfunctional epigenetic splicing code, including altered enrichment in histone post-translational modifications. This review describes the main findings related to the effect of histone modifications and variants on splicing outcome and how a dysfunctional epigenetic splicing code triggers aberrant AS in cancer. In addition, it highlights recent advances in programmable DNA-targeting technologies and their possible application for AS targeted epigenetic modulation.
Platelet-Rich Fibrin Reduces IL-1β Release from Macrophages Undergoing Pyroptosis
Authors: Sordi Mariane Beatriz , Panahipour Layla , Kargarpour Zahra , Gruber Reinhard
Published: July 2022

Background: Pyroptosis is a catabolic process relevant to periodontal disorders for which interleukin-1β (IL-1β) inflammation is central to the pathophysiology of the disease. Despite platelet-rich fibrin (PRF) anti-inflammatory properties and its application to support periodontal regeneration, the capacity of PRF to modulate pyroptosis, specifically the production and release of IL-1β, remains unknown. The question arises whether PRF could regulate IL-1β release from macrophages in vitro. Methods: To answer this question, RAW 264.7 macrophages and primary macrophages obtained from murine bone marrow were primed with PRF before being challenged by lipopolysaccharide (LPS). Cells were then analysed for the pyroptosis signalling components by gene expression analyses and IL-1β secretion at the protein level. The release of mitochondrial reactive oxygen species (ROS) was also detected. Results: PRF lowered the LPS-induced expression of IL-1β and NLRP3 inflammasome, caspase-11 and IL-18 in primary macrophages, and IL-1β and caspase-11 in RAW 264.7 cells. Additionally, PRF diminished the secretion of IL-1β at the protein level in LPS-induced RAW 264.7 cells. This was shown through immunoassays performed with the supernatant and further confirmed by analysing the lysates of permeabilised cells. Furthermore, PRF reduced the ROS release provoked by LPS in RAW 264.7 cells. Finally, to enhance IL-1β release from the LPS-primed macrophages, we introduced a second signal with adenosine triphosphate (ATP). In this setting, PRF significantly reduced IL-1β release in RAW 264.7 cells and a trend to diminish IL-1β release in primary macrophages. Conclusion: These findings suggest that PRF can reduce IL-1β release and, at least in part, inhibit pyroptosis-related factors in LPS-challenged macrophages.
Comparative Transcriptome Analysis Reveals Coordinated Transcriptional Regulation of Central and Secondary Metabolism in the Trichomes of Cannabis Cultivars
Authors: Yeo Hock Chuan , Reddy Vaishnavi Amarr , Mun Bong-Gyu , Leong Sing Hui , Dhandapani Savitha , Rajani Sarojam , Jang In-Cheol
Published: July 2022

Cannabis is one of the few plant genera capable of producing cannabinoids, the effects of which are synergized by terpene interactions. As the biosynthesis of both metabolite classes requires the same intracellular feedstocks, this work describes the coordinated regulation of global metabolic pathways that allows for their joint copious production in vivo. To this end, a transcriptomics-based approach to characterize the glandular trichomes of five Cannabis cultivars was pursued. Besides revealing metabolic traits that enhanced and proportionated the supply of critical carbon precursors, in-depth analysis showed significantly increased gene expression of two particular enzymes to meet the huge nicotinamide adenine dinucleotide phosphate (NADPH) demand of secondary metabolite production. Furthermore, it led to a hypothesis that the methyl-d-erythritol 4-phosphate pathway might be utilized more than the mevalonic acid pathway in Cannabis trichomes. While both pathways were found to be activated in a modular and calibrated way that reflected their broad participation in physiological processes, the genes for hexanoate, cannabinoid, and terpene biosynthesis were, in contrast, up-regulated in an en bloc and multi-loci manner due to their specific roles in secondary metabolite production. In addition, three new terpene synthases were characterized based on both in silico and experimental assays. Altogether, the study enhances the current understanding of secondary metabolite production in Cannabis cultivars, which may assist in their characterization and development.
Neuronal ApoE Regulates the Cell-to-Cell Transmission of α-Synuclein
Authors: Kang Seo-Jun , Kim Soo-Jeong , Noh Hye Rin , Kim Beom Jin , Kim Jae-Bong , Jin Uram , Park Sun Ah , Park Sang Myun
Published: July 2022

The presence of protein inclusions, called Lewy bodies (LBs) and Lewy neurites (LNs), in the brain is the main feature of Parkinson’s disease (PD). Recent evidence that the prion-like propagation of α-synuclein (α-syn), as a major component of LBs and LNs, plays an important role in the progression of PD has gained much attention, although the molecular mechanism remains unclear. In this study, we evaluated whether neuronal ApoE regulates the cell-to-cell transmission of α-syn and explored its molecular mechanism using in vitro and in vivo model systems. We demonstrate that neuronal ApoE deficiency attenuates both α-syn uptake and release by downregulating LRP-1 and LDLR expression and enhancing chaperone-mediated autophagy activity, respectively, thereby contributing to α-syn propagation. In addition, we observed that α-syn propagation was attenuated in ApoE knockout mice injected with pre-formed mouse α-syn fibrils. This study will help our understanding of the molecular mechanisms underlying α-syn propagation.
Induced Zinc Loss Produces Heterogenous Biological Responses in Melanoma Cells
Authors: Rudolf Emil , Rudolf Kamil
Published: July 2022

