Miracle-dz/UniFAR-FTUs huggingface dataset:
New Insights into Red Blood Cell Microcytosis upon mTOR Inhibitor Administration

The aim of this study was to evaluate the effect of everolimus, a mammalian target of rapamycin (mTOR) inhibitor, on red blood cell parameters in the context of iron homeostasis in patients with tuberous sclerosis complex (TSC) and evaluate its effect on cell size in vitro. Everolimus has a significant impact on red blood cell parameters in patients with TSC. The most common alteration was microcytosis. The mean MCV value decreased by 9.2%, 12%, and 11.8% after 3, 6, and 12 months of everolimus treatment. The iron level declined during the first 3 months, and human soluble transferrin receptor concentration increased during 6 months of therapy. The size of K562 cells decreased when cultured in the presence of 5 μM everolimus by approximately 8%. The addition of hemin to the cell culture with 5 μM everolimus did not prevent any decrease in cell size. The stage of erythroid maturation did not affect the response to everolimus. Our results showed that the mTOR inhibitor everolimus caused red blood cell microcytosis in vivo and in vitro. This effect is not clearly related to a deficit of iron and erythroid maturation. This observation confirms that mTOR signaling plays a complex role in the control of cell size.
Ground-State Properties and Phase Separation of Binary Mixtures in Mesoscopic Ring Lattices

We investigated the spatial phase separation of the two components forming a bosonic mixture distributed in a four-well lattice with a ring geometry. We studied the ground state of this system, described by means of a binary Bose–Hubbard Hamiltonian, by implementing a well-known coherent-state picture which allowed us to find the semi-classical equations determining the distribution of boson components in the ring lattice. Their fully analytic solutions, in the limit of large boson numbers, provide the boson populations at each well as a function of the interspecies interaction and of other significant model parameters, while allowing to reconstruct the non-trivial architecture of the ground-state four-well phase diagram. The comparison with the L-well (L=2,3) phase diagrams highlights how increasing the number of wells considerably modifies the phase diagram structure and the transition mechanism from the full-mixing to the full-demixing phase controlled by the interspecies interaction. Despite the fact that the phase diagrams for L=2,3,4 share various general properties, we show that, unlike attractive binary mixtures, repulsive mixtures do not feature a transition mechanism which can be extended to an arbitrary lattice of size L.
Trajectories of Procedural and Interactional Justice as Predictors of Retirement among Swedish Workers: Differences between Three Groups of Retirees

Organizational justice is an important aspect of the psychosocial work environment, but there is a lack of studies on whether justice perceptions also predict retirement decisions. The aim of this study is to examine trajectories of procedural and interactional justice perceptions prior to retirement of three groups of retirees while considering self-rated health and important demographics. Data from the Swedish Longitudinal Occupational Survey of Health (2006–2018, N = 3000) were used. Respondents were grouped into early retirement, normative retirement and late retirement. Latent growth curve models and multinomial logistic regressions were conducted to test whether trajectories of justice perceptions prior to retirement differed between retirement groups while controlling for self-rated health development and demographic variables. Late retirees had higher intercept levels of interactional justice and higher intercept levels of self-rated health prior to retirement, compared to early retirees. Late retirees also showed a slower decrease in procedural justice compared to early retirees. Only intercept levels of self-rated health differed between early retirees and normative retirees, such that early retirees had lower levels of self-rated health prior to retirement. Keeping employees in the workforce is a major challenge for any aging society. Organizational justice perceptions in the years prior to retirement seem particularly influential for delaying retirement.
Utility of the Global Respiratory Severity Score for predicting the need for respiratory support in infants with respiratory syncytial virus infection

