Set Of Markers Research Articles

Clinical impacts of immunomodulator withdrawal from anti-tumor necrosis factor combination therapy in pediatric inflammatory bowel disease.

Combination therapy consists of both anti-tumor necrosis factor (anti-TNF) and an immunomodulator (IMM) and has been shown to improve outcomes in patients with inflammatory bowel disease (IBD). This study assesses the impacts of IMM withdrawal from combination therapy to anti-TNF monotherapy in children with IBD. This single-center retrospective cohort study included children with IBD initiated on combination therapy between 2014 and 2019 who discontinued the IMM. We evaluated whether IMM withdrawal impacts laboratory values and disease activity. Linear mixed effects models with random intercepts were used to compare differences between groups. Chi-square and Kruskal-Wallis tests were used for comparisons between patients who did and did not require subsequent escalation of therapy. One hundred and fifty-two patients discontinued the IMM which did not significantly affect disease activity. However, 18% of patients escalated therapy after IMM withdrawal, primarily due to low anti-TNF levels. Lower anti-TNF and higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels before IMM withdrawal were associated with subsequent escalation of therapy. Overall, there was no statistically significant effect on anti-TNF drug levels. Patients with Crohn's disease (CD) on infliximab (IFX) and methotrexate (MTX) who discontinued the IMM had an increase in mean ESR and CRP (p < 0.05). IMM withdrawal from anti-TNF combination therapy may be considered safe in the setting of higher anti-TNF levels and normal serum inflammatory markers. Clinicians should consider assessing anti-TNF levels and inflammatory markers after IMM withdrawal, especially in patients with CD receiving IFX who discontinued MTX.

Abstract 2448: Field cancerization proteomic analysis provides a novel class of functional risk biomarkers for non small cell lung cancer

Abstract Lung cancer carcinogenesis is the outcome of a field of premalignant changes that occur in the bronchial tree leading to the overt emergence of the malignant lung cancer (field cancerization). A tissue or blood proteomic signature of these premalignant changes represent a novel concept of risk biomarkers that can predict the probability of future emergence of Lung Cancer. In this study, we analyzed two independent cohorts of non-small cell lung cancer (NSCLC) patients. One cohort consisted of 18 patients who donated blood before and after tumor resection surgery and matched tissue samples (UAMS Medical Center). The second set derived from a longitudinal case-control study of plasma sample collected during the physician health study that were donated at different times prior to the diagnosis of Non-Small Cell Lung Cancer (N=272). We used affinity-enriched mass spectrometry analysis and statistical learning techniques to identify a set of common markers that discriminated plasma cases and controls and were conserved in different bronchial tissue compartments including tumor and adjacent tissue. The tumor microenvironment adjacent to and surrounding cancer cells undergoes to progressive stages of carcinogenesis during field cancerization. We identified 22 proteins involved in cell adhesion, protein folding, immune response, angiogenesis, and cancer proliferation. This is a novel class of functional risk biomarkers to determine the probability of NSCLC onset. In conclusion, our findings shed light on a new class of functional biomarkers that underly tumor pathogenesis mechanisms and can provide hints for new strategies of tumor prevention therapy or lifestyle modification. Citation Format: Rayan Ibrahim Alhammad, Ngoc Bao Vuong, Weidong Zhou, Donald J Johann Jr, Barbara Birkaya, Lance Liotta, Alessandra Luchini. Field cancerization proteomic analysis provides a novel class of functional risk biomarkers for non small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2448.

Population genetic structure of the pioneer weed Cyperus ligularis in urban areas

AbstractHumans change the environment according to their need, causing modifications and affecting the local biodiversity. This work applied a set of dominant markers to test if urban populations of Cyperus ligularis L. (Cyperaceae) present less genetic diversity compared to forest/non‐urban populations, and if these environmental differences (land use) influence gene flow and population structure. Six available populations of C. ligularis were collected in different types of environments in Recife (Brazil). Overall 15 primers of DNA Amplification Fingerprinting and Inter Simple Sequence Repeat were applied and analyzed by proper statistics. The results revealed moderate genetic diversity, significant pairwise gene flow (Nem), and low differentiation between populations (FST). Land use had no direct correlation with genetic diversity or structure, however, an insular population showed higher differentiation from the remaining. Urban environments may not influence gene flow among C. ligularis populations in such environments; therefore, the genetic diversity is homogeneous in the analyzed area.