Zinc levels in serum and/or tissue are reported to be altered in melanoma with unknown effects on melanoma development and biology. The purpose of this study was to examine the effects of acute chelation of free intracellular zinc pools in melanoma cell lines Bowes and A375, as well as selected melanoma tissue explants with high or low intracellular free zinc. Zinc chelating agent TPEN at the concentration of 25 µM was employed during 48 h, which significantly reduced intracellular free zinc while decreasing melanoma cell proliferation, inducing G1/S arrest and cell damage leading to mitochondrial, caspase-dependent apoptosis. Chelation of free zinc was also associated with increased generation of superoxide in cell lines but not marked lysosomal membrane damage. Conversely, melanoma explant cultures mostly displayed time-dependent loss of lysosomal membrane integrity in the presence of slowly growing superoxide levels. Loss of free zinc-dependent p53 activity was similarly disparate in individual melanoma models. Surviving melanoma cells were arrested in the cell cycle, and varying proportions of them exhibited features characteristic of premature senescence, which increased in time despite zinc reloading. The present results show that melanoma cells with varying free zinc levels respond to its acute loss in a number of individual ways, reflecting activated mechanisms including oxidative stress, lysosomal damage, and p53 activity leading to heterogenous outcomes including cell death, transient, and/or permanent cell cycle arrest and premature senescence.
Adropin’s Role in Energy Homeostasis and Metabolic Disorders
Authors: Ali Ifrah Ismail , D’Souza Crystal , Singh Jaipaul , Adeghate Ernest
Published: July 2022

Adropin is a novel 76-amino acid-peptide that is expressed in different tissues and cells including the liver, pancreas, heart and vascular tissues, kidney, milk, serum, plasma and many parts of the brain. Adropin, encoded by the Enho gene, plays a crucial role in energy homeostasis. The literature review indicates that adropin alleviates the degree of insulin resistance by reducing endogenous hepatic glucose production. Adropin improves glucose metabolism by enhancing glucose utilization in mice, including the sensitization of insulin signaling pathways such as Akt phosphorylation and the activation of the glucose transporter 4 receptor. Several studies have also demonstrated that adropin improves cardiac function, cardiac efficiency and coronary blood flow in mice. Adropin can also reduce the levels of serum triglycerides, total cholesterol and low-density lipoprotein cholesterol. In contrast, it increases the level of high-density lipoprotein cholesterol, often referred to as the beneficial cholesterol. Adropin inhibits inflammation by reducing the tissue level of pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6. The protective effect of adropin on the vascular endothelium is through an increase in the expression of endothelial nitric oxide synthase. This article provides an overview of the existing literature about the role of adropin in different pathological conditions.
Microbeam Irradiation as a Simultaneously Integrated Boost in a Conventional Whole-Brain Radiotherapy Protocol
Authors: Jaekel Felix , Bräuer-Krisch Elke , Bartzsch Stefan , Laissue Jean , Blattmann Hans , Scholz Marten , Soloviova Julia , Hildebrandt Guido , Schültke Elisabeth
Published: July 2022

Microbeam radiotherapy (MRT), an experimental high-dose rate concept with spatial fractionation at the micrometre range, has shown a high therapeutic potential as well as good preservation of normal tissue function in pre-clinical studies. We investigated the suitability of MRT as a simultaneously integrated boost (SIB) in conventional whole-brain irradiation (WBRT). A 174 Gy MRT SIB was administered with an array of quasi-parallel, 50 µm wide microbeams spaced at a centre-to-centre distance of 400 µm either on the first or last day of a 5 × 4 Gy radiotherapy schedule in healthy adult C57 BL/6J mice and in F98 glioma cell cultures. The animals were observed for signs of intracranial pressure and focal neurologic signs. Colony counts were conducted in F98 glioma cell cultures. No signs of acute adverse effects were observed in any of the irradiated animals within 3 days after the last irradiation fraction. The tumoricidal effect on F98 cell in vitro was higher when the MRT boost was delivered on the first day of the irradiation course, as opposed to the last day. Therefore, the MRT SIB should be integrated into a clinical radiotherapy schedule as early as possible.
Metformin: When Should We Fear Lactic Acidosis?
Authors: Di Mauro Stefania , Filippello Agnese , Scamporrino Alessandra , Purrello Francesco , Piro Salvatore , Malaguarnera Roberta
Published: July 2022

Metformin, a molecule belonging to the biguanide family, represents one of the most commonly prescribed medications for the treatment of diabetes mellitus in the world. Over the sixty years during which it has been used, many benefits have been described, which are not limited to the treatment of diabetes mellitus. However, since metformin is similar to other members of the same drug family, there is still much concern regarding the risk of lactic acidosis. This article aims to highlight the correlation between the use of metformin and the onset of renal damage or lactic acidosis. Metformin-associated lactic acidosis exists; however, it is rare. The appropriate use of the drug, under safe conditions, induces benefits without risks.
Vitamin D Receptor and Its Influence on Multiple Sclerosis Risk and Severity: From Gene Polymorphisms to Protein Expression
Authors: Pistono Cristiana , Osera Cecilia , Monti Maria Cristina , Boiocchi Chiara , Mallucci Giulia , Cuccia Mariaclara , Montomoli Cristina , Bergamaschi Roberto , Pascale Alessia
Published: July 2022

