Miracle-dz/UniFAR-FTUs huggingface dataset:
Radon protection in apartments using a ventilation system wireless-controlled by radon activity concentration

The new German Radiation Protection Act (StrlSchG) of 31 December 2018 established a reference value of 300 Bq m−3 for the annual average radon activity concentration in buildings with recreation and living rooms, as well as in workplaces. It is expected that the reference value will be exceeded in a vast number of buildings throughout Germany and that radon protection measures will become indispensable. A simple and inexpensive radon protection measure for existing buildings is ventilation. In the scope of a joint project, ventilation systems with zone control and heat recovery are to be extended by the control parameter radon activity concentration. A highly sensitive, miniaturized radon monitor will be developed for this purpose, which can be integrated wirelessly into ventilation systems. Radon measurements were carried out in 13 apartments of an unoccupied heated apartment block in Germany over a period of three weeks in the wintertime. High radon activity concentrations were found on all three floors. The maximum values were 14000 Bq m−3 on the first floor, 6000 Bq m−3 on the second floor, and 2000 Bq m−3 on the third floor. Ventilation experiments were carried out in an apartment with high radon activity concentration. Two decentralized ventilation systems with heat recovery were installed in each of the two opposite outside walls. The controlling device of the system was activated wirelessly depending on the radon activity concentration. The radon activity concentration was reduced from 8000 Bq m−3 to 800 Bq m−3 in a first experiment in the living room.
Micro-biopsy for detection of gene expression changes in ischemic swine myocardium: A pilot study

Micro-endomyocardial biopsy (micro-EMB) is a novel catheter-based biopsy technique, aiming to increase flexibility and safety compared to conventional EMB. The technique was developed and evaluated in healthy swine. Therefore, the ability to detect disease related tissue changes could not be evaluated. The aim of the present pilot study was to investigate the ability to detect disease related gene expression changes using micro-EMB. Myocardial infarction was induced in three swine by coronary artery balloon occlusion. Micro-EMB samples (n = 164) were collected before, during, and after occlusion. RNA-sequencing was performed on 85 samples, and 53 of these were selected for bioinformatic analysis. A large number of responding genes was detected from the infarcted area (n = 1911). The early responding genes (n = 1268) were mostly related to apoptosis and inflammation. There were fewer responding genes two days after infarction (n = 6), which were related to extra-cellular matrix changes, and none after 14 days. In contrast to the infarcted area, samples harvested from a non-infarcted myocardial region showed considerably fewer regulated genes (n = 33). Deconvolution analysis, to estimate the proportion of different cell types, revealed a higher proportion of fibroblasts and a reduced proportion of cardiomyocytes two days after occlusion compared to baseline (p < 0.02 and p < 0.01, respectively. S5 File). In conclusion, this pilot study demonstrates the capabilities of micro-EMB to detect local gene expression responses at an early stage after ischemia, but not at later timepoints.
Investigating the effects of carvacrol in rats using oxygen-induced retinopathy model

Purpose: Investigating the effects of intraperitoneal carvacrol administration in rats using the oxygen-induced retinopathy (OIR) model. Methods: A total of 28 newborn Sprague Dawley rats were used and the OIR model was created using the 50/10% oxygen model. The study composed of four groups in total. While the OIR model was not used in Group I (control group), it was created for Groups II, III, and IV. About 0.01 mL carvacrol, bevacizumab, or 0.9% NaCl was administered intraperitoneal (IP) to the rats in all groups on postnatal day (PND) 14 as follows: Group I and Group II were administered 0.9% NaCl, Group III was administered bevacizumab, and Group IV was administered carvacrol. On PND 18, rats were sacrificed and their right eyes were enucleated. Results: Histopathological and immunohistochemical studies showed that the number of vascular endothelial cells (VECs), vascular endothelial growth factor (VEGF), and tumor necrosis factor-α (TNF-α) decreased similarly in Group III and Group IV compared with Group II. VECs values for Group I, Group II, Group III, and Group IV were measured as 0 ± 0, 26.45 ± 4.57, 7.75 ± 1.98, and 5.78 ± 1.72, respectively, and it differed significantly between groups (P < 0.001). Likewise, VEGF levels were observed as 0.06 ± 0.01, 3.31 ± 0.53, 2.47 ± 0.44, and 2.49 ± 0.52, respectively, and it differed significantly between groups (P < 0.001). TNF-α levels were recorded as 0.06 ± 0.01, 3.58 ± 0.38, 2.46 ± 0.49, and 2.29 ± 0.25, respectively, and it differed significantly between groups (P < 0.001). VECs, VEGF, and TNF-α were similar between Group III and IV (range of P values were 0.486–0.998). Conclusion: The study demonstrated that carvacrol significantly reduced retinal pathological angiogenesis, NV, VEC nuclei count, VEGF, and TNF-α levels. Moreover, the observed effects were comparable to those of bevacizumab.
Microdiversity of Enterococcus faecalis isolates in cases of infective endocarditis: selection of non-synonymous mutations and large deletions is associated with phenotypic modifications

