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A transcription-driven cellular response is activated upon UV stress. Here the authors reveal mechanistic insights into the regulatory process affecting transcription and chromatin dynamics, showing how maintaining Pol II firing safeguards the integrity of cells’ transcriptome

Background The controlled attenuation parameter (CAP) enables the noninvasive assessment of liver steatosis. We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of CAP for identifying liver steatosis in patients at risk for metabolic dysfunctionassociated steatotic liver disease (MASLD), using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. Method We searched Medline, Embase, Cochrane Library and gray literature sources up to March 2024. We defined MASLD as MRI-PDFF =5%. We also assessed the accuracy of CAP for identifying patients with MRI-PDFF =10%. We calculated pooled sensitivity and specificity estimates using hierarchical random-effects models. We assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool, and the certainty in meta-analysis estimates using the Grading of Recommendations Assessment, Development and Evaluation framework. Results We included 8 studies with 1116 participants. The prevalence of MASLD ranged from 65.2-93.9%. Pooled sensitivity and specificity of CAP for MRI-PDFF =5% were 0.84 (95% confidence interval [CI] 0.79-0.88) and 0.77 (95%CI 0.68-0.84), respectively, with an area under the receiver operating characteristic curve (AUROC) of 0.88. The pooled sensitivity and specificity for MRI-PDFF =10% were 0.83 (95%CI 0.80-0.87) and 0.72 (95%CI 0.59-0.82), with an AUROC of 0.85. The certainty in our estimates was low to very low because of the high risk of bias, inconsistency and imprecision. Conclusions CAP has acceptable diagnostic accuracy for both MRI-PDFF =5% and MRI-PDFF =10%. Adequately powered and rigorously conducted diagnostic accuracy studies are warranted to establish the optimal CAP thresholds. [ABSTRACT FROM AUTHOR]

The present study is an overview of systematic reviews focusing on adverse events of antimyeloma treatments. It provides a systematic description of adverse events as they are reported in the systematic reviews as well as a critical appraisal of included reviews. We conducted a comprehensive literature search in the most widely used electronic databases looking for systematic reviews that had an adverse event of an antimyeloma treatment intervention as primary outcome. Two independent reviewers conducted selection of included studies and data extraction on predesigned online forms and assessed study quality using AMSTAR 2. Overall corrected covered area (CCA) was calculated to examine the overlap of primary studies across systematic reviews. After screening eligible studies, 23 systematic reviews were included in this overview. Seven reviews with overall CCA of 14.7% examined cardiovascular adverse events of different drugs, including immunomodulatory drugs and proteasome inhibitors (mainly carfilzomib). Nine focused on infections, presenting with overall CCA of 5.8%, each one focused on a different drug or drug class. Three studied thromboembolism in patients treated either with lenalidomide, any immunomodulatory drug, or with daratumumab and had an overall CCA equal to 1.5%. Four more reviews focused on bortezomib-associated neurotoxicity, carfilzomib-associated renal toxicity, or second primary malignancies as an adverse event of lenalidomide or anti-CD38 monoclonal antibody treatment. The quality of included studies as judged by AMSTAR 2 was mostly critically low. Absence of a priori registered protocol and formal assessment of risk of bias of included primary studies were the most common shortcomings. Reporting of antimyeloma drug-associated toxicity is supported by multiple systematic reviews; nevertheless, methodological quality of existing reviews is mostly low. [ABSTRACT FROM AUTHOR]

Holothurians are prominent marine organisms in benthic ecosystems, exploited as food for centuries and, recently, as nutraceuticals. Moreover, they constitute a significant source of beneficial and medicinally valuable metabolites that have anticancer properties. Hypoxia, or low oxygen levels, and the stimulation of HIFs as a result of rapid cell proliferation and a restricted blood supply are characteristics shared by the majority of cancers, which give them resistance to standard treatment. The present study examines the effect of Holothuria tubulosa extract on the proliferation, HIF‐α protein expression, and their transcriptional activity in hepatocarcinoma‐derived Huh7 cells. Specimens of H. tubulosa were collected from the Aegean Sea, and their extract decreased the proliferation in Huh7 cells under normoxia and hypoxia in a dose‐dependent manner by MTT assay. The extract modified HIF‐1α protein expression by western blot analysis, downregulated hypoxia‐induced VEGF promoter by luciferase assay, and decreased the expression of known HIF‐1 and HIF‐2‐specific target genes, PGK and EPO, as revealed by real‐time PCR. H. tubulosa extract had the ability to reduce the phosphorylated form of ERK1/2 explaining its inhibitory effect on proliferation and HIF activity. These data reveal new roles of H. tubulosa with promising anticancer properties in liver cancer cells. [ABSTRACT FROM AUTHOR]