Multiple sclerosis (MS) is a multifactorial neurodegenerative disease. Low levels of vitamin D are a risk factor for MS and alterations in the vitamin D receptor (VDR) might be a risk factor as well. This study aimed to evaluate whether the VDR rs731236 (Taq-I) and rs4334089 (HpyCH4V) gene polymorphisms and VDR protein expression are associated with MS risk and severity. Vitamin D plasma levels were analyzed in a group of patients. Additional analyses of VDR protein expression and vitamin D levels of patients with different forms of MS (MSSS < 3 and MSSS ≥ 3) were performed. The analysis of the genotypic and allelic frequencies revealed that the rs731236 (Taq-I) gene polymorphism is significantly associated with MS presence. Although the total, cytosolic and nuclear VDR protein contents do not change between MS patients and healthy controls and between patients with different MS severity, vitamin D levels decrease in parallel with an increase in MSSS.
Fluoro-Germanium (IV) Cations with Neutral Co-Ligands—Synthesis, Properties and Comparison with Neutral GeF4 Adducts
Authors: Woodward Madeleine S. , King Rhys P. , Bannister Robert D. , Grigg Julian , McRobbie Graeme , Levason William , Reid Gillian
Published: July 2022

The reaction of [GeF4L2], L = dmso (Me2SO), dmf (Me2NCHO), py (pyridine), pyNO (pyridine-N-oxide), OPPh3, OPMe3, with Me3SiO3SCF3 (TMSOTf) and monodentate ligands, L, in a 1:1:1 molar ratio in anhydrous CH2Cl2 formed the monocations [GeF3L3][OTf]. These rare trifluoro-germanium (IV) cations were characterised by microanalysis, IR, 1H, 19F{1H} and, where appropriate, 31P{1H} NMR spectroscopy. The 19F{1H} NMR data show that in CH3NO2 solution the complexes exist as a mixture of mer and fac isomers, with the mer isomer invariably having the higher abundance. The X-ray structure of mer-[GeF3(OPPh3)3][OTf] is also reported. The attempts to remove a second fluoride using a further equivalent of TMSOTf and L were mostly unsuccessful, although a mixture of [GeF2(OAsPh3)4][OTf]2 and [GeF3(OAsPh3)3][OTf] was obtained using excess TMSOTf and OAsPh3. The reaction of [GeF4(MeCN)2] with TMSOTf in CH2Cl2 solution, followed by the addition of 2,2′:6′,2”-terpyridine (terpy) formed mer-[GeF3(terpy)][OTf], whilst a similar reaction with 1,4,7-trimethyl-1,4,7-triazacyclononane (Me3-tacn) in MeCN solution produced fac-[GeF3(Me3-tacn)][OTf]. Dicationic complexes bearing the GeF22+ fragment were isolated using the tetra-aza macrocycles, 1,4,7,10-tetramethyl-1,4,7,10-tetra-azacyclododecane (Me4-cyclen) and 1,4,8,11-tetramethyl-1,4,8,11-tetra-azacyclotetradecane (Me4-cyclam), which reacted with [GeF4(MeCN)2] and two equivalents of TMSOTf to cleanly form the dicationic difluoride salts, cis-[GeF2(Me4-cyclen)][OTf]2 and trans-[GeF2(Me4-cyclam)][OTf]2. The 19F{1H} NMR spectroscopy shows that in CH3NO2 solution there are four stereoisomers present for trans-[GeF2(Me4-cyclam)][OTf]2, whereas the smaller ring-size of Me4-cyclen accounts for the formation of only cis-[GeF2(Me4-cyclen)][OTf], and is confirmed crystallographically. New spectroscopic data are also reported for [GeF4(L)2] (L = dmso, dmf and pyNO). Density functional theory calculations were used to probe the effect on the bonding as fluoride ligands were sequentially removed from the germanium centre in the OPMe3 complexes.
Integrating Global Citizen Science Platforms to Enable Next-Generation Surveillance of Invasive and Vector Mosquitoes
Authors: Carney Ryan , Mapes Connor , Low Russanne , Long Alex , Bowser Anne , Durieux David , Rivera Karlene , Dekramanjian Berj , Bartumeus Frederic , Guerrero Daniel , Seltzer Carrie , Azam Farhat , Chellappan Sriram , Palmer John
Published: July 2022

Mosquito-borne diseases continue to ravage humankind with >700 million infections and nearly one million deaths every year. Yet only a small percentage of the >3500 mosquito species transmit diseases, necessitating both extensive surveillance and precise identification. Unfortunately, such efforts are costly, time-consuming, and require entomological expertise. As envisioned by the Global Mosquito Alert Consortium, citizen science can provide a scalable solution. However, disparate data standards across existing platforms have thus far precluded truly global integration. Here, utilizing Open Geospatial Consortium standards, we harmonized four data streams from three established mobile apps—Mosquito Alert, iNaturalist, and GLOBE Observer’s Mosquito Habitat Mapper and Land Cover—to facilitate interoperability and utility for researchers, mosquito control personnel, and policymakers. We also launched coordinated media campaigns that generated unprecedented numbers and types of observations, including successfully capturing the first images of targeted invasive and vector species. Additionally, we leveraged pooled image data to develop a toolset of artificial intelligence algorithms for future deployment in taxonomic and anatomical identification. Ultimately, by harnessing the combined powers of citizen science and artificial intelligence, we establish a next-generation surveillance framework to serve as a united front to combat the ongoing threat of mosquito-borne diseases worldwide.
Sex Differences in Acute Coronary Syndromes: A Global Perspective
Authors: Cader F Aaysha , Banerjee Shrilla , Gulati Martha
Published: July 2022

