Miracle-dz/UniFAR-FTUs huggingface dataset:
Accessory-cell-free differentiation of hematopoietic stem and progenitor cells into mature red blood cells

The culture and ex vivo engineering of red blood cells (RBCs) can help characterize genetic variants, model diseases, and may eventually spur the development of applications in transfusion medicine. In the last decade, improvements to the in vitro production of RBCs have enabled efficient erythroid progenitor proliferation and high enucleation levels from several sources of hematopoietic stem and progenitor cells (HSPCs). Despite these advances, there remains a need for refining the terminal step of in vitro human erythropoiesis — i.e., the terminal maturation of reticulocytes into erythrocytes — so that it can occur without feeder or accessory cells and animal components. Here, we describe the near-complete erythroid differentiation of cultured RBCs (cRBCs) from adult HSPCs in accessory-cell-free and animal-component-free conditions. The approach improves post-enucleation cell integrity and cell survival, and enables subsequent storage of cRBCs for up to 42 days in classical nutritive solution conditions, without any specialized equipment. We foresee that these improvements will facilitate the characterization of RBCs derived from gene-edited HSPCs. KEY POINTS Erythroid progenitors were differentiated into fully mature RBCs in a medium free of accessory cells Cultured RBCs can be stored up to 42 days in a standard nutritive solution
Shear-free normal cosmological models

Shear-free normal cosmological models are the perfect fluid solutions of Einstein's equations in which rotation and shear vanish, and which are not static (they were all found by A. Barnes, Gen. Relativ. Gravit. 4, 105 (1973)). They are either spherically, plane, or hyperbolically symmetric. Their symmetries are discussed in various coordinate systems and related to the conformal group of the three-dimensional flat space. A coordinate representation is introduced which unites all three cases into a single two-parameter family. The limiting transitions to the Friedman--Lemaitre--Robertson--Walker (FLRW) models and to the Schwarzschild--de Sitter-like solutions are presented.
Fr\'echet Quantum Supergroups

In this paper, we introduce Fr\'echet quantum supergroups and their representations. By using the universal deformation formula of the abelian supergroups R^{m|n} we construct various classes of Fr\'echet quantum supergroups that are deformation of classical ones. For such quantum supergroups, we find an analog of Kac-Takesaki operators that are superunitary and satisfy the pentagonal relation.
Efficient estimation for the proportional hazards model with interval censoring

The maximum likelihood estimator (MLE) for the proportional hazards model with case 1 interval censored data is studied. It is shown that the MLE for the regression parameter is asymptotically normal with √n convergence rate and achieves the information bound, even though the MLE for the baseline cumulative hazard function only converges at n 1/3 rate. Estimation of the asymptotic variance matrix for the MLE of the regression parameter is also considered. To prove our main results, we also establish a general theorem showing that the MLE of the finite-dimensional parameter in a class of semiparametric models is asymptotically efficient even though the MLE of the infinite-dimensional parameter converges at a rate slower than √n. The results are iliustrated by applying them to a data set from a tumorigenicity study.
Editorial: The role of rivers in the origins, evolution, adaptation, and distribution of biodiversity

COPYRIGHT © 2022 Naka, Werneck, Rosser, Pil and Boubli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: The role of rivers in the origins, evolution, adaptation, and distribution of biodiversity
The relationship between areas of life satisfaction, personality, and overall life satisfaction: An integrated account

A substantial amount of research has been conducted using a variety of methodological approaches to determine what influences life satisfaction. The bottom-up theory considers overall life satisfaction as a function of various areas of life satisfaction, whereas the top-down theory considers the areas of life satisfaction as a function of dispositional factors such as personality. We examined these models in a large-scale United Kingdom survey. Consistent with other studies, we found that both the bottom-up and top-down models of life satisfaction are supported in the United Kingdom by demonstrating that demographics, areas of life satsifaction, and personality traits can explain a significant portion of variances in overall areas of life satisfaction. We propose that future studies in life satisfaction research should consider the integrated account of life satisfaction rather than a unitary bottom-up or top-down perspective.
Potential mechanisms of acupuncture for neuropathic pain based on somatosensory system

