Major impacts of widespread structural variation on sorghum.

Genetic diversity is critical to crop breeding and improvement, and dissection of the genomic variation underlying agronomic traits can both assist breeding and give insight into basic biological mechanisms. Although recent genome analyses in plants reveal many structural variants (SVs), most current studies of crop genetic variation are dominated by single-nucleotide polymorphisms (SNPs). The extent of the impact of SVs on global trait variation, as well as their utility in genome-wide selection, is not yet understood. In this study, we built an SV data set based on whole-genome resequencing of diverse sorghum lines (n = 363), validated the correlation of photoperiod sensitivity and variety type, and identified SV hotspots underlying the divergent evolution of cellulosic and sweet sorghum. In addition, we showed the complementary contribution of SVs for heritability of traits related to sorghum adaptation. Importantly, inclusion of SV polymorphisms in association studies revealed genotype-phenotype associations not observed with SNPs alone. Three-way genome-wide association studies (GWAS) based on whole-genome SNP, SV, and integrated SNP + SV data sets showed substantial associations between SVs and sorghum traits. The addition of SVs to GWAS substantially increased heritability estimates for some traits, indicating their important contribution to functional allelic variation at the genome level. Our discovery of the widespread impacts of SVs on heritable gene expression variation could render a plausible mechanism for their disproportionate impact on phenotypic variation. This study expands our knowledge of SVs and emphasizes the extensive impacts of SVs on sorghum.

An NBS-LRR protein in the Rpp1 locus negates the dominance of Rpp1-mediated resistance against Phakopsora pachyrhizi in soybean.

The soybean Rpp1 locus confers resistance to Phakopsora pachyrhizi, causal agent of rust, and resistance is usually dominant over susceptibility. However, dominance of Rpp1-mediated resistance is lost when a resistant genotype (Rpp1 or Rpp1b) is crossed with susceptible line TMG06_0011, and the mechanism of this dominant susceptibility (DS) is unknown. Sequencing the Rpp1 region reveals that the TMG06_0011 Rpp1 locus has a single nucleotide-binding site leucine-rich repeat (NBS-LRR) gene (DS-R), whereas resistant PI 594760B (Rpp1b) is similar to PI 200492 (Rpp1) and has three NBS-LRR resistance gene candidates. Evidence that DS-R is the cause of DS was reflected in virus-induced gene silencing of DS-R in Rpp1b/DS-R or Rpp1/DS-R heterozygous plants with resistance partially restored. In heterozygous Rpp1b/DS-R plants, expression of Rpp1b candidate genes was not significantly altered, indicating no effect of DS-R on transcription. Physical interaction of the DS-R protein with candidate Rpp1b resistance proteins was supported by yeast two-hybrid studies and in silico modeling. Thus, we conclude that suppression of resistance most likely does not occur at the transcript level, but instead probably at the protein level, possibly with Rpp1 function inhibited by binding to the DS-R protein. The DS-R gene was found in other soybean lines, with an estimated allele frequency of 6% in a diverse population, and also found in wild soybean (Glycine soja). The identification of a dominant susceptible NBS-LRR gene provides insight into the behavior of NBS-LRR proteins and serves as a reminder to breeders that the dominance of an R gene can be influenced by a susceptibility allele.

Multi-trait association mapping for phosphorous efficiency reveals flexible root architectures in sorghum.

BACKGROUND: On tropical regions, phosphorus (P) fixation onto aluminum and iron oxides in soil clays restricts P diffusion from the soil to the root surface, limiting crop yields. While increased root surface area favors P uptake under low-P availability, the relationship between the three-dimensional arrangement of the root system and P efficiency remains elusive. Here, we simultaneously assessed allelic effects of loci associated with a variety of root and P efficiency traits, in addition to grain yield under low-P availability, using multi-trait genome-wide association. We also set out to establish the relationship between root architectural traits assessed in hydroponics and in a low-P soil. Our goal was to better understand the influence of root morphology and architecture in sorghum performance under low-P availability. RESULT: In general, the same alleles of associated SNPs increased root and P efficiency traits including grain yield in a low-P soil. We found that sorghum P efficiency relies on pleiotropic loci affecting root traits, which enhance grain yield under low-P availability. Root systems with enhanced surface area stemming from lateral root proliferation mostly up to 40 cm soil depth are important for sorghum adaptation to low-P soils, indicating that differences in root morphology leading to enhanced P uptake occur exactly in the soil layer where P is found at the highest concentration. CONCLUSION: Integrated QTLs detected in different mapping populations now provide a comprehensive molecular genetic framework for P efficiency studies in sorghum. This indicated extensive conservation of P efficiency QTL across populations and emphasized the terminal portion of chromosome 3 as an important region for P efficiency in sorghum. Increases in root surface area via enhancement of lateral root development is a relevant trait for sorghum low-P soil adaptation, impacting the overall architecture of the sorghum root system. In turn, particularly concerning the critical trait for water and nutrient uptake, root surface area, root system development in deeper soil layers does not occur at the expense of shallow rooting, which may be a key reason leading to the distinctive sorghum adaptation to tropical soils with multiple abiotic stresses including low P availability and drought.

Genome scans for selection signatures identify candidate virulence genes for adaptation of the soybean cyst nematode to host resistance.

Plant pathogens are constantly under selection pressure for host resistance adaptation. Soybean cyst nematode (SCN, Heterodera glycines) is a major pest of soybean primarily managed through resistant cultivars; however, SCN populations have evolved virulence in response to selection pressures driven by repeated monoculture of the same genetic resistance. Resistance to SCN is mediated by multiple epistatic interactions between Rhg (for resistance to H. glycines) genes. However, the identity of SCN virulence genes that confer the ability to overcome resistance remains unknown. To identify candidate genomic regions showing signatures of selection for increased virulence, we conducted whole genome resequencing of pooled individuals (Pool-Seq) from two pairs of SCN populations adapted on soybeans with Peking-type (rhg1-a, rhg2, and Rhg4) resistance. Population differentiation and principal component analysis-based approaches identified approximately 0.72-0.79 million SNPs, the frequency of which showed potential selection signatures across multiple genomic regions. Chromosomes 3 and 6 between population pairs showed the greatest density of outlier SNPs with high population differentiation. Conducting multiple outlier detection tests to identify overlapping SNPs resulted in a total of 966 significantly differentiated SNPs, of which 285 exon SNPs were mapped to 97 genes. Of these, six genes encoded members of known stylet-secreted effector protein families potentially involved in host defence modulation including venom-allergen-like, annexin, glutathione synthetase, SPRYSEC, chitinase, and CLE effector proteins. Further functional analysis of identified candidate genes will provide new insights into the genetic mechanisms by which SCN overcomes soybean resistance and inform the development of molecular markers for rapidly screening the virulence profile of an SCN-infested field.

Uterine tone: A neglected criterion for the selection of bovine embryo transfer recipients.

This study evaluated the relationship between CL features assessed by ultrasound (luteal tissue area and blood flow, BF) or rectal palpation (size), uterine tone (UT), plasma progesterone (P4) concentration on Day 7 (D7) and subsequent pregnancy outcomes in bovine embryo recipients. A total of 163 cows and heifers were included in this study. The expected day of ovulation after the synchronization protocol was designated as D0. On D7, ovaries and uterus were examined by ultrasonography and rectal palpation, and subjective scores (1-3 scale) were assigned for CL size, area and BF, and for UT. Blood samples were collected for further P4 analysis. Each embryo recipient then received a grade I frozen-thawed in vivo-produced blastocyst, which was transferred to the uterine horn ipsilateral to the CL. Pregnancy diagnosis was performed on D35, and the results were retrospectively compared with the assigned scores for CL and UT. We observed a significant (p < .02) interaction between CL size and UT, with a progressive increase in the likelihood of pregnancy for recipients bearing a large CL among those with turgid UT. Ultrasound scoring of the CL using B-mode and Doppler-mode did not significantly predict pregnancy rates on D35 (p < .6 and p < .5, respectively). However, logistic regression analysis revealed a trend towards a quadratic effect (p < .08 and p < .06) indicating that the probability of pregnancy varied according to the area of luteal tissue and P4 concentrations, respectively. No significant (p > .05) association was found between the probability of pregnancy and the BF area of the CL. In summary, UT before embryo transfer may reflect successful recipient synchronization. Elevated P4 levels, assessed by CL size, may offset uterine contractility, mitigating adverse effects. Additionally, the CL area may be more important than its vascularization area when evaluating recipients D7 after ovulation.

Severity of illness and risk of mortality from all patient refined-diagnosis related groups: Two scales of different concepts or two sides of the same coin?

All patient refined-diagnosis related groups (APR-DRGs) includes severity of illness (SOI) and risk of mortality (ROM) subclasses. For predictions, both subscales are used together or interchangeably. We aimed to compare SOI and ROM by evaluating the reliability and agreement between both. We performed a retrospective observational study using mainland Portuguese public hospitalisations of adult patients from 2011 to 2016. Reliability (quadratic weighted kappa) and agreement (proportion of agreement) between SOI and ROM were analysed overall and by APR-DRG. While overall reliability and agreement between SOI and ROM were high (weighted kappa: 0.717, 95% CI 0.717-0.718; proportion of agreement: 69.0%, 95% CI 69.0-69.0) there was high heterogeneity across APR-DRGs, ranging from 0.016 to 0.846 on reliability and from 23.1% to 94.8% on agreement. Most of APR-DRGs (263 out of 284) showed a higher proportion of episodes with ROM level above the SOI level than the opposite. In conclusion, SOI and Risk of Mortality measures must be clearly distinguished and are 'two scales of different concepts' rather than 'two sides of the same coin'. However, this is more evident for some APR-DRGs than for others.