ABSTRACT Context: Today, infective endocarditis (IE) caused by Enterococcus faecalis represents 10% of all IE and is marked by its difficult management and the frequency of relapses. Although the precise reasons for that remain to be elucidated, the evolution of the culprit strain under selective pressure through microdiversification could be, at least in part, involved. Material and methods: To further study the in situ genetic microdiversity and its possible phenotypic manifestations in E. faecalis IE, we sequenced and compared multiple isolates from the valves, blood culture and joint fluid of five patients who underwent valvular surgery. Growth rate and early biofilm production of selected isolates were also compared. Results: By sequencing a total of 58 E. faecalis genomes, we detected a considerable genomic microdiversity, not only among strains from different anatomical origins, but also between isolates from the same studied cardiac valves. Interestingly, deletions of thousands of bases including the well-known virulence factors ebpA/B/C, and srtC, as well as other large prophage sequences containing genes coding for proteins implicated in platelet binding (PlbA and PlbB) were evidenced. The study of mutations helped unveil common patterns in genes related to the cell cycle as well as central metabolism, suggesting an evolutionary convergence in these isolates. As expected, such modifications were associated with a significant impact on the in-vitro phenotypic heterogeneity, growth, and early biofilm production. Conclusion: Genome modifications associated with phenotypic variations may allow bacterial adaptation to both antibiotic and immune selective pressures, and thus promote relapses.
Examining the relationships between income inequalities and different dimensions of well-being in selected Central Eastern European (CEE) countries

This article examines the relationships between different dimensions of well-being and income inequalities across selected Central Eastern European countries after joining the European Union in 2004. Regarding the multivariety of well-being concept, it explores its 5 dimensions (material dimension, health dimension, education dimension, environmental dimension, happiness). Accounting for the interactions between dimensions of well-being matters for the inequalities, we conducted an in-depth analysis by adopting PMG estimation and panel ARDL model to assess the short-run and long-run links between variables. The results of conducted analysis allowed us to identify the canals through which income inequalities are linked directly or indirectly with the particular dimensions of well-being. In the long run, all the dimensions of well-being significantly affected income inequalities, and income inequality shaped material dimension, health, education, natural environment, and happiness. However, in the short run, the only dimension that shaped income inequalities was education. Income inequalities directly affected both health dimension and happiness.
Appropriate fixative for MEM-G/9 staining of cultured human HLA-G-positive JEG-3 trophoblast tumor cells

ABSTRACT Human leukocyte antigen (HLA-G) participates in immunosuppression and is useful for prenatal diagnostics. Isolation of fetal cells positive for HLA-G by HLA-G antibody conjugated nanoparticles from the cervix of pregnant women is the basis for non-invasive prenatal testing. Endocervical specimens are fixed in transport medium before isolation using antibody conjugated nanoparticles. Staining of HLA-G using MEM-G/9 antibody, however, is restricted to unfixed cells. We investigated the effect of several fixatives on the interaction of HLA-G with MEM-G/9 in the HLA-G-positive cell line, JEG-3. We investigated absolute methanol, 1:1 acetate buffer:methanol, Pap solution and paraformaldehyde. The effects of these fixatives were evaluated using immunofluorescence. We found no MEM-G/9 surface staining of methanol fixed cells. Approximately 40% of JEG-3 cells fixed with paraformaldehyde failed to stain. Nearly all cells were stained with MEM-G/9 following fixation with acetate buffer:methanol or Pap solution. Our findings indicate the importance of using an appropriate fixative for preserving HLA-G cell surface antigen for studies using the MEM-G/9 antibody.
HbA1c changes in patients with diabetes following periodontal therapy