Hypoalbuminemia, but not derived neutrophil to lymphocyte ratio (dNLR), predicts overall survival in neuroendocrine tumours undergoing peptide receptor radionuclide therapy: A retrospective, cohort study of 557 patients.

Several inflammation scores have shown association with survival outcomes for patients with neuroendocrine tumours (NET) treated with peptide receptor radionuclide therapy (PRRT). However, whether these scores add value to established prognostic factors remains unknown. In this retrospective, cohort study of 557 NET patients undergoing PRRT in a tertiary referral centre from 2005 to 2015, we examined inflammatory markers and scores previously associated with cancer outcomes, using Cox proportional hazard models and Akaike's information criterion. Lower albumin (hazard ratio [95% confidence interval], .91 [.87-.95] per unit), as well as higher C-reactive protein (CRP; 1.02 [1.01-1.02]), Glasgow Prognostic Score (GPS; 1 vs. 0: 1.67 [1.14-2.44], 2 vs. 0 3.60 [2.24-5.79]), CRP/albumin ratio (1.84 [1.43-2.37]) and platelet count (Plt) × CRP, but not white blood cell, neutrophil and thrombocyte counts or derived neutrophil to lymphocyte ratio (dNLR), were associated with shorter median overall survival (OS) in an adjusted analysis. The addition of parameters based on albumin and CRP, but not dNLR, to a base model including age, chromogranin A, the cell proliferation marker Ki-67, performance status, tumour site and previous treatments improved the predictive accuracy of the base model. In an exploratory analysis of patients with available erythrocyte sedimentation rate (ESR) and CRP, ESR emerged as the most powerful predictor. When added to a prognostic model for OS in NET patients treated with PRRT, most inflammation scores further improved the model. Albumin was the single marker adding most value to the set of established prognostic markers, whereas dNLR did not seem to improve the model's prognostic ability.

Development of S Haplotype-Specific Markers to Identify Genotypes of Self-Incompatibility in Radish (Raphanus sativus L.).

Radish (Raphanus sativus L.), a root vegetable belonging to the Brassicaceae family, is considered one of the representative crops displaying sporophytic self-incompatibility (SSI). The utilization of a self-incompatibility system in F1 breeding can improve the efficiency of cross-combinations, leading to a reduction in breeding time and aiding in the development of novel F1 varieties. The successful implementation of this system necessitates the rapid and accurate identification of S haplotypes in parental lines. In this study, we identified a total of nine S haplotypes among 22 elite radish lines through Sanger sequencing. Subsequently, we obtained sequences for showing a 95% similarity to nine S haplotypes, along with sequences identified by other researchers using BLAST. Following this, multiple sequence alignment (MSA) was conducted to identify SRK and SLG sequence similarities, as well as polymorphisms within the class I and II groups. Subsequently, S haplotype-specific marker sets were developed, targeting polymorphic regions of SRK and SLG alleles. These markers successfully amplified each of the nine S haplotypes. These markers will play a crucial role in the rapid and precise identification of parental S haplotypes in the radish F1 breeding process, proving instrumental in the radish F1 purity test.

