Miracle-dz/UniFAR-FTUs huggingface dataset:
Screening of Cellular Stress Responses Induced by Ambient Aerosol Ultrafine Particle Fraction PM0.5 in A549 Cells

Effects of airborne particles on the expression status of markers of cellular toxic stress and on the release of eicosanoids, linked with inflammation and oxidative damage, remain poorly characterized. Therefore, we proposed a set of various methodological approaches in order to address complexity of PM0.5-induced toxicity. For this purpose, we used a well-characterized model of A549 pulmonary epithelial cells exposed to a non-cytotoxic concentration of ambient aerosol particle fraction PM0.5 for 24 h. Electron microscopy confirmed accumulation of PM0.5 within A549 cells, yet, autophagy was not induced. Expression profiles of various cellular stress response genes that have been previously shown to be involved in early stress responses, namely unfolded protein response, DNA damage response, and in aryl hydrocarbon receptor (AhR) and p53 signaling, were analyzed. This analysis revealed induction of GREM1, EGR1, CYP1A1, CDK1A, PUMA, NOXA and GDF15 and suppression of SOX9 in response to PM0.5 exposure. Analysis of eicosanoids showed no oxidative damage and only a weak anti-inflammatory response. In conclusion, this study helps to identify novel gene markers, GREM1, EGR1, GDF15 and SOX9, that may represent a valuable tool for routine testing of PM0.5-induced in vitro toxicity in lung epithelial cells.
Physical Activity and Fitness in White- and Blue-Collar Retired Men

The average life expectancy has increased and despite a distinct feminization of aging, the number of older males continues to grow. Physical activity has a positive effect on health and helps to slow down the negative consequences of aging. The aim of the study was to evaluate possible relationships between physical fitness, physical activity and type of work during occupational activity among retired men (aged ≥65 years), no longer professionally active. The study included 104 men (aged from 65 to 90 years), further stratified into blue- and white-collar groups (66 and 38 subjects, respectively). The International Physical Activity Questionnaire (IPAQ) was used to assess their physical activity levels. Physical performance was assessed using the Short Physical Performance Battery test (SPPB) and handgrip strength (HGS) measurement. Geriatric Depression Scale (GDS) was used to identify the risk for depression. Mean physical activity in the study population was moderate in almost 70%, high in 19% and low in 11% of the subjects. Men with high physical activity levels had better SPPB and GDS scores (p = .01 and p = .001, respectively). In the blue-collar group, the IPAQ scores were lower than in the white-collar group, although the differences were statistically insignificant. The SPPB scores and mean HGS for the dominant hand were similar in both groups. Occupational physical activity should not substitute other forms of physical activity. Regardless of the type of work performed before retirement, the men obtained similar results in terms of their physical activity.
The lncRNAs RP1-261G23.7, RP11-69E11.4 and SATB2-AS1 are a novel clinical signature for predicting recurrent osteosarcoma

Abstract Background: Osteosarcoma is the most common primary bone malignancy in children and adolescents. In order to find factors related to its recurrence, and thus improve recovery prospects, a powerful clinical signature is needed. Long noncoding RNAs (lncRNAs) are essential in osteosarcoma processes and development, and here we report significant lncRNAs to aid in earlier diagnosis of osteosarcoma. Methods: A univariate Cox proportional hazards regression analysis and a multivariate Cox regression analysis were used to analyze osteosarcoma patients’ lncRNA expression data from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET), a public database. Results: A lncRNA signature consisting of three lncRNAs (RP1-261G23.7, RP11-69E11.4 and SATB2-AS1) was selected. The signature was used to sort patients into high-risk and low-risk groups with meaningful recurrence rates (median recurrence time 16.80 vs. >128.22 months, log-rank test, P<0.001) in the training group, and predictive ability was validated in a test dataset (median 16.32 vs. >143.80 months, log-rank test, P=0.006). A multivariate Cox regression analysis showed that the significant lncRNA was an independent prognostic factor for osteosarcoma patients. Functional analysis suggests that these lncRNAs were related to the PI3K-Akt signaling pathway, the Wnt signaling pathway, and the G-protein coupled receptor signaling pathway, all of which have various, important roles in osteosarcoma development. The significant 3-lncRNA set could be a novel prediction biomarker that could aid in treatment and also predict the likelihood of recurrence of osteosarcoma in patients.
Occupational exposure to airborne formaldehyde in hospital: setting an automatic sampling system, comparing different monitoring methods and applying them to assess exposure