Despite increasing evidence and improvements in the care of acute coronary syndromes (ACS), sex disparities in presentation, comorbidities, access to care and invasive therapies remain, even in the most developed countries. Much of the currently available data are derived from more developed regions of the world, particularly Europe and the Americas. In contrast, in more resource-constrained settings, especially in Sub-Saharan Africa and some parts of Asia, more data are needed to identify the prevalence of sex disparities in ACS, as well as factors responsible for these disparities, particularly cultural, socioeconomic, educational and psychosocial. This review summarizes the available evidence of sex differences in ACS, including risk factors, pathophysiology and biases in care from a global perspective, with a focus on each of the six different World Health Organization (WHO) regions of the world. Regional trends and disparities, gaps in evidence and solutions to mitigate these disparities are also discussed.
The Effect of Dental Treatments in Caries Management on Stress and Salivary Protein Levels
Authors: Vacaru Raluca-Paula , Didilescu Andreea Cristiana , Sfeatcu Ruxandra , Tănase Mihaela , Munteanu Aneta , Miricescu Daniela , Kaman Wendy Esmeralda , Brand Hendrik Simon
Published: July 2022

A great burden is put on healthcare systems by dental caries and understanding patients’ treatment needs is of utmost importance. The aim of this pre–post study was to assess dental anxiety and the psychological stress induced by two different types of dental treatment (prophylaxis and cavity preparation), by combining psychometric evaluations with salivary biomarkers, in a group of 28 schoolchildren presenting in a university clinic. Pre- and post-treatment unstimulated whole saliva was collected and levels of cortisol, alpha-amylase (sAA) and total protein content were measured. The State–Trait Anxiety Inventory for Children and the Frankl Behaviour Rating Scale (FBRS) were applied. Statistical analysis was performed using the Stata/IC 16 (StataCorp) programme. All salivary parameters showed strong positive correlations between pre- and post-treatment levels. Post-treatment, salivary cortisol decreased (p = 0.008, paired t-test), sAA did not change significantly (p = 0.572, sign test), while the sAA/cortisol ratio (AOC) increased (p = 0.036, sign test). There were no correlations between state and trait anxiety levels. State anxiety scores registered significantly higher values for children with an FBRS score of 3 compared with a score of 4 (p < 0.001, unpaired t-test). The post-treatment decrease in the salivary cortisol level was higher for prophylaxis compared with the cavity preparation group (p = 0.024, t-test). These results demonstrate that sAA and cortisol levels are altered differently by psychological stress induced by two different types of dental treatment.
Neuroendocrine Tumors: Challenges and Future Perspectives
Authors: Lamberti Giuseppe , La Salvia Anna
Published: July 2022

The awareness and interest of the scientific community towards Neuroendocrine tumors (NETs) has progressively increased in the last few decades [...]
Is Pulmonary Artery Pulsatility Index (PAPi) a Predictor of Outcome after Pulmonary Endarterectomy?
Authors: Martin-Suarez Sofia , Gliozzi Gregorio , Cavalli Giulio Giovanni , Orioli Valentina , Loforte Antonio , Pastore Saverio , Rossi Barbara , Zardin Davide , Galiè Nazzareno , Palazzini Massimiliano , Dardi Fabio , Saia Francesco , Niro Fabio , Pacini Davide
Published: July 2022

Background: Pulmonary endarterectomy (PEA) is the gold standard therapy for chronic thromboembolic pulmonary hypertension (CTEPH). Traditionally, pulmonary vascular resistance (PVR) represents the main prognostic factor after surgery. The pulmonary artery pulsatility index (PAPi) has been proposed for the assessment of RV in advanced heart failure, but it has never been applied in CTEPH patients. The aim of the present study is to describe PAPi in patients who underwent PEA, before and after surgery, and to define its predictive impact on postoperative outcomes. Methods: We retrospectively reviewed 188 consecutive adult patients who underwent PEA, between December 2003 and December 2021. PAPi was calculated for 186 patients and reported. Patients were partitioned in two groups using median preoperative PAPi as cutoff value: Group 1 with PAPi ≤ 8.6 (n = 94) and Group 2 with PAPi > 8.6 (n = 92). The propensity-score-matched analysis identified 67 pairs: Early outcomes were compared between two groups. Results: Mean preoperative PAPi was 10.3 ± 7.2. Considering matched populations, no differences emerged in terms of postoperative hemodynamics; Group 1 demonstrated higher 90-day mortality significance (10.4% vs. 3.0%, p = 0.082); the need for mechanical circulatory support (MCS) was similar, but successful weaning was unlikely (25% vs. 85.7%, p = 0.032). Conclusions: Mean PAPi in the CTEPH population is higher than in other diseases. Low PAPi (≤8.6) seems to be associated with lower postoperative survival and successful weaning from MCS.
Transurethral Incisions for Bladder Neck Contracture: Comparable Results without Intralesional Injections
Authors: Nealon Samantha W. , Bhanvadia Raj R. , Badkhshan Shervin , Sanders Sarah C. , Hudak Steven J. , Morey Allen F.
Published: July 2022