Purpose This retrospective cohort study aimed to assess the effect of nonsurgical periodontal therapy on glycated hemoglobin (HbA1c) levels in patients with both type 2 diabetes and chronic periodontitis. Methods The intervention cohort (IC) comprised 133 patients with type 2 diabetes who received nonsurgical periodontal treatment, while the matching cohort (MC) included 4787 patients with type 2 diabetes who visited the Department of Endocrinology and Metabolism of Asan Medical Center. The patients in each cohort were divided into 3 groups according to their baseline HbA1c level: subgroup 1, HbA1c <7%; subgroup 2, 7%≤ HbA1c <9%; and subgroup 3, HbA1c ≥9%. Changes in HbA1c levels from baseline to 6 and 12 months were analyzed. In addition, the association between changes in HbA1c levels and the number of periodontal maintenance visits was investigated. Results There were no statistically significant changes in HbA1c levels in the IC and MC or their subgroups when evaluated with repeated-measures analysis of variance. However, the IC showed maintenance of baseline HbA1c levels, while the MC had a trend for HbA1c levels to steadily increase as shown by pairwise comparisons (baseline to 6 months and baseline to 12 months). IC subgroup 1 also maintained steady HbA1c levels from 6 months to 12 months, whereas MC subgroup 1 presented a steady increase during the same period. The number of periodontal maintenance visits had no association with changes in HbA1c levels during the 1-year study duration. Conclusions For patients with both type 2 diabetes and periodontitis, nonsurgical periodontal treatment and periodontal maintenance may help to control HbA1c levels.
ATRX limits the accessibility of histone H3-occupied HSV genomes during lytic infection

Histones are rapidly loaded on the HSV genome upon entry into the nucleus of human fibroblasts, but the effects of histone loading on viral replication have not been fully defined. We showed recently that ATRX is dispensable for de novo deposition of H3 to HSV genomes after nuclear entry but restricted infection through maintenance of viral heterochromatin. To further investigate the roles that ATRX and other histone H3 chaperones play in restriction of HSV, we infected human fibroblasts that were systematically depleted of nuclear H3 chaperones. We found that the ATRX/DAXX complex is unique among nuclear H3 chaperones in its capacity to restrict ICP0-null HSV infection. Only depletion of ATRX significantly alleviated restriction of viral replication. Interestingly, no individual nuclear H3 chaperone was required for deposition of H3 onto input viral genomes, suggesting that during lytic infection, H3 deposition may occur through multiple pathways. ChIP-seq for total histone H3 in control and ATRX-KO cells infected with ICP0-null HSV showed that HSV DNA is loaded with high levels of histones across the entire viral genome. Despite high levels of H3, ATAC-seq analysis revealed that HSV DNA is highly accessible, especially in regions of high GC content, and is not organized largely into ordered nucleosomes during lytic infection. ATRX reduced accessibility of viral DNA to the activity of a TN5 transposase and enhanced accumulation of viral DNA fragment sizes associated with nucleosome-like structures. Together, these findings support a model in which ATRX restricts viral infection by altering the structure of histone H3-loaded viral chromatin that reduces viral DNA accessibility for transcription. High GC rich regions of the HSV genome, especially the S component inverted repeats of the HSV-1 genome, show increased accessibility, which may lead to increased ability to transcribe the IE genes encoded in these regions during initiation of infection.
A comparison of speech intelligibility and subjective quality with hearing-aid processing in older adults with hearing loss

Abstract Objective This study characterised the relationship between speech intelligibility and quality in listeners with hearing loss for a range of hearing-aid processing settings and acoustic conditions. Design Binaural speech intelligibility scores and quality ratings were measured for sentences presented in babble noise and processed through a hearing-aid simulation. The intelligibility–quality relationship was investigated by (1) assessing the effects of experimental conditions on each task; (2) directly comparing intelligibility scores and quality ratings for each participant across the range of conditions; and (3) comparing the association between signal envelope fidelity (represented by a cepstral correlation metric) and intelligibility and quality. Study sample Participants were 15 adults (7 females; age range 59–81 years) with mild to moderately severe sensorineural hearing loss. Results Intelligibility and quality showed a positive association both with each other and with changes to signal fidelity introduced by the entire acoustic and signal-processing system including the additive noise and the hearing-aid output. As signal fidelity decreased, quality ratings changed at a slower rate than intelligibility scores. Individual psychometric functions were more variable for quality compared to intelligibility. Conclusions Variability in the intelligibility–quality relationship reinforces the importance of measuring both intelligibility and quality in clinical hearing-aid fittings.
Development of molecular tools for diagnosis of Alzheimer’s disease that are based on detection of amyloidogenic proteins