Background: In recent years, under-vacuum sealing (UVS) and containers with formalin encapsulated in the lid have been proposed for the reduction of occupational exposure to airborne formaldehyde (FA) in healthcare environments. Objectives: We are presenting a study focused on the assessment of FA in hospitals: an automatic sampling system was set, different sampling devices were compared, and the concentration of FA was assessed, following its use in different scenarios. Methods: Three different devices for sampling/measuring FA were compared. They are based on: 1. silica gel cartridges impregnated with 2,4-dinitrophenylhydrazine (2,4-DNPH); 2. SPME® fiber using O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine; 3. direct reading commercial instrumentation. Three typical scenarios using FA were investigated: operating theatres where small biopsies are soaked into closed-circuit system 4% FA containers, secretariat of pathology laboratories during the registration of biopsies and pathology laboratories during the filling procedure by UVS and the slicing of biopsies. Results: The automatic sampling system allowed short-, long-, and in continuous-sampling time to measure airborne FA. Different sampling devices provided comparable results when tested to assess FA concentration ranging from 0.020-0.320 ppm in a test chamber, although the devices based on 2,4-DNPH were the best in terms of sensitivity and accuracy. The results of 246 samples showed that the FA concentration was less than 0.04 ppm in 91% of the measurements. Conclusions: The automatic methods efficiently allow sampling and measurement of FA in hospital settings. When using safe practices, the concentration of FA is well below occupational limit values.
Heterodimerization of TFAP2 pioneer factors drives epigenomic remodeling during neural crest specification

Cell fate commitment involves the progressive restriction of developmental potential. Recent studies have shown that this process requires not only shifts in gene expression but also an extensive remodeling of the epigenomic landscape. To examine how chromatin states are reorganized during cellular specification in an in vivo system, we examined the function of pioneer factor TFAP2A at discrete stages of neural crest development. Our results show that TFAP2A activates distinct sets of genomic regions during induction of the neural plate border and specification of neural crest cells. Genomic occupancy analysis revealed that the repertoire of TFAP2A targets depends upon its dimerization with paralogous proteins TFAP2C and TFAP2B. During gastrula stages, TFAP2A/C heterodimers activate components of the neural plate border induction program. As neurulation begins, TFAP2A trades partners, and TFAP2A/B heterodimers reorganize the epigenomic landscape of progenitor cells to promote neural crest specification. We propose that this molecular switch acts to drive progressive cell commitment, remodeling the epigenomic landscape to define the presumptive neural crest. Our findings show how pioneer factors regulate distinct genomic targets in a stage-specific manner and highlight how paralogy can serve as an evolutionary strategy to diversify the function of the regulators that control embryonic development.
Hypoxia induces a time- and tissue-specific response that elicits intertissue circadian clock misalignment

Significance Circadian clocks are present in most cells of the body and act in concert to coordinate our daily physiology and behavior with the environment. Circadian misalignment between body clocks and the environment has been implicated in various pathologies. Here, we show that circadian misalignment can also occur between clocks of different peripheral tissues following exposure to hypoxia and that it stems from the differential response of core clock components to hypoxia. Intertissue circadian misalignment also occurs upon intermittent hypoxia, a model for obstructive sleep apnea (OSA). Our findings highlight the potential role of internal circadian misalignment in the pathophysiology of OSA and potentially other hypoxia-related diseases. The occurrence and sequelae of disorders that lead to hypoxic spells such as asthma, chronic obstructive pulmonary disease, and obstructive sleep apnea (OSA) exhibit daily variance. This prompted us to examine the interaction between the hypoxic response and the circadian clock in vivo. We found that the global transcriptional response to acute hypoxia is tissue-specific and time-of-day–dependent. In particular, clock components differentially responded at the transcriptional and posttranscriptional level, and these responses depended on an intact circadian clock. Importantly, exposure to hypoxia phase-shifted clocks in a tissue-dependent manner led to intertissue circadian clock misalignment. This differential response relied on the intrinsic properties of each tissue and could be recapitulated ex vivo. Notably, circadian misalignment was also elicited by intermittent hypoxia, a widely used model for OSA. Given that phase coherence between circadian clocks is considered favorable, we propose that hypoxia leads to circadian misalignment, contributing to the pathophysiology of OSA and potentially other diseases that involve hypoxia.
Comparison of Intensity Discrimination between Children Using Cochlear Implants and Typically Developing Children.

