Business intelligence success: The roles of BI capabilities and decision environments

This study examines the role of the decision environment in how well business intelligence (BI) capabilities are leveraged to achieve BI success. We examine the decision environment in terms of the types of decisions made and the information processing needs of the organization. Our findings suggest that technological capabilities such as data quality, user access and the integration of BI with other systems are necessary for BI success, regardless of the decision environment. However, the decision environment does influence the relationship between BI success and capabilities, such as the extent to which BI supports flexibility and risk in decision making.     

Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation

Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT–angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic β2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms.     

Microsatellite Instability in Russian Patients with Colorectal Cancer

The aim of this study was to determine the characteristics of Russian patients with microsatellite instability (MSI) tumors. MSI in the tumor was determined in 514 patients with colon cancer using PCR and subsequent fragment analysis for five markers (NR21, NR24, BAT25, BAT26, and NR27). In the presence of microsatellite instability, the mismatch repair (MMR) system genes were examined using the NGS and MLPA methods to establish the diagnosis of Lynch syndrome. The overall frequency of MSI tumors was 15%: at stage I—19% (9/48), at stage II—21% (44/213), at stage III—16% (26/160), and at stage IV—2% (2/93). Patients with MSI tumors differed in the age of diagnosis, tumor localization, time of cancer recurrence, and stage of the disease. The overall and disease-free survival of patients whose tumors had MSI status was higher than that of patients with microsatellite-stable status, p = 0.04 and p = 0.02, respectively. Analysis of overall and disease-free survival of patients with Lynch syndrome and patients with sporadic colon cancer, but with MSI status, did not reveal significant differences, p = 0.52 and p = 0.24, respectively. The age of patients with Lynch syndrome was significantly younger than that of patients with sporadic colon cancer whose tumors had MSI status (p < 0.001).     

A Fully-Human Antibody Specifically Targeting a Membrane-Bound Fragment of CADM1 Potentiates the T Cell-Mediated Death of Human Small-Cell Lung Cancer Cells

Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer and the leading cause of global cancer-related mortality. Despite the earlier identification of membrane-proximal cleavage of cell adhesion molecule 1 (CADM1) in cancers, the role of the membrane-bound fragment of CAMD1 (MF-CADM1) is yet to be clearly identified. In this study, we first isolated MF-CADM1-specific fully human single-chain variable fragments (scFvs) from the human synthetic scFv antibody library using the phage display technology. Following the selected scFv conversion to human immunoglobulin G1 (IgG1) scFv-Fc antibodies (K103.1–4), multiple characterization studies, including antibody cross-species reactivity, purity, production yield, and binding affinity, were verified. Finally, via intensive in vitro efficacy and toxicity evaluation studies, we identified K103.3 as a lead antibody that potently promotes the death of human SCLC cell lines, including NCI-H69, NCI-H146, and NCI-H187, by activated Jurkat T cells without severe endothelial toxicity. Taken together, these findings suggest that antibody-based targeting of MF-CADM1 may be an effective strategy to potentiate T cell-mediated SCLC death, and MF-CADM1 may be a novel potential therapeutic target in SCLC for antibody therapy.     

Effects of Non-Opioid Analgesics on the Cell Membrane of Skin and Gastrointestinal Cancers

Skin and gastrointestinal cancer cells are the target of research by many scientists due to the increasing morbidity and mortality rates around the world. New indications for drugs used in various conditions are being discovered. Non-opioid analgesics are worth noting as very popular, widely available, relatively cheap medications. They also have the ability to modulate the membrane components of tumor cells. The aim of this review is to analyze the impact of diclofenac, ibuprofen, naproxen, acetylsalicylic acid and paracetamol on skin and gastrointestinal cancers cell membrane. These drugs may affect the membrane through topical application, at the in vitro and in vivo level after oral or parenteral administration. They can lead to up- or downregulated expression of receptors, transporters and other molecules associated with plasma membrane. Medications may also alter the lipid bilayer composition of membrane, resulting in changes in its integrity and fluidity. Described modulations can cause the visualization of cancer cells, enhanced response of the immune system and the initiation of cell death. The outcome of this is inhibition of progression or reduction of tumor mass and supports chemotherapy. In conclusion, non-opioid analgesics may be used in the future as adjunctive therapy for the treatment of these cancers.     

