Systemic Immune-Inflammation Index (SII) Predicts Poor Survival in Pancreatic Cancer Patients Undergoing Resection

Background: The systemic immune-inflammation index based on peripheral neutrophil, lymphocyte, and platelet counts has shown a prognostic impact in several malignancies. The aim of this study was to determine the prognostic role of systemic immune-inflammation index in patients with pancreatic ductal adenocarcinoma undergoing resection. Methods: Consecutive patients who underwent surgical resection at the department of surgery at the Medical University of Vienna between 1995 and 2014 were included into this study. The systemic immune-inflammation index was calculated by the formula platelet*neutrophil/lymphocyte. Optimal cutoffs were determined using Youden's index. Uni-and multivariate analyses were calculated by the Cox proportional hazard regression model for overall survival. Results Three hundred twenty-one patients were included in this study. Clinical data was achieved from a prospective patient database. In univariate survival analysis, elevated systemic immune-inflammation index was found to be significantly associated with shortened patients' overall survival (p = 0.007). In multivariate survival analysis, systemic immune-inflammation index remained an independent prognostic factor for overall survival (p = 0.004). No statistical significance could be found for platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in multivariate analysis. Furthermore, area under the curve analysis showed a higher prognostic significance for systemic immune-inflammation index, compared to platelet to lymphocyte ratio and neutrophil to lymphocyte ratio. Conclusion: A high systemic immune-inflammation index is an independent, preoperative available prognostic factor in patients with resectable pancreatic ductal adenocarcinoma and is superior to platelet to lymphocyte ratio and neutrophil to lymphocyte ratio for predicting overall survival in pancreatic ductal adenocarcinoma patients

The Determination of Immunomodulation and Its Impact on Survival of Rectal Cancer Patients Depends on the Area Comprising a Tissue Microarray.

BACKGROUND: T cell density in colorectal cancer (CRC) has proven to be of high prognostic importance. Here, we evaluated the influence of a hyperfractionated preoperative short-term radiation protocol (25 Gy) on immune cell density in tumor samples of rectal cancer (RC) patients and on patient survival. In addition, we assessed spatial tumor heterogeneity by comparison of analogue T cell quantification on full tissue sections with digital T cell quantification on a virtually established tissue microarray (TMA). METHODS: A total of 75 RC patients (60 irradiated, 15 treatment-naïve) were defined for retrospective analysis. RC samples were processed for immunohistochemistry (CD3, CD8, PD-1, PD-L1). Analogue (score 0-3) as well as digital quantification (TMA: 2 cores vs. 6 cores, mean T cell count) of marker expression in 2 areas (central tumor, CT; invasive margin, IM) was performed. Survival was estimated on the basis of analogue as well as digital marker densities calculated from 2 cores (Immunoscore: CD3/CD8 ratio) and 6 cores per tumor area. RESULTS: Irradiated RC samples showed a significant decrease in CD3 and CD8 positive T cells, independent of quantification mode. T cell densities of 6 virtual cores approximated to T cell densities of full tissue sections, independent of individual core density or location. Survival analysis based on full tissue section quantification demonstrated that CD3 and CD8 positive T cells as well as PD-1 positive tumor infiltrating leucocytes (TILs) in the CT and the IM had a significant impact on disease-free survival (DFS) as well as overall survival (OS). In addition, CD3 and CD8 positive T cells as well as PD-1 positive TILs in the IM proved as independent prognostic factors for DFS and OS; in the CT, PD-1 positive TILs predicted DFS and CD3 and CD8 positive T cells as well as PD-1 positive TILs predicted OS. Survival analysis based on virtual TMA showed no impact on DFS or OS. CONCLUSION: Spatial tumor heterogeneity might result in inadequate quantification of immune marker expression; however, if using a TMA, 6 cores per tumor area and patient sample represent comparable amounts of T cell densities to those quantified on full tissue sections. Consistently, the tissue area used for immune marker quantification represents a crucial factor for the evaluation of prognostic and predictive biomarker potential

Framing and Context of the Report

The Intergovernmental Panel on Climate Change (IPCC) is the leading international body for assessing the science related to climate change. It provides policymakers with regular assessments of the scientific basis of human-induced climate change, its impacts and future risks, and options for adaptation and mitigation. This IPCC Special Report on the Ocean and Cryosphere in a Changing Climate is the most comprehensive and up-to-date assessment of the observed and projected changes to the ocean and cryosphere and their associated impacts and risks, with a focus on resilience, risk management response options, and adaptation measures, considering both their potential and limitations. It brings together knowledge on physical and biogeochemical changes, the interplay with ecosystem changes, and the implications for human communities. It serves policymakers, decision makers, stakeholders, and all interested parties with unbiased, up-to-date, policy-relevant information. Chapter 1: This special report assesses new knowledge since the IPCC 5th Assessment Report (AR5) and the Special Report on Global Warming of 1.5ºC (SR15) on how the ocean and cryosphere have and are expected to change with ongoing global warming, the risks and opportunities these changes bring to ecosystems and people, and mitigation, adaptation and governance options for reducing future risks. Chapter 1 provides context on the importance of the ocean and cryosphere, and the framework for the assessments in subsequent chapters of the report. All people on Earth depend directly or indirectly on the ocean and cryosphere. The fundamental roles of the ocean and cryosphere in the Earth system include the uptake and redistribution of anthropogenic carbon dioxide and heat by the ocean, as well as their crucial involvement of in the hydrological cycle. The cryosphere also amplifies climate changes through snow, ice and permafrost feedbacks. Services provided to people by the ocean and/or cryosphere include food and freshwater, renewable energy, health and wellbeing, cultural values, trade and transport. {1.1, 1.2, 1.5} Sustainable development is at risk from emerging and intensifying ocean and cryosphere changes. Ocean and cryosphere changes interact with each of the United Nations Sustainable Development Goals (SDGs). Progress on climate action (SDG 13) would reduce risks to aspects of sustainable development that are fundamentally linked to the ocean and cryosphere and the services they provide (high confidence1 ). Progress on achieving the SDGs can contribute to reducing the exposure or vulnerabilities of people and communities to the risks of ocean and cryosphere change (medium confidence). {1.1} Communities living in close connection with polar, mountain, and coastal environments are particularly exposed to the current and future hazards of ocean and cryosphere change. Coasts are home to approximately 28% of the global population, including around 11% living on land less than 10 m above sea level. Almost 10% of the global population lives in the Arctic or high mountain regions. People in these regions face the greatest exposure to ocean and cryosphere change, and poor and marginalised people here are particularly vulnerable to climate-related hazards and risks (very high confidence). The adaptive capacity of people, communities and nations is shaped by social, political, cultural, economic, technological, institutional, geographical and demographic factors. {1.1, 1.5, 1.6, Cross-Chapter Box 2 in Chapter 1} Ocean and cryosphere changes are pervasive and observedfrom high mountains, to the polar regions, to coasts, and intothe deep ocean. AR5 assessed that the ocean is warming (0 to700 m: virtually certain2; 700 to 2,000 m: likely), sea level is rising(high confidence), and ocean acidity is increasing (high confidence).Most glaciers are shrinking (high confidence), the Greenland andAntarctic ice sheets are losing mass (high confidence), sea ice extent inthe Arctic is decreasing (very high confidence), Northern Hemispheresnow cover is decreasing (very high confidence), and permafrosttemperatures are increasing (high confidence). Improvementssince AR5 in observation systems, techniques, reconstructions andmodel developments, have advanced scientific characterisationand understanding of ocean and cryosphere change, including inpreviously identified areas of concern such as ice sheets and AtlanticMeridional Overturning Circulation (AMOC). {1.1, 1.4, 1.8.1}Evidence and understanding of the human causes of climatewarming, and of associated ocean and cryosphere changes,has increased over the past 30 years of IPCC assessments (veryhigh confidence). Human activities are estimated to have causedapproximately 1.0ºC of global warming above pre-industrial levels(SR15). Areas of concern in earlier IPCC reports, such as the expectedacceleration of sea level rise, are now observed (high confidence).Evidence for expected slow-down of AMOC is emerging in sustainedobservations and from long-term palaeoclimate reconstructions(medium confidence), and may be related with anthropogenic forcingaccording to model simulations, although this remains to be properlyattributed. Significant sea level rise contributions from Antarctic icesheet mass loss (very high confidence), which earlier reports did notexpect to manifest this century, are already being observed. {1.1, 1.4}Ocean and cryosphere changes and risks by the end-of-century(2081?2100) will be larger under high greenhouse gas emissionscenarios, compared with low emission scenarios (very highconfidence). Projections and assessments of future climate, oceanand cryosphere changes in the Special Report on the Ocean andCryosphere in a Changing Climate (SROCC) are commonly basedon coordinated climate model experiments from the Coupled ModelIntercomparison Project Phase 5 (CMIP5) forced with RepresentativeConcentration Pathways (RCPs) of future radiative forcing. Currentemissions continue to grow at a rate consistent with a high emissionfuture without effective climate change mitigation policies (referredto as RCP8.5). The SROCC assessment contrasts this high greenhousegas emission future with a low greenhouse gas emission, highmitigation future (referred to as RCP2.6) that gives a two in threechance of limiting warming by the end of the century to less than 2oC above pre-industrial. {Cross-Chapter Box 1 in Chapter 1} Characteristics of ocean and cryosphere change include thresholds of abrupt change, long-term changes that cannot be avoided, and irreversibility (high confidence). Ocean warming, acidification and deoxygenation, ice sheet and glacier mass loss, and permafrost degradation are expected to be irreversible on time scales relevant to human societies and ecosystems. Long response times of decades to millennia mean that the ocean and cryosphere are committed to long-term change even after atmospheric greenhouse gas concentrations and radiative forcing stabilise (high confidence). Ice-melt or the thawing of permafrost involve thresholds (state changes) that allow for abrupt, nonlinear responses to ongoing climate warming (high confidence). These characteristics of ocean and cryosphere change pose risks and challenges to adaptation. {1.1, Box 1.1, 1.3} Societies will be exposed, and challenged to adapt, to changes in the ocean and cryosphere even if current and future efforts to reduce greenhouse gas emissions keep global warming well below 2ºC (very high confidence). Ocean and cryosphere-related mitigation and adaptation measures include options that address the causes of climate change, support biological and ecological adaptation, or enhance societal adaptation. Most ocean-based local mitigation and adaptation measures have limited effectiveness to mitigate climate change and reduce its consequences at the global scale, but are useful to implement because they address local risks, often have co-benefits such as biodiversity conservation, and have few adverse side effects. Effective mitigation at a global scale will reduce the need and cost of adaptation, and reduce the risks of surpassing limits to adaptation. Ocean-based carbon dioxide removal at the global scale has potentially large negative ecosystem consequences. {1.6.1, 1.6.2, Cross-Chapter Box 2 in Chapter 1} The scale and cross-boundary dimensions of changes in the ocean and cryosphere challenge the ability of communities, cultures and nations to respond effectively within existing governance frameworks (high confidence). Profound economic and institutional transformations are needed if climate-resilient development is to be achieved (high confidence). Changes in the ocean and cryosphere, the ecosystem services that they provide, the drivers of those changes, and the risks to marine, coastal, polar and mountain ecosystems, occur on spatial and temporal scales that may not align within existing governance structures and practices (medium confidence). This report highlights the requirements for transformative governance, international and transboundary cooperation, and greater empowerment of local communities in the governance of the ocean, coasts, and cryosphere in a changing climate. {1.5, 1.7, Cross-Chapter Box 2 in Chapter 1, Cross-Chapter Box 3 in Chapter 1} Robust assessments of ocean and cryosphere change, and the development of context-specific governance and response options, depend on utilising and strengthening all available knowledge systems (high confidence). Scientific knowledge from observations, models and syntheses provides global to local scale understandings of climate change (very high confidence). Indigenous knowledge (IK) and local knowledge (LK) provide context-specific and socio-culturally relevant understandings for effective responses and policies (medium confidence). Education and climate literacy enable climate action and adaptation (high confidence). {1.8, Cross-Chapter Box 4 in Chapter 1} Long-term sustained observations and continued modelling are critical for detecting, understanding and predicting ocean and cryosphere change, providing the knowledge to inform risk assessments and adaptation planning (high confidence). Knowledge gaps exist in scientific knowledge for important regions, parameters and processes of ocean and cryosphere change, including for physically plausible, high impact changes like high end sea level rise scenarios that would be costly if realised without effective adaptation planning and even then may exceed limits to adaptation. Means such as expert judgement, scenario building, and invoking multiple lines of evidence enable comprehensive risk assessments even in cases of uncertain future ocean and cryosphere changes.Fil: Abram, Nerilie. Australian National University; AustraliaFil: Gattuso, Jean Pierre. Centre National de la Recherche Scientifique; FranciaFil: Prakash, Anjal. Teri School Of Advanced Studies; IndiaFil: Cheng, Lijing. Chinese Academy Of Science; ChinaFil: Chidichimo, María Paz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; ArgentinaFil: Crate, Susan. George Mason University; Estados UnidosFil: Enomoto, H.. National Polar Agency; JapónFil: Garschagen, M.. Technische Universitat München; AlemaniaFil: Gruber, N.. Swiss Federal Institute of Technology Zurich; SuizaFil: Harper, S.. University Of Alberta. Faculty Of Agricultural, Life And Environmental Sciences. Departament Of Agricultural, Food And Nutritional Science.; CanadáFil: Holland, Elisabeth. University Of South Pacific; FiyiFil: Kudela, Raphael Martin. University of California at San Diego. Scripps Institution of Oceanography; Estados UnidosFil: Rice, Jake. University of Toronto; CanadáFil: Steffen, Konrad. Swiss Federal Institute for Forest, Snow and Landscape Research; SuizaFil: Von Schuckmann, Karina. Mercator Ocean International; Franci