OBJECTIVES Differential sensitivity of intensity is known to be important for the perception of the relative distance of sounds in the environment, emotions of speakers, and localize sounds. However, a few features in listening devices, such as cochlear implants, used by individuals with hearing loss alter the output intensity heard by them. This makes soft sounds loud and loud sounds soft. Hence, the aim of the present study was to compare the intensity discrimination of children using cochlear implants with that of typically developing children. MATERIALS AND METHODS Intensity discrimination of 30 children (15 using cochlear implants and 15 typically developing children) was obtained for three warble tones (500 Hz, 1000 Hz, and 4000 Hz) and three vowels (/a/, /i/, and /u/). The responses of the two participant groups, obtained using a 3-alternative forced-choice technique, were compared. RESULTS Children using cochlear implants performed significantly poorer than typically developing children for the 4000 Hz warble tone and for the vowels /a/ and /u/. However, there was no significant difference for the remaining stimuli. CONCLUSION The study indicated that the intensity discrimination threshold varies as a function of the frequency of the signals in children using cochlear implants. Intensity discrimination for high-frequency tones was significantly poorer for typically developing children, but not for low-frequency tones. In contrast, children using cochlear implants performed similarly to typically developing children for the high-frequency vowel but not for the mid- and low-frequency vowel.
A Selenone-Functionalized Polyhedral Oligomeric Silsesquioxane for Selective Detection and Adsorption of Hg2+ ions in Aqueous Solutions

Developing novel functional polyhedral oligomeric silsesquioxane (POSS) for various applications is highly desirable. Herein we present the first example of a novel selenone-functionalized POSS (POSS-Se) by treating an imidazolium-containing POSS with selenium powder under mild condition. The structure of POSS-Se was characterized by FT-IR, 1H NMR, 13C NMR, 29Si NMR, and elemental analysis. Acid treatment of POSS-Se results in a hydrophilic red-orange colored solid, which is highly sensitive and selective for the detection of Hg2+ ions in aqueous solutions by visually observing the color change to pale yellow, and to white. Interestingly, POSS-Se has no activity on this detection. This finding is due to the Se–Se formation by acid-treatment and subsequent coordination-induced cleavage upon the addition of Hg2+ ions. The detection behavior can be precisely monitored by a “turn-on” fluorescence phenomenon with the limit of detection (LOD) of 8.48 ppb, comparable to or higher than many reported Hg2+ sensors. Moreover, POSS-Se demonstrates a selective and efficient adsorption of Hg2+ ions with a maximum capacity of 952 mg g–1. The value is higher than most reported adsorbents for Hg2+ ions, typically thiol and/or thioether functional materials, indicating its promise as an efficient adsorbent for the selective removal of Hg2+ ions from industrial wastewater. This work may open up new horizons for the exploration of selenium-containing functional POSS.
Identification of σE-Dependent Promoter Upstream of clpB from the Pathogenic Spirochaete Leptospira interrogans by Applying an E. coli Two-Plasmid System