Investigation of stair ascending and descending activities on the lifespan of hip implants

Total hip arthroplasty (THA) surgeries among young patients are on the increase, so it is crucial to predict the lifespan of hip implants correctly and produce solutions to improve longevity. Current implants are designed and tested against walking conditions to predict the wear rates. However, it would be reasonable to include the additional effects of other daily life activities on wear rates to predict convergent results to clinical outputs. In this study, 14 participants are recruited to perform stair ascending (AS), descending (DS), and walking activities to obtain kinematic and kinetic data for each cycle using marker based Qualisys motion capture (MOCAP) system. AnyBody Modeling System using the Calibrated Anatomical System Technique (CAST) full body marker set are performed Multibody simulations. The 3D generic musculoskeletal model used in this study is a marker-based full-body motion capture model (AMMR,2.3.1 MoCapModel) consisting of the upper extremity and the Twente Lower Extremity Model (TLEM2). The dynamic wear prediction model detailing the intermittent and overall wear rates for CoCr-on-XLPE bearing couple is developed to investigate the wear mechanism under 3D loading for AS, DS, and walking activities over 5 million cycles (Mc) by using finite element modelling technique. The volumetric wear rates of XLPE liner under AS, DS, and walking activities over 5-Mc are predicted as 27.43, 23.22, and 18.84 mm3/Mc respectively. Additionally, the wear rate was predicted by combining stair activities and gait cycles based on the walk-to-stair ratio. By adding the effect of stair activities, the volumetric wear rate of XLPE is predicted as 22.02 mm3/Mc which is equivalent to 19.41% of walking. In conclusion, in this study, the effect of including other daily life activities is demonstrated and evidence is provided by matching them to the clinical data as opposed to simulator test results of implants under ISO 14242 boundary conditions.

The prognostic value of LAYN in HPV-related head and neck squamous cell carcinoma and its influence on immune cell infiltration

BackgroundHPV-positive head and neck squamous cell carcinoma (HNSCC) exhibits different characteristics from HPV-negative tumors in terms of tumor development, clinical features, treatment response, and prognosis. Layilin (LAYN), which contains homology with C-type lectins, plays a critical role in tumorigenesis and cancer progression. However, the prognostic value of LAYN and the relationship between LAYN and immune infiltration levels in HPV-related HNSCC patients still require a comprehensive understanding. Herein, we aimed to assess the prognostic value of LAYN and to investigate its underlying immunological function in HPV-related HNSCC.MethodsThrough various bioinformatics methods, we analyzed the data from The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to explore the potential underlying oncogenic impression of LAYN, including the relevance of LAYN to survival outcomes, clinicopathological factors, immune cell infiltration, and immune marker sets in HPV-related HNSCC. The expression levels of LAYN and HPV were also verified in HNSCC patient tissues.ResultsLAYN was differentially expressed in a variety of tumors. The expression of LAYN in HNSCC was significantly higher than that in adjacent normal tissues (P < 0.0001), and high expression of LAYN was correlated with poor overall survival (OS) in HNSCC patients (Hazard Ratio (HR) = 1.3, P = 0.035). Moreover, LAYN expression level in HPV-positive HNSCC patients was significantly lower than that in HPV-negative patients, with HPV-positive HNSCC patients displaying a trend of favorable prognosis. In addition, the relationship between LAYN expression and immune infiltration levels in HPV-positive HNSCC group was less tightly correlated than that in HPV-negative HNSCC group, and there was a strong relationship between LAYN expression and markers of M2 macrophage (P < 0.001) and exhausted T cells (P < 0.05) in HPV-negative HNSCC. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis suggested that LAYN potentially influenced tumor progression through HPV infection and other cancer-related pathways.ConclusionsLAYN might contribute to tumorigenesis via its positive correlation with immune checkpoint molecules and tumor-associated macrophages (TAMs). Our study might provide a novel prognostic biomarker and latent therapeutic target for the treatment of HPV-related HNSCC.

