Do Oil Shocks Affect Financial Stress? Evidence from Oil-Exporting and -Importing Countries

In recent years, there is increasing attention to examining the relationship between oil prices, financial markets, and the economy. Relatively little is known about the dynamic relationship between structural oil shocks and financial market stress of countries, which are majorly dependent on oil price fluctuations. This paper examines the impact of structural oil shocks (oil supply shocks, global aggregate demand shocks, speculative shocks, and other oil shocks) on the financial stress of major oil-exporting and-importing economies. In this study, we construct a financial stress index and using a structural vector autoregression model, we investigate the effects of oil price shocks on the financial stress of major oil-exporting and importing economies. We find evidence that global demand shocks, followed by speculative demand shocks, have significant impacts on financial stress. Furthermore, the US subprime crisis has a significant bearing on the response of the financial stress index to structural oil shocks. The magnitude of oil price shocks on financial stress has subdued during the post-crisis period

KDM4C is an Oncogenic Histone Demethylase in Pancreatic Cancer

https://openworks.mdanderson.org/sumexp21/1230/thumbnail.jp

The Histone Demethylase KDM4C is a Putative Oncogene in Pancreatic Cancer

https://openworks.mdanderson.org/sumexp22/1132/thumbnail.jp

Liquid Biopsy Transcriptomics of Extracellular Vesicles (EV) in Plasma of Pancreatic Ductal Adenocarcinoma (PDAC)

https://openworks.mdanderson.org/sumexp22/1089/thumbnail.jp

Comparison of Ondansetron and Dexamethasone for Prophylaxis of Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic Surgeries: A Meta-Analysis of Randomized Controlled Trials

Background. Postoperative nausea and vomiting (PONV) is a significant complication after laparoscopic surgeries. Ondansetron and dexamethasone are most commonly used drugs for PONV prophylaxis. Comparisons of these two drugs have not been systematically reviewed till date. Methods. PubMed, PubMed Central, and CENTRAL databases were searched with the following words: “dexamethasone,” “ondansetron,” “laparoscopy,” and “PONV” to identify randomized trials that compared ondansetron and dexamethasone for PONV prophylaxis after laparoscopic surgeries. Results. Data of 592 patients from 7 RCTs have been included in this meta-analysis. Incidence of postoperative nausea at 4–6 h is significantly lower when dexamethasone was used instead of ondansetron (p=0.04; OR 0.49, 95% CI 0.24–0.98, M-H fixed). Incidence of nausea is similar at 24 hours (p=0.08, OR 0.71, 95% CI 0.48, 1.05; M-H fixed); vomiting is also similar at 4–6 h (p=0.43, OR 1.27, 95% CI 0.70–2.27; M-H fixed) and also at 24 h (p=0.46, OR 0.92, 95% CI 0.73, 1.16; M-H fixed). Conclusion. Dexamethasone is superior to ondansetron in preventing postoperative nausea after 4–6 h of laparoscopic surgeries. However, both the drugs are of equal efficacy in preventing postoperative vomiting up to 24 h after surgery. However, results should be interpreted with caution due to clinical heterogeneity in the included studies

Ecological patterns and processes of temporal turnover within lung infection microbiota

Background: Chronic infection and consequent airway inflammation are the leading causes of morbidity and early mortality for people living with cystic fibrosis (CF). However, lower airway infections across a range of chronic respiratory diseases, including in CF, do not follow classical ‘one microbe, one disease’ concepts of infection pathogenesis. Instead, they are comprised of diverse and temporally dynamic lung infection microbiota. Consequently, temporal dynamics need to be considered when attempting to associate lung microbiota with changes in disease status. Set within an island biogeography framework, we aimed to determine the ecological patterns and processes of temporal turnover within the lung microbiota of 30 paediatric and adult CF patients prospectively sampled over a 3-year period. Moreover, we aimed to ascertain the contributions of constituent chronic and intermittent colonizers on turnover within the wider microbiota. Results: The lung microbiota within individual patients was partitioned into constituent chronic and intermittent colonizing groups using the Leeds criteria and visualised with persistence-abundance relationships. This revealed bacteria chronically infecting a patient were both persistent and common through time, whereas intermittently infecting taxa were infrequent and rare; respectively representing the resident and transient portions of the wider microbiota. It also indicated that the extent of chronic colonization was far greater than could be appreciated with microbiological culture alone. Using species-time relationships to measure temporal turnover and Vellend’s rationalized ecological processes demonstrated turnover in the resident chronic infecting groups was conserved and underpinned principally by the deterministic process of homogenizing dispersal. Conversely, intermittent colonizing groups, representing newly arrived immigrants and transient species, drove turnover in the wider microbiota and were predominately underpinned by the stochastic process of drift. For adult patients, homogenizing dispersal and drift were found to be significantly associated with lung function. Where a greater frequency of homogenizing dispersal was observed with worsening lung function and conversely drift increased with better lung function. Conclusions: Our work provides a novel ecological framework for understanding the temporal dynamics of polymicrobial infection in CF that has translational potential to guide and improve therapeutic targeting of lung microbiota in CF and across a range of chronic airway diseases. AWnQWdeG2wJZnAAmwW9_w- Video Abstrac