There is limited information on gene expression in the pathogenic spirochaete Leptospira interrogans and genetic mechanisms controlling its virulence. Transcription is the first step in gene expression that is often determined by environmental effects, including infection-induced stresses. Alterations in the environment result in significant changes in the transcription of many genes, allowing effective adaptation of Leptospira to mammalian hosts. Thus, promoter and transcriptional start site identification are crucial for determining gene expression regulation and for the understanding of genetic regulatory mechanisms existing in Leptospira. Here, we characterized the promoter region of the L. interrogans clpB gene (clpBLi) encoding an AAA+ molecular chaperone ClpB essential for the survival of this spirochaete under thermal and oxidative stresses, and also during infection of the host. Primer extension analysis demonstrated that transcription of clpB in L. interrogans initiates at a cytidine located 41 bp upstream of the ATG initiation codon, and, to a lesser extent, at an adenine located 2 bp downstream of the identified site. Transcription of both transcripts was heat-inducible. Determination of clpBLi transcription start site, combined with promoter transcriptional activity assays using a modified two-plasmid system in E. coli, revealed that clpBLi transcription is controlled by the ECF σE factor. Of the ten L. interrogans ECF σ factors, the factor encoded by LIC_12757 (LA0876) is most likely to be the key regulator of clpB gene expression in Leptospira cells, especially under thermal stress. Furthermore, clpB expression may be mediated by ppGpp in Leptospira.
Feasibility of thin-slice abdominal CT in overweight patients using a vendor neutral image-based denoising algorithm: Assessment of image noise, contrast, and quality

The purpose of this study was to investigate whether the novel image-based noise reduction software (NRS) improves image quality, and to assess the feasibility of using this software in combination with hybrid iterative reconstruction (IR) in image quality on thin-slice abdominal CT. In this retrospective study, 54 patients who underwent dynamic liver CT between April and July 2017 and had a body mass index higher than 25 kg/m2 were included. Three image sets of each patient were reconstructed as follows: hybrid IR images with 1-mm slice thickness (group A), hybrid IR images with 5-mm slice thickness (group B), and hybrid IR images with 1-mm slice thickness denoised using NRS (group C). The mean image noise and contrast-to-noise ratio relative to the muscle of the aorta and liver were assessed. Subjective image quality was evaluated by two radiologists for sharpness, noise, contrast, and overall quality using 5-point scales. The mean image noise was significantly lower in group C than in group A (p < 0.01), but no significant difference was observed between groups B and C. The contrast-to-noise ratio was significantly higher in group C than in group A (p < 0.01 and p = 0.01, respectively). Subjective image quality was also significantly higher in group C than in group A (p < 0.01), in terms of noise and overall quality, but not in terms of sharpness and contrast (p = 0.65 and 0.07, respectively). The contrast of images in group C was greater than that in group A, but this difference was not significant. Compared with hybrid IR alone, the novel NRS combined with a hybrid IR could result in significant noise reduction without sacrificing image quality on CT. This combined approach will likely be particularly useful for thin-slice abdominal CT examinations of overweight patients.
Conjunctive Analyses of BSA-Seq and BSR-Seq to Reveal the Molecular Pathway of Leafy Head Formation in Chinese Cabbage

As the storage organ of Chinese cabbage, the leafy head was harvested as a commercial product due to its edible value. In this study, the bulked segregant analysis (BSA) and bulked segregant RNA-Seq (BSR) were performed with F2 separation progeny to study the molecular mechanism of leafy head formation in Chinese cabbage. BSA-Seq analysis located four candidate regions containing 40 candidate genes, while BSR-Seq analysis revealed eight candidate regions containing 607 candidate genes. The conjunctive analyses of these two methods identified that Casein kinase gene BrCKL8 (Bra035974) is the common candidate gene related with leafy head formation in Chinese cabbage, and it showed high expression levels at the three segments of heading type plant leaves. The differentially expressed genes (DEGs) between two set pairs of cDNA sequencing bulks were divided into two categories: one category was related with five hormone pathways (Auxin, Ethylene, Abscisic acid, Jasmonic acid and Gibberellin), the other category was composed of genes that associate with the calcium signaling pathway. Moreover, a series of upregulated transcriptional factors (TFs) were also identified by the association analysis of BSR-Seq analysis. The leafy head development was regulated by various biological processes and effected by diverse external environment factors, so our research will contribute to the breeding of perfect leaf-heading types of Chinese cabbage.
Alveolar Dead-Space Fraction and Arterial Saturation Predict Postoperative Course in Fontan Patients*