An adaptive harmonic polynomial cell method for three-dimensional fully nonlinear wave-structure interaction with immersed boundaries

To accurately simulate wave-structure interaction based on fully nonlinear potential flow theory, a three-dimensional (3 D) high-order immersed-boundary adaptive harmonic polynomial cell (IB-AHPC) method is proposed. Both the free surface and body surface are immersed in background octree cells that are adaptively refined near the boundaries of interest, thereby dramatically reducing computational costs without loss of accuracy. We also propose an easy-to-implement IB strategy to deal with possible instabilities in the time-domain solution arising from the intersection of Dirichlet–Neumann boundaries. For a linearized problem of wave-wall interaction, a matrix-based stability analysis is performed, providing mathematical support for the robustness of the proposed IB strategy. In contrast to the two-dimensional HPC method, compressed cells are found to offer superior stability compared to stretched cells in the vertical direction, while equal mesh aspect ratio in the horizontal plane is superior. Cubic octree cells are, however, still preferred in practice. The free surface is primarily described by a set of massless background wave markers; however, to address the challenges of IB methods in tracking the free surface evolution near the structure, additional body-fitted wave markers are introduced close to the waterline. The information exchange between these two sets of wave markers is realized by radial basis function (RBF) interpolation. While standard RBF schemes have grid-size-dependent filtering performance, we propose a normalized RBF scheme, which is then optimized in terms of the number of neighboring nodes, a smoothing coefficient and the basis functions. Excellent accuracy properties of the proposed 3 D IB-AHPC method are demonstrated by studying fully nonlinear wave propagation. The method is further applied to study relevant fully nonlinear wave-structure interaction problems, including sloshing in 3 D rectangular tanks and wave diffraction of a bottom-mounted cylinder in regular waves. Satisfactory agreement is demonstrated with existing experimental and numerical results, suggesting that the proposed 3 D IB-AHPC method is a promising potential-flow method in marine hydrodynamics.

A collaborative approach to develop indicators for quality of care for ST segment Elevation Myocardial Infarction in networks without coronary intervention: A position paper.

Data about performance measures (PM) in patients with ST segment Elevation Myocardial Infarction (STEMI) in low- and middle-income countries is really scarce. One of the reasons is the lack of appropriate measures for these scenarios where coronary intervention is not the standard treatment. This study aimed to develop a set of PM and quality markers for patients with STEMI in these countries. Two investigators systematically reviewed existing guidelines and scientific literature to identify potential PM by referring to documents searched through PubMed from 2010 through 2019, using terms "Myocardial Infarction", "STEMI", "quality indicator", and "performance measure". A modified Delphi technique, involving multidisciplinary panel interview, was used. A 15-member multidisciplinary expert panel individually rated each potential indicator on a scale of 1 (lowest) to 5 (highest) during three rounds. All indicators that received a median score ≥4.5, in final round without significant disagreement were included as PM. Through the consensus-building process, 84 potential indicators were found, of which 10 were proposed as performance measures and 2 as quality metrics, as follows: Pre-Hospital Electrocardiogram; Patients with reperfusion therapy; Pre-hospital Reperfusion; Ischemic time less than 120 minutes; System delay time less than 90 minutes; In-hospital Mortality; Complete in-hospital Treatment; Complete in-hospital Treatment in patients with Heart Failure; 30 day-Re-admissions; 30 day-mortality; Patients with in-hospital stress test performed; and, Patients included in rehabilitation programs. This document provides the official set of PM of attention in ST segment Elevation Myocardial Infarction of the Cuban Society of Cardiology and Cuban National Group of Cardiology.

Natural origins of social essentialism: Ethnic groups, identities, and cultural transmission

This paper argues that the term ‘social essence’ is overused in psychological research and includes instances that are not covered by the basic definition of an essentialist cognition with living beings. Imagining an essence of living beings is conceptualized as a meta-cognition that wraps up an exemplars' characteristics as a marker and assigns it a kind or species. This paper develops a framework of how social essentialism can be conceptualised to originate in natural contexts. Ethnic groups maintain a group identity that is defined by a set of diacritical markers and secured by a rule of endogamy, which functionally replicates the procreative pattern in animal species. This ‘functional homological’ relationship construes a group identity in the image of animal kinds. Thus construed, an ethnic identity appears as a natural given that safeguards the group’s cohesion and stability across generations. Hence, group-related essentialism primarily serves identity formation and provides a cognitive mechanism to distinguish the ingroup from outgroups. The intuition of an essentialised identity is perpetuated across generations by bio-social processes of enculturation. Such processes can explain an historically stable group essentialism, as well as group-biased judgements in former and contemporary societies without the need for innate sources of psychological essentialism.

