Probabilistic Handshake in All-to-all Broadcast Coded Slotted ALOHA

We propose a probabilistic handshake mechanism for all-to-all broadcast coded slotted ALOHA. We consider a fully connected network where each user acts as both transmitter and receiver in a half-duplex mode. Users attempt to exchange messages with each other and to establish one-to-one handshakes, in the sense that each user decides whether its packet was successfully received by the other users: After performing decoding, each user estimates in which slots the resolved users transmitted their packets and, based on that, decides if these users successfully received its packet. The simulation results show that the proposed handshake algorithm allows the users to reliably perform the handshake. The paper also provides some analytical bounds on the performance of the proposed algorithm which are in good agreement with the simulation results

Topical Corticosteroids Normalize both Skin and Systemic Inflammatory Markers in Infant Atopic Dermatitis

Background: Atopic dermatitis (AD) is the most common inflammatory skin disease. It is highly heterogeneous in clinical presentation, treatment response, disease trajectory and associated atopic comorbidities. Immune biomarkers are dysregulated in skin and peripheral blood. Aims: We used noninvasive skin and peripheral biomarkers to observe the effects of real-world topical corticosteroid (TCS) treatment in infants with AD, by measuring skin and blood biomarkers before and after therapy. Methods: Seventy-four treatment-naïve infants with AD underwent 6 weeks of TCS treatment. Stratum corneum (SC) and plasma blood biomarkers as well as SC natural moisturizing factor (NMF) were measured before and after TCS therapy. Immune markers included innate, T helper (Th)1 and Th2 immunity, angiogenesis, and vascular factors. AD severity was assessed by the Scoring Atopic Dermatitis index, and skin barrier function by transepidermal water loss (TEWL). Twenty healthy infants were recruited as controls. Results: TCS therapy predictably led to improvement in disease severity. Levels of immune markers in the skin and in the peripheral blood showed significant change from baseline, though most did not reach healthy control levels. The most prominent change from baseline in the SC was in markers of innate immune activation, interleukin (IL)-18, IL-8 and IL-1α, and the Th2 chemokines C-C motif chemokine (CCL)17 and CCL22. In blood, the largest changes were in Th2-skewed biomarkers: CCL17, IL-13, CCL22, IL-5, and CCL26. TEWL decreased after therapy; no significant changes from baseline were found for NMF. Conclusions: The profound impact of topical therapy on systemic biomarkers suggests that the skin compartment generates a major component of dysregulated systemic cytokines in infant AD. There may be long-term beneficial effects of correcting systemic immune dysregulation through topical therapy

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients—An Open-Label Phase II Clinical Trial

Background: COVID-19 convalescent plasma (CCP) is an important antiviral option for selected patients with COVID-19. Materials and Methods: In this open-label, phase 2, clinical trial conducted from 30 April 2020 till 10 May 2021 in the Republic of North Macedonia, we evaluated the efficacy and safety of CCP in hospitalized patients. Treatment was with a single unit of CCP having an anti-RBD IgG concentration higher than 5 AU/mL. Results: There were 189 patients that completed the study, of which 65 (34.4%) had WHO 8-point clinical progression scale score of 3 (requiring hospital care but not oxygen support), 65 (34.4%) had a score of 4 (hospitalized and requiring supplemental oxygen by mask or nasal prongs), and 59 (31.2%) had a score of 5 (hospitalized and requiring supplemental oxygen by non-invasive ventilation or high-flow oxygen). Mean age was 57 years (range 22–94), 78.5% were males, 80.4% had elevated body mass index, and 70.9% had comorbidity. Following CCP transfusion, we observed clinical improvement with increase rates in oxygenation-free days of 32.3% and 58.5% at 24 h and seven days after CCP transfusion, a decline in WHO scores, and reduced progression to severe disease (only one patient was admitted to ICU after CCP transfusion). Mortality in the entire cohort was 11.6% (22/189). We recorded 0% mortality in WHO score 3 (0/65) and in patients that received CCP transfusion in the first seven days of disease, 4.6% mortality in WHO score 4 (3/65), and 30.5% mortality in WHO score 5 (18/59). Mortality correlated with WHO score (Chi-square 19.3, p < 0.001) and with stay in the ICU (Chi-square 55.526, p ≤ 0.001). No severe adverse events were reported. Conclusions: This study showed that early administration of CCP to patients with moderate disease was a safe and potentially effective treatment for hospitalized COVID-19 patients. The trial was registered at clinicaltrials.gov (NCT04397523)

Use of the linear absorption coefficient for absolute comparison of plasma films in the mid-IR range

In this work, we present the mid-infrared analysis of analogues of Titan's aerosols produced in a radio frequency capacitively coupled plasma (RF-CCP). The influence of the gas mixture on aerosols spectra is also studied through the analysis of the carbonaceous bands of the spectra, and its Gaussian deconvolution.Представлен анализ в среднем инфракрасном диапазоне аналогов титановых аэрозолей, которые производятся в радиочастотных источниках плазмы с емкостной связью (РЧ-ЕСС). Также изучено влияние газовой смеси на спектры аэрозолей с помощью анализа углеродсодержащих полос спектра и ее гауссовой деконволюции (обратная свертка).Представлено аналіз у середньому інфрачервоному діапазоні аналогів титанових аерозолів, які проводяться в радіочастотних джерелах плазми з ємнісним зв'язком (РЧ-ЕСС). Також вивчено вплив газової суміші на спектри аерозолів за допомогою аналізу вуглецевмісних смуг спектра і її гауссової деконволюції (зворотня згортка)

Use of the linear absorption coefficient for absolute comparison of plasma films in the mid-IR range

In this work, we present the mid-infrared analysis of analogues of Titan's aerosols produced in a radio frequency capacitively coupled plasma (RF-CCP). The influence of the gas mixture on aerosols spectra is also studied through the analysis of the carbonaceous bands of the spectra, and its Gaussian deconvolution.Представлен анализ в среднем инфракрасном диапазоне аналогов титановых аэрозолей, которые производятся в радиочастотных источниках плазмы с емкостной связью (РЧ-ЕСС). Также изучено влияние газовой смеси на спектры аэрозолей с помощью анализа углеродсодержащих полос спектра и ее гауссовой деконволюции (обратная свертка).Представлено аналіз у середньому інфрачервоному діапазоні аналогів титанових аерозолів, які проводяться в радіочастотних джерелах плазми з ємнісним зв'язком (РЧ-ЕСС). Також вивчено вплив газової суміші на спектри аерозолів за допомогою аналізу вуглецевмісних смуг спектра і її гауссової деконволюції (зворотня згортка)

Antiapoptotic BCL-2 proteins determine Sorafenib/regorafenib resistance and BH3-mimetic efficacy in hepatocellular carcinoma

Sorafenib, systemic treatment for advanced hepatocellular carcinoma (HCC), and regorafenib, novel second line treatment after sorafenib failure, have efficacy limited by evasive mechanisms of acquired-drug resistance. BCL-2 proteins participate in the response to tyrosine kinase inhibitors; however, their role in HCC therapy with sorafenib/regorafenib remains uncertain. BH3-mimetic ABT-263 (navitoclax) enhanced sorafenib activity, inducing cell death via a mitochondrial caspase-dependent mechanism, after BCL-xL/BCL-2 inhibition. Sorafenib-resistant hepatoma cells (HepG2R and Hep3BR) exhibited altered mRNA expression of BCL-2 and other anti-apoptotic family members, such as MCL-1, priming drug-resistant cancer cells to death by BH3-mimetics. ABT-263 restored sorafenib efficacy in sorafenib-resistant cell lines and HCC mouse models. Moreover, in mice xenografts from patient-derived BCLC9 cells, better tumor response to sorafenib was associated to higher changes in the BCL-2 mRNA pattern. HCC non-treated patients displayed altered BCL-2, MCL-1 and BCL-xL mRNA levels respect to adjacent non-tumoral biopsies and an increased BCL-2/MCL-1 ratio, predictive of navitoclax efficacy. Moreover, regorafenib administration also modified the BCL-2/MCL-1 ratio and navitoclax sensitized hepatoma cells to regorafenib by a mitochondrial caspase-dependent mechanism. In conclusion, sorafenib/regorafenib response is determined by BCL-2 proteins, while increased BCL-2/MCL-1 ratio in HCC sensitizes drug resistant-tumors against ABT-263 co-administration. Thus, changes in the BCL-2 profile, altered in HCC patients, could help to follow-up sorafenib efficacy, allowing patient selection for combined therapy with BH3-mimetics or early switch them to second line therapy

Metals and kidney markers in adult offspring of endemic nephropathy patients and controls: a two-year follow-up study

Abstract Background The etiology of Balkan Endemic Nephropathy, (BEN), a tubulointerstitial kidney disease, is unknown. Although this disease is endemic in rural areas of Bosnia, Bulgaria, Croatia, Romania, and Serbia, similar manifestations are reported to occur in other regions, for instance Tunisia and Sri Lanka. A number of explanations have been stated including lignites, aristolochic acid, ochratoxin A, metals, and metalloids. Etiologic claims are often based on one or a few studies without sound scientific evidence. In this systematic study, we tested whether exposures to metals (cadmium and lead) and metalloids (arsenic and selenium) are related to Balkan Endemic Nephropathy. Methods In 2003/04 we recruited 102 adults whose parents had BEN and who resided in one of three communities (Vratza, Bistretz, or Beli Izvor, Bulgaria). A control group comprised of 99 adults having non-BEN hospitalized parents was enrolled in the study during the same time. We conducted face-to-face interviews, ultrasound kidney measurements, and determined kidney function in two consecutive investigations (2003/04 and 2004/05). Metals and metalloids were measured in urine and blood samples. To assess the agreement between these consecutive measurements, we calculated intraclass correlation coefficients. Repeated measurement data were analyzed using mixed models. Results We found that cadmium and arsenic were associated with neither kidney size nor function. Lead had a significant but negligible effect on creatinine clearance. Selenium showed a weak but significant negative association with two of the four kidney parameters, namely creatinine clearance and β2-microglobulin. It was positively related to kidney length. These associations were not restricted to the offspring of BEN patients. Adding credence to these findings are reports showing comparable kidney effects in animals exposed to selenium. Conclusion The findings of this 2-year follow-up study indicate that metals and metalloids do not play a role in the etiology of Balkan Endemic Nephropathy. Against the assumption in the literature, selenium was not protective but a risk factor. Since comparable associations were observed in animals, future studies are needed to explore whether selenium may have adverse renal effects in humans.</p

A synthetic snRNA m3G-CAP enhances nuclear delivery of exogenous proteins and nucleic acids

Accessing the nucleus through the surrounding membrane poses one of the major obstacles for therapeutic molecules large enough to be excluded due to nuclear pore size limits. In some therapeutic applications the large size of some nucleic acids, like plasmid DNA, hampers their access to the nuclear compartment. However, also for small oligonucleotides, achieving higher nuclear concentrations could be of great benefit. We report on the synthesis and possible applications of a natural RNA 5′-end nuclear localization signal composed of a 2,2,7-trimethylguanosine cap (m3G-CAP). The cap is found in the small nuclear RNAs that are constitutive part of the small nuclear ribonucleoprotein complexes involved in nuclear splicing. We demonstrate the use of the m3G signal as an adaptor that can be attached to different oligonucleotides, thereby conferring nuclear targeting capabilities with capacity to transport large-size cargo molecules. The synthetic capping of oligos interfering with splicing may have immediate clinical applications