Zimmermanfleming1705

Integrating transcriptome and m6A-seq analyses reveal that WTAP increases the expression of its critical target gene HK2 by enhancing the HK2 m6A level, thereby promoting the progression of DLBCL. Together, the piRNA-30473/WTAP/HK2 axis contributes to tumorigenesis by regulating m6A RNA methylation in DLBCL. Furthermore, by comprehensively analyzing our clinical data and datasets, we discover that the m6A regulatory genes piRNA-30473 and WTAP improve survival prediction in DLBCL patients. Our study highlights the functional importance of the m6A modification in DLBCL and might assist in the development of a prognostic stratification and therapeutic approach for DLBCL.CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy has shown significant efficacy for relapsed or refractory (R/R) B-cell malignancies. Yet, CD19 CAR T cells fail to induce durable responses in most patients. Second infusions of CD19 CAR T cells (CART2) have been considered as a possible approach to improve outcomes. We analyzed data from 44 patients with R/R B-cell malignancies (acute lymphoblastic leukemia [ALL], n = 14; chronic lymphocytic leukemia [CLL], n = 9; non-Hodgkin lymphoma [NHL], n = 21) who received CART2 on a phase 1/2 trial (NCT01865617) at our institution. Despite a CART2 dose increase in 82% of patients, we observed a low incidence of severe toxicity after CART2 (grade ≥3 cytokine release syndrome, 9%; grade ≥3 neurotoxicity, 11%). After CART2, complete response (CR) was achieved in 22% of CLL, 19% of NHL, and 21% of ALL patients. The median durations of response after CART2 in CLL, NHL, and ALL patients were 33, 6, and 4 months, respectively. Addition of fludarabine to cyclophosphamide-based lymphodepletion before the first CAR T-cell infusion (CART1) and an increase in the CART2 dose compared with CART1 were independently associated with higher overall response rates and longer progression-free survival after CART2. We observed durable CAR T-cell persistence after CART2 in patients who received cyclophosphamide and fludarabine (Cy-Flu) lymphodepletion before CART1 and a higher CART2 compared with CART1 cell dose. The identification of 2 modifiable pretreatment factors independently associated with better outcomes after CART2 suggests strategies to improve in vivo CAR T-cell kinetics and responses after repeat CAR T-cell infusions, and has implications for the design of trials of novel CAR T-cell products after failure of prior CAR T-cell immunotherapies.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in late 2019 in China and is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. To mitigate the effects of the virus on public health, the economy and society, a vaccine is urgently needed. Here I review the development of vaccines against SARS-CoV-2. Development was initiated when the genetic sequence of the virus became available in early January 2020, and has moved at an unprecedented speed a phase I trial started in March 2020 and there are currently more than 180 vaccines at various stages of development. Data from phase I and phase II trials are already available for several vaccine candidates, and many have moved into phase III trials. The data available so far suggest that effective and safe vaccines might become available within months, rather than years.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (first detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the findings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19.

Preterm birth places infants at higher risk of adverse long-term behavioral and cognitive outcomes. Combining biobehavioral measures and molecular biomarkers may improve tools to predict the risk of long-term developmental delays.

The Neonatal Neurobehavior and Outcomes in Very Preterm Infants study was conducted at nine neonatal intensive care units between April 2014 and June 2016. Cries were recorded and buccal swabs collected during the neurobehavioral exam. Cry episodes were extracted and analyzed using a computer system and the data were summarized using factor analysis. Genomic DNA was extracted from buccal swabs, quantified using the Qubit Fluorometer, and aliquoted into standardized concentrations. DNA methylation was measured with the Illumina MethylationEPIC BeadArray, and an epigenome-wide association study was performed using cry factors (n = 335).

Eighteen CpGs were associated with the cry factors at genome-wide significance (α = 7.08E - 09). Two CpG sites, one intergenic and one linked toprematurity, has been linked to a variety of medical conditions. Biobehavioral measures and molecular biomarkers can improve prediction tools for long-term developmental risks of preterm birth. Variation in epigenetic modulation in preterm infants provides a potential link between preterm birth and unfavorable developmental outcomes.

Reduced cerebral regional oxygen saturation (crSO

) variability in neonates, as measured by near-infrared spectroscopy, following cardiac surgery with deep hypothermic circulatory arrest (DHCA) is associated with poor neurodevelopmental outcomes. We sought to evaluate the variability of crSO

in a cohort of neonates following cardiac surgery with brief or no exposure to DHCA.

Variability of averaged 1-min crSO

values was calculated for the first 48 h following cardiac surgery in consecutive neonates over a 30-month period. Neonates requiring aortic arch repair underwent antegrade cerebral perfusion with either brief or no exposure to DHCA.

There were 115 neonates included in the study. Reduced crSO

variability was observed in neonates with aortic arch obstruction (p = 0.02) and non-survivors (p = 0.02). BI-3406 in vivo Post hoc analysis demonstrated that the reduction in crSO

variability was not as marked as in previously studied neonates with aortic arch obstruction who received DHCA alone (p < 0.001).

Neonates with aortic arch obstruction have reduced crSO

variability following cardiac surgery.