The association between incarceration and housing insecurity and advanced immune age during late life

Emerging evidence suggests that psychosocial stress ages the immune system. Accordingly, immune aging may be an important potential mechanism linking psychosocial stress to aging-related decline and disease. Incarceration and housing insecurity represent severe and complex experiences of a multitude of psychosocial stressors, including discrimination, violence, and poverty. In this study, we investigated the association between incarceration and/or housing insecurity and advanced immune age in adults aged 55 and older. Our sample was derived from the Health and Retirement Survey (HRS), with n = 7003 individuals with valid housing insecurity data and n = 7523 with valid incarceration data. From 2016 Venous Blood Study data, we assessed immune aging using a comprehensive set of immune markers including inflammatory markers (IL-6, CRP, s-TNFR1), markers of viral control (CMV IgG antibodies), and ratios of T cell phenotypes (CD8+:CD4+, CD+ Memory: Naïve, CD4+ Memory: Naïve, CD8+ Memory: Naïve ratios). We found that both incarceration and housing insecurity were strongly associated with more advanced immune aging as indicated by increased inflammation, reduced viral control, and reduction in naïve T cells relative to memory T cells. Given that those who experienced incarceration, housing insecurity, and/or are racialized minorities were less likely to be included in this study, our results likely underestimated these associations. Despite these limitations, our study provided strong evidence that experiencing incarceration and/or housing insecurity may accelerate the aging of the immune system.

Development of a set of SNP markers for population genetics of the sea rose, Pentapora fascialis

Development of a set of SNP markers for population genetics of the sea rose, Pentapora fascialis

Identification and Characterization of Relict Olive Varieties (Olea europaea L.) in the Northwest of the Iberian Peninsula

Olives (Olea europaea L.) are an important crop in the Mediterranean Basin, but it is not well-known that they have also been grown in other areas, such as Galicia in northwestern Spain. Although commercial production ended long ago in this peripheral growing region, it remains home to olive resources that are well-adapted to the prevailing environmental conditions, providing a valuable but largely undocumented source of genetic variation. Following a survey of Galicia to locate examples of centuries-old olive trees, those detected were subjected to molecular characterization using a set of microsatellite markers, as well as full botanical characterization using the features established by the International Union for the Protection of New Varieties of Plants, along with others proposed by the present authors. These procedures allowed 11 undescribed varieties to be identified, which are new genetic resources that might be of use in olive improvement programs or studies of how the species adapts to different climates. The trees also underwent preliminary health checks, allowing disease-free specimens of each variety to be propagated. The addition of this material to the Community Plant Variety Office’s register of commercial varieties is underway.

Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS-CoV-2 nucleocapsid protein and its liquid-liquid phase separation.

When the SARS-CoV-2virus infects humans, it leads to a condition called COVID-19that has a wide spectrum of clinical manifestations, from no symptoms to acute respiratory distress syndrome. The virus initiates damage by attaching to the ACE-2protein on the surface of endothelial cells that line the blood vessels and using these cells as hosts for replication. Reactive oxygen species levels are increased during viral replication, which leads to oxidative stress. About three-fifths(~60%) of the people who get infected with the virus eradicate it from their body after 28 days and recover their normal activity. However, a large fraction (~40%) of the people who are infected with the virus suffer from various symptoms (anosmia and/or ageusia, fatigue, cough, myalgia, cognitive impairment, insomnia, dyspnea, and tachycardia) beyond 12 weeks and are diagnosed with a syndrome called long COVID. Long-term clinical studies in a group of people who contracted SARS-CoV-2have been contrasted with a noninfected matched group of people. A subset of infected people can be distinguished by a set of cytokine markers to have persistent, low-grade inflammation and often self-report two or more bothersome symptoms. No medication can alleviate their symptoms efficiently. Coronavirus nucleocapsid proteins have been investigated extensively as potential drug targets due to their key roles in virus replication, among which is their ability to bind their respective genomic RNAs for incorporation into emerging virions. This review highlights basic studies of the nucleocapsid protein and its ability to undergo liquid-liquid phase separation. We hypothesize that this ability of the nucleocapsid protein for phase separation may contribute to long COVID. This hypothesis unlocks new investigation angles and could potentially open novel avenues for a better understanding of long COVID and treating this condition.

Male Pedigree Toolbox: A Versatile Software for Y-STR Data Analyses.

Y-chromosomal short tandem repeats (Y-STRs) are widely used in forensic, genealogical, and population genetics. With the recent increase in the number of rapidly mutating (RM) Y-STRs, an unprecedented level of male differentiation can be achieved, widening and improving the applications of Y-STRs in various fields, including forensics. The growing complexity of Y-STR data increases the need for automated data analyses, but dedicated software tools are scarce. To address this, we present the Male Pedigree Toolbox (MPT), a software tool for the automated analysis of Y-STR data in the context of patrilineal genealogical relationships. The MPT can estimate mutation rates and male relative differentiation rates from input Y-STR pedigree data. It can aid in determining ancestral haplotypes within a pedigree and visualize the genetic variation within pedigrees in all branches of family trees. Additionally, it can provide probabilistic classifications using machine learning, helping to establish or prove the structure of the pedigree and the level of relatedness between males, even for closely related individuals with highly similar haplotypes. The tool is flexible and easy to use and can be adjusted to any set of Y-STR markers by modifying the intuitive input file formats. We introduce the MPT software tool v1.0 and make it publicly available with the goal of encouraging and supporting forensic, genealogical, and other geneticists in utilizing the full potential of Y-STRs for both research purposes and practical applications, including criminal casework.

Genome-wide search for associations method for identification of molecular markers and candidate genes of breed affiliation of sheep of the North Caucasian meat and wool breed

To determine the loci associated with pedigree traits, a genome-wide search was conducted for associations of 275 heads of Russian sheep breeds genotyped using 600 thousand single nucleotide polymorphisms (SNPs). The studies were conducted according to the “case-control” type, where the “case” group is represented by animals of the North Caucasian meat and wool breed, the “control” included animals of other breeds (Karachay, Romanovskaya, Dzhalginsky merino and Russian meat merino). In this study, over 100 SNPs were identified with highly reliable differences in the frequency of occurrence in sheep of the North Caucasian meat and wool breed. For the subsequent analysis, 18 single nucleotides with the highest confidence indices localized on chromosomes were selected 1, 10, 11, 15, 17. As a result of a genome-wide study, significant SNP markers characteristic of the sheep breed under study, located directly in the genes or close to them, were determined. The conducted studies provide a set of new SNP markers and candidate genes associated with the breed characteristics of North Caucasian meat-wool sheep.

Performance of a 74-Microhaplotype Assay in Kinship Analyses.

Microhaplotypes (MHs) consisting of multiple SNPs and indels on short stretches of DNA are new and interesting loci for forensic genetic investigations. In this study, we analysed 74 previously defined MHs in two of the populations that our laboratory provides with forensic genetic services, Danes and Greenlanders. In addition to the 229 SNPs that originally made up the 74 MHs, 66 SNPs and 3 indels were identified in the two populations, and 45 of these variants were included in new definitions of the MHs, whereas 24 SNPs were considered rare and of little value for case work. The average effective number of alleles (Ae) was 3.2, 3.0, and 2.6 in Danes, West Greenlanders, and East Greenlanders, respectively. High levels of linkage disequilibrium were observed in East Greenlanders, which reflects the characteristics of this population that has a small size, and signs of admixture and substructure. Pairwise kinship simulations of full siblings, half-siblings, first cousins, and unrelated individuals were performed using allele frequencies from MHs, STRs and SNPs from Danish and Greenlandic populations. The MH panel outperformed the currently used STR and SNP marker sets and was able to differentiate siblings from unrelated individuals with a 0% false positive rate and a 1.1% false negative rate using an LR threshold of 10,000 in the Danish population. However, the panel was not able to differentiate half-siblings or first cousins from unrelated individuals. The results generated in this study will be used to implement MHs as investigative markers for relationship testing in our laboratory.