Background Respiratory syncytial virus (RSV) is a common cause of acute respiratory infection in children. One of the most important strategies for treatment of an RSV infection is to decide whether the patient needs respiratory support. This study aimed to assess the validity and clinical benefit of the Global Respiratory Severity Score (GRSS) and the Wang bronchiolitis severity score (WBSS) for clinical decision-making regarding providing respiratory support (high-flow nasal cannula, nasal continuous positive airway pressure, or ventilator) in infants with an RSV infection. Study design and methods This retrospective cohort study enrolled 250 infants aged under 10 months who were admitted to Atsugi City Hospital with an RSV infection between January 2012 and December 2019. The utility of these scores was evaluated for assessing the need for respiratory support through decision curve analysis by calculating the optimal GRSS and WBSS cut-offs for predicting the need for respiratory support. Results Twenty-six infants (10.4%) received respiratory support. The optimal cut-offs for the GRSS and the WBSS were 4.52 and 7, respectively. Decision curve analysis suggested that the GRSS was a better predictive tool than the WBSS if the probability of needing respiratory support was 10–40%. Conclusions The GRSS was clinically useful in determining the need for respiratory support in infants aged under 10 months with an RSV infection.
Insight to Microbial Fe(III) Reduction Mediated by Redox-Active Humic Acids with Varied Redox Potentials

Redox-active humic acids (HA) are ubiquitous in terrestrial and aquatic systems and are involved in numerous electron transfer reactions affecting biogeochemical processes and fates of pollutants in soil environments. Redox-active contaminants are trapped in soil micropores (<2 nm) that have limited access to microbes and HA. Therefore, the contaminants whose molecular structure and properties are not damaged accumulate in the soil micropores and become potential pollution sources. Electron transfer capacities (ETC) of HA reflecting redox activities of low molecular weight fraction (LMWF, <2.5) HA can be detected by an electrochemical method, which is related to redox potentials (Eh) in soil and aquatic environments. Nevertheless, electron accepting capacities (EAC) and electron donating capacities (EDC) of these LMWF HA at different Eh are still unknown. EDC and EAC of different molecular weight HA at different Eh were analyzed using electrochemical methods. EAC of LMWF at −0.59 V was 12 times higher than that at −0.49 V, while EAC increased to 2.6 times when the Eh decreased from −0.59 V to −0.69 V. Afterward, LMWF can act as a shuttle to stimulate microbial Fe(III) reduction processes in microbial reduction experiments. Additionally, EAC by electrochemical analysis at a range of −0.49–−0.59 V was comparable to total calculated ETC of different molecular weight fractions of HA by microbial reduction. Therefore, it is indicated that redox-active functional groups that can be reduced at Eh range of −0.49–−0.59 are available to microbial reduction. This finding contributes to a novel perspective in the protection and remediation of the groundwater environment in the biogeochemistry process.
Advances in laser-assisted conversion of polymeric and graphitic carbon into nanodiamond films

Nanodiamond (ND) synthesis by nanosecond laser irradiation has sparked tremendous scientific and technological interest. This review describes efforts to obtain cost-effective ND synthesis from polymers and carbon nanotubes (CNT) by the melting route. For polymers, ultraviolet (UV) irradiation triggers intricate photothermal and photochemical processes that result in photochemical degradation, subsequently generating an amorphous carbon film; this process is followed by melting and undercooling of the carbon film at rates exceeding 109 K s−1. Multiple laser shots increase the absorption coefficient of PTFE, resulting in the growth of 〈110〉 oriented ND film. Multiple laser shots on CNTs result in pseudo topotactic diamond growth to form a diamond fiber. This technique is useful for fabricating 4–50 nm sized NDs. These NDs can further be employed as seed materials that are used in bulk epitaxial growth of microdiamonds using chemical vapor deposition, particularly for use with non-lattice matched substrates that formerly did not form continuous and adherent films. We also provide insights into biocompatible precursors for ND synthesis such as polybenzimidazole fiber. ND fabrication by UV irradiation of graphitic and polymeric carbon opens up a pathway for preparing selective coatings of polymer-diamond composites, doped nanodiamonds, and graphene composites for quantum computing and biomedical applications.
Statistical Modelling of SPADs for Time-of-Flight LiDAR

