Efficiency is a key organizing principle in modern natural product synthesis. Practical criteria include time, cost, and effort expended to synthesize the target, which tracks with step-count and scale. The execution of a natural product synthesis, that is, the sum and identity of each reaction employed therein, falls along a continuum of chemical (abiotic) synthesis on one extreme, followed by the hybrid chemoenzymatic approach, and ultimately biological (biosynthesis) on the other, acknowledging the first synthesis belongs to Nature. Starting materials also span a continuum of structural complexity approaching the target with constituent elements on one extreme, followed by petroleum-derived and “chiral pool” building blocks, and complex natural products (i.e., semisynthesis) on the other. Herein, we detail our approach toward realizing the first synthesis of (−)-melodinine K, a complex bis-indole alkaloid. The total syntheses of monomers (−)-tabersonine and (−)-16-methoxytabersonine employing our domino Michael/Mannich annulation is described. Isolation of (−)-tabersonine from Voacanga africana and strategic biotransformation with tabersonine 16-hydroxylase for site-specific C–H oxidation enabled a scalable route. The Polonovski–Potier reaction was employed in biomimetic fragment coupling. Subsequent manipulations delivered the target. We conclude with a discussion of efficiency in natural products synthesis and how chemical and biological technologies define the synthetic frontier.

IntroductionFoundational to a well-functioning health system is a strong routine health information system (RHIS) that informs decisions and actions at all levels of the health system. In the context of decentralization across low- and middle-income countries, RHIS has the promise of supporting sub-national health staff to take data-informed actions to improve health system performance. However, there is wide variation in how “RHIS data use” is defined and measured in the literature, impeding the development and evaluation of interventions that effectively promote RHIS data use.MethodsAn integrative review methodology was used to: (1) synthesize the state of the literature on how RHIS data use in low- and middle-income countries is conceptualized and measured; (2) propose a refined RHIS data use framework and develop a common definition for RHIS data use; and (3) propose improved approaches to measure RHIS data use. Four electronic databases were searched for peer-reviewed articles published between 2009 and 2021 investigating RHIS data use.ResultsA total of 45 articles, including 24 articles measuring RHIS data use, met the inclusion criteria. Less than half of included articles (42%) explicitly defined RHIS data use. There were differences across the literature whether RHIS data tasks such as data analysis preceded or were a part of RHIS data use; there was broad consensus that data-informed decisions and actions were essential steps within the RHIS data use process. Based on the synthesis, the Performance of Routine Information System Management (PRISM) framework was refined to specify the steps of the RHIS data use process.ConclusionConceptualizing RHIS data use as a process that includes data-informed actions emphasizes the importance of actions in improving health system performance. Future studies and implementation strategies should be designed with consideration for the different support needs for each step of the RHIS data use process.

This digital GIS dataset and accompanying nonspatial files synthesize the model outputs from a regional-scale volumetric 3-D geologic model that portrays the generalized subsurface geology of western South Dakota from a wide variety of input data sources.The study area includes all of western South Dakota from west of the Missouri River to the Black Hills uplift and Wyoming border. The model data released here consist of the stratigraphic contact elevation of major Phanerozoic sedimentary units that broadly define the geometry of the subsurface, the elevation of Tertiary intrusive and Precambrian basement rocks, and point data representing the three-dimensional geometry of fault surfaces. the presence of folds and unconformities are implied by the 3D geometry of the stratigraphic units, but these are not included as discrete features in this data release. The 3D geologic model was constructed from a wide variety of publicly available surface and subsurface geologic data; none of these input data are part of this Data Release, but data sources are thoroughly documented such that a user could obtain these data from other sources if desired. This model was created as part of the U.S. Geological Survey’s (USGS) National Geologic Synthesis (NGS) project—a part of the National Cooperative Geologic Mapping Program (NCGMP). The WSouthDakota3D geodatabase contains twenty-five (25) subsurface horizons in raster format that represent the tops of modeled subsurface units, and a feature dataset “GeologicModel”. The GeologicModel feature dataset contains a feature class of thirty-five (35) faults served in elevation grid format (FaultPoints). The feature class “ModelBoundary” describes the footprint of the geologic model, and was included to meet the NCGMP’s GeMS data schema. Nonspatial tables define the data sources used (DataSources), define terms used in the dataset (Glossary), and provide a description of the modeled surfaces (DescriptionOfModelUnits). Separate file folders contain the vector data in shapefile format, the raster data in ASCII format, and the nonspatial tables as comma-separated values. In addition, a tabular data dictionary describes the entity and attribute information for all attributes of the geospatial data and the accompanying nonspatial tables (EntityAndAttributes). An included READ_ME file documents the process of manipulating and interpreting publicly available surface and subsurface geologic data to create the model. It additionally contains critical information about model units, and uncertainty regarding their ability to predict true ground conditions. Accompanying this data release is the “WSouthDakotaInputSummaryTable.csv”, which tabulates the global settings for each fault block, the stratigraphic horizons modeled in each fault block, the types and quantity of data inputs for each stratigraphic horizon, and then the settings associated with each data input.

