A predominant enhancer co-amplified with the SOX2 oncogene is necessary and sufficient for its expression in squamous cancer

Amplification and overexpression of the SOX2 oncogene represent a hallmark of squamous cancers originating from diverse tissue types. Here, we find that squamous cancers selectively amplify a 3’ noncoding region together with SOX2, which harbors squamous cancer-specific chromatin accessible regions. We identify a single enhancer e1 that predominantly drives SOX2 expression. Repression of e1 in SOX2-high cells causes collapse of the surrounding enhancers, remarkable reduction in SOX2 expression, and a global transcriptional change reminiscent of SOX2 knockout. The e1 enhancer is driven by a combination of transcription factors including SOX2 itself and the AP-1 complex, which facilitates recruitment of the co-activator BRD4. CRISPR-mediated activation of e1 in SOX2-low cells is sufficient to rebuild the e1-SOX2 loop and activate SOX2 expression. Our study shows that squamous cancers selectively amplify a predominant enhancer to drive SOX2 overexpression, uncovering functional links among enhancer activation, chromatin looping, and lineage-specific copy number amplifications of oncogenes.

Could potentially calprotectin be a promising biomarker to oracle biologic therapy response in rheumatoid arthritis?

Background The advent of novel biologic agents for the treatment of rheumatoid arthritis (RA) has proven to be highly productive. Nonetheless, high cost, side effects, and unresponsiveness to these agents dictates the assignment of biomarkers that can foretell treatment response. Currently, calprotectin (a member of the S100 protein family) is amongst the enormously studied candidates in this perspective. Yet, conflicting results have been published. The main purpose of this study was to explore the role of serum concentration of calprotectin to predict the response to biological therapy in RA patients, so as to customize RA treatment. Results Baseline serum calprotectin levels were significantly higher in RA patients compared to the control subjects (P value < 0.001). After receiving biologic therapy, a remarkable reduction (P < 0.001) in serum calprotectin was noted in RA cohort. Moreover, no correlation was found between the 28 joint count disease activity score (DAS28) and serum calprotectin levels neither before or after biologics. Intriguingly, no statistically significant association was detected between circulating calprotectin level and response to biological therapy. Conclusion Serum calprotectin concentrations could not be used as a biomarker to forecast clinical response to biological therapy in RA patients. However, further studies involving larger cohort of RA patients should be carried out to deliver more insight in this regard.

Comparative Analysis of Dalbavancin versus Other Antimicrobial Options for Gram-Positive cocci Infections: Effectiveness, Hospital Stay and Mortality

Dalbavancin is a new antibiotic that is effective against Gram-positive microorganisms, including methicillin-resistant Staphylococci, and offers the possibility of administering intravenous therapy once weekly in an ambulatory setting. We conducted a multicenter observational case-control study, comparing all patients who received dalbavancin (cases) with hospitalized patients who were treated instead with daptomycin, linezolid or vancomycin (controls), based on clinical diagnosis, main microorganism involved, and age. The primary outcome was the length of hospital stay after starting the study antimicrobial. Secondary outcomes were 7-day and 30-day efficacy, 30-day mortality, 90-day recurrence, 90-day and 6-month hospitalization, presence of adverse events and healthcare-associated infections; 161 patients (44 cases and 117 controls) were included. Bivariate analysis showed that dalbavancin reduced the total length of hospital stay (p < 0.001), with fewer 90-day recurrences (p = 0.005), 6-month hospitalizations related to the same infection (p = 0.004) and non-related hospitalizations (p = 0.035). Multivariate analyses showed that length of hospital stay was significantly shorter in patients treated with dalbavancin (−12.05 days 95% CI [−17.00, −7.11], p < 0.001), and 30-day efficacy was higher in the dalbavancin group (OR 2.62 95% CI [1.07, 6.37], p = 0.034). Although sample size of the study may be a limitation, we can conclude that Dalbavancin is a useful antimicrobial drug against Gram-positive infections, including multidrug-resistant pathogens, and allows for a remarkable reduction in length of hospital stay with greater 30-day efficacy.

RRAM-based CAM combined with time-domain circuits for hyperdimensional computing

Content addressable memory (CAM) for search and match operations demands high speed and low power for near real-time decision-making across many critical domains. Resistive RAM (RRAM)-based in-memory computing has high potential in realizing an efficient static CAM for artificial intelligence tasks, especially on resource-constrained platforms. This paper presents an XNOR-based RRAM-CAM with a time-domain analog adder for efficient winning class computation. The CAM compares two operands, one voltage and the second one resistance, and outputs a voltage proportional to the similarity between the input query and the pre-stored patterns. Processing the summation of the output similarity voltages in the time-domain helps avoid voltage saturation, variation, and noise dominating the analog voltage-based computing. After that, to determine the winning class among the multiple classes, a digital realization is utilized to consider the class with the longest pulse width as the winning class. As a demonstrator, hyperdimensional computing for efficient MNIST classification is considered. The proposed design uses 65 nm CMOS foundry technology and realistic data for RRAM with total area of 0.0077 mm2, consumes 13.6 pJ of energy per 1 k query within 10 ns clock cycle. It shows a reduction of ~ 31 × in area and ~ 3 × in energy consumption compared to fully digital ASIC implementation using 65 nm foundry technology. The proposed design exhibits a remarkable reduction in area and energy compared to two of the state-of-the-art RRAM designs.

A comparative study of serological diagnosis of Dengue outbreak 2019

Purpose: The interpretation & correlation of the different laboratory parameters in positive dengue cases in order to eval- uate that which laboratory test is more significant for diagnosis of Dengue. Methods: Prospective examination of samples (patients’ serum) for dengue virus of different genotype by using multiplex anti-dengue IgM, IgG. We have done NS-1 test by (ICT) immunochromatographic devices, and complete blood picture (CBC) by Sysmex XP-100. Result: Detection of Viral RNA in 100 patients showed effects in the total of 73 (73.0%) samples. This graphical compar- ison shows the whole positive cases including dengue NS-I antigen, dengue serology (IgM & IgG), total 62 positive cases of NS-I are detected, 10 positive cases of dengue IgM and 9 positive cases of IgG detected, in which Complete Blood Test (CBC) shows remarkable reduction in Platelets (32 cases) and Leucopenia in (24 positive cases). Conclusion: In this research, it is concluded that the diagnosis of dengue cases is preliminary limited to initial stages i.e. CBC or sometimes dengue NS-I, as dengue IgM severity is more effective than that of Dengue NS-I & IgG. Many patients who had negative results in CBC and NS-1 testing, became positive when IgM and IgG serology testing has been done. Keywords: Dengue; NS-1; IgG; IgM; Immunochrometographic test.

Studies on the Development of Benzoyl Peroxide Catalysed Rapid Oil Tanning using Linseed Oil

Leather tanning is a stabilisation process of skin fibers. This is achieved by the interaction of collagen amino acids with tanning agents to stabilise skin from putrefaction. Tanning of collagen with oil is a special class of tanning known as chamois tanning. Chemically, the oil tanning involves oxidation of unsaturation present in the oil, which is generally achieved by exposing oil treated skins to air. In this study, Benzoyl peroxide has been used as an accelerating agent for oxidation of unsaturated bonds present in the linseed oil for oil tanning process. Results shows remarkable reduction in tanning duration from fifteen days to two days. The chamois leathers prepared using oxidation accelerant (Benzoyl peroxide) have been evaluated for physical properties such as water absorption (611%), tensile strength (18 N/mm2) and percentage of elongation (66 %) which are found to be better than control leathers.

The Impact of COVID-19 Outbreak on Syncope Units Activities in Italy: A Report from the Italian Multidisciplinary Working Group on Syncope (GIMSI)

The aim of our study was to evaluate the impact of the COVID-19 outbreak on Syncope Units (SUs) Activities in Italy. Methods: Data about types of SU activities and admissions were obtained from 10 SUs throughout Italy, certified by the Italian Multidisciplinary Working Group on Syncope (GIMSI), from 10 March 2020 to 31 December 2020 and compared with the same time frame in 2019. Results: A remarkable reduction in overall non-invasive diagnostic tests (−67%; p < 0.001) and cardiac invasive procedure. Elective cardiac pacing procedures disclosed a significant decrease (−62.7%; p < 0.001); conversely, the decrease of urgent procedures was not significant (−50%; p = 0.08). There was a significantly increased rate of patients who underwent both telemedicine follow-up visits (+225%, p < 0.001) and cardiac implantable electronic devices (CIEDs) remote monitoring follow-up visits (+100%; p < 0.001). Conclusion: The COVID-19 outbreak was associated with a remarkable decrease in all clinical activities of Syncope Units in Italy, including both non-invasive tests and cardiac invasive procedures; conversely, a significant increase in telehealth activities was shown.

Hydrodynamical Model for Charge Transport in Graphene Nanoribbons

We present a hydrodynamical model for graphene nanoribbons that takes into account the electron collisions with the lattice and with the edge of the ribbon. Moreover the bandgap due to the low dimension of the ribbon is considered. The simulation shows that the model describes qualitatively the macroscopic behavior of the charges and the results are comparable with that ones obtained by solving numerically the Boltzmann equation but with a remarkable reduction of the computational time.

Audio compression using transforms and high order entropy encoding

<span>Digital audio is required to transmit large sizes of audio information through the most common communication systems; in turn this leads to more challenges in both storage and archieving. In this paper, an efficient audio compressive scheme is proposed, it depends on combined transform coding scheme; it is consist of i) bi-orthogonal (tab 9/7) wavelet transform to decompose the audio signal into low &amp; multi high sub-bands, ii) then the produced sub-bands passed through DCT to de-correlate the signal, iii) the product of the combined transform stage is passed through progressive hierarchical quantization, then traditional run-length encoding (RLE), iv) and finally LZW coding to generate the output mate bitstream. The measures Peak signal-to-noise ratio (PSNR) and compression ratio (CR) were used to conduct a comparative analysis for the performance of the whole system. Many audio test samples were utilized to test the performance behavior; the used samples have various sizes and vary in features. The simulation results appear the efficiency of these combined transforms when using LZW within the domain of data compression. The compression results are encouraging and show a remarkable reduction in audio file size with good fidelity.</span>