Neuropathic pain, caused by a lesion or disease of the somatosensory system, is common and distressing. In view of the high human and economic burden, more effective treatment strategies were urgently needed. Acupuncture has been increasingly used as an adjuvant or complementary therapy for neuropathic pain. Although the therapeutic effects of acupuncture have been demonstrated in various high-quality randomized controlled trials, there is significant heterogeneity in the underlying mechanisms. This review aimed to summarize the potential mechanisms of acupuncture on neuropathic pain based on the somatosensory system, and guided for future both foundational and clinical studies. Here, we argued that acupuncture may have the potential to inhibit neuronal activity caused by neuropathic pain, through reducing the activation of pain-related ion channels and suppressing glial cells (including microglia and astrocytes) to release inflammatory cytokines, chemokines, amongst others. Meanwhile, acupuncture as a non-pharmacologic treatment, may have potential to activate descending pain control system via increasing the level of spinal or brain 5-hydroxytryptamine (5-HT), norepinephrine (NE), and opioid peptides. And the types of endogenously opioid peptides was influenced by electroacupuncture-frequency. The cumulative evidence demonstrated that acupuncture provided an alternative or adjunctive therapy for neuropathic pain.
10-year time course of Hg and organic compounds in Augusta Bay: Bioavailability and biological effects in marine organisms

In the last century, many Mediterranean coastal areas have been subjected to anthropogenic disturbances from industrial activities, uncontrolled landfills, shipyards, and high maritime traffic. The Augusta Bay (eastern Sicily, Italy) represents an example of a strongly impacted coastal environment with an elevated level of sediments contamination due to the presence of one of the largest European petrochemical plants, combined with an extensive commercial and military harbor. The most significant contaminants were represented by mercury (Hg) and hexachlorobenzene (HCB), derived from a former chlor-alkali plant, and other organic compounds like polycyclic aromatic hydrocarbons (PAHs) and polychlorobiphenyls (PCBs). Since the 1970s, Augusta Bay has become internationally recognized as a contaminated marine environment, although very little information is available regarding the temporal trend of contaminants bioavailability and biological impacts on aquatic organisms. In this study, the Hg and HCB concentrations were investigated over 10 years (from 2003 to 2013) in sediments and invertebrate and vertebrate organisms; these two contaminants' ecotoxicity was further evaluated at a biochemical and cellular level by analyzing the induction of organic biotransformation processes and DNA damages. The results showed high concentrations of Hg and HCB in sediments and their strong bioaccumulation in different species with significantly higher values than those measured in reference sites. This trend was paralleled by increased micronuclei frequency (DNA damage biomarker) and activity of the biotransformation system. While levels of chemicals in sediments remained elevated during the time course, their bioavailability and biological effects showed a gradual decrease after 2003, when the chlor-alkali plant was closed. Environmental persistence of Hg and HCB availability facilitates their bioaccumulation and affects the health status of marine organisms, with possible implications for environmental risk, pollutants transfer, and human health.
Therapeutic potential of vasoactive intestinal peptide and its receptor VPAC2 in type 2 diabetes

Owing to the increasing prevalence of type 2 diabetes, the development of novel hypoglycemic drugs has become a research hotspot, with the ultimate goal of developing therapeutic drugs that stimulate glucose-induced insulin secretion without inducing hypoglycemia. Vasoactive intestinal peptide (VIP), a 28-amino-acid peptide, can stimulate glucose-dependent insulin secretion, particularly by binding to VPAC2 receptors. VIP also promotes islet β-cell proliferation through the forkhead box M1 pathway, but the specific molecular mechanism remains to be studied. The clinical application of VIP is limited because of its short half-life and wide distribution in the human body. Based on the binding properties of VIP and VPAC2 receptors, VPAC2-selective agonists have been developed to serve as novel hypoglycemic drugs. This review summarizes the physiological significance of VIP in glucose homeostasis and the potential therapeutic value of VPAC2-selective agonists in type 2 diabetes.
Assessing the long-term in vivo degradation behavior of magnesium alloys - a high resolution synchrotron radiation micro computed tomography study

