bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining novel causal SNPs and linked phenotypes at melanoma-associated loci
Authors: Castaneda-Garcia Carolina , Iyer Vivek , Nsengimana Jérémie , Trower Adam , Droop Alastair , Brown Kevin M , Choi Jiyeon , Zhang Tongwu , Harland Mark , Newton-Bishop Julia A , Bishop D Timothy , Adams David J , Iles Mark M , Robles-Espinoza Carla Daniela 
Published: March 2022

AbstractA number of genomic regions have been associated with melanoma risk through genome-wide association studies; however, the causal variants underlying the majority of these associations remain unknown. Here, we sequenced either the full locus or the functional regions including exons of 19 melanoma-associated loci in 1959 British melanoma cases and 737 controls. Variant filtering followed by Fisher’s exact test analyses identified 66 variants associated with melanoma risk. Sequential conditional logistic regression identified the distinct haplotypes on which variants reside, and massively parallel reporter assays provided biological insights into how these variants influence gene function. We performed further analyses to link variants to melanoma risk phenotypes and assessed their association with melanoma-specific survival. Our analyses replicate previously known associations in the melanocortin 1 receptor (MC1R) and tyrosinase (TYR) loci, while identifying novel potentially causal variants at the MTAP/CDKN2A and CASP8 loci. These results improve our understanding of the architecture of melanoma risk and outcome.
Genome-wide association study and genomic prediction of white rust resistance in USDA GRIN spinach germplasm
Authors: Shi Ainong , Bhattarai Gehendra , Xiong Haizheng , Avila Carlos A , Feng Chunda , Liu Bo , Joshi Vijay , Stein Larry , Mou Beiquan , du Toit Lindsey J , Correll James C 
Published: March 2022

Abstract
White rust, caused by Albugo occidentalis, is one of the major yield-limiting diseases of spinach (Spinacia oleracea) in some major commercial production areas, particularly in southern Texas in the United States. The use of host resistance is the most economical and environment-friendly approach to managing white rust in spinach production. The objectives of this study were to conduct a genome-wide associating study (GWAS), to identify single nucleotide polymorphism (SNP) markers associated with white rust resistance in spinach, and to perform genomic prediction (GP) to estimate the prediction accuracy (PA). A GWAS panel of 346 USDA (US Dept. of Agriculture) germplasm accessions was phenotyped for white rust resistance under field conditions and GWAS was performed using 13 235 whole-genome resequencing (WGR) generated SNPs. Nine SNPs, chr2_53 049 132, chr3_58 479 501, chr3_95 114 909, chr4_9 176 069, chr4_17 807 168, chr4_83 938 338, chr4_87 601 768, chr6_1 877 096, and chr6_31 287 118, located on chromosomes 2, 3, 4, and 6 were associated with white rust resistance in this GWAS panel. Four scenarios were tested for PA using Pearson’s correlation coefficient (r) between the genomic estimation breeding value (GEBV) and the observed values: (1) different ratios between the training set and testing set (fold), (2) different GP models, (3) different SNP numbers in three different SNP sets, and (4) the use of GWAS-derived significant SNP markers. The results indicated that a 2- to 10-fold difference in the various GP models had similar, although not identical, averaged r values in each SNP set; using GWAS-derived significant SNP markers would increase PA with a high r-value up to 0.84. The SNP markers and the high PA can provide valuable information for breeders to improve spinach by marker-assisted selection (MAS) and genomic selection (GS).
Heterografted chrysanthemums enhance salt stress tolerance by integrating reactive oxygen species, soluble sugar, and proline
Authors: Li Wenjie , Meng Rui , Liu Ye , Chen Sumei , Jiang Jiafu , Wang Likai , Zhao Shuang , Wang Zhenxing , Fang Weimin , Chen Fadi , Guan Zhiyong 
Published: March 2022

