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ObjectiveArtificial stone dust (ASD) contains high levels of ultrafine particles (UFP <1 µm) which penetrate deeply into the lungs. This study aimed to demonstrate the direct effect of UFP in the lungs of ASD-exposed workers on functional inflammatory and imaging parameters.Methods68 workers with up to 20 years of ASD exposure at the workplace were recruited from small enterprises throughout the country and compared with 48 non-exposed individuals. Pulmonary function test (PFT), CT, induced sputum (IS) and cytokine analyses were performed by conventional methods. The CT scans were evaluated for features indicative of silicosis in three zones of each lung. UFP were quantitated by the NanoSight LM20 system (NanoSight, Salisbury) using the Nanoparticle Tracking Analysis. Interleukin (IL)-6, IL-8 and tumour necrosis factor alpha (TNF-α) levels were measured by Luminex (R&D Systems).ResultsThirty-four patients had CT scores between 0 and 42, and 29 of them were diagnosed with silicosis. Content of the UFP retrieved from IS supernatants correlated negatively with the PFT results (total lung capacity r=−0.347, p=0.011; forced expiratory volume in 1 s r=−0.299, p=0.046; diffusion lung carbon monoxide in a single breath r=−0.425, p=0.004) and with the CT score (r=0.378, p=0.023), and with the inflammatory cytokines IL-8 (r=0.336, p=0.024), IL-6 (r=0.294, p=0.065) and TNF-α (r=0.409, p=0.007). Raw material of ASD was left to sedimentate in water for <15 min, and 50% of the floating particles were UFP. A cut-off of 8×106 UFP/mL in IS samples had a sensitivity of 77% to predict pulmonary disease.ConclusionsThis is the first demonstration of an association between UFP-related decreased PFT results, worsening of CT findings and elevation of inflammatory cytokines, which may be attributed to high-dose inhalation of UFP of ASD at the workplace.

Methods for identifying patients at high risk for osteoporotic fractures, including dual-energy X-ray absorptiometry (DXA) 1 , 2 and risk predictors like the Fracture Risk Assessment Tool (FRAX) 3 – 6 , are underutilized. We assessed the feasibility of automatic, opportunistic fracture risk evaluation based on routine abdomen or chest computed tomography (CT) scans. A CT-based predictor was created using three automatically generated bone imaging biomarkers (vertebral compression fractures (VCFs), simulated DXA T-scores and lumbar trabecular density) and CT metadata of age and sex. A cohort of 48,227 individuals (51.8% women) aged 50–90 with available CTs before 2012 (index date) were assessed for 5-year fracture risk using FRAX with no bone mineral density (BMD) input (FRAXnb) and the CT-based predictor. Predictions were compared to outcomes of major osteoporotic fractures and hip fractures during 2012–2017 (follow-up period). Compared with FRAXnb, the major osteoporotic fracture CT-based predictor presented better receiver operating characteristic area under curve (AUC), sensitivity and positive predictive value (PPV) (+1.9%, +2.4% and +0.7%, respectively). The AUC, sensitivity and PPV measures of the hip fracture CT-based predictor were noninferior to FRAXnb at a noninferiority margin of 1%. When FRAXnb inputs are not available, the initial evaluation of fracture risk can be done completely automatically based on a single abdomen or chest CT, which is often available for screening candidates 7 , 8 . A retrospective analysis of existing computed tomography scans shows the feasibility of an automated process for evaluating osteoporotic fracture risk that could be used as an initial screening tool when FRAX inputs are unavailable.

In bacteria, determination of the 3’ termini of transcripts plays an essential role in regulation of gene expression, affecting the functionality and stability of the transcript. Several experimental approaches were developed to identify the 3’ termini of transcripts, however, these were applied only to a limited number of bacteria and growth conditions. Here we present a straightforward approach to identify 3’ termini from widely available RNA-seq data without the need for additional experiments. Our approach relies on the observation that the RNAtag-seq sequencing protocol results in overabundance of reads mapped to transcript 3’ termini. We present TRS (Termini by Read Starts), a computational pipeline exploiting this property to identify 3’ termini in RNAtag-seq data, and show that the identified 3’ termini are highly reliable. Since RNAtag-seq data are widely available for many bacteria and growth conditions, our approach paves the way for studying bacterial transcription termination in an unprecedented scope. TRS is a new method for determining 3’ transcript termini in bacteria, using data generated by the RNAtag-seq protocol. This methodology opens the door to study the evolution of transcription termini and their condition-dependent dynamics.