To present our 12-year experience using an endoscopic approach to manage bladder neck contracture (BNC) without adjunctive intralesional agents and compare it to published series not incorporating them, we retrospectively reviewed 123 patients treated for BNC from 2008 to 2020. All underwent 24 Fr balloon dilation followed by transurethral incision of BNC (TUIBNC) with deep incisions at 3 and 9 o’clock using a Collins knife without the use of intralesional injections. Success was defined as a patent bladder neck and 16 Fr cystoscope passage into the bladder two months later. Most with recurrent BNC underwent repeat TUIBNC. Success rates, demographics, and BNC characteristics were analyzed. The etiology of BNC in our cohort was most commonly radical prostatectomy with or without radiation (36/123, 29.3%, 40/123, 32.5%). Some had BNC treatment prior to referral (30/123, 24.4%). At 12-month follow-up, bladder neck patency was observed in 101/123 (82.1%) after one TUIBNC. An additional 15 patients (116/123, 94.3%) had success after two TUIBNCs. On univariate and multivariate analyses, ≥2 endoscopic treatments was the only factor associated with failure. TUIBNC via balloon dilation and deep bilateral incisions without the use of adjunctive intralesional injections has a high patency rate. History of two or more prior endoscopic procedures is associated with failure.
Association between Cardiorespiratory Fitness and Hypertensive Disorders of Pregnancy: A Systematic Review and Meta-Analysis
Authors: Al-Huda Farah , Shapiro Gabriel D. , Davenport Margie H. , Bertagnolli Mariane , Dayan Natalie
Published: July 2022

Hypertensive disorders of pregnancy (HDP) are associated with future cardiovascular disease (CVD), which may be mediated by diminished cardiorespiratory fitness (CRF). In this systematic review and meta-analysis, we summarize evidence linking CRF with HDP before, during, and after pregnancy. We searched relevant databases to identify observational or randomized studies that measured CRF (VO2 max or peak, VO2 at anaerobic threshold, or work rate at peak VO2) in women with and without HDP. We pooled results using random effects models. Fourteen studies (n = 2406 women) reporting on CRF before, during, and after pregnancy were included. Before pregnancy, women who developed HDP had lower CRF (e.g., VO2max < 37 vs. ≥37 mL O2/min) than those without HDP (two studies, 811 women). VO2max at 14–18 weeks of pregnancy was marginally lower among women who developed preeclampsia vs. normotensive women (three studies, 275 women; mean difference 0.43 mL/kg/min [95% CI 0.97, 0.10]). Postpartum, there was a trend towards lower VO2peak in women with previous preeclampsia (three studies, 208 women; 0.26 mL/kg/min [−0.54, 0.02]). While exploratory, our findings raise the possibility that CRF can identify women at risk for HDP, and furthermore, that HDP confers a hit to a woman’s cardiorespiratory reserve.
Plasma Transfusion in Septic Shock—A Secondary Analysis of a Retrospective Single-Center Cohort
Authors: Dietrich Maximilian , Hölle Tobias , Lalev Lazar Detelinov , Loos Martin , Schmitt Felix Carl Fabian , Fiedler Mascha Onida , Hackert Thilo , Richter Daniel Christoph , Weigand Markus Alexander , Fischer Dania
Published: July 2022

In sepsis, both beneficial and detrimental effects of fresh frozen plasma (FFP) transfusion have been reported. The aim of this study was to analyze the indication for and effect of FFP transfusion in patients with septic shock. We performed a secondary analysis of a retrospective single-center cohort of all patients treated for septic shock at the interdisciplinary surgical intensive care unit (ICU) of the Heidelberg University Hospital. Septic shock was defined according to sepsis-3 criteria. To assess the effects of FFP administration in the early phase of septic shock, we compared patients with and without FFP transfusion during the first 48 h of septic shock. Patients who died during the first 48 h of septic shock were excluded from the analysis. Primary endpoints were 30- and 90-day mortality. A total of 261 patients were identified, of which 100 (38.3%) received FFP transfusion within the first 48 h after septic shock onset. The unmatched analysis showed a trend toward higher 30- and 90-d mortality in the FFP group (30 d: +7% p = 0.261; 90 d: +11.9% p = 0.061). In the propensity-matched analysis, 30- and 90-day mortality were similar between groups. Plasma administration did not influence fluid or vasopressor need, lactate levels, ICU stay, or days on a ventilator. We found no significant harm or associated benefit of FFP use in the early phase of septic shock. Finally, plasma should only be used in patients with a strong indication according to current recommendations, as a conclusive evaluation of the risk-benefit ratio for plasma transfusion in septic shock cannot be made based on the current data.
Novel Therapies and Approaches to Inflammatory Bowel Disease (IBD)
Authors: Furfaro Federica , Ragaini Elisa , Peyrin-Biroulet Laurent , Danese Silvio
Published: July 2022

Inflammatory bowel diseases (IBDs), divided into two predominant groups, Crohn’s disease (CD) and ulcerative colitis (UC), are chronic relapsing inflammatory diseases of the gastrointestinal tract, resulting from an aberrant immune response to microbes in the gut, in genetically susceptible patients [...]
The Role of Protein Kinase CK2 in Development and Disease Progression: A Critical Review
Authors: Halloran Daniel , Pandit Venu , Nohe Anja
Published: July 2022