The role of stromal cancer-associated fibroblasts in pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer generally refractory to conventional treatments. Cancer-associated fibroblasts (CAFs) are cellular components of the desmoplastic stroma characteristic to the tumor that contributes to this treatment resistance. Various markers for CAFs have been explored including palladin and CD146 that have prognostic and functional roles in the pathobiology of PDAC. Mechanisms of CAF-tumor cell interaction have been described including exosomal transfer and paracrine signaling mediated by cytokines such as GM-CSF and IL-6. The role of downstream signaling pathways including JAK/STAT, mTOR, sonic hedge hog (SHH), and NFkB have also been shown to play an important function in PDAC-CAF cross talk. The role of autophagy and other metabolic effects on each cell type within the tumor have also been proposed to play roles in facilitating CAF secretory function and enhancing tumor growth in a low-glucose microenvironment. Targeting the stroma has gained interest with multiple preclinical and clinical trials targeting SHH, JAK2, and methods of either exploiting the secretory capability of CAFs to enhance drug delivery or inhibiting it to prevent its influence on cancer cell chemoresistance. This review summarizes the most recent progress made in understanding stromal formation; its contribution to tumor proliferation, invasion, and metastasis; its role in chemoresistance; and potential therapeutic strategies on the horizon.https://deepblue.lib.umich.edu/bitstream/2027.42/136216/1/13045_2017_Article_448.pd

Exploiting the neoantigen landscape for immunotherapy of pancreatic ductal adenocarcinoma

Immunotherapy approaches for pancreatic ductal adenocarcinoma (PDAC) have met with limited success. It has been postulated that a low mutation load may lead to a paucity of T cells within the tumor microenvironment (TME). However, it is also possible that while neoantigens are present, an effective immune response cannot be generated due to an immune suppressive TME. To discern whether targetable neoantigens exist in PDAC, we performed a comprehensive study using genomic profiles of 221 PDAC cases extracted from public databases. Our findings reveal that: (a) nearly all PDAC samples harbor potentially targetable neoantigens; (b) T cells are present but generally show a reduced activation signature; and (c) markers of efficient antigen presentation are associated with a reduced signature of markers characterizing cytotoxic T cells. These findings suggest that despite the presence of tumor specific neoepitopes, T cell activation is actively suppressed in PDAC. Further, we identify iNOS as a potential mediator of immune suppression that might be actionable using pharmacological avenues

Identifying Differences in Spatial Transcriptomics Between Subtypes of Pancreatic Ductal Adenocarcinoma

https://openworks.mdanderson.org/sumexp22/1072/thumbnail.jp

Mitochondrial DNA mutations in preneoplastic lesions of the gastrointestinal tract: A biomarker for the early detection of cancer

BACKGROUND: Somatic mutations of mitochondrial DNA (mtDNA) are common in many human cancers. We have described an oligonucleotide microarray ("MitoChip") for rapid sequencing of the entire mitochondrial genome (Zhou et al, J Mol Diagn 2006), facilitating the analysis of mtDNA mutations in preneoplastic lesions. We examined 14 precancerous lesions, including seven Barrett esophagus biopsies, with or without associated dysplasia; four colorectal adenomas; and three inflammatory colitis-associated dysplasia specimens. In all cases, matched normal tissues from the corresponding site were obtained as germline control. MitoChip analysis was performed on DNA obtained from cryostat-embedded specimens. RESULTS: A total of 513,639 bases of mtDNA were sequenced in the 14 samples, with 490,224 bases (95.4%) bases assigned by the automated genotyping software. All preneoplastic lesions examined demonstrated at least one somatic mtDNA sequence alteration. Of the 100 somatic mtDNA alterations observed in the 14 cases, 27 were non-synonymous coding region mutations (i.e., resulting in an amino acid change), 36 were synonymous, and 37 involved non-coding mtDNA. Overall, somatic alterations most commonly involved the COI, ND4 and ND5 genes. Notably, somatic mtDNA alterations were observed in preneoplastic lesions of the gastrointestinal tract even in the absence of histopathologic evidence of dysplasia, suggesting that the mitochondrial genome is susceptible at the earliest stages of multistep cancer progression. CONCLUSION: Our findings further substantiate the rationale for exploring the mitochondrial genome as a biomarker for the early diagnosis of cancer, and confirm the utility of a high-throughput array-based platform for this purpose from a clinical applicability standpoint