Abstract
Chrysanthemum, one of the most important commercial ornamental crops, is susceptible to salinity, which limits its cultivation and application in coastal and inland saline areas. Grafting is widely used to improve the salt tolerance of horticultural crops, but the mechanisms of grafted chrysanthemum responses to salt stress remain unclear. In this study, we showed that heterografted chrysanthemums with Artemisia annua as rootstock exhibited increased salt tolerance compared with self-grafted and self-rooted chrysanthemums. Under high salt stress, the roots of heterografted chrysanthemums enrich Na+, resulting in a reduction of Na+ toxicity in the scion, with only a small amount of Na+ being transported to the leaves. On the other hand, the roots of heterografted chrysanthemums alleviated high Na+ stress via enhanced catalase enzyme activity, downregulation of the expression of reactive oxygen species (ROS) accumulation-related genes, massive accumulation of soluble sugars and proline, and upregulation of the expression of heat shock protein-related genes to enhance salt tolerance. In addition, the leaves of heterografted chrysanthemums respond to low Na+ stress by increasing peroxidase enzyme activity and soluble sugar and proline contents, to maintain a healthy state. However, self-grafted and self-rooted plants could not integrate ROS, soluble sugars, and proline in response to salt stress, and thus exhibited a salt-sensitive phenotype. Our research reveals the mechanisms underlying the increased salt tolerance of heterografted chrysanthemums and makes it possible to have large-scale cultivation of chrysanthemums in saline areas.
Patient Involvement in RSV Research: Towards Patients Setting the Research Agenda
Authors: Derksen-Lazet Nicole D , Parmentier Corline E J , Wildenbeest Joanne G , Bont Louis J ,   RESCEU Investigators, Derksen-Lazet Nicole , Parmentier Corline , Bont Louis , Wildenbeest Joanne , Nair Harish , Campbell Harry , Beutels Philippe , Pollard Andrew , Openshaw Peter , Martinon-Torres Federico , Heikkinen Terho , Meijer Adam , Fischer Thea , van den Berge Maarten , Giaquinto Carlo , Abram Michael , Kena Swanson Tin Tin Myint , Rizkalla Bishoy , Vernhes Charlotte , Gallichan Scott , Aerssens Jeroen , Kumar Veena , Molero Eva 
Published: March 2022

Abstract
Respiratory syncytial virus (RSV) causes a substantial disease burden among children, elderly and immunocompromised adults. Recognition of patient involvement in research is gradually increasing. Most research is being carried out without active patient involvement other than patients participating as study subjects, and most knowledge gained through research only partially reaches the general public. Since 2016, the RSV Patient Advisory Board has officially been involved as an advisory group in the Respiratory Syncytial Virus Consortium in Europe (RESCEU). What started as a small single-center initiative, is now growing towards an international organization providing patient perspectives as inputs to scientists, and improving awareness of RSV. This article summarizes the history, current role, and future aims of the RSV Patient Advisory Board as an advocate to improve patient involvement in research. RSV patients and their representatives are important stakeholders in setting the global research agenda, and educating patients, professionals, and the general public.
Applying a socioecological framework to chronic disease management: implications for social informatics interventions in safety-net healthcare settings
Authors: Nguyen Kim Hanh , Cemballi Anupama G , Fields Jessica D , Brown William , Pantell Matthew S , Lyles Courtney Rees 
Published: March 2022

Abstract

Objective
Vulnerable populations face numerous barriers in managing chronic disease(s). As healthcare systems work toward integrating social risk factors into electronic health records and healthcare delivery, we need better understanding of the interrelated nature of social needs within patients’ everyday lives to inform effective informatics interventions to advance health equity.

Materials and Methods
We conducted in-depth interviews, participant-led neighborhood tours, and clinic visit observations involving 10 patients with diabetes in underserved San Francisco neighborhoods and 10 community leaders serving those neighborhoods. We coded health barriers and facilitators using a socioecological framework. We also linked these qualitative data with early persona development, focusing on patients’ experiences in these communities and within the healthcare system, as a starting place for our future informatics design.

Results
We identified social risk and protective factors across almost every socioecological domain and level—from physical disability to household context to neighborhood environment. We then detailed the complex interplay across domains and levels within two critical aspects of patients’ lives: housing and food. Finally, from these data we generated 3 personas that capture the intersectional nature of these determinants.