Time-of-Flight (TOF) based Light Detection and Ranging (LiDAR) is a widespread technique for distance measurements in both single-spot depth ranging and 3D mapping. Single Photon Avalanche Diode (SPAD) detectors provide single-photon sensitivity and allow in-pixel integration of a Time-to-Digital Converter (TDC) to measure the TOF of single-photons. From the repetitive acquisition of photons returning from multiple laser shots, it is possible to accumulate a TOF histogram, so as to identify the laser pulse return from unwelcome ambient light and compute the desired distance information. In order to properly predict the TOF histogram distribution and design each component of the LiDAR system, from SPAD to TDC and histogram processing, we present a detailed statistical modelling of the acquisition chain and we show the perfect matching with Monte Carlo simulations in very different operating conditions and very high background levels. We take into consideration SPAD non-idealities such as hold-off time, afterpulsing, and crosstalk, and we show the heavy pile-up distortion in case of high background. Moreover, we also model non-idealities of timing electronics chain, namely, TDC dead-time, limited number of storage cells for TOF data, and TDC sharing. Eventually, we show how the exploit the modelling to reversely extract the original LiDAR return signal from the distorted measured TOF data in different operating conditions.
Chronology of COVID-19 Symptoms in Very Old Patients: Study of a Hospital Outbreak

Background: We wanted to better understand the frequency and temporal distribution of symptoms of COVID-19 in very old patients, which are currently not well defined. Methods: In an observational, descriptive study, we followed all patients being at three geriatric convalescence and rehabilitation units when a COVID-19 outbreak emerged in those units in March 2020. For those who developed the disease, we recorded any new symptom occurring at diagnosis, in the previous 14 and the following 21 days. A group of SARS-Cov-2-negative patients served as controls. Results: Sixty-nine of the 176 inpatients (mean age: 86 years) were infected by SARS-Cov-2 during the outbreak. At the moment of diagnosis, a majority of patients had fever (71.0%), malaise-asthenia (24.6%), or respiratory symptoms (66.7%). However, 48 patients (69.6% of all SARS-Cov-2 positive patients) also presented, usually several days before, other symptoms: (a) gastrointestinal symptoms (39.1% of all patients, median onset eight days before diagnosis, IQR −9 to +3 days); (b) neurological symptoms (30.4% of all patients, median onset five days before diagnosis, IQR −11 to −3 days), notably delirium (24.6%); and (c) other symptoms, like falls and unexplained decompensation of chronic conditions (29.0% of all patients, median onset four days before diagnosis, IQR −10 to 0). None of those symptoms were observed in similar proportion in 25 control SARS-CoV-2-negative patients, hospitalized during the same period. Conclusions: Diarrhea, nausea-vomiting, delirium, falls, and unexplained decompensation of chronic conditions were the first symptoms of COVID-19 in a majority of older patients in this cohort, preceding typical symptoms by several days. Recognizing those early symptoms could hasten the diagnosis of COVID-19 in this population.
A Risk-Based IoT Decision-Making Framework Based on Literature Review with Human Activity Recognition Case Studies

The Internet of Things (IoT) is a key and growing technology for many critical real-life applications, where it can be used to improve decision making. The existence of several sources of uncertainty in the IoT infrastructure, however, can lead decision makers into taking inappropriate actions. The present work focuses on proposing a risk-based IoT decision-making framework in order to effectively manage uncertainties in addition to integrating domain knowledge in the decision-making process. A structured literature review of the risks and sources of uncertainty in IoT decision-making systems is the basis for the development of the framework and Human Activity Recognition (HAR) case studies. More specifically, as one of the main targeted challenges, the potential sources of uncertainties in an IoT framework, at different levels of abstraction, are firstly reviewed and then summarized. The modules included in the framework are detailed, with the main focus given to a novel risk-based analytics module, where an ensemble-based data analytic approach, called Calibrated Random Forest (CRF), is proposed to extract useful information while quantifying and managing the uncertainty associated with predictions, by using confidence scores. Its output is subsequently integrated with domain knowledge-based action rules to perform decision making in a cost-sensitive and rational manner. The proposed CRF method is firstly evaluated and demonstrated on a HAR scenario in a Smart Home environment in case study I and is further evaluated and illustrated with a remote health monitoring scenario for a diabetes use case in case study II. The experimental results indicate that using the framework’s raw sensor data can be converted into meaningful actions despite several sources of uncertainty. The comparison of the proposed framework to existing approaches highlights the key metrics that make decision making more rational and transparent.
High-Throughput Identification of Organic Compounds from Polygoni Multiflori Radix Praeparata (Zhiheshouwu) by UHPLC-Q-Exactive Orbitrap-MS