GenSeed-HMM: A tool for progressive assembly using profile HMMs as seeds and its application in Alpavirinae viral discovery from metagenomic data

This work reports the development of GenSeed-HMM, a program that implements seed-driven progressive assembly, an approach to reconstruct specific sequences from unassembled data, starting from short nucleotide or protein seed sequences or profile Hidden Markov Models (HMM). The program can use any one of a number of sequence assemblers. Assembly is performed in multiple steps and relatively few reads are used in each cycle, consequently the program demands low computational resources. As a proof-of-concept and to demonstrate the power of HMM-driven progressive assemblies, GenSeed-HMM was applied to metagenomic datasets in the search for diverse ssDNA bacteriophages from the recently described Alpavirinae subfamily. Profile HMMs were built using Alpavirinae-specific regions from multiple sequence alignments using either the viral protein 1 (VP1) (major capsid protein) or VP4 (genome replication initiation protein). These profile HMMs were used by GenSeed-HMM (running Newbler assembler) as seeds to reconstruct viral genomes from sequencing datasets of human fecal samples. All contigs obtained were annotated and taxonomically classified using similarity searches and phylogenetic analyses. The most specific profile HMM seed enabled the reconstruction of 45 partial or complete Alpavirinae genomic sequences. A comparison with conventional (global) assembly of the same original dataset, using Newbler in a standalone execution, revealed that GenSeed-HMM outperformed global genomic assembly in several metrics employed. This approach is capable of detecting organisms that have not been used in the construction of the profile HMM, which opens up the possibility of diagnosing novel viruses, without previous specific information, constituting a de novo diagnosis. Additional applications include, but are not limited to, the specific assembly of extrachromosomal elements such as plastid and mitochondrial genomes from metagenomic data. Profile HMM seeds can also be used to reconstruct specific protein coding genes for gene diversity studies, and to determine all possible gene variants present in a metagenomic sample. Such surveys could be useful to detect the emergence of drug-resistance variants in sensitive environments such as hospitals and animal production facilities, where antibiotics are regularly used. Finally, GenSeed-HMM can be used as an adjunct for gap closure on assembly finishing projects, by using multiple contig ends as anchored seeds