Conclusion
Drawing from different disciplines, our study provides a socioecological approach to understanding health promotion for patients with chronic disease in a safety-net healthcare system, using multiple methodologies. Future digital health research should center the lived experiences of marginalized patients to effectively design and implement informatics solutions for this audience.
T4 Validation of the Burn Survivor Fear-avoidance Questionnaire
Authors: Nedelec Bernadette , Chen Jocelyn , Caluori Cassandra , Alberton Laura , Zhang Jinny , Shashoua Danielle , Calva Valérie , Gauthier Nathalie , de Oliveira Ana , Marois-Pagé Elisabeth 
Published: March 2022

Abstract

Introduction
According to the Fear-Avoidance (FA) Model, FA beliefs can lead to disability due to avoidance of activities expected to result in pain or further injury. Extensive research on the relationship of FA, pain, catastrophizing, and disability has been generated with patients suffering from chronic neck and back pain, but little research has been conducted with burn survivors. To address the need for a valid evaluation of FA in burn survivors, Langlois and colleagues developed, but did not validate, the Burn Survivor Fear-Avoidance Questionnaire (BSFAQ). Thus, the primary objective of this study was to investigate the construct validity of the BSFAQ among burn survivors. The secondary objective was to examine the relationship between FA and (i) pain intensity and (ii) catastrophizing at baseline (admission to rehab), 3 months and 6 months post-burn, and (iii) disability among burn survivors at 6 months post-burn.

Methods
A prospective mixed methods approach was used to examine the construct validity by comparing the quantitative scores of the BSFAQ to independently performed qualitative interviews of burn survivors (n=31) that explored their lived-experiences, to determine if the BSFAQ discriminated those who had, from those who did not have FA beliefs and behaviors. Data for the secondary objective, scores of burn survivors (n=51) pain intensity (measured by the Numeric Rating Scale), catastrophizing (measured by the Pain Catastrophizing Scale), and disability (measured by the Burn Specific Health Scale-brief), were collected through a retrospective chart review.

Results
For the primary objective, Wilcoxon Rank Sum Test results showed a statistically significant difference (p=0.015) between the BSFAQ scores of participants who were identified from the qualitative interviews as fear-avoidant compared to those who were identified as non-fear-avoidant. For the secondary objective, the Spearman correlation test results showed a moderate correlation between FA and (i) pain at baseline (r=0.466, p=0.002), a moderate correlation with (ii) catastrophizing thoughts over time (r=0.557, p=0.000; r=0.470, p=0.00; r=0.559, p=0.002 respectively at each time point), and a moderate correlation with (iii) disability at 6 months post-burn (r=-0.639, p=0.000).

Conclusions
These results support that the BSFAQ is able to discriminate which BS are experiencing fear-avoidant beliefs and behaviours. As has been reported in other patient populations, burn survivors who express FA are more likely to report higher levels of pain early during their recovery that correlates with elevated catastrophizing thoughts, which are maintained across time and ultimately results in higher self-reported disability, which is consistent with the FA model.
29 Efficacy of a Novel LAM Femoral Cutaneous Block Technique for Acute Donor Site Pain
Authors: Hill David M , Velamuri Sai R , Desai Jay P , Ly Austin , Ly Eric , Jones Jerry 
Published: March 2022

Abstract

Introduction
Patients with severe burn injuries often require split thickness skin grafting to expedite would healing with the thigh being a common donor site. Uncontrolled pain is associated with increased opioid consumption, longer lengths of stay, and delay in functional recovery. Regional nerve blocks are increasing in popularity although supportive literature is limited, and techniques vary. Recently, we presented a case demonstrating a novel LAM (lateral, anterior, medial) femoral cutaneous block technique. The purpose of the case series is to assess the safety, feasibility, and clinical efficacy in a larger cohort.

Methods
The study was a dual IRB approved, observational case series from a single verified burn center. The electronic health record was retrospectively reviewed for patients admitted between June 2018 to June 2020 who had the LAM block placed for donor site pain by the acute pain service (APS) team. Patient demographics, and data pertinent to the LAM regional anesthesia block were collected (eg opioid usage before and after the block, pain, and physical therapy outcomes). The data were tabulated and analyzed using Microsoft Excel© and SPSS version 27.0. Descriptive statistics were utilized to describe the patient demographics and LAM block feasibility & safety. Morphine Milligram Equivalent (MME) were statistically compared utilizing repeated measures ANOVA on ranks and graphically presented.