ABSTRACT Alzheimer’s disease (AD) is the most common form of dementia that usually occurs among older people. AD results from neuronal degeneration that leads to the cognitive impairment and death. AD is incurable, typically develops over the course of many years and is accompanied by a loss of functional autonomy, making a patient completely dependent on family members and/or healthcare workers. Critical features of AD are pathological polymerization of Aβ peptide and microtubule-associated protein tau, accompanied by alterations of their conformations and resulting in accumulation of cross-β fibrils (amyloids) in human brains. AD apparently progresses asymptomatically for years or even decades before the appearance of symptoms. Therefore, development of the early AD diagnosis at a pre-symptomatic stage is essential for potential therapies. This review is focused on current and potential molecular tools (including non-invasive methods) that are based on detection of amyloidogenic proteins and can be applicable to early diagnosis of AD. Abbreviations: Aβ – amyloid-β peptide; AβO – amyloid-β oligomers; AD – Alzheimer’s disease; ADRDA – Alzheimer’s Disease and Related Disorders Association; APH1 - anterior pharynx defective 1; APP – amyloid precursor protein; BACE1 – β-site APP-cleaving enzyme 1; BBB – brain blood barrier; CJD - Creutzfeldt-Jakob disease; CRM – certified reference material; CSF – cerebrospinal fluid; ELISA – enzyme-linked immunosorbent assay; FGD – 18F-fluorodesoxyglucose (2-deoxy-2-[18F]fluoro-D-glucose); IP-MS – immunoprecipitation-mass spectrometry assay; MCI – mild cognitive impairment; MDS – multimer detection system; MRI – magnetic resonance imaging; NIA-AA – National Institute on Ageing and Alzheimer’s Association; NINCDS – National Institute of Neurological and Communicative Disorders and Stroke; PEN2 – presenilin enhancer 2; PET – positron emission tomography; PiB – Pittsburgh Compound B; PiB-SUVR - PIB standardized uptake value ratio; PMCA – Protein Misfolding Cycling Amplification; PrP – Prion Protein; P-tau – hyperphosphorylated tau protein; RMP – reference measurement procedure; RT-QuIC - real-time quaking-induced conversion; SiMoA – single-molecule array; ThT – thioflavin T; TSEs – Transmissible Spongiform Encephslopathies; T-tau – total tau protein
Analgesic efficacy of remifentanil patient-controlled analgesia versus combined spinal-epidural technique in multiparous women during labour.

OBJECTIVES To compare the analgesic profile of remifentanil patient-controlled analgesia (RPCA) and combined spinal-epidural analgesia technique (CSEA) in multiparous women during the entire labour. We hypothesized that CSEA would provide a better and more sustained pain reduction than RPCA. MATERIAL AND METHODS A prospective observational trial under ID NCT02963337 at a university hospital in Slovenia 2017-2018. Analgesic efficacy, satisfaction with pain-relief, adverse effects, labour progress, and outcomes between RPCA (80) and CSEA (81) were compared. RESULTS CSEA provided significantly lower pain scores during the entire labour. Compared to baseline, significant pain reduction was recorded in both groups after 15 min. No difference was recorded compared to baseline with RPCA and CSEA after 45 and 90 mins, respectively. CSEA provided higher satisfaction than RPCA (5 [5-5] vs 5 [4-5], p < 0.0001). More patients with CSEA opted for the same technique for the next labour [CSEA; 77 (95%) vs RPCA; 65 (81%), p = 0.003]. No crossovers were observed. RPCA was associated with desaturation (34%), bradypnea (21%) and apnoea (25%), which were transitional and easily managed. None had severe sedation. No differences were recorded in labour progress and outcomes. Apgar scores were reassuring in all neonates (> 8). None had umbilical artery pH < 7.0. CONCLUSIONS In multiparas, CSEA provided superior analgesia and satisfaction than RPCA. Nevertheless, RPCA provided a satisfactory experience, suggesting it could be used when neuraxial analgesia is not available, preferred, or contraindicated. In that case, constant presence of midwife is mandatory for management of clinically significant hypoventilation.
Brain endothelial tricellular junctions as novel sites for T cell diapedesis across the blood–brain barrier