Biodegradable magnesium (Mg) implants are emerging as a potential game changer in implant technology in situations where the implant temporarily supports the bone thereby avoiding secondary surgery for implant removal. However, the consequences of the alteration in the degradation rate to bone healing and the localization of degradation and alloying products in the long term remain unknown. In this study, we present the long-term osseointegration of three different biodegradable Mg alloys, Mg-10Gd, Mg-4Y-3RE and Mg-2Ag, which were implanted into rabbit femur for 6 and 9 months. In addition, we have investigated the effect of blood pre-incubation on the in vivo performance of the aforementioned alloys. Using high-resolution synchrotron radiation based micro computed tomography, the bone implant contact (BIC), bone volume fraction (BV/TV) and implant morphology were studied. The elemental traces have been characterized using micro X-ray fluorescence. Qualitative histological evaluation of the surrounding bone was also performed. Matured bone formed around all three implant types and Ca as well as P which represent parts of the degradation layer were in intimate contact with the bone. Blood pre-incubation prior to implantation significantly improved BIC in Mg-2Ag screws at 9 months. Despite different implant degradation morphologies pointing toward different degradation dynamics, Mg-10Gd, Mg-4Y-3RE and Mg-2Ag induced a similar long-term bone response based on our quantified parameters. Importantly, RE elements Gd and Y used in the alloys remained at the implantation site implying that they might be released later on or might persist in the implantation site forever. As the bone formation was not disturbed by their presence, it might be concluded that Gd and Y are non-deleterious. Consequently, we have shown that short and mid-term in vivo evaluations do not fully represent indicators for long-term osseointegration of Mg-based implants.
Hydrological connectivity promotes coalescence of bacterial communities in a floodplain

Floodplains play essential roles in the ecological functions of regional environments. The merging and coalescence of bacterial communities in aquatic environments results in periodic patterns driven by regular hydrological activities, which may, in turn, influence ecological activities. However, the degree of bacterial community coalescence in the lateral and vertical directions as well as the underlying hydrological mechanism of floodplain ecosystems is poorly understood. Therefore, we investigated the spatiotemporal patterns and coalescence processes of planktonic and sedimentary bacterial communities during normal and high-water periods in a floodplain ecosystem of the Yellow River source region. We classified bacterial operational taxonomic units (OTUs) based on 16S rRNA gene sequencing, and quantified community coalescence by calculating the proportions of overlapping OTUs, the contributions of upstream sources to downstream sinks, and positive/negative cohesion. The results revealed major differences in the composition and diversity of planktonic and sedimentary bacterial communities. Bacterial community diversity in the high-water period was higher than in the normal period. Laterally, hydrological connectivity promoted the immigration and coalescence of bacterial communities to oxbow lakes in both the mainstream and tributaries, with the coalescence degree of planktonic bacteria (2.9%) higher than that of sedimentary bacteria (1.7%). Vertically, the coalescence degree of mainstream planktonic and sedimentary bacterial communities was highest, reaching 2.9%. Co-occurrence network analysis revealed that hydrological connectivity increased the complexity of the bacterial network and enhanced the coalescence of keystone species to oxbow lakes. Furthermore, community coalescence improved the competitiveness and dispersal of bacterial communities. This study demonstrated that coalescence of bacterial communities is driven by hydrological connectivity in a floodplain ecosystem. Further studies should investigate the processes of bacterial community coalescence in floodplains in more detail, which could provide new approaches for environmental protection and ecological function preservation.
A novel grid-connected microgrid energy management system with optimal sizing using hybrid grey wolf and cuckoo search optimization algorithm

