Defining Transabdominal Intestinal Ultrasound Treatment Response and Remission in Inflammatory Bowel Disease: Systematic Review and Expert Consensus Statement

Background and Aims No consensus exists on defining intestinal ultrasound response, transmural healing, or transmural remission in inflammatory bowel disease, nor clear guidance for optimal timing of assessment during treatment. This systematic review and expert consensus study aimed to define such recommendations, along with key parameters included in response reporting. Methods Electronic databases were searched from inception to July 26, 2021, using pre-defined terms. Studies were eligible if at least two intestinal ultrasound [IUS] assessments at different time points during treatment were reported, along with an appropriate reference standard. The QUADAS-2 tool was used to examine study-level risk of bias. An international panel of experts [n = 18] rated an initial 196 statements [RAND/UCLA process, scale 1–9]. Two videoconferences were conducted, resulting in additional ratings of 149 and 13 statements, respectively. Results Out of 5826 records, 31 full-text articles, 16 abstracts, and one research letter were included; 83% [40/48] of included studies showed a low concern of applicability, and 96% [46/48] had a high risk of bias. A consensus was reached on 41 statements, with clear definitions of IUS treatment response, transmural healing, transmural remission, timing of assessment, and general considerations when using intestinal ultrasound in inflammatory bowel disease. Conclusions Response criteria and time points of response assessment varied between studies, complicating direct comparison of parameter changes and their relation to treatment outcomes. To ensure a unified approach in routine care and clinical trials, we provide recommendations and definitions for key parameters for intestinal ultrasound response, to incorporate into future prospective studies.publishedVersio

Climate-smart agriculture global research agenda: Scientific basis for action

Background: Climate-smart agriculture (CSA) addresses the challenge of meeting the growing demand for food, fibre and fuel, despite the changing climate and fewer opportunities for agricultural expansion on additional lands. CSA focuses on contributing to economic development, poverty reduction and food security; maintaining and enhancing the productivity and resilience of natural and agricultural ecosystem functions, thus building natural capital; and reducing trade-offs involved in meeting these goals. Current gaps in knowledge, work within CSA, and agendas for interdisciplinary research and science-based actions identified at the 2013 Global Science Conference on Climate-Smart Agriculture (Davis, CA, USA) are described here within three themes: (1) farm and food systems, (2) landscape and regional issues and (3) institutional and policy aspects. The first two themes comprise crop physiology and genetics, mitigation and adaptation for livestock and agriculture, barriers to adoption of CSA practices, climate risk management and energy and biofuels (theme 1); and modelling adaptation and uncertainty, achieving multifunctionality, food and fishery systems, forest biodiversity and ecosystem services, rural migration from climate change and metrics (theme 2). Theme 3 comprises designing research that bridges disciplines, integrating stakeholder input to directly link science, action and governance. Outcomes: In addition to interdisciplinary research among these themes, imperatives include developing (1) models that include adaptation and transformation at either the farm or landscape level; (2) capacity approaches to examine multifunctional solutions for agronomic, ecological and socioeconomic challenges; (3) scenarios that are validated by direct evidence and metrics to support behaviours that foster resilience and natural capital; (4) reductions in the risk that can present formidable barriers for farmers during adoption of new technology and practices; and (5) an understanding of how climate affects the rural labour force, land tenure and cultural integrity, and thus the stability of food production. Effective work in CSA will involve stakeholders, address governance issues, examine uncertainties, incorporate social benefits with technological change, and establish climate finance within a green development framework. Here, the socioecological approach is intended to reduce development controversies associated with CSA and to identify technologies, policies and approaches leading to sustainable food production and consumption patterns in a changing climate

Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease

Background--Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI-1 on CHD risk. Methods and Results--To evaluate the association between PAI-1 and CHD, we applied a 3-step strategy. First, we investigated the observational association between PAI-1 and CHD incidence using a systematic review based on a literature search for PAI-1 and CHD studies. Second, we explored the causal association between PAI-1 and CHD using a Mendelian randomization approach using summary statistics from large genome-wide association studies. Finally, we explored the causal effect of PAI-1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta-analysis, the highest quantile of blood PAI-1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age- and sex-adjusted model. The effect size was reduced in studies using a multivariable-adjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI-1 level on CHD risk (odds ratio=1.22 per unit increase of log-transformed PAI-1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI-1 on elevating blood glucose and high-density lipoprotein cholesterol. Conclusions--Our study indicates a causal effect of elevated PAI-1 level on CHD risk, which may be mediated by glucose dysfunction

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Characterization of two related <i>Erwinia</i> myoviruses that are distant relatives of the PhiKZ-like Jumbo phages

<div><p>Bacteriophages are a major force in the evolution of bacteria due to their sheer abundance as well as their ability to infect and kill their hosts and to transfer genetic material. Bacteriophages that infect the <i>Enterobacteriaceae</i> family are of particular interest because this bacterial family contains dangerous animal and plant pathogens. Herein we report the isolation and characterization of two jumbo myovirus <i>Erwinia</i> phages, RisingSun and Joad, collected from apple trees. These two genomes are nearly identical with Joad harboring two additional putative gene products. Despite mass spectrometry data that support the putative annotation, 43% of their gene products have no significant BLASTP hit. These phages are also more closely related to <i>Pseudomonas</i> and <i>Vibrio</i> phages than to published <i>Enterobacteriaceae</i> phages. Of the 140 gene products with a BLASTP hit, 81% and 63% of the closest hits correspond to gene products from <i>Pseudomonas</i> and <i>Vibrio</i> phages, respectively. This relatedness may reflect their ecological niche, rather than the evolutionary history of their host. Despite the presence of over 800 <i>Enterobacteriaceae</i> phages on NCBI, the uniqueness of these two phages highlights the diversity of <i>Enterobacteriaceae</i> phages still to be discovered.</p></div

RisingSun and Joad are unique phages whose proteomes contain novel proteins.

<p><b>A)</b> Distribution of proteins in RisingSun based upon BLASTP hits that are novel, have no known function, and putative function. <b>B)</b> Putative gene ontology in RisingSun. <b>C)</b> Percentage of RisingSun gene products with BLASTP hits to proteins in other phages/organisms.</p

Host range of phage Joad suggests narrow specificity towards <i>Erwinia amylovora</i> and the closely related <i>Pantoea vegans</i> bacteria.

<p>The bacteria tested is provided along with the plaque forming units from three independent assays.</p

Locations of one motif discovered in five different structural genes.

<p><b>A)</b> Exact location of motif sites, p and q-values, sequence of motifs (conserved nucleotides shown in red), and putative gene function. Logogram shows motif sequence and larger letters represent frequent conservation. <b>B)</b> Arrows show approximate location of motif site. Genes were analyzed from the RisingSun annotation and thus locations are shown in the RisingSun phamerator map.</p

Joad and RisingSun are a unique cluster of phages when compared to others using whole genomes, MCP amino acid sequences, and terminase amino acid sequences.

<p><b>2A)</b> Similarity of seven phage genomes according to Average Nucleotide Identity (ANI). <b>2B)</b> Percent identity of major capsid proteins (MCP) amongst seven phages. <b>2C)</b> Percent identity of terminase proteins amongst seven phages. Percent identity was determined by BLASTP analysis.</p

General characteristics of <i>Erwinia amylovora</i> phages Joad and RisingSun.

<p>General characteristics of <i>Erwinia amylovora</i> phages Joad and RisingSun.</p