Microbiome Metadata Standards: Report of the National Microbiome Data Collaborative's Workshop and Follow-On Activities.

Microbiome samples are inherently defined by the environment in which they are found. Therefore, data that provide context and enable interpretation of measurements produced from biological samples, often referred to as metadata, are critical. Important contributions have been made in the development of community-driven metadata standards; however, these standards have not been uniformly embraced by the microbiome research community. To understand how these standards are being adopted, or the barriers to adoption, across research domains, institutions, and funding agencies, the National Microbiome Data Collaborative (NMDC) hosted a workshop in October 2019. This report provides a summary of discussions that took place throughout the workshop, as well as outcomes of the working groups initiated at the workshop.

Challenges in Bioinformatics Workflows for Processing Microbiome Omics Data at Scale.

The nascent field of microbiome science is transitioning from a descriptive approach of cataloging taxa and functions present in an environment to applying multi-omics methods to investigate microbiome dynamics and function. A large number of new tools and algorithms have been designed and used for very specific purposes on samples collected by individual investigators or groups. While these developments have been quite instructive, the ability to compare microbiome data generated by many groups of researchers is impeded by the lack of standardized application of bioinformatics methods. Additionally, there are few examples of broad bioinformatics workflows that can process metagenome, metatranscriptome, metaproteome and metabolomic data at scale, and no central hub that allows processing, or provides varied omics data that are findable, accessible, interoperable and reusable (FAIR). Here, we review some of the challenges that exist in analyzing omics data within the microbiome research sphere, and provide context on how the National Microbiome Data Collaborative has adopted a standardized and open access approach to address such challenges.

Irreversible electroporation ablation (IRE) of unresectable soft tissue tumors: learning curve evaluation in the first 150 patients treated.

BACKGROUND: Irreversible electroporation (IRE) is a novel technology that uses peri-target discrete probes to deliver high-voltage localized electric current to induce cell death without thermal-induced coagulative necrosis. "Learnability" and consistently effective results by novice practitioners is essential for determining acceptance of novel techniques. This multi-center prospectively-collected database study evaluates the learning curve of IRE. METHODS: Analysis of 150 consecutive patients over 7 institutions from 9/2010-7/2012 was performed with patients treated divided into 3 groups A (1(st) 50 patients treated), B (2(nd) 50) and C (3(rd) 50 patients treated) chronologically and analyzed for outcomes. RESULTS: A total of 167 IRE procedures were performed, with a majority being liver(39.5%) and pancreatic(35.5%) lesions. The three groups were similar with respect to co-morbidities and demographics. Group C had larger lesions (3.9 vs 3 cm,p=0.001), more numerous lesions (3.2 vs 2.2,p=0.07), more vascular invasion(p=0.001), underwent more associated procedures(p=0.001) and had longer operative times(p<0.001). Despite this, they had similar complication and high-grade complication rates(p=0.24). Attributable morbidity rate was 13.3%(total 29.3%) and high-grade complications were seen in 4.19%(total 12.6%). Pancreatic lesions(p=0.001) and laparotomy(p=0.001) were associated with complications. CONCLUSION: The review represents that single largest review of IRE soft tissue ablation demonstrating initial patient selection and safety. Over time, complex treatments of larger lesions and lesions with greater vascular involvement were performed without a significant increase in adverse effects or impact on local relapse free survival. This evolution demonstrates the safety profile of IRE and speed of graduation to more complex lesions, which was greater than 5 cases by institution. IRE is a safe and effective alternative to conventional ablation with a demonstrable learning curve of at least 5 cases to become proficient.

Deprotonation and regioselective addition of 2H-pyrazolo[3,4-c]quinolines to electrophiles.

The deprotonation and regioselective reaction of 2H-pyrazolo[3,4-c]quinolines with a variety of electrophiles is described. Electrophiles include benzaldehyde, DMF, carbon dioxide, and iodine. This method provides a direct route to a class of pharmacologically interesting compounds.

The evolution of cognition. 1990.

With cultural evolution, new processes of thought appear. Abstraction is universal, but rationalization first appeared in ancient Greece, theorization in Renaissance Italy, and model building in twentieth-century Europe. These processes employ the methods of metaphor, metalingual definition, algorithm, and control, respectively. The intellectual and practical achievements of populations guided by the several processes and exploiting the different mechanisms differ so greatly as to warrant separation into cultural ranks. The fourth rank is not completely formed, while regions of the world and parts of every population continue to operate by the processes of earlier ranks.

Bu(3)SnH-Mediated Pinacol Coupling of 1,5- and 1,6-Dicarbonyl Compounds: Synthetic and Mechanistic Studies.

A new method is described for the intramolecular pinacol coupling of 1,5- and 1,6-dicarbonyl compounds, employing Bu(3)SnH as the stoichiometric reductant. The key steps in this pinacol cyclization are the addition of a tin ketyl to a carbonyl group and a subsequent intramolecular S(H)2 reaction. The isolation of 1,3-dioxa-2-stannolanes, along with other product and labeling studies, provides strong support for the proposed homolytic substitution step, which distinguishes the pinacol cyclization from other reductive cyclizations of tin ketyls, all of which proceed through abstraction of hydrogen from Bu(3)SnH in the final step. An interesting consequence of the S(H)2 pathway is very high cis selectivity in the cyclization of 1,5-dicarbonyl compounds. Mechanistic studies furnish evidence that the steps that precede homolytic substitution, including C-C bond formation, are reversible under the reaction conditions.