Genomic prediction for agronomic traits in a diverse Flax (Linum usitatissimum L.) germplasm collection

Breeding programs require exhaustive phenotyping of germplasms, which is time-demanding and expensive. Genomic prediction helps breeders harness the diversity of any collection to bypass phenotyping. Here, we examined the genomic prediction’s potential for seed yield and nine agronomic traits using 26,171 single nucleotide polymorphism (SNP) markers in a set of 337 flax (Linum usitatissimum L.) germplasm, phenotyped in five environments. We evaluated 14 prediction models and several factors affecting predictive ability based on cross-validation schemes. Models yielded significant variation among predictive ability values across traits for the whole marker set. The ridge regression (RR) model covering additive gene action yielded better predictive ability for most of the traits, whereas it was higher for low heritable traits by models capturing epistatic gene action. Marker subsets based on linkage disequilibrium decay distance gave significantly higher predictive abilities to the whole marker set, but for randomly selected markers, it reached a plateau above 3000 markers. Markers having significant association with traits improved predictive abilities compared to the whole marker set when marker selection was made on the whole population instead of the training set indicating a clear overfitting. The correction for population structure did not increase predictive abilities compared to the whole collection. However, stratified sampling by picking representative genotypes from each cluster improved predictive abilities. The indirect predictive ability for a trait was proportionate to its correlation with other traits. These results will help breeders to select the best models, optimum marker set, and suitable genotype set to perform an indirect selection for quantitative traits in this diverse flax germplasm collection.

Predictors of HIV rebound differ by timing of antiretroviral therapy initiation.

BACKGROUNDIdentifying factors that predict the timing of HIV rebound after treatment interruption will be crucial for designing and evaluating interventions for HIV remission.METHODSWe performed a broad evaluation of viral and immune factors that predict viral rebound (AIDS Clinical Trials Group A5345). Participants initiated antiretroviral therapy (ART) during chronic (N = 33) or early (N = 12) HIV infection with ≥ 2 years of suppressive ART and restarted ART if they had 2 viral loads ≥ 1,000 copies/mL after treatment interruption.RESULTSCompared with chronic-treated participants, early-treated individuals had smaller and fewer transcriptionally active HIV reservoirs. A higher percentage of HIV Gag-specific CD8+ T cell cytotoxic response was associated with lower intact proviral DNA. Predictors of HIV rebound timing differed between early- versus chronic-treated participants, as the strongest reservoir predictor of time to HIV rebound was level of residual viremia in early-treated participants and intact DNA level in chronic-treated individuals. We also identified distinct sets of pre-treatment interruption viral, immune, and inflammatory markers that differentiated participants who had rapid versus slow rebound.CONCLUSIONThe results provide an in-depth overview of the complex interplay of viral, immunologic, and inflammatory predictors of viral rebound and demonstrate that the timing of ART initiation modifies the features of rapid and slow viral rebound.TRIAL REGISTRATIONClinicalTrials.gov NCT03001128FUNDINGNIH National Institute of Allergy and Infectious Diseases, Merck.