Protein kinase CK2 (CK2) is a ubiquitous holoenzyme involved in a wide array of developmental processes. The involvement of CK2 in events such as neurogenesis, cardiogenesis, skeletogenesis, and spermatogenesis is essential for the viability of almost all organisms, and its role has been conserved throughout evolution. Further into adulthood, CK2 continues to function as a key regulator of pathways affecting crucial processes such as osteogenesis, adipogenesis, chondrogenesis, neuron differentiation, and the immune response. Due to its vast role in a multitude of pathways, aberrant functioning of this kinase leads to embryonic lethality and numerous diseases and disorders, including cancer and neurological disorders. As a result, CK2 is a popular target for interventions aiming to treat the aforementioned diseases. Specifically, two CK2 inhibitors, namely CX-4945 and CIBG-300, are in the early stages of clinical testing and exhibit promise for treating cancer and other disorders. Further, other researchers around the world are focusing on CK2 to treat bone disorders. This review summarizes the current understanding of CK2 in development, the structure of CK2, the targets and signaling pathways of CK2, the implication of CK2 in disease progression, and the recent therapeutics developed to inhibit the dysregulation of CK2 function in various diseases.
Geometry-Based Computational Fluid Dynamic Model for Predicting the Biological Behavior of Bone Tissue Engineering Scaffolds
Authors: Omar Abdalla M. , Hassan Mohamed H. , Daskalakis Evangelos , Ates Gokhan , Bright Charlie J. , Xu Zhanyan , Powell Emily J. , Mirihanage Wajira , Bartolo Paulo J. D. S.
Published: July 2022

The use of biocompatible and biodegradable porous scaffolds produced via additive manufacturing is one of the most common approaches in tissue engineering. The geometric design of tissue engineering scaffolds (e.g., pore size, pore shape, and pore distribution) has a significant impact on their biological behavior. Fluid flow dynamics are important for understanding blood flow through a porous structure, as they determine the transport of nutrients and oxygen to cells and the flushing of toxic waste. The aim of this study is to investigate the impact of the scaffold architecture, pore size and distribution on its biological performance using Computational Fluid Dynamics (CFD). Different blood flow velocities (BFV) induce wall shear stresses (WSS) on cells. WSS values above 30 mPa are detrimental to their growth. In this study, two scaffold designs were considered: rectangular scaffolds with uniform square pores (300, 350, and 450 µm), and anatomically designed circular scaffolds with a bone-like structure and pore size gradient (476–979 µm). The anatomically designed scaffolds provided the best fluid flow conditions, suggesting a 24.21% improvement in the biological performance compared to the rectangular scaffolds. The numerical observations are aligned with those of previously reported biological studies.
High-Temporal-Resolution Object Detection and Tracking Using Images and Events
Authors: El Shair Zaid , Rawashdeh Samir A.
Published: July 2022

Event-based vision is an emerging field of computer vision that offers unique properties, such as asynchronous visual output, high temporal resolutions, and dependence on brightness changes, to generate data. These properties can enable robust high-temporal-resolution object detection and tracking when combined with frame-based vision. In this paper, we present a hybrid, high-temporal-resolution object detection and tracking approach that combines learned and classical methods using synchronized images and event data. Off-the-shelf frame-based object detectors are used for initial object detection and classification. Then, event masks, generated per detection, are used to enable inter-frame tracking at varying temporal resolutions using the event data. Detections are associated across time using a simple, low-cost association metric. Moreover, we collect and label a traffic dataset using the hybrid sensor DAVIS 240c. This dataset is utilized for quantitative evaluation using state-of-the-art detection and tracking metrics. We provide ground truth bounding boxes and object IDs for each vehicle annotation. Further, we generate high-temporal-resolution ground truth data to analyze tracking performance at different temporal rates. Our approach shows promising results, with minimal performance deterioration at higher temporal resolutions (48–384 Hz) when compared with the baseline frame-based performance at 24 Hz.
Research of Intelligent Logistics and High-Quality Economy Development for Yangtze River Cold Chain Shipping Based on Carbon Neutrality
Authors: Xiao Ruiqi , Pan Lin , Xiao Hanbin , Xiao Han , Zhu Ze
Published: July 2022

The current status of intelligent logistics and cold chain shipping research is a hot topic worldwide. Meanwhile, the study of regional logistics and regional economy, shipping logistics and regional economic theory and application methods, and the empirical analysis of the correlation between the Yangtze River shipping and the Yangtze River shipping economy have attracted a lot of attention. This research has revealed that the Internet of Things of Yangtze River shipping has a great impact on the Yangtze River and the importance of inland river economic development. This study presents the empirical analysis on the correlation between shipping logistics and the inland river economy, starting from qualitative and quantitative aspects, and taking Yangtze River shipping as the representative. The proposed mathematical models and qualitative data analysis are made on the relevant effects of intelligent logistics and cold chain shipping on an inland river economy including its impact on the industrial layout, international trade, and urbanization. The research results provide administrative decisions or guidance values for the economic development of inland river ports in the Yangtze River.
A Direct Damage Stability Calculation Method for an Onboard Loading Computer
Authors: Liu Chunlei , Huang Lianzhong , Sun Xiaofeng , Yin Yong
Published: July 2022