Amos Tanay and colleagues characterize DNA methylation polymorphism within cell populations and track immortalized fibroblasts in culture for over 300 generations to show that formation of differentially methylated regions occurs through a stochastic process and nearly deterministic epigenetic remodeling. DNA methylation has been comprehensively profiled in normal and cancer cells, but the dynamics that form, maintain and reprogram differentially methylated regions remain enigmatic. Here, we show that methylation patterns within populations of cells from individual somatic tissues are heterogeneous and polymorphic. Using in vitro evolution of immortalized fibroblasts for over 300 generations, we track the dynamics of polymorphic methylation at regions developing significant differential methylation on average. The data indicate that changes in population-averaged methylation occur through a stochastic process that generates a stream of local and uncorrelated methylation aberrations. Despite the stochastic nature of the process, nearly deterministic epigenetic remodeling emerges on average at loci that lose or gain resistance to methylation accumulation. Changes in the susceptibility to methylation accumulation are correlated with changes in histone modification and CTCF occupancy. Characterizing epigenomic polymorphism within cell populations is therefore critical to understanding methylation dynamics in normal and cancer cells.

Beachrock is composed of intertidal-associated sediments, rapidly cemented by calcium carbonate, and has important implications for understanding coastal morphological processes. This study focuses on the morphodynamic erosion patterns of Late Holocene beachrock outcrops along the Mediterranean coast of Israel that have formed since the sea reached its present level about 4000 years ago. Exposed beachrock is subjected to erosion, affecting its seaward and landward facing fronts and upper surface, and creating distinct morphological features due to wave pounding and coastal currents which remove unconsolidated sediment supporting layers. The current state of beachrock morphology is presented, based on field measurements and field relation interpretations of selected sites, backed by petrographic and sedimentological data. It shows and studies selected beachrock exposures along Israel’s coast, and characterizes their morphological features in various field-relation configurations. A classification is developed of the main erosion patterns of beachrock embedded on loose, hard, partly hard and partly loose substrate.

Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterized by a progressive and irreversible deterioration of lung function. Exacerbations of COPD have prolonged negative effects on pulmonary function and a major impact on health status and outcomes. NLRP3 inflammasome is a cardinal component of the inflammatory response, with marked evidence in stable and exacerbations of COPD. The aim of our study was to evaluate the NLRP3 inflammasome activity during COPD exacerbation by using an in vitro model. A549 cells were stimulated with different concentrations (10%, 4%, 2%) of cigarette smoke extract (CSE) with or without LPS (0.1μg/ml) for 24 hours. Cell viability was assessed by using XTT test. Levels of inflammatory cytokines (IL-8, MCP-1, and IL-1β) were measured by ELISA and the activity level of NLRP-3 was evaluated by flow cytometry. Cells exposed to CSE present an increase in inflammatory cytokines (IL-8 and MCP-1) production in a dose-dependent manner. Incubation with LPS to these cells results in higher levels of IL-8 and MCP-1 compared to stimulation of CSE alone. NLRP3 inflammasome activity and IL-1β levels were significantly increased in cells exposed to both CSE and LPS compared to CSE alone. NLRP3 inflammasome is upregulated in an in-vitro model of COPD and COPD exacerbation. Our findings provide novel biomarkers for COPD exacerbation and may present new targets for future research.

Beachrock is a sedimentary rock that forms rapidly through the cementation of beach-associated clasts by calcium carbonate within the intertidal zone. On the southern coast of Israel, Holocene beachrock exposures typically appear as linear, shore-parallel platforms that dip seawards. In the archeological record, beachrock was exploited as a natural resource for various purposes, including the production of querns, millstones, basins, building stones, and other architectural elements. At Tel Yavne, a site continuously settled from the Chalcolithic period to the present day, excavations in the eastern and southern fringes revealed an extensive industrial compound dating to the Byzantine and early Islamic periods. This compound underscores the settlement’s economic and industrial prominence during those eras. Numerous beachrock artifacts were uncovered, and this study examines their practical applications while characterizing their composition and microstructure. This research highlights the role of beachrock as a key resource, providing insights into inland–coastal economic interactions in antiquity and broadening our understanding of its use within the socio-economic landscape of the region.