Pilot study: Insights into the validity of Opencap to assess knee kinematics during the back squat

Introduction&#x0D; Advancements in technology have revolutionized the field of sports science, enabling researchers to gain deeper insights into the biomechanics of athletes' movements (Baca et al., 2022). Among these technological advancements, OpenCap has emerged as a powerful tool for biomechanical analysis (Uhlrich et al., 2023). Integrating OpenCap with other innovative technologies, such as motion capture systems and data analytics, further enhances the understanding of human movement. However, the effective implementation of new technologies requires rigorous scientific validation and a nuanced approach to their comparison with already established techniques. The primary goal of this research is to establish basic characteristics for comparing biomechanical analysis results obtained from OpenCap and VICON.&#x0D; Methods&#x0D; A total of 3 healthy 23-29-year-old women with a minimum of one year of experience in strength training were recruited for the study. For OpenCap (opensimModel: LaiArnoldModified2017_poly_withArms_weldHand, posemodel: openpose, augmentermodel: v0.2), the system paired cameras of two iOS devices with a web app running on a standard laptop recording videos at 60Hz. A VICON system consisting of 10 cameras (200 Hz, Oxford Metrics Group, Oxford UK) was used for 3D motion analysis. The Plug-In Gait marker set (from the VICON system), comprising 42 markers with a diameter of 16mm, was employed along with two manual markers for tracking the barbell position. Ground reaction forces were measured using two force plates (1000 Hz, Kistler AG, Winterthur, CH). The collected data served as reference data for scaling the models and running OpenSim simulations. Barbell loads were adjusted based on body weight, with loads of 25% or 50% for the free-weight back squat. Each exercise consisted of three cycles of five repetitions, enabling subsequent calculation of average values for further analysis and evaluation.&#x0D; Results&#x0D; The analysis incorporated 22 valid squats. Statistical mapping revealed significant discrepancies in knee angles between Opencap and the OpenSim model throughout most of the back squat cycle, except from 10 to 35%. The average difference was 16.9 degrees (SD = 18.3 degrees). An RMSE of 24.9 and an ICC 3.1 of 0.503 (p = 0.006076) suggest moderate agreement between the models.&#x0D; Discussion/Conclusion&#x0D; Ongoing technological advancements are pushing the frontiers of sport biomechanics through groundbreaking innovations. To achieve a comprehensive assessment and comparison of new technologies, it is vital to perform correlation analyses on identical parameters produced by diverse models (Jing et al., 2023). The ICC results indicated a moderate agreement between the models, with the OpenCap model significantly underestimating knee angles. This lesser agreement, as compared to existing literature (Lima et al., 2023), may be attributed to the potential misinterpretation of the barbell by the model. Pending updates from the forthcoming augmenter model v0.3, we advise cautious application of Opencap technology in practical scenarios. However, we believe that with further technological advancement and continued refinement, it has the potential to greatly benefit the field of sports biomechanics.&#x0D; References&#x0D; Baca, A., Dabnichki, P., Hu, C. W., Kornfeind, P., &amp; Exel, J. (2022). Ubiquitous computing in sports and physical activity—Recent trends and developments. Sensors, 22(21), Article 8370. https://www.mdpi.com/1424-8220/22/21/8370&#x0D; Jing, Z., Han, J., &amp; Zhang, J. (2023). Comparison of biomechanical analysis results using different musculoskeletal models for children with cerebral palsy. Frontiers in Bioengineering and Biotechnology, 11, Article 1217918. https://doi.org/10.3389/fbioe.2023.1217918&#x0D; Lima, Y., Collings, T., Hall, M., Bourne, M., Diamond, L. (2023). Assessing lower-limb kinematics via OpenCap during dynamic tasks relevant to anterior cruciate ligament injury: A validity study. Journal of Science and Medicine in Sport, 26(Suppl2), S105. https://doi.org/10.1016/j.jsams.2023.08.123&#x0D; Uhlrich, S. D., Falisse, A., Kidziński, Ł., Muccini, J., Ko, M., Chaudhari, A. S., Hicks, J. L., &amp; Delp, S. L. (2023). OpenCap: Human movement dynamics from smartphone videos. PLoS Computational Biology, 19(10), Article e1011462. https://doi.org/10.1371/journal.pcbi.1011462&#x0D; Acknowledgement&#x0D; This study was funded by the Swiss National Foundation (192289).