Results
Twenty-four patients had total of 27 blocks placed, where 3 patients received the LAM block on two separate occasions. One patient had bilateral LAM blocks placed and was included as the single instance for the analysis. The majority were Caucasian males, but mechanism of injury varied. Two-thirds had a neurologic or psychiatric history. Seventy-one percent used tobacco and a quarter had a history of polysubstance abuse. Median area of the donor site was 360 cm2 (207, 1140). Median day from admission to LAM was 8 (3, 12) with a median duration of 4 (3, 5) days. Median day until first ambulation after LAM was 3 (1,3). Eighty percent reported a decreased temperature sensation at the donor site. Pain was adequately controlled, and there were no adverse events or quadricep weakness noted. There was a significant reduction in MME after block placement (Figure 1).

Conclusions
Regional nerve blocks offer an advantageous means of analgesia, while reducing potential adverse events associated with opioids. While the novel LAM technique reduced some sensation, early ambulation was not inhibited and patients able to participate with rehabilitation therapy.
39 Implementation of a Screening Tool for Wellbeing in the Burn Clinic for Patients &lt; 5 Years
Authors: Magnuson Erica Y , Joe Victor C , Chin Theresa L 
Published: March 2022

Abstract

Introduction
Pediatric burn survivors and their parents experience higher rates of psychological disorders compared to their uninjured peers. In the early years, children experience rapidly changing development, which can impact responses to psychological outcomes. Early identification of developmental delays is vital to recovery and coping with burn injury. As a quality improvement project, a survey tool was implemented in the burn clinic to screen for issues impacting pediatric burn survivors and their family’s coping, who may benefit from additional referrals.

Methods
A free comprehensive tool, which screens for behavior, development and family stressors was chosen based on its high reliability, validity, and usability including being available in multiple languages. Prior to implementation and following the trial phase, staff completed qualitative and quantitative surveys regarding their input on the importance of screening and ease of execution. The Child Life Specialist (CLS) screened and scored children ages 12 to 65 months upon their initial visit and were rescreened two to four months later if they scored “Needs Review” in any category, indicating additional assessment was needed. Those who scored 50% of expected score for their age on initial assessment or a repeat “Needs Review” on the second assessment, were referred to additional resources by the CLS, social worker or physician team.

Results
Of the 43 children whose parents completed the survey (3 in Spanish), there were 25 males and 18 females. The median age was 2.6 years (IQR:2.0-3.52). The score of the survey determined that 42% (n=18) of children evaluated as “Needs Review” or ≤50% expected in one or more category on initial assessment. Only 5 children were already receiving services and two children scored ≤50% threshold score for immediate referral. Initial surveys demonstrated staff (n=9) strongly agreed assessing children’s need for support services was important. Majority (88%) of children were assessed upon their initial visit to the outpatient burn clinic. Most staff agreed the tool had been effectively implemented in the outpatient clinic.

Conclusions
The tool was effectively integrated into the burn clinic and identified children who needed referral for support services. Screening in the burn clinic provides an opportunity to identify critical factors related to children’s development and behavior, which can compound psychological responses to burn injury and addresses parental concerns for development.
41 Peripheral Mononuclear Cell Expression of IL-10, IL-12, ARG1, & NOS2 Correlates with Outcomes After Burn
Authors: Mahung Cressida , Stepp Wesley H , Malfitano Madison , Wallet Shannon , Zhou Laura Y , Zhou Haibo , Maile Robert 
Published: March 2022

Abstract

Introduction
In the burned patient, clinical outcomes are inextricably linked with immune function. Patients are subject to an early pro-inflammatory response and a subsequent compensatory anti-inflammatory response syndrome. This dysregulation can lead to infection, multiple organ dysfunction syndrome, and death. Despite continuing efforts, a profile of immune gene expression from burn patients that can be transformed into an “immune suppression index”, which accurately reflects the underlying degree of immune insult and significantly correlates with the degree compromise, has yet to be developed. The development of such an approach that can predict graft failure, susceptibility to infection, length-of-stay in the hospital, and/or that can inform a provider on how to better manage the timing of surgical interventions would be transformative.

Objective
To determine a set of peripheral biomarkers that correlates with clinical outcomes of burn patients.

Methods
This observational study enrolled two participant cohorts within a single burn center. Initial unbiased analysis compared 23 burn patients and 6 healthy controls. Confirmatory outcomes analysis was performed in 109 burn patients and 19 healthy controls. We employed multiplex gene expression analysis to identify differential peripheral blood mononuclear cells (PBMC) immune gene expression. qPCR was used to validate these findings, identify, and model associations with outcomes.

Results
We identified 149 genes with a significant difference in expression within PBMCs from burn patients compared to controls (Figure 1a). Pathway analysis identified pathways related to IL-10 and inducible nitric oxide synthase (iNOS) signaling (Figure 1b). qPCR analysis of IL-10, IL-12, arginase-1 (ARG1), and iNOS demonstrated that burn injury was associated with increased expression of ARG1 and IL-10, and decreased expression of NOS2 and IL-12. Burn severity, acute lung injury (ALI), development of infection, failure of skin autograft, and mortality significantly correlated with expression of one or more of these genes. Ratios of IL-10/IL-12, ARG1/NOS2 and (ARG1+IL-10)/(NOS2+IL-12) transcript levels further improved the correlation with outcomes. A multivariate regression model, adjusting for confounders, demonstrated that (ARG1+IL-10)/(NOS2+IL-12) significantly correlated with burn severity and development of ALI (Table 1).

Conclusions
We present a robust model to predict patient outcomes early after burn injury using non-invasive methods, allowing early identification of underlying immune dysfunction.
43 Mapping the Hypermetabolic Response in Burn Patients
Authors: Knuth Carly M , Ricciuti Zachary , Barayan Dalia , Rehou Sarah , Jeschke Marc G 
Published: March 2022

Abstract

Introduction
Hypermetabolism, characterized by drastic increases in whole-body catabolism and resting energy expenditure (REE), is a hallmark response to a severe burn injury. This is believed to be driven in part by alterations in adipose tissue metabolism. We proposed to define the hypermetabolic response in adipose tissue from burn patients and create a roadmap of markers indicative of hypermetabolism to improve prognosis. We hypothesized that catabolic markers, such as uncoupling protein-1 (Ucp1) and growth differentiation factor-15 (Gdf15), would positively correlate with increasing days post-burn and REE.

Methods
Adult burn patients (n=65) admitted to our burn center between 2011—2019 were included in this study. Subcutaneous white adipose tissues (sWAT) from the site of injury (n=85) and plasma were collected from severely burned patients ( ³20% total body surface area). Gene expression and circulating cytokine levels were measured by RT-qPCR and multiplex assays, respectively.

Results
We found a significant correlation between increasing Ucp1 gene expression and days post-burn (p&lt; 0.0001). Moreover, when samples were stratified into acute (1-3 days post-burn), moderate (4-9 days post-burn), and long-term ( &gt;10 days post-burn) timepoints, a significant increase in Ucp1 gene expression was detected only in adipose tissues from long-term time points in comparison to non-burned control tissues (p&lt; 0.01). However, we found that REE remained stagnant throughout hospital stay after a burn injury in our patient cohort. Thus, we did not detect a significant correlation between Ucp1 gene expression and REE. Further, while Gdf15 expression was most pronounced, albeit statistically insignificant, during the moderate timepoints, we did not detect any significant differences when correlated with days post-burn. Additionally, we determined that circulating levels of IL-6, IL-10, and monocyte chemoattractant protein-1 (MCP-1) were greatly elevated within the first seven days post-burn and gradually decreased over time, while vascular endothelial growth factor (VEGF) concentrations followed a similar pattern to Ucp1 gene expression.

Conclusions
While Gdf15 expression may not accurately reflect catabolism in the adipose tissues of burn patients, Ucp1 gene expression may be used as a marker indicating a peak hypermetabolic period after ten days post-burn. This may also be reflected by circulating concentrations of VEGF. Moreover, IL-6, IL-10 and MCP-1 may be used as early determinants before the onset of hypermetabolism.