IntroductionFoundational to a well-functioning health system is a strong routine health information system (RHIS) that informs decisions and actions at all levels of the health system. In the context of decentralization across low- and middle-income countries, RHIS has the promise of supporting sub-national health staff to take data-informed actions to improve health system performance. However, there is wide variation in how “RHIS data use” is defined and measured in the literature, impeding the development and evaluation of interventions that effectively promote RHIS data use.MethodsAn integrative review methodology was used to: (1) synthesize the state of the literature on how RHIS data use in low- and middle-income countries is conceptualized and measured; (2) propose a refined RHIS data use framework and develop a common definition for RHIS data use; and (3) propose improved approaches to measure RHIS data use. Four electronic databases were searched for peer-reviewed articles published between 2009 and 2021 investigating RHIS data use.ResultsA total of 45 articles, including 24 articles measuring RHIS data use, met the inclusion criteria. Less than half of included articles (42%) explicitly defined RHIS data use. There were differences across the literature whether RHIS data tasks such as data analysis preceded or were a part of RHIS data use; there was broad consensus that data-informed decisions and actions were essential steps within the RHIS data use process. Based on the synthesis, the Performance of Routine Information System Management (PRISM) framework was refined to specify the steps of the RHIS data use process.ConclusionConceptualizing RHIS data use as a process that includes data-informed actions emphasizes the importance of actions in improving health system performance. Future studies and implementation strategies should be designed with consideration for the different support needs for each step of the RHIS data use process.

We report a methodology using machine learning to capture chemical intuition from a set of (partially) failed attempts to synthesize a metal organic framework. We define chemical intuition as the collection of unwritten guidelines used by synthetic chemists to find the right synthesis conditions. As (partially) failed experiments usually remain unreported, we have reconstructed a typical track of failed experiments in a successful search for finding the optimal synthesis conditions that yields HKUST-1 with the highest surface area reported to date. We illustrate the importance of quantifying this chemical intuition for the synthesis of novel materials.

This digital GIS dataset and accompanying nonspatial files synthesize model outputs from a regional-scale volumetric 3D geologic model that portrays the generalized subsurface geology of the Michigan Basin region of Michigan, Wisconsin, Illinois, Indiana, and Ohio. The intent of this product is to rapidly and efficiently synthesize large quantities of geologic data from a wide variety of sources into a multi-use geologic framework model applicable to natural resource exploration and management. Major geographic features within the study area include Lake Michigan and the Lower Peninsula of Michigan, and portions of the Upper Peninsula of Michigan, Lake Huron, Lake Saint Clair, and Lake Erie. Geologically, the study area incorporates major structures such as the Kankakee Arch, Findlay Arch, Wisconsin Arch, Algonquin Arch, Lake Superior Syncline, and the broader Michigan sedimentary basin from the Precambrian basement to the Earth's surface. Data released here consists of stratigraphic horizon grids of major Phanerozoic sedimentary units that broadly define the geometry of the subsurface, a stratigraphic horizon grid of the uppermost Precambrian basement rocks, and line data that estimate the two-dimensional geometry of fault planes that intersect stratigraphic horizon grids. The presence of folds and unconformities are implied by the 3D geometry of the stratigraphic units, but these are not included as discrete features in this data release. The 3D geologic model was constructed from a wide variety of private and public surface and subsurface geologic data; none of these input data are part of this data release, but data sources are thoroughly documented such that a user could obtain these data from other sources if desired. The MichiganBasin3D geodatabase contains 41 subsurface stratigraphic horizons in raster format, representing the tops of modeled subsurface units, as well as a feature dataset titled "GeologicModel." This feature dataset includes a line feature class of 180 fault segments that delineate faults with probable post-Precambrian offset extending into the Phanerozoic sedimentary layers (PrecambrianLevelFaults_Throughgoing). It also features a line class of 170 fault segments representing throughgoing faults at the level of the top Trenton Group (TrentonLevelFaults), along with a polygon feature class delineating the study area (ModelBoundary). Nonspatial tables provide definitions of data sources (DataSources), terminology used in the dataset (Glossary), and descriptions of the modeled surfaces (DescriptionOfModelUnits). Additional file folders contain vector data in shapefile format, raster data in ASCII format, and tables in comma-separated values format. A comprehensive data dictionary outlines the entity and attribute information for all geospatial data and accompanying nonspatial tables (EntityAndAttributes). Accompanying this data release is a workbook “MichiganBasinInputSummaryTable.csv”, which tabulates the stratigraphic horizons modeled in each fault block, and the types and quantity of data inputs for each stratigraphic horizon. Key references associated with each data input are found in the "MichiganBasinInputReferences" so any user could replicate this work if they desired. An associated USGS report: “A three-dimensional geologic framework model of the Michigan Basin region, Illinois, Indiana, Michigan, Ohio, and Wisconsin, USA” documents the process of manipulating and interpreting surface and subsurface geologic data to create the model. It additionally contains critical information about model units, and uncertainty regarding their ability to predict true ground conditions.

BackgroundSeveral studies have highlighted alteration in the gut microbiome associated with the onset and progression of diseases. Recognizing the potential of gut microbiota as biomarkers, this systematic review seeks to synthesize current data on the intricate relationship between the host gut microbiome profiles and their usefulness for the development of diagnostic, prognostic and therapeutic approaches to control human schistosomiasis.MethodsA systematic literature review was carried out by searching for relevant studies published until date, that is May 2024, using Medline, Embase, Global Health, Web of Science, and Global Index Medicus databases. The keywords used to select articles were "Gut microbiome", "Gut Microbiota", "Schistosomiasis", "Bilharziasis ", and "Human". Extracted data were analysed qualitatively from the selected articles.ResultsOf the 885 articles retrieved and screened, only 13 (1.47%) met the inclusion criteria and were included in this review. Of the included studies, 6 (46.2%) explored alterations of gut microbiome in schistosome-infected patients, 4 (30.7%) in patients with liver pathologies, and 3 (23.1%) in patients treated with praziquantel. Bacteria from the genera Bacteroides, Faecalibacterium, Blautia and Megasphaera were associated with S. japonicum and S. haematobium infection in school-aged children, whereas infection with S. mansoni rather associated with Klebsiella and Enterobacter. The gut microbiota signature in patient with schistosomiasis-induced liver pathology was reported only for S. japonicum, and the genus Prevotella appeared as a non-invasive biomarker of S. japonicum-associated liver fibrosis. For S. mansoni-infected school-aged children, it further appeared that the treatment outcome following praziquantel administration associated with the abundance in the gut microbiome of bacteria from the classes Fusobacteriales, Rickettsiales and Neisseriales.ConclusionThe host gut microbiome appears to be a valuable, non-invasive, but still poorly utilized, source of host biomarkers potentially informative for better diagnosing, prognosing and treating schistosomiasis. Further studies are therefore needed to comprehensively define such gut microbial biomarkers of human schistosomiasis and catalyse the informed development of gut microbiome-based tools of schistosomiasis control.

Research on CO/sub 2/ injection continued. The following tasks are reported on: (1) Work completed on the improved viscosity correlation, mechanistic modeling of high pressure gas/foam flow, and the effect of free gas on the development of miscibility; and (2) Recent work in three major subareas of the Task II research. The first of these subareas is concerned with rock and reservoir heterogeneity. The emphasis is to consider the effects of non-uniformity on displacement efficiency--both in the reservoir and in laboratory experiments. This work consists both of numerical experiments, in which the effects of large-scale reservoir heterogeneities on production and on tracer diagnostics are calculated, and of the analysis of unique 3-D miscible displacement experiments for the examination of smaller-scale features. Research in the second subarea is concerned with the development of direct thickeners--chemicals that will be soluble in CO/sub 2/ or other dense gases and produce polymeric solutions of high viscosity. The work reported here has been concerned with the synthesis of several new types of Method I hydrocarbon polymers. Their principal use in the research is as starting materials for further processing, to synthesize Method II ionomers. In the third subarea, recent developments of interest for the reservoir use of CO/sub 2/-foam are presented. It has become apparent that field use of this mobility-control additive can be considered at this time. Not only has our research been able to delineate the mobility decreases that can be expected, and the ranges of surfactant concentration and CO/sub 2/ fraction to be used, but it has been possible to define an additional advantage from the use of foam. We report a new measurement that defines the range of permeability over which this effect has been observed in our experiments, and over which it can be expected to be useful in the field. 11 refs., 60 figs., 9 tabs.

Many authors have published varying and sometimes competing accounts of the harm of the digital divide. These accounts are worth synthesizing in advance towards articulating the politics of the digital divide resistance. This systematic review adopts the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to synthesize evidence on the digital divide. Although the digital divide is not always a moral wrong, this review has found that the harm of the digital divide commonly entails capability deprivation. There are three orders of the digital divide, and these orders can occur at the macro, meso, and micro levels. The antithesis of the digital divide is digital inclusion. However, digital inclusion can fail to be empowering or address the divide if they do not address the factors that moderate the digital divide, account for the context where the digital inclusion work will be undertaken, or other variables that may have implications for the digital inclusion strategies that are developed. Many scholars increasingly recognise the importance of digital inclusion for flourishing today. However, a failure to articulate its harm or what must be targeted to bridge the gap could have devastating implications for the digital inclusion work.