Identification of avoidable patients at triage in a Paediatric Emergency Department: a decision support system using predictive analytics.

BACKGROUND: Crowding has been a longstanding issue in emergency departments. To address this, a fast-track system for avoidable patients is being implemented in the Paediatric Emergency Department where our study is conducted. Our goal is to develop an optimized Decision Support System that helps in directing patients to this fast track. We evaluated various Machine Learning models, focusing on a balance between complexity, predictive performance, and interpretability. METHODS: This is a retrospective study considering all visits to a university-affiliated metropolitan hospital's PED between 2014 and 2019. Using information available at the time of triage, we trained several models to predict whether a visit is avoidable and should be directed to a fast-track area. RESULTS: A total of 507,708 visits to the PED were used in the training and testing of the models. Regarding the outcome, 41.6% of the visits were considered avoidable. Except for the classification made by triage rules, i.e. considering levels 1,2, and 3 as non-avoidable and 4 and 5 as avoidable, all models had similar results in model's evaluation metrics, e.g. Area Under the Curve ranging from 74% to 80%. CONCLUSIONS: Regarding predictive performance, the pruned decision tree had evaluation metrics results that were comparable to the other ML models. Furthermore, it offers a low complexity and easy to implement solution. When considering interpretability, a paramount requisite in healthcare since it relates to the trustworthiness and transparency of the system, the pruned decision tree excels. Overall, this paper contributes to the growing body of research on the use of machine learning in healthcare. It highlights practical benefits for patients and healthcare systems of the use ML-based DSS in emergency medicine. Moreover, the obtained results can potentially help to design patients' flow management strategies in PED settings, which has been sought as a solution for addressing the long-standing problem of overcrowding.

Combined low-carbohydrate diet and long-term exercise in hypoxia in type 2 diabetes: A randomized controlled trial protocol to assess glycemic control, cardiovascular risk factors and body composition.

Background: Cardiovascular disease is the leading cause of mortality associated with diabetes, which is characterized by chronic hyperglycemia. Low-carbohydrate diet has gained popularity as an intervention in patients with type 2 diabetes mellitus, acting to improve glycemic profile and serum lipids. In its turn, exercise in hypoxia induces specific adaptations, mostly modulated via hypoxia-induced transcription factor signaling cascade, which increases with exposure to altitude, and promotes angiogenesis, glycogen supply, glucose tolerance, and raises GLUT-4 expression. Aim: Given that hyperglycemia decreases HIF-1α and it is better controlled when following a low-carbohydrate diet, this study aims to examine the hypothesis that a combination of both low-carbohydrate diet and chronic exercise in hypoxia in type 2 diabetes mellitus is associated with improved glycemic control and cardiovascular parameters, whose protocol is described. Methods: Patients with type 2 diabetes mellitus (n = 48) will be recruited and randomized into one of the three groups: (a) Control group: Control diet (low-fat and moderate-carbohydrate diet) + exercise in normoxia; (2) exercise in hypoxia group: Control diet + exercise in hypoxia; (3) intervention group: Low-carbohydrate diet (low-carbohydrate and high-fat diet) + exercise in hypoxia. Before and after 8 weeks of interventions, cardiopulmonary tests (Bruce protocol), body composition and blood pressure will be evaluated. Blood samples will be collected to measure hypoxia-induced transcription factor, C-reactive protein, glycemic and lipid profiles. Summary: This will be the first trial to examine the isolated and combined effect of chronic exercise in hypoxia and low-carbohydrate diet in type 2 diabetes mellitus. This trial will help to fill a significant research gap, guide future research and contribute to the combined nutrition and exercise approach to type 2 diabetes mellitus.

Astrocyte structural heterogeneity in the mouse hippocampus.