We present results of the Near-Earth objects Lunar Impacts and Optical TrAnsients (NELIOTA) campaign for lunar impact flashes observed with the 1.2 m Kryoneri telescope. From August 2019 to August 2023, we report 113 validated and 70 suspected flashes. For the validated flashes, we calculate the physical parameters (masses, radii) of the corresponding projectiles, the temperatures developed during the impacts, and the expected crater sizes. For the multiframe flashes, we present light curves and thermal evolution plots. Using the whole sample of NELIOTA that encompasses 192 validated flashes in total from 2017, the statistics of the physical parameters of the meteoroids, the peak temperatures of the impacts, and the expected crater sizes has been updated. Using this large sample, empirical relations correlating the luminous energies per photometric band were derived and used to roughly estimate the parameters of 92 suspected flashes of the NELIOTA archive. For a typical value of the luminous efficiency, we found that the majority (>75%) of the impacting meteoroids have masses between 1 and 200 g, radii between 0.5 and 3 cm and produced craters up to 3.5 m. 85% of the peak temperatures of the impacts range between 2000 and 4500 K. Statistics regarding the magnitude decline and the cooling rates of the multiframe flashes are also presented. The recalculation of the appearance frequency of meteoroids (lying within the aforementioned ranges of physical parameters) on the Moon yields that the total lunar surface is bombarded with 7.4 sporadic meteoroids per hour and up to 12.6 meteoroids per hour when the Earth-Moon system passes through a strong meteoroid stream. By extrapolating these rates on Earth, the respective rates for various distances from its surface are calculated and used to estimate the probability of an impact of a meteoroid with a hypothetical infrastructure on the Moon, or with a satellite orbiting Earth for various impact surfaces and duration times of the missions. [ABSTRACT FROM AUTHOR]

How can a post-Christian, secular audience understand the devoutly Christian, sacred music of Johann Sebastian Bach's St. Matthew Passion ? This article addresses this question with reference to the hermeneutics of Hans-Georg Gadamer and Hans Blumenberg. Their confrontation reveals broad implications for the theory of humanistic interpretation at large. Gadamer celebrates Bach as a 'classical' touchstone of Western culture whom we may productively interpret through a 'fusion of horizons'. Blumenberg, by contrast, cautions that our relation to Bach's Passion is fractured because it is impossible to 'pace off the horizon'. Blumenberg emphasizes the first-person experience of the diminution of historical meaning, a position this article calls 'shattered hermeneutics'. The article concludes that Blumenberg's interpretation of Bach and his critique of Gadamer thereby usefully and plausibly deepen and radicalize hermeneutics. [ABSTRACT FROM AUTHOR]

Ioannis Avgerinos,1 Aris Liakos,1,2 Apostolos Tsapas,1–3 Eleni Bekiari1,2 1Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Diabetes Centre, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Harris Manchester College, University of Oxford, Oxford, UKCorrespondence: Ioannis AvgerinosClinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Konstantinoupoleos 49, Thessaloniki 54642, GreeceEmail iavgerik@auth.grAbstract: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are currently used as second-line therapy for treatment of patients with type 2 diabetes mellitus (T2DM). Based on the results from dedicated cardiovascular outcome trials (CVOTs), current guidelines suggest the use of SGLT-2 inhibitors for patients with T2DM and established atherosclerotic cardiovascular disease (ASCVD) or heart failure. The cardiovascular safety profile of dapagliflozin, a novel SGLT-2 inhibitor, has been recently explored in large CVOTs. Treatment with dapagliflozin reduced the risk of the composite outcome of cardiovascular mortality or hospitalization for heart failure compared with placebo, both among patients with T2DM who had or were at risk of ASCVD, as well as among patients with heart failure and a reduced ejection fraction. The observed cardiovascular benefit was mainly attributed to the lower rate of hospitalization for heart failure. Additionally, treatment with dapagliflozin was associated with a lower rate of renal adverse events. The safety and efficacy of dapagliflozin on glycemic and non-glycemic endpoints has been also well established in a series of other clinical trials and real-word studies. The aim of the present review is to summarize the available evidence regarding the cardiovascular profile of dapagliflozin in patients with T2DM. Overall, by reducing the rate of hospitalization for heart failure and ameliorating renal adverse events, dapagliflozin is a valuable option for the management of patients with T2DM and multiple cardiovascular risk factors.Keywords: dapagliflozin, sodium-glucose co-transporter 2 inhibitors, SGLT-2 inhibitors, type 2 diabetes, cardiovascular risk

