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These functional effects highlight a cooperative down-modulation of MYCN and its down-stream targets, ALK and LIN28B, exerted by miR-34a and let-7b that reactivate regulatory networks leading to a favorable therapeutic response. These findings demonstrate a promising therapeutic efficacy of miR-34a and let-7b combined replacement and support its clinical application as adjuvant therapy for high-risk NB patients. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Concomitant chemo-radiotherapy (cCRT) with 60 Gy in 30 fractions is the standard of care for stage 111 non-small cell lung cancer (NSCLC). With a median overall survival of 28.7 months at best and maximum locoregional control rates of 70% at two years, the prognosis for these patients is still dismal. This systematic review summarizes data on dose escalation by alternative fractionation, which has been explored as a primary strategy to improve both local control and overall survival over the past three decades. A Pubmed literature search was performed according to the PRISMA guidelines. Because of the large variety of radiation regimens total doses were converted to EQD2,T . Only studies using an EQD2,T of at least 49.5 Gy, which corresponds to the conventional 60 Gy in six weeks, were included. In a total of 3256 patients, the median OS was 17 months (range 7.4-30 months). While OS was better for patients treated after the year 2000 (P = 0.003) or with a mandatory 18 F-FDG-PET-CT in the diagnostic work-up (Poncomitant CRT. © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.INTRODUCTION To examine associations of history of traumatic brain injuries (TBIs) with loss of consciousness (LOC) with dementia incidence and memory decline. METHODS We studied 2718 participants from the 1992 enrollment cohort of the Health and Retirement Study (HRS) aged 65 years or older in 2000. History of TBI with LOC was self-reported in 1992. Dementia was assessed using four algorithms established in HRS. Participants were followed from 2000 to 2014 with repeated measures of dementia and memory performance. Cox models and linear mixed-effects models were used. RESULTS In 1992, 11.9% of the participants reported a history of TBI with LOC. In fully adjusted models for all four algorithms, participants with a history of TBI with LOC had no statistically significant difference in dementia incidence nor in memory decline, compared to participants without TBI history. DISCUSSION Our study did not find evidence of a long-term association between history of TBI with LOC (of unknown frequency and severity) and dementia incidence or memory decline. © 2020 the Alzheimer's Association.RATIONALE The effort required to cycle and breathe intensify as power increases during incremental exercise. It is currently unclear how changes in FEV1 in the presence or absence of airflow limitation) impacts the intensity of dyspnea and leg effort. This is clinically important as the improvement in FEV1 is often the target for improving dyspnea. OBJECTIVES To investigate the relationship between dyspnea (D), leg effort, power (P), and FEV1 with and without airflow limitation using direct psychophysical scaling performed during incremental exercise testing to symptom limited capacity. METHODS Retrospective analysis of consecutive patients over the age of 35 referred for cardio-pulmonary exercise testing at McMaster University Medical Centre from 1988-2012.The modified Borg scale was used to measure dyspnea throughout incremental exercise testing. MEASUREMENTS AND RESULTS 38,788 patients were included in the analysis [Mean Age 58.6 years (SD ±11.8), Males 61%, BMI 28.1 kg/m2 (SD ±5.1), FEV1 was 2.7 L (SD ±0.85), 95% predicted (SD ±20.4), FVC 3.4 L (SD ± 1.0), 94% predicted (SD ±17.0)], and 10.9% had airflow limitation (AL, FEV1 /FVC  less then  70%). In a nonlinear regression analysis, the intensity of dyspnea increased in a positively accelerating manner with power and as the FEV1 % predicted decreased Dyspnea = 0.06 * Power1.03  * FEV1 %Pred-0.66 (r = .63). The intensity of leg effort increased with power and declining quadricep strength and FEV1% predicted Leg Effort = 0.06 * Power1.22  * Quad-0.56 *FEV1 %Pred-0.39 (r = .73). There was no independent effect of AL on dyspnea of leg effort. CONCLUSION Power, quadriceps strength and FEV1 are the dominant factors contributing to dyspnea and leg effort, irrespective of the degree of airflow limitation. © 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.HLA-A*310134 differs from HLA-A*31010201 by one nucleotide substitution at position 123 C>G. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Biofilm-associated infections are difficult to treat effectively with antibiotics despite repeated treatments. Polymeric microdevices (microcontainers) have previously been shown to engulf in mucus layers and to provide tunable release. Such devices may overcome the challenge of delivering antibiotics into the biofilm, increasing the local drug concentration and hence improve local bacterial killing. In this work, microcontainers are loaded with the antibiotic, ciprofloxacin hydrochloride, and functionalized with polymeric lids of polyethylene glycol (PEG), chitosan, or Eudragit S100. The PEG lid gives rise to a drug release comparable to uncoated microcontainers showing complete release after 8 h, whereas chitosan and Eudragit S100 lids result in continuous release during the course of 24 h. ACY-775 All antibiotic-containing microcontainers inhibit planktonic growth of Pseudomonas aeruginosa (PAO1) cells, but the degree of inhibition depends on the coating. Microcontainers with ciprofloxacin hydrochloride kill about three times more biofilm-associated PAO1 cells compared with a single standard bolus. Moreover, the use of microcontainers in biofilm result in bacterial killing equal to a constant flow of a three times higher concentration of solubilized antibiotics. These studies suggest that microcontainers can be useful for antibiotic delivery in treatment of biofilm-associated infections, resulting in more effective treatment and reduced use of antibiotics. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.