Elara: A Phase 2 Trial Investigating The Efficacy And Safety Of Tisagenlecleucel In Adult Patients With Refractory/Relapsed Follicular Lymphoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149492/1/hon6_2632.pd

Anti-SARS-CoV2 antibody responses in serum and cerebrospinal fluid of COVID-19 patients with neurological symptoms

Antibody responses to SARS-CoV-2 in serum and CSF from 16 COVID-19 patients with neurological symptoms were assessed using two independent methods. IgG specific for the virus spike protein was found in 81% of cases in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in two cases with negative serology. Levels of IgG in both serum and CSF were associated with disease severity (p<0.05). All patients with elevated markers of CNS damage in CSF also had CSF antibodies (p=0.002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables

Structural and electronic determinants of lytic polysaccharide monooxygenase reactivity on polysaccharide substrates

Lytic polysaccharide monooxygenases (LPMOs) are industrially important copper-dependent enzymes that oxidatively cleave polysaccharides. Here we present a functional and structural characterization of two closely related AA9-family LPMOs from Lentinus similis (LsAA9A) and Collariella virescens (CvAA9A). LsAA9A and CvAA9A cleave a range of polysaccharides, including cellulose, xyloglucan, mixed-linkage glucan and glucomannan. LsAA9A additionally cleaves isolated xylan substrates. The structures of CvAA9A and of LsAA9A bound to cellulosic and non-cellulosic oligosaccharides provide insight into the molecular determinants of their specificity. Spectroscopic measurements reveal differences in copper co-ordination upon the binding of xylan and glucans. LsAA9A activity is less sensitive to the reducing agent potential when cleaving xylan, suggesting that distinct catalytic mechanisms exist for xylan and glucan cleavage. Overall, these data show that AA9 LPMOs can display different apparent substrate specificities dependent upon both productive protein–carbohydrate interactions across a binding surface and also electronic considerations at the copper active site

A Systematic Review and Meta-Analysis to Inform Cancer Screening Guidelines in Idiopathic Inflammatory Myopathies

OBJECTIVES: To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer screening. METHODS: A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared to the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesised via narrative review. RESULTS: Sixty nine studies were included in the meta-analysis. Dermatomyositis subtype (RR 2.21), older age (WMD 11.19), male gender (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73), and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. Polymyositis (RR 0.49) and clinically amyopathic dermatomyositis (RR 0.44) subtypes, Raynaud's phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD -1189.96) or lactate dehydrogenase (WMD -336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. Computed tomography (CT) scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers. DISCUSSION: Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients

A holin and an endopeptidase are essential for chitinolytic protein secretion in <i>Serratia marcescens</i>

Pathogenic bacteria adapt to their environment and manipulate the biochemistry of hosts by secretion of effector molecules. Serratia marcescens is an opportunistic pathogen associated with healthcare-acquired infections and is a prolific secretor of proteins, including three chitinases (ChiA, ChiB, and ChiC) and a chitin binding protein (Cbp21). In this work, genetic, biochemical, and proteomic approaches identified genes that were required for secretion of all three chitinases and Cbp21. A genetic screen identified a holin-like protein (ChiW) and a putative l-alanyl-d-glutamate endopeptidase (ChiX), and subsequent biochemical analyses established that both were required for nonlytic secretion of the entire chitinolytic machinery, with chitinase secretion being blocked at a late stage in the mutants. In addition, live-cell imaging experiments demonstrated bimodal and coordinated expression of chiX and chiA and revealed that cells expressing chiA remained viable. It is proposed that ChiW and ChiX operate in tandem as components of a protein secretion system used by gram-negative bacteria

The Effects of the Massachusetts Health Reform on Financial Distress

A major benefit of health insurance coverage is that it protects the insured from unexpected medical costs that may devastate their personal finances. In this paper, we use detailed credit report information on a large panel of individuals to examine the effect of a major health care reform in Massachusetts in 2006 on a broad set of financial outcomes. The Massachusetts model served as the basis for the Affordable Care Act and allows us to examine the effect of coverage on financial outcomes for the entire population of the uninsured, not just those with very low incomes. We exploit plausibly exogenous variation in the impact of the reform across counties and age groups using levels of pre-reform insurance coverage as a measure of the potential effect of the reform. We find that the reform reduced the total amount of debt that was past due, the fraction of all debt that was past due, improved credit scores and reduced personal bankruptcies. We also find suggestive evidence that the reform lowered the total amount of debt and decreased third party collections. The effects are most pronounced for individuals who had limited access to credit markets before the reform. These results show that health care reform has implications that extend well beyond the health and health care utilization of those who gain insurance coverage

Examination of the Singapore Shift in Japan's Foreign Direct Investment in Services in ASEAN

Asia is fast becoming the largest recipient of Japan's foreign direct investment (FDI). Within the Asian region, the Association of Southeast Asian Nations (ASEAN) has been the major investment destination of Japan. In the manufacturing sectors, however, the investment flows from Japan to ASEAN - with Thailand being the largest recipient - has been declining. In contrast, Japan's FDI in the services sectors in ASEAN has been growing rapidly. The recent phenomenon of the Singapore Shift in Japan's FDI in the ASEAN services sectors proves interesting. The prominent strategy of Japanese companies is to establish a commercial presence in Singapore, which they expect to be the hub of Southeast Asia, thereby enabling them to supply services to the entire ASEAN region. The magnitude of the Singapore Shift varies for every services sub-sector. By comparing transport and logistics with finance and insurance industries, this paper considers the critical determinants of the Singapore Shift

Active learning and optimal climate policy

This paper develops a climate-economy model with uncertainty, irreversibility, and active learning. Whereas previous papers assume learning from one observation per period, or experiment with control variables to gain additional information, this paper considers active learning from investment in monitoring, specifically in improved observations of the global mean temperature. We find that the decision maker invests a significant amount of money in climate research, far more than the current level, in order to increase the rate of learning about climate change. This helps the decision maker make improved decisions. The level of uncertainty decreases more rapidly in the active learning model than in the passive learning model with only temperature observations. As the uncertainty about climate change is smaller, active learning reduces the optimal carbon tax. The greater the risk, the larger is the effect of learning. The method proposed here is applicable to any dynamic control problem where the quality of monitoring is a choice variable, for instance, the precision at which we observe GDP, unemployment, or the quality of education