The stability analysis of a damaged ship is both important and challenging for an onboard loading computer. To help ship operators make reasonable decisions, a Simplified Newton Iteration Method is proposed to calculate damage stability in real time based on 3D geometric models of the ship. A 7500-dead-weight-tonnage (DWT) asphalt tanker, “TAI HUA WAN”, is used to illustrate the effectiveness of the proposed approach. The damage stability results of 18 typical loading conditions are calculated. The average error of righting lever GZ is 0.002 m, and the average number of iterations is nine. The calculation results show that the proposed method is simple, with real-time processes, robustness, accuracy, and certain practical value for engineering. Furthermore, based on the proposed method, a loading computer, “SMART LOAD”, has been developed and approved by LR, DNV, CCS, ABS, NK and the BV Classification Society and has been installed on more than 150 vessels worldwide.
CFD-FEM Analysis of Flow-Induced Vibrations in Waterjet Propulsion Unit
Authors: Dai Yuanxing , Liu Zhenghao , Zhang Wei , Chen Jianping , Liu Jianguo
Published: July 2022

This paper investigates the problem of vibration in an axial flow waterjet propeller with high power density and low specific speed. Based on fluid–structure coupling vibration analysis, combined with modal analysis and ship tests, the unsteady fluid–structure coupling of a waterjet propeller is examined, and the vibration characteristics of the propeller under different speed conditions are studied. The results show that the vibrations of the waterjet propeller mainly come from the frequency response of the rotor and the structural resonance response. The frequency distribution characteristics and amplitude intensity are observed to increase with increasing rotation speed. The variations in the propeller vibration characteristics, with respect to parameter changes, are analyzed at different gap spacings between the rotor and stator, allowing the variation law of vibration intensity with rotor stator spacing to be obtained.
Molecular Characterization, Evolution and Expression Analysis of TNFSF14 and Three TNFSF Receptors in Spotted Gar Lepisosteus oculatus
Authors: Wu Yaxin , Jia Zhao , Dang Huifeng , Xiao Hehe , Huang Wenji , Liu Qin , Chen Kangyong , Zhang Lei , Zou Jun , Wang Junya
Published: July 2022

The tumor necrosis superfamily (TNFSF) and their receptors (TNFRs) play an essential role in inflammatory responses. In this study, tnfsf14, tnfrsf1a, tnfrsf1b and tnfrsf14 were identified in spotted gar. All the genes have conserved genomic organization and synteny with their respective homologs in zebrafish and humans. The putative TNFSF protein contains a typical TNF homology domain in the extracellular region. All three TNFRSFs possess characteristic cysteine-rich domains. TNFRSF1a has a death domain in the cytosolic region which is absent in the TNFRSF1b and TNFRSF14. Notably, TNFRSF14 lacks a transmembrane domain and is predicted to be secreted. Protein structure modeling revealed that the key residues involved in the interaction between TNFSF14 and TNFRSF14 are well conserved in spotted gar. All four genes were ubiquitously expressed in the spleen, liver, kidney, gills and intestine. Infection with Klebsiella pneumoniae resulted in remarkable downregulation of tnfsf14 and tnfrsf14 in tissues but upregulation of tnfrsf1a and tnfrsf1b. The results indicate that tnfsf14, tnfrsf1a, tnfrsf1b and tnfrsf14 are involved in the immune response to bacterial infection, and expand knowledge on the TNF system in the primitive ray-finned fish.
The Seabed Makes the Dolphins: Physiographic Features Shape the Size and Structure of the Bottlenose Dolphin Geographical Units
Authors: Gnone Guido , Bellingeri Michela , Molinari Yvan , Dhermain Frank , Labach Hélène , Díaz López Bruno , David Léa , Di Meglio Nathalie , Azzinari Georges , Azzinari Caroline , Airoldi Sabina , Lanfredi Caterina , Gonzalvo Joan , De Santis Valentina , Nuti Silvio , Álvarez Chicote Carla , Gazo Manel , Mandich Alberta , Alessi Jessica , Azzellino Arianna , Tomasi Nicolas , Santoni Marie-Catherine , Mancusi Cecilia , Falabrino Marta , Cañadas Ana Maria
Published: July 2022

The common bottlenose dolphin (Tursiops truncatus) is a cosmopolitan delphinid, regularly present in the Mediterranean Sea. According to previous studies, this dolphin tends to form resident geographical units scattered on the continental shelf. We investigated how the physiographic characteristics of the area of residence, with special reference to the size and shape of the continental shelf, affect the home range and the group size of the local units. We analysed and compared data collected between 2004–2016 by 15 research groups operating in different study areas of the Mediterranean Sea: the Alboran Sea, in the South-Western Mediterranean, the Gulf of Lion and the Pelagos Sanctuary for the marine mammals, in the North-Western Mediterranean, and the Gulf of Ambracia, in the North-Central Mediterranean Sea. We have found that in areas characterised by a wide continental platform, dolphins have wider home ranges and aggregate into larger groups. In areas characterized by a narrow continental platform, dolphins show much smaller home ranges and aggregate into smaller groups. The results obtained from this collective research effort highlight the importance of data sharing to improve our scientific knowledge in the field of cetaceans and beyond.
Evaluation of Anti-Candida Potential of Piper nigrum Extract in Inhibiting Growth, Yeast-Hyphal Transition, Virulent Enzymes, and Biofilm Formation
Authors: Bravo-Chaucanés Claudia Patrícia , Vargas-Casanova Yerly , Chitiva-Chitiva Luis Carlos , Ceballos-Garzon Andrés , Modesti-Costa Geison , Parra-Giraldo Claudia Marcela
Published: July 2022