ABSTRACT The migration of activated T cells across the blood–brain barrier (BBB) is a critical step in central nervous system (CNS) immune surveillance and inflammation. Whereas T cell diapedesis across the intact BBB seems to occur preferentially through the BBB cellular junctions, impaired BBB integrity during neuroinflammation is accompanied by increased transcellular T cell diapedesis. The underlying mechanisms directing T cells to paracellular versus transcellular sites of diapedesis across the BBB remain to be explored. By combining in vitro live-cell imaging of T cell migration across primary mouse brain microvascular endothelial cells (pMBMECs) under physiological flow with serial block-face scanning electron microscopy (SBF-SEM), we have identified BBB tricellular junctions as novel sites for T cell diapedesis across the BBB. Downregulated expression of tricellular junctional proteins or protein-based targeting of their interactions in pMBMEC monolayers correlated with enhanced transcellular T cell diapedesis, and abluminal presence of chemokines increased T cell diapedesis through tricellular junctions. Our observations assign an entirely novel role to BBB tricellular junctions in regulating T cell entry into the CNS. This article has an associated First Person interview with the first author of the paper.
Fundus evaluation in COVID-19 positives with non-severe disease

Purpose: The aim of this work was to study and document retinal changes in coronavirus disease-2019 (COVID-19) positive patients with nonsevere disease using a nonmydriatic handheld fundus camera. Methods: A cross-sectional observational study was conducted on patients affected by COVID-19 who were admitted at our center. Our study included patients with no, mild, and moderate symptoms (nonsevere cases). Intensive care unit (ICU)-admitted patients were excluded considering the difficulty in procuring the fundus image by the handheld camera due to patients positioning. Patients with systemic conditions (diabetes, hypertension, and severe anemia) known to cause retinopathy were also excluded. Bedside anterior segment examination, fundus examination using indirect ophthalmoscopy and fundus imaging of each patient using a nonmydriatic handheld fundus camera was done by a trained ophthalmologist posted for COVID duty. Results: In a cohort of 138 patients, 94 (68.1%) were men and 44 (31.9%) were women. A total of 276 eyes were evaluated. The mean age of the patients was 38.51 ± 14.4 years. Anterior segment evaluation showed no abnormality in any of the eyes. On fundus screening using nonmydriatic handheld camera, a single streak of superficial retinal hemorrhage was noted at the posterior pole of the fundus in the left eye of one patient (0.72%), which was away from fovea. Laboratory tests revealed low hemoglobin (between 10 and 10.9 g/dL falling under mild Anemia) in 12 patients, elevated total leucocyte count in 6 patients, raised LDH in majority of patients (323 ± 101 Units/L) and elevated CRP (14.6 ± 30.99 mg/L). Rest of the lab parameters were within the normal range. Conclusion: In our study, COVID patients with mild-to-moderate symptoms did not show any inflammatory/infective or vaso-occlusive lesions in the retina attributable to COVID-19 infection, except one patient who had a single streak hemorrhage in the macula away from fovea, probably incidental.
Integrating Biomaterials and Genome Editing Approaches to Advance Biomedical Science.

The recent discovery and subsequent development of the clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated (Cas) platform as a precise genome editing tool have transformed biomedicine. As these CRISPR-based tools have matured, multiple stages of the gene editing process and the bioengineering of human cells and tissues have advanced. Here, we highlight recent intersections in the development of biomaterials and genome editing technologies. These intersections include the delivery of macromolecules, where biomaterial platforms have been harnessed to enable nonviral delivery of genome engineering tools to cells and tissues in vivo. Further, engineering native-like biomaterial platforms for cell culture facilitates complex modeling of human development and disease when combined with genome engineering tools. Deeper integration of biomaterial platforms in these fields could play a significant role in enabling new breakthroughs in the application of gene editing for the treatment of human disease. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 23 is June 2021. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.