Development of a Mortality Prediction Model in Hospitalised SARS-CoV-2 Positive Patients Based on Routine Kidney Biomarkers

Acute kidney injury (AKI) is a prevalent complication in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive inpatients, which is linked to an increased mortality rate compared to patients without AKI. Here we analysed the difference in kidney blood biomarkers in SARS-CoV-2 positive patients with non-fatal or fatal outcome, in order to develop a mortality prediction model for hospitalised SARS-CoV-2 positive patients. A retrospective cohort study including data from suspected SARS-CoV-2 positive patients admitted to a large National Health Service (NHS) Foundation Trust hospital in the Yorkshire and Humber regions, United Kingdom, between 1 March 2020 and 30 August 2020. Hospitalised adult patients (aged ≥ 18 years) with at least one confirmed positive RT-PCR test for SARS-CoV-2 and blood tests of kidney biomarkers within 36 h of the RT-PCR test were included. The main outcome measure was 90-day in-hospital mortality in SARS-CoV-2 infected patients. The logistic regression and random forest (RF) models incorporated six predictors including three routine kidney function tests (sodium, urea; creatinine only in RF), along with age, sex, and ethnicity. The mortality prediction performance of the logistic regression model achieved an area under receiver operating characteristic (AUROC) curve of 0.772 in the test dataset (95% CI: 0.694–0.823), while the RF model attained the AUROC of 0.820 in the same test cohort (95% CI: 0.740–0.870). The resulting validated prediction model is the first to focus on kidney biomarkers specifically on in-hospital mortality over a 90-day period.     

Novel Insights into Factor D Inhibition

Complement-mediated diseases or complementopathies, such as Paroxysmal nocturnal hemoglobinuria (PNH), cold agglutinin disease (CAD), and transplant-associated thrombotic microangiopathy (TA-TMA), demand advanced complement diagnostics and therapeutics be adopted in a vast field of medical specialties, such as hematology, transplantation, rheumatology, and nephrology. The miracle of complement inhibitors as “orphan drugs” has dramatically improved morbidity and mortality in patients with otherwise life-threatening complementopathies. Efficacy has been significantly improved by upstream inhibition in patients with PNH. Different molecules may exert diverse characteristics in vitro and in vivo. Further studies remain to show safety and efficacy of upstream inhibition in other complementopathies. In addition, cost and availability issues are major drawbacks of current treatments. Therefore, further developments are warranted to address the unmet clinical needs in the field of complementopathies. This state-of-the-art narrative review aims to delineate novel insights into factor D inhibition as a promising target for complementopathies.     

The P2X7R-NLRP3 and AIM2 Inflammasome Platforms Mark the Complexity/Severity of Viral or Metabolic Liver Damage

P2X7R-NLRP3 and AIM2 inflammasomes activate caspase-1 and the release of cytokines involved in viral-related liver disease. Little is known about their role in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steato-hepatitis (NASH). We characterized the role of inflammasomes in NAFLD, NASH, and HCV. Gene expression and subcellular localization of P2X7R/P2X4R-NLRP3 and AIM2 inflammasome components were examined in histopathological preparations of 46 patients with biopsy-proven viral and metabolic liver disease using real-time PCR and immunofluorescence. P2X7R, P2X4R, and Caspase-1 are two- to five-fold more expressed in patients with NAFLD/NASH associated with chronic HCV infection than those with metabolic damage only (p ≤ 0.01 for all comparisons). The AIM2 inflammasome is 4.4 times more expressed in patients with chronic HCV infection, regardless of coexistent metabolic abnormalities (p = 0.0006). IL-2, a cytokine playing a pivotal role during chronic HCV infection, showed a similar expression in HCV and NASH patients (p = 0.77) but was virtually absent in NAFLD. The P2X7R-NLRP3 complex prevailed in infiltrating macrophages, while AIM2 was localized in Kupffer cells. Caspase-1 expression correlated with elastography-based liver fibrosis (r = 0.35, p = 0.02), whereas P2X7R, P2X4R, NRLP3, Caspase-1, and IL-2 expression correlated with circulating markers of disease severity. P2X7R and P2X4R play a major role in liver inflammation accompanying chronic HCV infection, especially when combined with metabolic damage, while AIM2 is specifically expressed in chronic viral hepatitis. We describe for the first time the hepatic expression of IL-2 in NASH, so far considered a peculiarity of HCV-related liver damage.