Polygoni Multiflori Radix Praeparata (PMRP), as the processed product of tuberous roots of Polygonum multiflorum Thunb. , is one of the most famous traditional Chinese medicines, with a long history. However, in recent years, liver adverse reactions linked to PMRP have been frequently reported. Our work attempted to investigate the chemical constituents of PMRP for clinical research and safe medication. In this study, an effective and rapid method was established to separate and characterize the constituents in PMRP by combining ultra-high performance liquid chromatography with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). Based on the accurate mass measurements for molecular and characteristic fragment ions, a total of 103 compounds, including 24 anthraquinones, 21 stilbenes, 15 phenolic acids, 14 flavones, and 29 other compounds were identified or tentatively characterized. Forty-eight compounds were tentatively characterized from PMRP for the first time, and their fragmentation behaviors were summarized. There were 101 components in PMRP ethanol extract (PMRPE) and 91 components in PMRP water extract (PMRPW). Simultaneously, the peak areas of several potential xenobiotic components were compared in the detection, which showed that PMRPE has a higher content of anthraquinones and stilbenes. The obtained results can be used in pharmacological and toxicological research and provided useful information for further in vitro and in vivo studies.
Impact of Adding Polysaccharides on the Stability of Egg Yolk/Fish Oil Emulsions under Accelerated Shelf-Life Conditions

Polysaccharides can form interfacial complexes with proteins to form emulsions with enhanced stability. We assessed the effect of adding gum guar or gum arabic to egg yolk/fish oil emulsions. The emulsions were produced using simple or high-pressure homogenization, stored for up to 10 days at 45 °C, and characterized for their particle size and distribution, viscosity, encapsulation efficiency, oxidative stability, and cytotoxicity. Emulsions containing gum guar and/or triglycerides had the highest viscosity. There was no significant difference in the encapsulation efficiency of emulsions regardless of the polysaccharide used. However, emulsions containing gum arabic displayed a bridging flocculation effect, resulting in less stability over time compared to those using gum guar. Emulsions produced using high-pressure homogenization displayed a narrower size distribution and higher stability. The formation of peroxides and propanal was lower in emulsions containing gum guar and was attributed to the surface oil. No significant toxicity toward Caco-2 cells was found from the emulsions over time. On the other hand, after 10 days of storage, nonencapsulated fish oil reduced the cell viability to about 80%. The results showed that gum guar can increase the particle stability of egg yolk/fish oil emulsions and decrease the oxidation rate of omega-3 fatty acids.
Integrated Analysis of miR-430 on Steroidogenesis-Related Gene Expression of Larval Rice Field Eel Monopterus albus