Due to the increased incidence of fungal infections and the emergence of antifungal resistance mainly by Candida species, the need for safe and effective novel therapies is imperative. Consequently, plants and herbs are a powerful source to combat infections. Here, we evaluated the anti-Candida potential of an ethanolic extract from Piper nigrum. The phytochemical analysis of P. nigrum revealed bioactive compounds such as alkaloids, terpenoids, and tannis. Our results showed that P. nigrum extract suppressed the virulence factors of C. albicans strains, including hyphae formation in both liquid and solid media, reduced secretion of phospholipases/proteinases, and affected biofilm formation. Furthermore, the P. nigrum extract showed no hemolytic effect in vitro and exhibited reduced cytotoxicity on Vero cells and G. mellonella larvae at concentrations that inhibited hyphae and biofilm in C. albicans. Moreover, the extract demonstrated antifungal activity against C. auris strains. In conclusion, the P. nigrum extract affected the growth and morphogenesis of Candida (even in resistant strains), demonstrating that this plant has an anti-candida activity and represents a promising resource for discovering novel antifungal compounds.
Actinomucor elegans and Podospora bulbillosa Positively Improves Endurance to Water Deficit and Salinity Stresses in Tomato Plants
Authors: Kazerooni Elham Ahmed , Maharachchikumbura Sajeewa S. N. , Al-Sadi Abdullah Mohammed , Rashid Umer , Kang Sang-Mo , Lee In-Jung
Published: July 2022

Fungal strains isolated from the rhizosphere of healthy Solanum lycopersicum were examined to mitigate symptoms of drought and salinity stresses. The fungal strains were identified as Actinomucor elegans and Podospora bulbillosa based on their DNA sequencing and morphological analysis. Additionally, the fungal strains were assayed for a number of plant growth promoting traits and abiotic stresses on solid media. Moreover, a greenhouse experiment was conducted and tomato seedlings were treated with 25% PEG or 1.5% NaCl for 12 days, and the impact of plant growth promoting fungi (PGPF) on tomato seedling performance under these conditions was examined. PGPF application raised the survival of the stressed tomato plants, which was evidenced by higher physiological and biochemical processes. The PGPF-inoculated plants exhibited higher chlorophyll, carotenoid, protein, amino acid, antioxidant activities, salicylic acid, glucose, fructose, and sucrose contents, and showed lower hydrogen peroxide, and lipid metabolism relative to control plants under stress. Analysis using gene expression showed enhanced expression of SlF3H gene and reduced expression of SlNCED1, SlDEAD31, SlbZIP38, and SlGRAS10 genes following PGPFs application. Overall, the outcomes of this study elucidate the function of these fungal strains and present candidates with potential implementation as biofertilizers and in promoting plant stress endurance.
The Role of Coefficient Drivers of Time-Varying Coefficients in Estimating the Total Effects of a Regressor on the Dependent Variable of an Equation
Authors: Swamy Paravastu Ananta Venkata Bhattanatha , Chang I-Lok , von zur Muehlen Peter , Achameesing Amit
Published: July 2022

Typically, the explanatory variables included in a regression model, in conjunction with the omitted relevant regressors implied by the usual error term, have both direct and indirect effects on the dependent variable. Attempts to obtain their separate estimates have been plagued with simultaneity issues. To circumvent these problems, this paper defines their sum as “total effects”, develops a time-varying coefficients methodology for their estimation without simultaneity bias, and applies these techniques to estimate the total effects of commercial bank credit per-capita on real GDP per-capita in Mauritius. An innovation is the introduction of extraneous variables that act as “coefficient drivers” chosen on the basis of best predictive performance, as measured by the smallest value of Theil’s U-statistic we were able to locate in the estimation.
Use of Natural and Cultural Resources by Tourism as a Strategy for Regional Development: Bibliometric Analysis
Authors: Maldonado-Erazo Claudia Patricia , del Río-Rama María de la Cruz , Álvarez-García José , Flores-Mancheno Ana Carola
Published: July 2022

Territories throughout different continents have a wide variety of natural and cultural resources, defined by the dynamics of spatiality, temporality, and functionality that have been generated by the human groups settled in these spaces. These resources have become an object of study of great interest since they constitute the initial sources for the definition of the tourism potential of destinations, as well as contributing to the generation of new tourism activities and modalities for those already consolidated. Although these resources were initially used as objects of exploitation, with the passage of time the dynamics have changed to the use of these resources, focusing on the foundation of the pillars of sustainability, a condition that implies practices of environmental valuation in situ, the recognition of the cultural heritage of the territories and the valuation of the interaction between culture–nature–human beings. The objective of this research is to identify the existing scientific production in which the relationship between the tourist exploitation of natural and cultural resources and regional development is explored. Bibliometric analysis based on the guidelines of the PRISMA method was used. The international databases considered were Web of Science and Scopus. The analysis was complemented with an overlap analysis to establish the relationship of information between the WoS and Scopus databases. A total of 507 documents on the subject were identified, which provided a preliminary X-ray that will allow future research work to be focused on this line of re-search. The results allowed us to observe that there is little literature on the relationship between the use of natural and cultural resources for tourism and the regional development of the territory, both from an economic and social point of view.