Renewable energy systems, particularly in countries with limited fossil fuel resources, are promising and environmentally sustainable sources of electricity generation. Wind, solar Photovoltaic (PV), and biomass gasifier-based systems have gotten much attention recently for providing electricity to energy-deficient areas. However, due to the intermittent nature of renewable energy, a completely renewable system is unreliable and may cause operation problems. Energy storage systems and volatile generation sources are the best way to combat the problem. This paper proposes a hybrid grid-connected wind-solar PV generation Microgrid (MG) with biomass and energy storage devices to meet the entire value of load demand for the adopted buildings in an intended region and ensure economic dispatch as well as make a trade in the electricity field by supplying/receiving energy to/from the utility grid. The control operation plan uses battery storage units to compensate energy gap if the priority resources (wind turbine and solar PV) are incapable of meeting demand. Additionally, the biomass gasifier is used as a fallback option if the batteries fail to perform their duty. At any time, any excess of energy can be utilized to charge the batteries and sell the rest to the utility. Additionally, if the adopted resources are insufficient to meet the demand, the required energy is acquired from the utility. A Hybrid Grey Wolf with Cuckoo Search Optimization (GWCSO) algorithm is adopted for achieving optimal sizing of the proposed grid-connected MG. To assess the proposed technique’s robustness, the results are compared to those obtained using the Grey Wolf Optimization (GWO) algorithm. The GWCSO method yielded a lower total number of component units, annual cost, total Net Present Cost (NPC), and Levelized Cost Of Energy (LCOE) than the GWO algorithm, whereas the GWCSO algorithm has the lowest deviation, indicating that it is more accurate and robust than the GWO algorithm.
Social Media Analytics by Virtual Operations Support Teams in disaster management: Situational awareness and actionable information for decision-makers

Virtual Operations Support Teams are groups of institutionalized digital volunteers in the field of disaster management who conduct Social Media Analytics tasks for decision-makers in Emergency Operation Centers (EOCs) during hazard situations such as floods. Through interagency integration into EOC structures, the volunteers provide analytical support using advanced tools and monitoring various social media platforms. The goal of VOSTs is to increase decision-makers’ situational awareness through need-oriented analysis and to improve decision-making by providing actionable information in a time-critical work context. In this case study, the data collected during the 2021 flood in Wuppertal, Germany by 22 VOST analysts was processed and analyzed. It was found that information from eight social media platforms could be classified into 23 distinct categories. The analysts’ prioritizations indicate differences in the formats of information and platforms. Disaster-related posts that pose a threat to the affected population’s health and safety (e.g., requests for help or false information) were more commonly prioritized than other posts. Image-heavy content was also rated higher than text-heavy data. A subsequent survey of EOC decision-makers examined the impact of VOST information on situational awareness during this flood. It also asked how actionable information impacted decisions. We found that VOST information contributes to expanded situational awareness of decision-makers and ensures people-centered risk and crisis communication. Based on the results from this case study, we discuss the need for future research in the area of integrating VOST analysts in decision-making processes in the field of time-critical disaster management.
Neuropilin-1 modulates the 3D invasive properties of glioblastoma stem-like cells

Glioblastoma multiforme (GBM) is a rare, yet devastating, primary brain tumor in adults. Current treatments remain generally ineffective and GBM almost invariably recurs, resulting in median survival of 15 months. This high malignancy sources notably from the resilience and invasive capabilities of tumor cells. Within GBM, exists a population of self-sustaining transformed cells with stem-like properties (GSCs), which are thought to be responsible for tumor initiation, growth, and invasion, as well as recurrence. In the tumor microenvironment, GSCs might be found in the vicinity of brain endothelial cells, which provide a protective habitat. Likewise, these resistant, quiescent GSCs may accumulate in hypoxic zones, away from the perivascular niche, or travel towards the healthy brain parenchyma, by eminently co-opting neuro-vascular tracks. Herein, we established an ex vivo model to explore GSC invasive behavior. We found that patient-derived cells massively invade the collagen matrix. In addition, we described that the glycoprotein Neuropilin-1 (NRP1) contributes to GSC spreading and invasion. Indeed, both RNA interference-mediated silencing and CRISPR-mediated gene editing deletion of NRP1 strongly impaired the 3D invasive properties of patient-derived GSCs and their close localization to the brain blood vessels. Of note, other typical features of GSCs, such as expansion and self-renewal were maintained. From a mechanistic standpoint, this biological effect might rely on the expression of the β3 subunit integrin cell-extracellular matrix adhesive receptor. Our data, therefore, propose a reliable approach to explore invasive properties of patient glioma cells ex vivo and identify NRP1 as a mediator in this malignant process.
Systemic exposure to propranolol in patients with chronic liver disease and its correlation with portal blood flow

Propranolol is a beta-blocker used for the prevention of variceal bleeding in cirrhotic patients. We investigated the pharmacokinetics of propranolol in patients with chronic liver disease compared to that in healthy individuals. The relative amount of portal blood flow was measured to investigate the correlation of portal blood flow and the systemic exposure of propranolol. Thirty healthy subjects, 18 patients with chronic active hepatitis (CAH), and 54 patients with cirrhosis were included in this prospective study. Blood samples for pharmacokinetic analysis were taken up to 8 h post-dose. The portal blood flow was estimated by H/L ratio using thallium-201 (201TI) per rectal scintigraphy. A total of 78 subjects completed the study. The area under the concentration-time curve (AUC) to the last measurable time (AUClast, ng⋅h/mL) were 150.2 ± 154.1, 112.2 ± 84.7, and 204.0 ± 137.3 in healthy subjects, CAH patients, and cirrhosis patients, respectively. AUCrmlast showed positive correlation with the H/L ratio in patients with chronic liver disease (r = 0.5817, p < 0.0001). In conclusion, the patients with cirrhosis showed higher systemic exposure to propranolol than healthy subjects or patients with CAH. The increase in systemic exposure to propranolol was correlated with the decrease in portal blood flow.
15-Deoxy-Delta-12,14-prostaglandin J2 modulates pro-labour and pro-inflammatory responses in human myocytes, vaginal and amnion epithelial cells

Background Prematurity is the leading cause of childhood death under the age of five. The aetiology of preterm birth is multifactorial; however, inflammation and infection are the most common causal factors, supporting a potential role for immunomodulation as a therapeutic strategy. 15-Deoxy-Delta-12,14-prostaglandin J2 (15dPGJ2) is an anti-inflammatory prostaglandin and has been shown to delay lipopolysaccharide (LPS) induced preterm labour in mice and improve pup survival. This study explores the immunomodulatory effect of 15dPGJ2 on the transcription factors NF-κB and AP-1, pro-inflammatory cytokines, and contraction associated proteins in human cultured myocytes, vaginal epithelial cell line (VECs) and primary amnion epithelial cells (AECs). Methods Cells were pre-incubated with 32µM of 15dPGJ2 and stimulated with 1ng/mL of IL-1β as an in vitro model of inflammation. Western immunoblotting was used to detect phosphorylated p-65 and phosphorylated c-Jun as markers of NF-κB and AP-1 activation, respectively. mRNA expression of the pro-inflammatory cytokines IL-6, IL-8, and TNF-α was examined, and protein expression of COX-2 and PGE2 were detected by western immunoblotting and ELISA respectively. Myometrial contractility was examined ex-vivo using a myograph. Results 15dPGJ2 inhibited IL-1β-induced activation of NF-κB and AP-1, and expression of IL-6, IL-8, TNF-α, COX-2 and PGE2 in myocytes, with no effect on myometrial contractility or cell viability. Despite inhibiting IL-1β-induced activation of NF-κB, expression of IL-6, TNF-α, and COX-2, 15dPGJ2 led to activation of AP-1, increased production of PGE2 and increased cell death in VECs and AECs. Conclusion We conclude that 15dPGJ2 has differential effects on inflammatory modulation depending on cell type and is therefore unlikely to be a useful therapeutic agent for the prevention of preterm birth.