Food systems are essential for the achievement of the United Nations Sustainable Development Goals in China. Here, using an integrated assessment modelling framework that considers country-specific pathways and covers 18 indicators, we find that most social and environmental targets for the Chinese food system under current trends are not aligned with the United Nations Agenda 2030. We further quantify the impacts of multiple measures, revealing potential trade-offs in pursuing strategies aimed at public health, environmental sustainability and livelihood improvement in isolation.
View Article and Find Full Text PDFCoronaviruses express their structural and accessory genes via a set of subgenomic RNAs, whose synthesis is directed by transcription regulatory sequences (TRSs) in the 5' genomic leader and upstream of each body open reading frame. In SARS-CoV-2, the TRS has the consensus AAACGAAC; upon searching for emergence of this motif in the global SARS-CoV-2 sequences, we find that it evolves frequently, especially in the 3' end of the genome. We show well-supported examples upstream of the Spike gene-within the nsp16 coding region of ORF1b-which is expressed during human infection, and upstream of the canonical Envelope gene TRS, both of which have evolved convergently in multiple lineages.
View Article and Find Full Text PDFFewer than 50% of metastatic deficient mismatch repair (dMMR) colorectal cancer (CRC) patients respond to immune checkpoint inhibition (ICI). Identifying and expanding this patient population remains a pressing clinical need. Here, we report that an interferon-high immunophenotype locally enriched in cytotoxic lymphocytes and antigen-presenting macrophages is required for response.
View Article and Find Full Text PDFBackground: Access to liver transplantation (LT) is affected by geographic disparities. Higher waitlist mortality is observed in patients residing farther from LT centres, but the impact of distance on post-LT outcomes is unclear.
Aims: To evaluate whether the distance LT recipients reside from their LT centre affects graft and patient outcomes.
Background: Community access to evidence-based information is critical, especially during a pandemic, as it can impact knowledge and adoption of health behaviors that affect health disparities. The field of dissemination and implementation (D&I) science is ideally positioned to address this need through its focus on reducing the research-to-practice gap through improved distribution of information. The purpose of this paper is to describe the creation of a weekly webinar series about COVID-19 directed toward community members, and the extent to which webinars were found useful and increased awareness of evidence-based information and services.
View Article and Find Full Text PDFBackground: HCC develops in the context of chronic inflammation; however, the opposing roles the immune system plays in both the development and control of tumors are not fully understood. Mapping immune cell interactions across the distinct tissue regions could provide greater insight into the role individual immune populations have within tumors.
Methods: A 39-parameter imaging mass cytometry panel was optimized with markers targeting immune cells, stromal cells, endothelial cells, hepatocytes, and tumor cells.
Powassan virus (POWV) is a pathogenic tick-borne flavivirus that causes fatal neuroinvasive disease in humans. There are currently no approved therapies or vaccines for POWV infection. Here, we develop a POW virus-like-particle (POW-VLP) based vaccine adjuvanted with the novel synthetic Toll-like receptor 7/8 agonist INI-4001.
View Article and Find Full Text PDFDuring meiosis, programmed DNA double-strand breaks (DSBs) are formed by the topoisomerase-like enzyme, Spo11, activating the DNA damage response (DDR) kinase Mec1ATR via the checkpoint clamp loader, Rad24RAD17. At single loci, loss of Mec1 and Rad24 activity alters DSB formation and recombination outcome, but their genome-wide roles have not been examined in detail. Here, we utilise two strategies-deletion of the mismatch repair protein, Msh2, and control of meiotic prophase length via regulation of the Ndt80 transcription factor-to help characterise the roles Mec1 and Rad24 play in meiotic recombination by enabling genome-wide mapping of meiotic progeny.
View Article and Find Full Text PDF•Intraosseous hibernomas are rare benign soft tissue tumors most often diagnosed incidentally.•Intraosseous hibernoma imaging characteristics can mimic bone metastases, including sclerosis, PET-avidity, and heterogenous enhancement.•Bone metastases seconadary to primary gynecologic cancers are rare, but present in 1 - 16% of cases.
View Article and Find Full Text PDFImportance: Leaders of healthcare organizations play a key role in developing, prioritizing, and implementing plans to adopt new evidence-based practices. This study examined whether a letter with peer comparison data and social norms messaging impacted healthcare leaders' decision to access a website with resources to support evidence-based practice adoption.
Methods: Pragmatic, parallel-group, randomized controlled trial completed from December 2019 -June 2020.
•Ruptured dermoids can present with chronic peritonitis which can mimic malignant disease.•Surgical washout is mainstay of treatment for chronic peritonitis with ruptured dermoids.•Corticosteroids can be considered as second line for chronic peritonitis when surgical washout alone is insufficient.
View Article and Find Full Text PDFBackground: Suprascapular neurodynamic tests are used to clinically test for suprascapular nerve mechanosensitivity. Various tests described in the literature are proposed to induce suprascapular nerve mechanical strain but their potential effects on nerve strain have not been established.
Methods: This observational cadaveric study used biomechanical measurements to evaluate and compare the strain undergone by the suprascapular nerve during five different neurodynamic positions: (1) Cervical contralateral rotation and scapular retraction; (2) Cervical contralateral sidebending + shoulder girdle depression; (3) Shoulder girdle depression, retraction, posterior tilt and downward rotation; (4) Position 3 + contralateral cervical sidebending; and (5) Scapular protraction + Cervical contralateral sidebending (protraction sidebending test).
Recent advances in machine perfusion have revolutionised the field of transplantation by prolonging preservation, permitting evaluation of viability prior to implant and rescue of discarded organs. Long-term perfusion for days-to-weeks provides time to modify these organs prior to transplantation. By using long-term normothermic machine perfusion to facilitate liver splitting and subsequent perfusion of both partial organs, possibilities even outside the clinical arena become possible.
View Article and Find Full Text PDFLearning to read is the most important outcome of primary education. However, despite substantial improvements in primary school enrolment, most students in low- and middle-income countries (LMICs) fail to learn to read by age 10. We report reading assessment data from over half a million pupils from 48 LMICs tested primarily in a language of instruction and show that these pupils are failing to acquire the most basic skills that contribute to reading comprehension.
View Article and Find Full Text PDFThere is an ongoing debate in the United Kingdom and in other countries about whether twice-yearly changes into and out of Daylight Saving Time should be abolished. Opinions are divided about whether any abolition of Daylight Saving Time should result in permanent Standard Time, or year-long Daylight Saving Time. The British Sleep Society concludes from the available scientific evidence that circadian and sleep health are affected negatively by enforced changes of clock time (especially in a forward direction) and positively by the availability of natural daylight during the morning.
View Article and Find Full Text PDFBackground: Hypothermic Oxygenated machine PErfusion (HOPE) can reduce ischemic reperfusion injury and improve outcomes for liver transplant recipients. However, the effect of HOPE on high-risk extended criteria donor (ECD) and donation after circulatory death determination (DCDD) grafts is incomplete, despite the expectation that this cohort benefit maximally from HOPE. Accordingly, this paper aims to characterize the effect of HOPE on ECD and DCDD grafts.
View Article and Find Full Text PDFPurpose: This study aims to understand global and segmental spinal ROM in surgical and nonsurgical AIS patients.
Methods: This systematic review examined segmental vertebral ROM in AIS patients using PubMed, SPORTDiscus, MEDLINE, and Web of Science until October 8th, 2023. Inclusion criteria were articles on segmental motion in AIS patients, both operative and non-operative, under 18 years old.
A series of 3-aryl(()-3-fluoropyrrolidin-1-yl)butanoic acids were developed as potent orally bioavailable αβ integrin inhibitors. Starting from a zwitterionic peptidomimetic series optimized for inhaled administration, the balancing of potency and passive permeability to achieve suitable oral agents through modification and exploration of aryl substituents and p of the central cyclic amine is described. ()-4-(()-3-Fluoro-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)-3-(3-(2-methoxyethoxy)phenyl)butanoic acid was found to have highly desirable oral pharmacokinetic profiles in rat, dog, and minipig, with low to moderate clearance (26%, 7%, and 18% liver blood flow, respectively), moderate volumes of distribution (3.
View Article and Find Full Text PDFThe transcriptional coactivators EP300 and CREBBP are critical regulators of gene expression that share high sequence identity but exhibit nonredundant functions in basal and pathological contexts. Here, we report the development of a bifunctional small molecule, MC-1, capable of selectively degrading EP300 over CREBBP. Using a potent aminopyridine-based inhibitor of the EP300/CREBBP catalytic domain in combination with a VHL ligand, we demonstrate that MC-1 preferentially degrades EP300 in a proteasome-dependent manner.
View Article and Find Full Text PDFIn both plant breeding and crop management, interpretability plays a crucial role in instilling trust in AI-driven approaches and enabling the provision of actionable insights. The primary objective of this research is to explore and evaluate the potential contributions of deep learning network architectures that employ stacked LSTM for end-of-season maize grain yield prediction. A secondary aim is to expand the capabilities of these networks by adapting them to better accommodate and leverage the multi-modality properties of remote sensing data.
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