The present study aims to reveal the mechanism by which miR-430s regulate steroidogenesis in larval rice field eel Monopterus albus. To this end, M. albus embryos were respectively microinjected with miRNA-overexpressing mimics (agomir430a, agomir430b, and agomir430c) or miRNA-knockdown inhibitors (antagomir430a, antagomir430b, and antagomir430c). Transcriptome profiling of the larvae indicated that a total of more than 149 differentially expressed genes (DEGs) were identified among the eight treatments. Specifically, DEGs related to steroidogenesis, the GnRH signaling pathway, the erbB signaling pathway, the Wnt signaling pathway, and other pathways were characterized in the transcriptome. We found that steroidogenesis-related genes (hydroxysteroid 17-beta dehydrogenase 3 (17β-hsdb3), hydroxysteroid 17-beta dehydrogenase 7 (17β-hsdb7), hydroxysteroid 17-beta dehydrogenase 12 (17β-hsdb12), and cytochrome P450 family 19 subfamily a (cyp19a1b)) were significantly downregulated in miR-430 knockdown groups. The differential expressions of miR-430 in three gonads indicated different roles of three miR-430 (a, b, and c) isoforms in regulating steroidogenesis and sex differentiation. Mutation of the miR-430 sites reversed the downregulation of cytochrome P450 family 17 (cyp17), cyp19a1b, and forkhead box L2 (foxl2) reporter activities by miR-430, indicating that miR-430 directly interacted with cyp17, cyp19a1b, and foxl2 genes to inhibit their expressions. Combining these findings, we concluded that miR-430 regulated the steroidogenesis and the biosynthesis of steroid hormones by targeting cyp19a1b in larval M. albus. Our results provide a novel insight into steroidogenesis at the early stage of fish at the molecular level.
Natural Merosesquiterpenes Activate the DNA Damage Response via DNA Strand Break Formation and Trigger Apoptotic Cell Death in p53-Wild-Type and Mutant Colorectal Cancer

Simple Summary Bowel cancer is a serious disease, which affects many people worldwide. Unfortunately, the disease is often diagnosed in an advanced stage, which impairs the chance of survival. Furthermore, resistance to therapy occurs frequently. Thus, novel therapeutic approaches are required to improve cancer therapy. Here, we studied whether merosesquiterpenes might be useful for cancer treatment. These compounds occur in marine sponges and were isolated by our group. We were able to identify three compounds with potent cytotoxic activity in different cell lines established from human large bowel cancer. Our experiments provided evidence that the compounds cause DNA damage and trigger cell death, so-called mitochondrial apoptosis, which was attested in cancer cells with expression of wild-type and mutated p53 tumor suppressor. Finally, we show that merosesquiterpenes also kill intestinal tumor organoids, an ex vivo model of large bowel cancer. Abstract Colorectal cancer (CRC) is a frequently occurring malignant disease with still low survival rates, highlighting the need for novel therapeutics. Merosesquiterpenes are secondary metabolites from marine sponges, which might be useful as antitumor agents. To address this issue, we made use of a compound library comprising 11 isolated merosesquiterpenes. The most cytotoxic compounds were smenospongine > ilimaquinone ≈ dactylospontriol, as shown in different human CRC cell lines. Alkaline Comet assays and γH2AX immunofluorescence microscopy demonstrated DNA strand break formation in CRC cells. Western blot analysis revealed an activation of the DNA damage response with CHK1 phosphorylation, stabilization of p53 and p21, which occurred both in CRC cells with p53 knockout and in p53-mutated CRC cells. This resulted in cell cycle arrest followed by a strong increase in the subG1 population, indicative of apoptosis, and typical morphological alterations. In consistency, cell death measurements showed apoptosis following exposure to merosesquiterpenes. Gene expression studies and analysis of caspase cleavage revealed mitochondrial apoptosis via BAX, BIM, and caspase-9 as the main cell death pathway. Interestingly, the compounds were equally effective in p53-wild-type and p53-mutant CRC cells. Finally, the cytotoxic activity of the merosesquiterpenes was corroborated in intestinal tumor organoids, emphasizing their potential for CRC chemotherapy.
The EXPAND-Model: A Hermeneutical Application of a Lifeworld-Led Prehospital Emergency Nursing Care

Prehospital emergency care is the response to a patient’s life-threatening and critical medical condition out of hospital. Patients experience this as both existential and physical suffering. There is therefore a need to combine medical care and treatment with a caring science approach in order to provide lifeworld-led nursing care. A model for the application of lifeworld-led prehospital emergency nursing care was developed using Paul Ricoeur’s philosophy, bringing together the concepts understanding and explanation. The model comprises the phases of primary understanding, structural explanation, and secondary understanding, which together integrate medical care with a lifeworld perspective on the patient’s illness or injury.