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These findings show marked improvements in the survival of CLL patients at the population level subsequently to the approval of anti-CD 20 antibodies like rituximab, ofatumumab or obinutuzumab for CLL treatment.High-entropy alloys (HEAs) with unique physicochemical properties have attracted tremendous attention in many fields, yet the precise control on dimension and morphology at atomic level remains formidable challenges. Herein, we synthesize unique PtRuNiCoFeMo HEA subnanometer nanowires (SNWs) for alkaline hydrogen oxidation reaction (HOR). The mass and specific activities of HEA SNWs/C reach 6.75 A mgPt+Ru-1 and 8.96 mA cm-2, respectively, which are 2.8/2.6, 4.1/2.4, and 19.8/18.7 times higher than those of HEA NPs/C, commercial PtRu/C and Pt/C, respectively. It can even display enhanced resistance to CO poisoning during HOR in the presence of 1000 ppm CO. Density functional theory calculations reveal that the strong interactions between different metal sites in HEA SNWs can greatly regulate the binding strength of proton and hydroxyl, and therefore enhances the HOR activity. This work not only provides a viable synthetic route for the fabrication of Pt-based HEA subnano/nano materials, but also promotes the fundamental researches on catalysis and beyond.BACKGROUND Several cases of herpes simplex virus type 1 meningoencephalitis (HSVE) have been reported in patients receiving steroids, but the exact contribution of steroids to the disorder remains unclear because other risk factors, such as chemotherapy, brain radiation, or surgery, were present in almost all cases. CASE REPORT We report the case of a 76-year-old man who developed HSVE following the administration of pulse-dose steroids. The patient had occupational asbestos exposure and a chronic interstitial lung disease of unclear etiology (sarcoidosis versus hypersensitivity pneumonitis) and was admitted for acute-on-chronic respiratory failure requiring mechanical ventilation. After a negative infectious workup and several days of antibiotics without improvement, pulse-dose steroids were administered. In the following days, the patient developed a fever and worsening encephalopathy. A lumbar puncture showed elevated nucleated cells and positive polymerase chain reaction for herpes simplex virus 1 in the cerebrospinal fluid, confirming the diagnosis of HSVE. Acyclovir treatment was initiated, but the patient later died as a result of persistent severe encephalopathy and respiratory failure with an inability to wean mechanical ventilation. CONCLUSIONS Clinicians should keep in mind that HSVE is a potential complication of steroids and carefully consider the benefit/risk ratio of pulse-dose steroids, taking into account associated factors of immunosuppression. A high level of awareness should be especially maintained in critically ill patients because of associated risk factors (critical illness immune paralysis) and because neurological signs of HSVE may be missed in mechanically ventilated, sedated patients.BACKGROUND Numerous studies have shown that esophageal cancer (ESCA) contains areas of intertumoral hypoxia. It is widely accepted that the association of hypoxia with cancer stemness in the tumor microenvironment of ESCA is of profound clinical significance. However, reliable prognostic signatures based on hypoxia and cancer stemness are still lacking in ESCA. MATERIAL AND METHODS The t-SNE algorithm was used to estimate the hypoxia status based on the transcriptome profiles of the discovery cohort in the TCGA database. Median values of the stemness index were used to group and identify stemness-associated differentially expressed genes (DEGs). The LASSO method and Cox regression model were combined to screen for prognostic genes and to establish a genetic signature based on hypoxia-stemness. The robustness of the prognostic model was then tested in an external independent validation cohort of the GEO database. RESULTS A total of 8 genes - FBLN2, IL17RB, CYP2W1, AMTN, FABP1, FOXA2, GAS1, and CTSF - were identified to construct a gene signature for ESCA risk stratification. Overall survival was significantly lower in the high-risk group than in the low-risk group in both the internal discovery set and the external validation set. The risk score was found to be an independent prognostic factor for ESCA patients. In addition, a higher risk score was significantly associated with the sensitivity of ESCA patients to gefitinib, bexarotene, dasatinib, and imatinib. CONCLUSIONS The hypoxia-stemness-based genetic signature established for the first time in our study could be a promising tool for ESCA cancer risk stratification.

Osteosarcoma (OS) is a highly prevalent bone malignancy with poor clinical outcomes. Expression of the circular RNA, hsa_circ_0078767 (circFAM120B) is elevated in OS, however, its mechanisms in OS are unclear.

CircFAM120B levels were detected in OS tissue and cell lines. Silenced circFAM120B experiments were performed to assess its effects on OS

cancer phenotypes and

tumor growth. Then, bioinformatics analyses were used to predict circFAM120B target microRNAs (miRNAs) and associated genes.

CircFAM120B and the transcription factor, PTBP1 were elevated in OS tissue and cell lines, while miR-1205 was poorly expressed. Silenced circFAM120B significantly suppressed

OS cell proliferation and invasion, and inhibited

tumor growth. CircFAM120B also appeared to function as an miR-1205 sponge, as miR-1205 bound to PTBP1. Interestingly, overexpressed PTBP1 (or miR-1205 inhibition) reversed the inhibitory effects mediated by circFAM120B downregulation in OS cells.

We hypothesize circFAM120B functions as a miR-1205 sponge to elevate PTBP1 levels, enhancing OS progression and associated malignant phenotypes. Thus, circFAM120B may function as a crucial mediator during OS progression.

We hypothesize circFAM120B functions as a miR-1205 sponge to elevate PTBP1 levels, enhancing OS progression and associated malignant phenotypes. Thus, circFAM120B may function as a crucial mediator during OS progression.

Heated tobacco products, including Marlboro IQOS, are available globally. In the USA, IQOS was authorised to be advertised with claims about reduced toxicant exposure relative to cigarettes. The effects of such modified risk claims and health warnings have not been studied among young adult cigarette smokers and non-smokers.

In 2020, US young adult (18-30 years, n=1328) cigarette smokers and non-smokers viewed an IQOS ad in a 4 (modified risk claim variations or none) by 3 (warning variations or none) between-subjects experiment. Outcome measures assessed perceived credibility and effectiveness of the health or risk message for discouraging IQOS use, perceived harms, efficacy beliefs, and IQOS use intentions.

Smokers reported significantly higher (p<0.05) perceived credibility, lower perceived effectiveness, higher efficacy beliefs about switching to IQOS and higher intentions to use IQOS than non-smokers. Among smokers, health warnings increased perceived credibility (p<0.001) and effectiveness (effectiveness, but the Food and Drug Administration-authorised reduced exposure claim increased intentions to use IQOS. Research is warranted to understand how the content of modified risk claims and health warnings for IQOS affects IQOS use in this population.

Extubation to non-invasive ventilation (NIV) has been investigated as a strategy to wean critically ill adults from invasive ventilation and reduce ventilator-related complications.

We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, proceedings of four conferences and bibliographies (to June 2020) for randomised and quasi-randomised trials that compared extubation with immediate application of NIV to continued invasive weaning in intubated adults and reported mortality (primary outcome) or other outcomes. Two reviewers independently screened citations, assessed trial quality and abstracted data.

We identified 28 trials, of moderate-to-good quality, involving 2066 patients, 44.6% with chronic obstructive pulmonary disease (COPD). Non-invasive weaning significantly reduced mortality (risk ratio (RR) 0.57, 95% CI 0.44 to 0.74; high quality), weaning failures (RR 0.59, 95% CI 0.43 to 0.81; high quality), pneumonia (RR 0.30, 95% CI 0.22 to 0.41; high quality), intensive care unit (ICU) (mean difference (MD) -4.62 days, 95% CI -5.91 to -3.34) and hospital stay (MD -6.29 days, 95% CI -8.90 to -3.68). Non-invasive weaning also significantly reduced the total duration of ventilation, duration of invasive ventilation and duration of ventilation related to weaning (MD -0.57, 95% CI -1.08 to -0.07) and tracheostomy rate. Mortality, pneumonia, reintubation and ICU stay were significantly lower in trials enrolling COPD (vs mixed) populations.

Non-invasive weaning significantly reduced mortality, pneumonia and the duration of ventilation related to weaning, particularly in patients with COPD. Beneficial effects are less clear (or more careful patient selection is required) in non-COPD patients.

CRD42020201402.

CRD42020201402.

The chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) antagonist timapiprant improved lung function and asthma control in a phase 2 study, with evidence suggesting reduced exacerbations. We aimed to assess whether timapiprant attenuated or prevented asthma exacerbations induced by experimental rhinovirus (RV) infection. compound library inhibitor We furthermore hypothesised that timapiprant would dampen RV-induced type 2 inflammation and consequently improve antiviral immune responses.

Atopic patients with partially controlled asthma on maintenance inhaled corticosteroids were randomised to timapiprant (n=22) or placebo (n=22) and challenged with RV-A16 3 weeks later. The primary endpoint was the cumulative lower respiratory symptom score over the 14 days post infection. Upper respiratory symptoms, spirometry, airway hyperresponsiveness, exhaled nitric oxide, RV-A16 virus load and soluble mediators in upper and lower airways samples, and CRTH2 staining in bronchial biopsies were additionally as asthma.Lung cancer screening is effective if offered to people at increased risk of the disease. Currently, direct contact with potential participants is required for evaluating risk. A way to reduce the number of ineligible people contacted might be to apply risk-prediction models directly to digital primary care data, but model performance in this setting is unknown.

The Clinical Practice Research Datalink, a computerised, longitudinal primary care database, was used to evaluate the Liverpool Lung Project V.2 (LLP

) and Prostate Lung Colorectal and Ovarian (modified 2012) (PLCO

) models. Lung cancer occurrence over 5-6 years was measured in ever-smokers aged 50-80 years and compared with 5-year (LLP

) and 6-year (PLCO

) predicted risk.

Over 5 and 6 years, 7123 and 7876 lung cancers occurred, respectively, from a cohort of 842 109 ever-smokers. After recalibration, LLP

produced a c-statistic of 0.700 (0.694-0.710), but mean predicted risk was over-estimated (predicted 4.61%, actual 0.9%). PLCO

showed simty, at the cost of missing some lung cancers. Further work is needed to establish whether newer models have improved performance in primary care data.

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