Objectives: Fontan surgery, the final surgical stage in single ventricle palliation, redirects systemic venous blood into the pulmonary circulation for gas exchange. A decrease in pulmonary blood flow can lead to major complications and grave outcomes. Alveolar dead-space fraction represents the portion of inhaled air that does not participate in gas exchange and hence quantifies ventilation-perfusion abnormalities in the lung. Increased alveolar dead-space fraction has been associated with prolonged mechanical ventilation and worse outcome after congenital heart surgery. The association of alveolar dead-space fraction with clinical outcomes in patients undergoing Fontan operation has not been reported. Interventions: None. Design, Setting, and Patients: A retrospective charts review of all pediatric patients who underwent Fontan surgery during June 2010–November 2018 in a tertiary-care pediatric hospital. Associations between alveolar dead-space fraction and arterial oxyhemoglobin saturation to a composite outcome (surgical or catheter-based intervention, extracorporeal membrane oxygenation use, prolonged ventilation, prolonged hospital length of stay, or death) were explored. Secondary endpoints were parameters of severity of illness, chest drainage duration, and length of stay. Measurements and Main Results: Of 128 patients undergoing Fontan operation, 34 met criteria for composite outcome. Alveolar dead-space fraction was significantly higher in the composite (0.33 ± 0.14) versus control (0.25 ± 0.26; p = 0.016) group. Alveolar dead-space fraction greater than or equal to 0.29 indicated a 37% increase in risk to meet composite criteria. Admission arterial oxygen saturation was significantly lower in composite versus control group (93.4% vs 97.1%; p = 0.005). Alveolar dead-space fraction was significantly associated with increased durations of mechanical ventilation, ICU length of stay, duration of thoracic drainage, and parameters of severity of illness. Conclusions: Alveolar dead-space fraction and arterial saturation may predict complicated postoperative course in patients undergoing the Fontan operation.
Transoral robotic surgery: a 4-year learning experience in a single Danish Cancer Centre

Abstract Background: The main indication for transoral robotic surgery (TORS) has been the primary treatment of oropharyngeal squamous cell carcinoma (OPSCC). In the western world this is highly relevant due to the increasing incidence of human papillomavirus (HPV)-positive OPSCC. In Denmark, TORS was implemented in 2013 for use in the protocolled primary treatment of OPSCC. Aims/objectives: To perform a year-by-year comparative analysis of indications for TORS, hospitalization and complication rates to identify optimal future indications for TORS. Methods and materials: This is a retrospective single-centre case review from 2013-2017. Data were collected from patient files through electronic health care systems. Results: Since 2013, there has been a change of indications from performing benign and salvage surgery to mainly primary treatment of OPSCC and diagnostic use in patients with cancer of unknown primary (CUP). The overall complication rates have reduced considerably over time. Conclusions and significance: Lower complication rates may be explained by improved surgical experience, through better patient selection and changes in indications for TORS. Future applications of TORS will be in the management of CUP and as part of a Danish national randomized clinical trial aiming to compare long-term functional outcomes after treatment of early-stage OPSCC with TORS versus radiation treatment.
Identification and Description of Potentially Influential Social Network Members using the Strategic Player Approach

Abstract Background: Diffusion of innovations theory posits that ideas and behaviors can be spread through social network ties. In intervention work, intervening upon certain network members may lead to intervention effects “diffusing” into the network to affect the behavior of network members who did not receive the intervention. The strategic players (SP) method, an extension of Borgatti’s Key Players approach, is used to balance the (sometimes) opposing goals of spreading the intervention to as many members of the target group as possible, while preventing the spread of the intervention to others. Objectives: We sought to test whether members of the SP set have network position and non-network differences (such as demographic, attitudinal, or behavioral differences) compared to the remaining members of the target group (non-SPs). Methods: A first-year class at a private residential university (N = 1342) completed network and non-network measures. Analyses were restricted only to heavy drinkers, leading to a final analytic sample of 529. Results: SPs and non-SPs differed on multiple network variables, but did not differ on most demographic, attitudinal, and behavior variables. Conclusions: As designed, the SP program identified participants who were distinguished by their network position. The fact that they did not also differ on other characteristics shows the SPs are not significantly different than heavy drinkers who were not selected.