What we learned in kindergarten: five tips for collaboration in oncology

As you read the five tenets presented here, think about these simple truths of leading and influencing others, managing failure, thinking strategically, and resolving conflicts. Ap - ply them to the world in which we all now live and play. Far too often work (the place) is viewed simply as where work (the action) occurs. What we are saying is that, although institutional targets (such as reducing wait times to see new patients) are all laudable goals, there has to be more, and play has to become an essential component of work. What can we uncover, rediscover, and create to make the time spent with one another the best possible experience for everyone involved? Even more importantly, what must we do to ensure that what we create and share has the possibil - ity and potential to make our lives and the world a better place? Play isn’t something we do as a part of life—it is life.info:eu-repo/semantics/publishedVersio

Collective Epithelial Migration Drives Kidney Repair after Acute Injury

Acute kidney injury (AKI) is a common and significant medical problem. Despite the kidney’s remarkable regenerative capacity, the mortality rate for the AKI patients is high. Thus, there remains a need to better understand the cellular mechanisms of nephron repair in order to develop new strategies that would enhance the intrinsic ability of kidney tissue to regenerate. Here, using a novel, laser ablation-based, zebrafish model of AKI, we show that collective migration of kidney epithelial cells is a primary early response to acute injury. We also show that cell proliferation is a late response of regenerating kidney epithelia that follows cell migration during kidney repair. We propose a computational model that predicts this temporal relationship and suggests that cell stretch is a mechanical link between migration and proliferation, and present experimental evidence in support of this hypothesis. Overall, this study advances our understanding of kidney repair mechanisms by highlighting a primary role for collective cell migration, laying a foundation for new approaches to treatment of AKI

Liver transplantation for glycogen storage disease types I, III, and IV

Glycogen storage disease (GSD) types I, III, and IV can be associated with severe liver disease. The possible development of hepatocellular carcinoma and/or hepatic failure make these GSDs potential candidates for liver transplantation. Early diagnosis and initiation of effective dietary therapy have dramatically improved the outcome of GSD type I by reducing the incidence of liver adenoma and renal insufficiency. Nine type I and 3 type III patients have received liver transplants because of poor metabolic control, multiple liver adenomas, or progressive liver failure. Metabolic abnormalities were corrected in all GSD type I and type III patients, while catch-up growth was reported only in two patients. Whether liver transplantation results in reversal and/or prevention of renal disease remains unclear. Neutropenia persisted in both GSDIb patients post liver transplantation necessitating continuous granulocyte colony stimulating factor treatment. Thirteen GSD type IV patients were liver transplanted because of progressive liver cirrhosis and failure. All but one patient have not had neuromuscular or cardiac complications during follow-up periods for as long as 13 years. Four have died within a week and 5 years after transplantation. Caution should be taken in selecting GSD type IV candidates for liver transplantation because of the variable phenotype, which may include life-limiting extrahepatic manifestations. It remains to be evaluated, whether a genotype-phenotype correlation exists for GSD type IV, which may aid in the decision making. Conclusion Liver transplantation should be considered for patients with glycogen storage disease who have developed liver malignancy or hepatic failure, and for type IV patients with the classical and progressive hepatic form

Specificity and overlap in gene segment-defined antibody repertoires

BACKGROUND: To date several studies have sought to catalog the full suite of antibodies that humans naturally produce against single antigens or other specificities (repertoire). Here we analyze the properties of all sequenced repertoires in order to better understand the specificity of antibody responses. Specifically, we ask whether the large-scale sequencing of antibody repertoires might provide a diagnostic tool for detecting antigen exposure. We do this by examining the overlap in V(H)-, D-, and J(H)- segment usage among sequenced repertoires. RESULTS: We find that repertoire overlap in V(H)-, D-, and J(H)-segment use is least for V(H )segments and greatest for J(H )segments, consistent with there being more V(H )than J(H )segments in the human genome. We find that for any two antigens chosen at random, chances are 90 percent that their repertoires' V(H )segments will overlap by less than half, and 98 percent that their VDJ(H )combinations will overlap by ≤10 percent. We ran computer simulations to test whether enrichment for specific VDJ(H )combinations could be detected in "antigen-exposed" populations, and found that enrichment is detectable with moderate-to-high sensitivity and high specificity, even when some VDJ(H )combinations are not represented at all in some test sets. CONCLUSION: Thus, as large-scale sequencing becomes cost-effective for clinical testing, we suggest that sequencing an individual's expressed antibody repertoire has the potential to become a useful diagnostic modality

The next frontier: Fostering innovation by improving health data access and utilization

Beneath most lively policy debates sit dry-as-dust theoretical and methodological discussions. Current disputes over the EU Adaptive Pathways initiative and the proposed US 21st Century Cures Act may ultimately rest on addressing arcane issues of data curation, standardization, and utilization. Improved extraction of inform ation on the safety and effectiveness of drugs-in-use must parallel adjustments in evidence requirements at the time of licensing. To do otherwise may compromise safety and efficacy in the name of fostering innovation

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin