Deep Ensemble of Weighted Viterbi Decoders for Tail-Biting Convolutional Codes.

Tail-biting convolutional codes extend the classical zero-termination convolutional codes: Both encoding schemes force the equality of start and end states, but under the tail-biting each state is a valid termination. This paper proposes a machine learning approach to improve the state-of-the-art decoding of tail-biting codes, focusing on the widely employed short length regime as in the LTE standard. This standard also includes a CRC code. First, we parameterize the circular Viterbi algorithm, a baseline decoder that exploits the circular nature of the underlying trellis. An ensemble combines multiple such weighted decoders, and each decoder specializes in decoding words from a specific region of the channel words' distribution. A region corresponds to a subset of termination states; the ensemble covers the entire states space. A non-learnable gating satisfies two goals: it filters easily decoded words and mitigates the overhead of executing multiple weighted decoders. The CRC criterion is employed to choose only a subset of experts for decoding purpose. Our method achieves FER improvement of up to 0.75 dB over the CVA in the waterfall region for multiple code lengths, adding negligible computational complexity compared to the circular Viterbi algorithm in high signal-to-noise ratios (SNRs).

The role of bacterial translocation in sepsis: a new target for therapy.

Sepsis is a leading cause of death in critically ill patients, primarily due to multiple organ failures. It is associated with a systemic inflammatory response that plays a role in the pathogenesis of the disease. Intestinal barrier dysfunction and bacterial translocation (BT) play pivotal roles in the pathogenesis of sepsis and associated organ failure. In this review, we describe recent advances in understanding the mechanisms by which the gut microbiome and BT contribute to the pathogenesis of sepsis. We also discuss several potential treatment modalities that target the microbiome as therapeutic tools for patients with sepsis.

Codivir suppresses SARS-Cov-2 viral replication and stabilizes clinical outcome: In vitro and Phase I clinical trial results.

BACKGROUND: Treatment of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) remains a significant challenge in the face of increased worldwide morbidity and mortality. The acute illness caused by SARS-CoV-2 is initiated by a viral phase, followed by an inflammatory phase. Numerous anti-inflammatory and anti-viral therapies, with a relatively minor clinical effect, have been applied. Developing a safe and efficient direct anti-viral treatment is essential as it can block disease progression before significant complications ensue and potentially prevent transmission. AIM: The present phase 1 study aimed to determine the safety of Codivir, a newly developed anti-viral agent, and to preliminarily assess its anti-viral activity in patients infected by COVID-19. METHODS: In vitro studies were conducted to determine the direct anti-viral effect of Codivir using an immunofluorescence-based assay and to assess its cytotoxic effect by tetrazolium assay (MTT). In a phase I clinical trial, Codivir was administered for ten days in 12 patients who were followed for its safety. Patients were followed for clinical manifestations during administration. Sequential nasal viral PCR titers (Cycle Threshold, CT) were determined preceding and during treatment. RESULTS: In vitro, Codivir showed activity against SARS-CoV-2 with 90% viral replication suppression and minimal cytotoxicity. The anti-viral activity was demonstrated at the early stages of infection, post-entry of the virus in the cell. Codivir was safe in all 12 patients in phase I clinical trial and significantly suppressed viral replication in 5/7 fully assessed patients, with an anti-viral effect noted as early as three days. SUMMARY: The present study's data support the safety of Codivir administration in humans and suggest its significant anti-COVID-19 effect. These results support the testing of the drug in more extensive controlled trials in patients with SARS-CoV-2.

A digital health platform for assisting the diagnosis and monitoring of COVID-19 progression: An adjuvant approach for augmenting the antiviral response and mitigating the immune-mediated target organ damage.

Coronavirus disease 2019 (COVID-19), which is a respiratory illness associated with high mortality, has been classified as a pandemic. The major obstacles for the clinicians to contain the disease are limited information availability, difficulty in disease diagnosis, predicting disease prognosis, and lack of disease monitoring tools. Additionally, the lack of valid therapies has further contributed to the difficulties in containing the pandemic. Recent studies have reported that the dysregulation of the immune system leads to an ineffective antiviral response and promotes pathological immune response, which manifests as ARDS, myocarditis, and hepatitis. In this study, a novel platform has been described for disseminating information to physicians for the diagnosis and monitoring of patients with COVID-19. An adjuvant approach using compounds that can potentiate antiviral immune response and mitigate COVID-19-induced immune-mediated target organ damage has been presented. A prolonged beneficial effect is achieved by implementing algorithm-based individualized variability measures in the treatment regimen.

Tumor-Associated Neutrophils Drive B-cell Recruitment and Their Differentiation to Plasma Cells.

A major mechanism through which neutrophils have been suggested to modulate tumor progression involves the interaction and subsequent modulation of other infiltrating immune cells. B cells have been found to infiltrate various cancer types and play a role in tumor immunity, offering new immunotherapy opportunities. Nevertheless, the specific impact of tumor-associated neutrophils (TAN) on B cells has largely been overlooked. In the current study, we aimed to characterize the role of TANs in the recruitment and modulation of B cells in the tumor microenvironment (TME). We showed that TANs actively participate in the recruitment of B cells to the TME and identified TNFα as the major cytokine mediating B-cell chemotaxis by TANs. The recruitment of CD45+B220+CD138- splenic B cells by TANs in vitro resulted in B-cell phenotypic modulation, with 68.6% ± 2.1% of the total migrated B cells displaying a CD45-B220+CD138+ phenotype, which is typical for plasma cells. This phenotype mirrored the large proportion (54.0% ± 6.1%) of CD45-B220+CD138+ intratumoral B cells (i.e., plasma cells) in Lewis lung carcinoma tumors. We next confirmed that the differentiation of CD45+B220+CD138- B cells to functionally active CD45-B220+CD138+ plasma cells required contact with TANs, was independent of T cells, and resulted in IgG production. We further identified membranal B-cell activating factor (BAFF) on TANs as a potential contact mechanism mediating B-cell differentiation, as blocking BAFF-receptor (BAFF-R) significantly reduced IgG production by 20%. Our study, therefore, demonstrates that TANs drive the recruitment and modulation of B cells into plasma cells in the TME, hence opening new avenues in the targeting of the immune system in cancer.

Targeting SARS-CoV-2 receptors as a means for reducing infectivity and improving antiviral and immune response: an algorithm-based method for overcoming resistance to antiviral agents.

The ongoing severe acute respiratory syndrome pandemic caused by the novel coronavirus 2 (SARS-CoV-2) is associated with high morbidity and mortality rates, and it has created a pressing global need for effective antiviral therapies against it. COVID-19 disease pathogenesis is characterized by an initial virus-mediated phase, followed by inappropriate hyperactivation of the immune system leading to organ damage. Targeting of the SARS-CoV-2 viral receptors is being explored as a therapeutic option for these patients. In this paper, we summarize several potential receptors associated with the infectivity of SARS-CoV-2 and discuss their association with the immune-mediated inflammatory response. The potential for the development of resistance towards antiviral drugs is also presented. An algorithm-based platform to improve the efficacy of and overcome resistance to viral receptor blockers through the introduction of personalized variability is described. This method is designed to ensure sustained antiviral effectiveness when using SARS-CoV-2 receptor blockers.

Association between CD14 gene polymorphisms and disease phenotype in sarcoidosis.

Although the etiology of sarcoidosis is unknown, genetic susceptibility has been demonstrated. Granuloma formation is a key feature in the pathophysiology of sarcoidosis and Crohn's Disease, raising the possibility that these diseases share common pathogenetic pathways. An association between sarcoidosis and the protein "CD14", a molecule that is part of the lipopolysaccharide (LPS) cell surface receptor complex, has been suggested. In the current study we evaluated the CD14 gene promoter 159 C-->T polymorphic site and soluble CD14 levels in a cohort of 74 sarcoidosis patients compared to 85 healthy controls. We further sought to identify correlations between clinical phenotype, specific genotypes and soluble CD14 levels. We found the TT genotype to be more prevalent in the sarcoidosis patient group than in controls (p=0.03). Serum levels of soluble CD14 were higher in the sarcoidosis patients (p=0.001). Within the patient cohort, CC homozygous patients presented at an older age with milder disease as assessed with the SAC score, longer time to diagnosis, and less impairment of pulmonary function tests. Our study suggests a role of CD14 in the pathogenesis of sarcoidosis, and a clinical phenotype-genotype association. Further mechanistic and epidemiologic studies are needed in order to establish the specific role of CD14 in the etiology, pathogenesis and clinical phenotype of sarcoidosis.