Impact of physical activity on activity of daily living in moderate to severe dementia: a critical review

The objectives of this study were to describe the different modalities of physical activity programs designed for moderate to severe dementia and to identify their impact on functional independence in activities of daily living (ADL). A critical review of randomized controlled trials related to the impact of physical activity programs in moderately to severely demented persons on ADL performance and meta-analysis of the identified studies were performed. Among the 303 identified articles, five responded to the selection criteria. Four out of the five studies demonstrated limited methodological quality. In one high-quality study, physical activity programs significantly delayed deterioration of ADL performance. The program components and ADL assessment tools vary widely across studies. Although the proposed treatments have not proven their efficiency in improving the ADL status of the patients, they were able to limit the decline in ADL functioning. Future research is warranted in order to identify clinically relevant modalities for physical activity programs for people with moderate to severe dementia

Evaluation of LHP® (1% hydrogen peroxide) cream versus petrolatum and untreated controls in open wounds in healthy horses: a randomized, blinded control study

<p>Abstract</p> <p>Background</p> <p>Treatment and protection of wounds in horses can be challenging; protecting bandages may be difficult to apply on the proximal extremities and the body. Unprotected wounds carry an increased risk of bacterial contamination and subsequent infection which can lead to delayed wound healing. Topical treatment with antimicrobials is one possibility to prevent bacterial colonization or infection, but the frequent use of antimicrobials ultimately leads to development of bacterial resistance which is an increasing concern in both human and veterinary medicine.</p> <p>Methods</p> <p>Standardized wounds were created in 10 Standardbred mares. Three wounds were made in each horse. Two wounds were randomly treated with LHP^®or petrolatum and the third wound served as untreated control. All wounds were assessed daily until complete epithelization. Protocol data were recorded on day 2, 6, 11, 16, 21 and 28. Data included clinical scores for inflammation and healing, photoplanimetry for calculating wound areas and swab cytology to assess bacterial colonization and inflammation. Bacterial cultures were obtained on day 2, 6 and 16.</p> <p>Results</p> <p>Mean time to complete healing for LHP^®treated wounds was 32 days (95%CI = 26.9-37.7). Mean time to complete healing for petrolatum and untreated control wounds were 41.6 days (95%CI = 36.2-47.0) and 44.0 days (95%CI = 38.6-49.4) respectively. Wound healing occurred significantly faster in LHP^®wounds compared to both petrolatum (p = 0.0004) and untreated controls (p < 0.0001). There was no significant difference in time for healing between petrolatum and untreated controls. Total scores for bacteria and neutrophils were significantly (p < 0.0001) lower for LHP^®treated wounds compared to petrolatum from day 16 and onwards. <it>Staphylococcus aureus </it>and <it>Streptococcus zooepidemicus </it>were only found in cultures from petrolatum treated wounds and untreated controls.</p> <p>Conclusions</p> <p>Treatment with LHP^®reduced bacterial colonization and was associated with earlier complete wound healing. LHP^®cream appears to be safe and effective for topical wound treatment or wound protection.</p

Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A

Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10−9, odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizure

16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10−6, odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10−4). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical R

Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.

BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures

Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice