CRISPR‐Cas12‐based field‐deployable system for rapid detection of synthetic DNA sequence of the monkeypox virus genome

alexandrossfakianakis shared this article with you from Inoreader CRISPR‐Cas12‐based field‐deployable system for rapid detection of synthetic DNA sequence of the monkeypox virus genome via Journal of Medical Virology Abstract The global outbreak of the monkeypox virus (MPXV) highlights the need for rapid and cost-effective MPXV detection tools to effectively monitor and control the monkeypox disease. Herein, we demonstrated a portable CRISPR-Cas-based system for naked-eye detection of MPXV. The system harnesses the high selectivity of CRISPR-Cas12 and the isothermal nucleic acid amplification potential of recombinase polymerase amplification (RPA). It can detect both the current circulating MPXV clade and the original clades. We reached an LoD of 22.4 aM (13.5 copies/µL) using a microtiter plate reader, while the visual LoD of the system is 75 aM (45 copies/µL) in a two-step assay, which is further reduced to 25 aM (15 copies/µL) in a one-pot system. We compared our results with quantitative (q) PCR and obtained satisfactory consistency. For clinical application, we demonstrated a sensitive and precise visual detection method with attomolar sensitivity and a sample-to-answer time of 35 minutes. This article is protected by copyright. All rights reserved. View on Web

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Gimap5 promoted RSV degradation through interaction with M6PR

alexandrossfakianakis shared this article with you from Inoreader Gimap5 promoted RSV degradation through interaction with M6PR via Journal of Medical Virology Abstract Backgroud Respiratory Syncytial Virus (RSV) is one of the main pathogens of viral pneumonia and bronchiolitis in infants and young children and a life threatening diseases among infants and young children. GTPases of the immune-associated protein family (GIMAP) are a new family members of immune-associated GTPases. In recent years, much attention has been paid to the function of the GIMAP family in coping with infection and stress. Gimap5 is a member of the GIMAP family, which may be correlated with anti-infectious immunity. Methods RT-qPCR, Western blot and indirect immunofluorescence (IFA) were used to detect the expression of Gimap5, M6PR and IGF1R(the major RSV receptor). Transmission electron microscopy (TEM) was used to detect the degradation of RSV in Gimap5-overexpressed or -silent cell lines. Computer virtual screening was used to screen small molecule compounds targeting Gimap5 and the anti-RSV effects were explored through in vivo and in vitro experiments. Results GIMAP5 and M6PR were significantly down-regulated after RSV infection. Gimap5 accelerated RSV degradation in lysosomes by interacting with M6PR, and further prevented RSV invasion by down-regulating the expression of RSV surface receptor IGF1R. Three small molecule compounds targeting Gimap5 were confirmed to be the agonists of Gimap5. The three compounds effectively inhibited RSV infection and RSV-induced complications. Conclusion Gimap5 promotes the degradation of RSV and its receptor through interacting with M6PR. Gimap5 agonists can effectively reduce RSV infection and RSV-induced complication in vivo and in vitro, which provides a new choice for the treatment of RSV. This article is protected by copyright. All rights reserved. View on Web

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Efficacy and safety of camrelizumab plus apatinib compared to apatinib monotherapy as third‐line or above therapy for metastatic colorectal cancer patients: A retrospective cohort study

alexandrossfakianakis shared this article with you from Inoreader Efficacy and safety of camrelizumab plus apatinib compared to apatinib monotherapy as third‐line or above therapy for metastatic colorectal cancer patients: A retrospective cohort study via Journal of Clinical Pharmacy and Therapeutics This study aimed to investigate the treatment efficacy and safety of camrelizumab (programmed cell death protein-1 (PD-1) inhibitor) plus apatinib as third-line or above therapy in metastatic colorectal cancer (mCRC) patients. Totally, 64 unresectable mCRC patients receiving camrelizumab plus apatinib (N = 31) and apatinib (N = 33) were retrospectively enrolled. It was found that disease control rate and objective response rate (ORR) were increased in camrelizumab plus apatinib group compared to apatinib group, but ORR did not achieve statistical significance. Besides, the median (95% confidence interval [CI]) progressive-free survival (PFS) and overall survival (OS) were 6.9 (3.7–10.1) and 11.5 (7.7–15.3) months in camrelizumab plus apatinib group, as well as 3.6 (1.7–5.5) and 6.7 (5.0–8.4) months in apatinib group. Additionally, PFS and OS were prolonged in camrelizumab plus apatinib group compared with apatinib group. The incidence of a dverse events did not differ between groups. Conclusively, camrelizumab (PD-1 inhibitor) plus apatinib achieves a better treatment efficacy than apatinib as third-line or above therapy with a good safety profile in mCRC patients. Abstract What Is Known and Objective Programmed cell death protein-1 (PD-1) inhibitors synergize apatinib for anti-tumour effect by regulating tumour microenvironment, vascular endothelial growth factor, hypoxia condition, immune response, etc. This study aimed to investigate the treatment efficacy and safety of camrelizumab (PD-1 inhibitor) plus apatinib as third-line or above therapy in metastatic colorectal cancer (mCRC) patients. Methods Totally, 64 unresectable mCRC patients receiving camrelizumab plus apatinib (N = 31) and apatinib (N = 33) were retrospectively enrolled. Results Disease control rate (80.6% vs. 57.6%) (P = 0.047) was elevated in camrelizumab plus apatinib group compared to apatinib group; however, objective response rate (22.6% vs. 6.1%) (P = 0.078) only showed an increasing trend but did not achieve statistical significance. Besides, the median (95% confidence interval [CI]) progressive-free survival (PFS) and overall survival (OS) were 6.9 (3.7–10.1) and 11.5 (7.7–15.3) months in camrelizumab plus apatinib group; meanwhile, the median (95% CI) PFS and OS were 3.6 (1.7–5.5) and 6.7 (5.0–8.4) months in the apatinib group. Additionally, PFS (P = 0.017) and OS (P = 0.006) were prolonged in camrelizumab plus apatinib group compared with apatinib group, which was confirmed by further multivariate Cox's proportional hazards regression analysis (hazard ratio [HR] = 0.340, P < 0.001 for PFS; HR = 0.271, P < 0.001 for OS). Th e incidence of total, grade 1–2, and grade 3–4 adverse events did not differ between groups (all P > 0.05). Conclusion Camrelizumab (PD-1 inhibitor) plus apatinib achieves a better treatment efficacy than apatinib as third-line or above therapy with a good safety profile in mCRC patients. View on Web

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Evaluation the efficacy and safety of N‐acetylcysteine inhalation spray in controlling the symptoms of patients with COVID‐19: An open‐label randomized controlled clinical trial

alexandrossfakianakis shared this article with you from Inoreader Evaluation the efficacy and safety of N‐acetylcysteine inhalation spray in controlling the symptoms of patients with COVID‐19: An open‐label randomized controlled clinical trial via Journal of Medical Virology Abstract Background The aim of this study was to evaluate the effect and safety of N-acetylcysteine (NAC) inhalation spray in the treatment of patients with coronavirus disease 2019 (COVID-19). Methods This randomized controlled clinical trial study was conducted on patients with COVID-19. Eligible patients (n=250) were randomly allocated into the intervention group (routine treatment + NAC inhaler spray one puff per 12 hours, for 7 days) or the control group who received routine treatment alone. Clinical features, hemodynamic, hematological, biochemical parameters and patient outcomes were assessed and compared before and after treatment. Results The mortality rate was significantly higher in the control group than in the intervention group (39.2% vs 3.2%, P<0.001). Significant differences were found between the two groups (intervention and control, respectively) for white blood cell count (6.2 vs 7.8, P<0.001), hemoglobin (12.3 vs 13.3, P=0.002), C-reactive protein (CRP: 6 vs 11.5, P<0.0001) and aspartate aminotransferase (AST: 32 vs 25.5, P<0.0001). No differences were seen for hospital length of stay (11.98±3.61 vs 11.81±3.52, P=0.814) or the requirement for ICU admission (7.2% vs 11.2%, P=0.274). Conclusions NAC was beneficial in reducing the mortality rate in patients with COVID-19 and inflammatory parameters, and a reduction in the development of severe respiratory failure; however, it did not affect the length of hospital stay or the need for ICU admission. Data on the effectiveness of NAC for SARS-CoV-2 is limited and further research is required. Clinical Trial Registration This study Registered at Iranian Registry of Clinical Trials (IRCT20080901001165N55) dated 23-05-2020. This article is protected by copyright. All rights reserved. View on Web

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The prognostic significance of hematogones in childhood B‐cell acute lymphoblastic leukemia

alexandrossfakianakis shared this article with you from Inoreader The prognostic significance of hematogones in childhood B‐cell acute lymphoblastic leukemia via Pediatric Blood & Cancer Abstract Background Recent studies have demonstrated hematogones (HGs) expansion to be associated with favorable outcomes in hematological diseases, especially in patients with acute myeloid leukemia and patients undergoing hematopoietic stem cell transplantation. Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children. As of now, minimal residual disease (MRD) remains the most compelling independent prognostic factor in childhood ALL. There is need for more prognostic tools for evaluating relapse risk. Procedure The goal of this study was to assess the prognostic value of HGs on relapse-free survival (RFS) and overall survival (OS) in childhood ALL. In this prospective cohort study, a total of 122 subjects with definitive diagnosis of precursor B lymphoblastic leukemia were evaluated. Flow cytometric HG detection was performed in bone marrow aspirates after induction and consolidation therapy. Results The median follow-up period of patients was 35.5 ± 9.4 (SD) months. Patients who had at least 1.0% HGs had a significantly better RFS (p = .023). Moreover, univariate and multivariate analyses confirmed that positive HGs were independently associated with longer RFS (unadjusted model: hazard ratio = 0.33, 95% CI = 0.12–0.91, p = .031; adjusted model: hazard ratio = 0.30, 95% CI = 0.11–0.82, p = .020). Conclusions Along with the role of MRD, our study shows the significance of HGs as an independent prognostic factor. The results indicate the independent prognostic value of HGs on RFS after adjustment for other prognostic factors, and can be beneficial for risk stratification and treatment modifications amongst pediatric B-cell ALL patients. View on Web

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Duration of antibiotic treatment for acute graft pyelonephritis: What's the standard of care?

alexandrossfakianakis shared this article with you from Inoreader Duration of antibiotic treatment for acute graft pyelonephritis: What's the standard of care? via Transplant Infectious Disease Abstract Background Limited evidence is available to inform the duration of antibiotic treatment in kidney transplant recipients with bacterial acute graft pyelonephritis. Guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation suggest a 14–21 day duration. Methods A four-question survey was constructed to determine the current standard of practice for the duration of treatment for acute graft pyelonephritis. The survey was distributed among members of the Infectious Diseases and the Kidney Pancreas Communities of Practice of the American Society of Transplantation. Results Among 144 survey respondents, 87 (60%) were infectious disease physicians, and 36 (25%) were transplant nephrologists. Although most (55%) respondents preferred a 14-day duration, a spread between 7 and 28 days was observed. Goals of treatment and drivers for longer duration differed between infectious disease physicians and transplant nephrologists. Conclusions Although most respondents prefer a 14-day duration of treatment for acute graft pyelonephritis, a wide range of responses was seen between 7 and 28 days. More evidence is needed to inform optimal treatment duration in this common infectious complication after transplantation. View on Web

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Pharmacokinetic/pharmacodynamic analysis of high‐dose tigecycline, by Monte Carlo simulation, in plasma and sputum of patients with hospital‐acquired pneumonia

alexandrossfakianakis shared this article with you from Inoreader Pharmacokinetic/pharmacodynamic analysis of high‐dose tigecycline, by Monte Carlo simulation, in plasma and sputum of patients with hospital‐acquired pneumonia via Journal of Clinical Pharmacy and Therapeutics The study collected 108 blood specimens and60 sputum specimens from 12 enrolled patients Subsequently, these specimens were assayedfor tigecycline drug concentrations by high-performance liquid chromatography (HPLC).The relevant pharmacokinetic (PK) parameters were estimated by the non-compartmental model usingWinNonlin software. And Crystal Ball software was used to carry out Monte Carlosimulations. The results of this study showed that the mean lung penetrationrate calculated by the sputum was 127.27% and the probability of targetattainments (PTAs) in plasma and sputum ≥90.00% when the minimal inhibit concentration (MIC) ≤ 4 mg/L. Hence, the findings of PK/PD parameters of high-dosetigecycline in patients with HAP caused by MDRB demonstrated that high-dosetigecycline could achieve better antimicrobial effects when the MIC was ≤4 mg/L. Abstract What is Known and Objective To Investigate the pharmacokinetic/pharmacodynamic (PK/PD) parameters of high-dose tigecycline in plasma and sputum of patients with hospital-acquired pneumonia (HAP), and provide a therapeutic regimen of multidrug-resistant bacteria (MDRB) infections. Methods Blood/sputum samples were collected at intervals after tigecycline had reached a steady-state. Tigecycline concentrations in specimens were determined by high-performance liquid chromatography (HLPC), PK parameters were evaluated by WinNonlin software using a non-compartment model. The probability of target attainments (PTAs) at different minimal inhibitory concentrations (MICs) were calculated for achieving the PK/PD index with Crystal Ball software by 10,000-patient Monte Carlo Simulation. Results In plasma, the maximum concentration (C max) and area under the concentration–time curve from 0 to 12 h (AUC0–12h) were 2.21 ± 0.17 mg/L and 15.29 ± 1.13 h mg/L, respectively. In sputum, they were 2.48 ± 0.21 mg/L and 19.46 ± 1.82 h mg/L, respectively. The mean lung penetration rate was 127.27%. At the MIC ≤4 mg/L, the PTAs in plasma and sputum were 100.00%. When the MIC increased to 8 mg/L, the PTAs in plasma and sputum mostly were < 90.00% according to two criteria. What is New and Conclusion In this study, we explored PK/PD of high-dose tigecycline in plasma and sputum. From a PK/PD perspective, high-dose tigecycline had greater therapeutic outcomes in HAP treatment caused by MDRB. Antimicrobial-drug concentrations should be determined to optimize their clinical use. View on Web

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