This study addressed a critical resource—soil—through the prism of processing big data at the continental scale. Rapid progress in technology and remote sensing has majorly improved data processing on extensive spatial and temporal scales. Here, the manuscript presents the results of a systematic effort to geo-process and analyze soil-relevant data. In addition, the main highlights include the difficulties associated with using data infrastructures, managing big geospatial data, decentralizing operations through remote access, mass processing, and automating the data-processing workflow using advanced programming languages. Challenges to this study included the reproducibility of the results, their presentation in a communicative way, and the harmonization of complex heterogeneous data in space and time based on high standards of accuracy. Accuracy was especially important as the results needed to be identical at all spatial scales (from point counts to aggregated countrywide data). The geospatial modeling of soil requires analysis at multiple spatial scales, from the pixel level, through multiple territorial units (national or regional), and river catchments, to the global scale. Advanced mapping methods (e.g., zonal statistics, map algebra, choropleth maps, and proportional symbols) were used to convey comprehensive and substantial information that would be of use to policymakers. More specifically, a variety of cartographic practices were employed, including vector and raster visualization and hexagon grid maps at the global or European scale and in several cartographic projections. The information was rendered in both grid format and as aggregated statistics per polygon (zonal statistics), combined with diagrams and an advanced graphical interface. The uncertainty was estimated and the results were validated in order to present the outputs in the most robust way. The study was also interdisciplinary in nature, requiring large-scale datasets to be integrated from different scientific domains, such as soil science, geography, hydrology, chemistry, climate change, and agriculture.

Indoor air pollutant sources are crucial in assessing IAQ, especially when outdoor air pollutant concentrations are low. In the present study, PM mass concentrations in a range of five sizes; CO, CO2, O3, NO, NO2, and TVOC concentrations; along with temperature and relative humidity were monitored in three indoor locations of a university. The monitoring took place in a building dedicated to teaching undergraduates. The first two locations, a professor’s office and a computer centre (laboratory), were not refurbished. The classroom under study is refurbished and now is airtight, as are all of the classrooms in this building. Air purifiers were installed in all of the classrooms to prevent the transmission of infectious pollutants. In all monitored locations, people were the main indoor source of PM, CO2, and TVOC. The operation of twelve computers in the small laboratory did not contribute to the air pollution, at least for the examined pollutants. The air purifier decreased the PM concentrations, but not the gaseous air pollutants.

This article considers the limitations, but also the insights, of Gadamerian hermeneutics for understanding and responding to the crisis precipitated by the Covid-19 pandemic. Our point of departure is the experience of deep disagreements amid the pandemic, and our primary example is ongoing debates in the United States about wearing masks. We argue that, during this dire situation, interpersonal mutual understanding is insufficient for resolving such bitter disputes. Rather, following Gadamer’s account of our dialogical experience with an artwork, we suggest that our encounter with the virus gives rise to new ways of seeing and experiencing ourselves and the world. Further, we draw on Gadamer’s account of the fusion of horizons to show how even competing perspectives on wearing masks arise within a shared space of meaning created by the virus. These insights provide hope for an improved model of political dialogue in the world of Covid-19.

Background:. One of the adverse effects of antiretroviral (ARV) drugs in the treatment of human immunodeficiency virus is lipodystrophy, which is often associated with metabolic complications such as hyperlipidemia, increased cardiovascular risk factors, and altered body fat distribution. This is characterized by a dorsal hump, hypermastia, or abdominal pannus deformity. The reasons for corrective surgery are aesthetic, psychosocial, and medical benefits. Methods:. This is a prospective study investigating 52 consecutive patients with ARV-induced lipodystrophy syndrome referred for surgical correction (liposuction for dorsal hump, abdominoplasty for increased abdominal pannus, and bilateral breast reduction for hypermastia). Fasting serum lipograms, including cholesterol, triglycerides, high-density cholesterol (HDL), and low-density cholesterol (LDL), were taken preoperatively and repeated 9–12 months post lipectomy/liposuction. Results:. A subgroup of 35 patients with deranged preoperative triglycerides (P = 0.004), cholesterol (P = 0.001), and or LDL cholesterol (P = 0.017) showed a statistically significant (P < 0.05) decrease in postoperative levels. If preoperative lipogram values were normal, there is no statistically significant reduction postoperatively. Conclusions:. In ARV-associated lipodystrophy, when the preoperative fasting lipograms are deranged, then after surgical correction there is a statistically significant reduction in triglyceride, total cholesterol, and LDL levels. This influences their cardiovascular risk profile, mortality, morbidity, and quality of life.

Introduction: Patients with End Stage Renal Disease on haemodialysis often suffer from depression and dementia. However, the relation between diabetes and depression and/or dementia in haemodialysis patients has not yet been efficiently researched. Objective: The purpose of the study was to explore the effect of diabetes mellitus on depression and dementia on haemodialysis patients. Methodology: Fifty three patients, out of which 27 diabetics, were on haemodialysis for 28.34 (±56.36) months. All patients answered the Mini Mental State Examination (MMSE) test and Hospital Anxiety and Depression Scale (HADS) in an interview during haemodialysis session in order to assess the level of depression and dementia. Moreover, blood samples were taken in order to determine haemoglobin, dialysis adequacy (kt/V), levels of blood sodium, potassium, calcium and phosphorus, as well as the levels of C-reactive protein (CRP). Statistical analysis was performed with SPSS 17.0. Results: The level of depression and dementia for the total patients was correspondent to a moderate level of illness (13.91±10.56 and 15.00±5.49, respectively). In a comparison between diabetics and nondiabetics the results indicated a statistically significant difference for diabetics who displayed a highlevel of depression (17.63±10.63 vs 10.04±9.15, p