In submerged landscapes, distinguishing anthropogenic features versus natural ones is often challenging. We have developed a set of criteria to validate the identification of submerged anthropogenic remains that include examining the geological context, sea-level considerations, associated archaeological finds (including coastal survey), and documenting the broader archaeological context. Furthermore, our experience demonstrates that, while progress has been made in applying remote-sensing technologies to detect anthropogenic features on the seabed, there is no substitute for direct, visual assessment by an underwater archaeologist for verification of their anthropogenic status. We have applied these criteria to examine two published case studies detailing suspected anthropogenic stone features on the seabed in the Sicilian Channel. Our examination has led us to conclude that both localities are not anthropogenic features. The Pantelleria Vecchia Bank features represent natural outcrops on a submerged paleo-landscape that were shaped by depositional and erosional processes during transgression and regression periods. The suspected Lampedusa cultic site comprises natural features that are located on a submerged neo-landscape formed due to erosion and retreat of the coastal cliff since the mid-Holocene, when the sea level reached its present level.

Background Pulmonary function is often affected by the inhalation of metal particles. The resulting pathology might trigger various lung diseases, e.g., parenchymal lung fibrosis and granulomatous lung disorders. We previously demonstrated that 6 % of tissue-proven sarcoid patients had a positive beryllium lymphocyte proliferation test (BeLPT), thus correcting the diagnosis to chronic beryllium disease. The aim of this study was to examine if MEmory Lymphocyte Immnuno Stimulation Assay (MELISA®), currently used for non-pulmonary diseases, can identify metals other than beryllium that can also trigger sensitization and induce granulomatous disease. Methods This pilot study included 13 sarcoid-like patients who underwent MELISA®. Eleven patients also underwent BeLPT. Biopsy samples were tested for metal content by scanning electron microscope. Eleven study patients had been exposed to metals at the workplace and 2 had silicone implants. Results Two patients who had undergone BeLPT were positive for beryllium. MELISA® detected 9 patients (9/13, 69 %) who were positive for at least one of the tested metals: 4 reacted positively to nickel, 4 to titanium, 2 to chromium, 2 to beryllium, 2 to silica, and one each to palladium, mercury and lead. Conclusion It is proposed that MELISA® can be exploited to also identify specific sensitization in individuals exposed to inhaled particles from a variety of metals.

Ultrafine particles (UFP) have been postulated to significantly contribute to the adverse health effects associated with exposure to particulate matter (PM). Due to their extremely small size (aerodynamic diameter <100 nm), UFP are able to deposit deep within the lung after inhalation and evade many mechanisms responsible for the clearance of larger particles. There is a lack of biologically relevant personal exposure metrics for exposure to occupational- and environmental-related micro- and nano-sized PM. The aim of the present study is to assess UFP in induced sputum (IS) and exhaled breath condensate (EBC) as possible biomarkers for assessing lung function impairment. Sputum induction and EBC testing were performed by conventional methods. UFP particles were assessed with the NanoSight LM20 (NanoSight Ltd, London, UK). The subjects included 35 exposed and 25 non-exposed workers. There were no group differences in pulmonary function test results and differential cell counts, but 63.6% of the exposed subjects had a higher percentage of neutrophils (OR3.28 p  = 0.03) compared to the non-exposed subjects. The exposed subjects had higher percentages of UFP between 10 and 50 nm (69.45 ± 18.70 vs 60.11 ± 17.52 for the non-exposed group, p  = 0.004). No differences were found in the IS samples. Years of exposure correlated positively to UFP content ( r  = 0.342 p  = 0.01) and macrophage content ( r  = −0.327 p  = 0.03). The percentage of small fraction of UFP in EBC, but not IS, is higher in exposed workers, and EBC may be a sensitive biomarker to assess exposure to nanoparticles.