Astrocytes are integral components of brain circuits, where they sense, process, and respond to surrounding activity, maintaining homeostasis and regulating synaptic transmission, the sum of which results in behavior modulation. These interactions are possible due to their complex morphology, composed of a tree-like structure of processes to cover defined territories ramifying in a mesh-like system of fine leaflets unresolved by conventional optic microscopy. While recent reports devoted more attention to leaflets and their dynamic interactions with synapses, our knowledge about the tree-like "backbone" structure in physiological conditions is incomplete. Recent transcriptomic studies described astrocyte molecular diversity, suggesting structural heterogeneity in regions such as the hippocampus, which is crucial for cognitive and emotional behaviors. In this study, we carried out the structural analysis of astrocytes across the hippocampal subfields of Cornu Ammonis area 1 (CA1) and dentate gyrus in the dorsoventral axis. We found that astrocytes display heterogeneity across the hippocampal subfields, which is conserved along the dorsoventral axis. We further found that astrocytes appear to contribute in an exocytosis-dependent manner to a signaling loop that maintains the backbone structure. These findings reveal astrocyte heterogeneity in the hippocampus, which appears to follow layer-specific cues and depend on the neuro-glial environment.

Prevalence of low bone mineral density (T-score ≤ - 2.5) in the whole spectrum of chronic kidney disease: a systematic review and meta-analysis.

The prevalence of low bone mineral density (LBMD) in people with chronic kidney disease (CKD) remains unknown. We identified a high prevalence of LBMD in CKD population. Thus, public health strategies should include efforts to prevent, early detect, and manage LBMD in CKD patients, especially in patients undergoing kidney replacement therapy. Mineral and bone disorders are common among patients with CKD, which affects bone mineral density. We conducted a systematic review and meta-analysis to estimate the prevalence of low bone mineral density (LBMD) in adults with CKD. We searched MEDLINE, EMBASE, Web of Science, CINAHL, and LILACS databases from inception to February 2021. Observational studies that reported the prevalence of LBMD in adults with CKD stages 3a-5D were included. The LBMD was defined according to the World Health Organization criterion (T-score ≤ - 2.5). Random-effect model meta-analyses were used to estimate the pooled prevalence of LBMD. Meta-regressions and subgroup analyses were conducted for stages of CKD, dialysis modality, gender, bone sites and morphology, and geographical region. This study was registered in PROSPERO, number CRD42020211077. One-hundred and fifty-three studies with 78,092 patients were included. The pooled global prevalence of LBMD in CKD was 24.5% (95% CI, 21.3 - 27.8%). Subgroup analyses indicated a higher prevalence of LBMD in dialysis patients (30%, 95% CI 25 - 35%) compared with non-dialysis CKD patients (12%, 95% CI 8 - 16%), cortical bone sites (28%, 95% CI 23 - 35%) relative to trabecular sites (19%, 95% CI 14 - 24%), while similar estimates in the European and the Asiatic continents (26%, 95% CI 21 - 30% vs 25%, 95% CI 21 - 29). The prevalence of LBMD in CKD patients is high, particularly in those undergoing dialysis and in cortical bone sites. Therefore, efforts to early diagnosis and management strategies should be implemented in clinical routine for an epidemiological control of LBMD in CKD patients.

Novel Approach to Intradialytic Progressive Resistance Exercise Training.

Physical activity levels are typically undesirably low in chronic kidney disease patients, especially in those undergoing haemodialysis, and particularly on dialysis days. Intradialytic exercise programmes could be a solution to this issue and have been reported to be safe and relatively easily implemented in dialysis clinics. Nevertheless, such implementation has been failing in part due to barriers such as the lack of funding, qualified personnel, equipment, and patient motivation. Intradialytic aerobic exercise has been the most used type of intervention in dialysis clinics. However, resistance exercise may be superior in eliciting potential benefits on indicators of muscle strength and mass. Yet, few intradialytic exercise programmes have focused on this type of intervention, and the ones which have report inconsistent benefits, diverging on prescribed exercise intensity, absent or subjective load progression, equipment availability, or exercise supervision. Commonly, intradialytic resistance exercise interventions use free weights, ankle cuffs, or elastic bands which hinder load progression and exercise intensity monitoring. Here, we introduce a recently developed intradialytic resistance exercise device and propose an accompanying innovative resistance exercise training protocol which aims to improve the quality of resistance exercise interventions within dialysis treatment sessions.

The Potential Modulatory Effects of Exercise on Skeletal Muscle Redox Status in Chronic Kidney Disease.

Chronic Kidney Disease (CKD) is a global health burden with high mortality and health costs. CKD patients exhibit lower cardiorespiratory and muscular fitness, strongly associated with morbidity/mortality, which is exacerbated when they reach the need for renal replacement therapies (RRT). Muscle wasting in CKD has been associated with an inflammatory/oxidative status affecting the resident cells' microenvironment, decreasing repair capacity and leading to atrophy. Exercise may help counteracting such effects; however, the molecular mechanisms remain uncertain. Thus, trying to pinpoint and understand these mechanisms is of particular interest. This review will start with a general background about myogenesis, followed by an overview of the impact of redox imbalance as a mechanism of muscle wasting in CKD, with focus on the modulatory effect of exercise on the skeletal muscle microenvironment.

Genetic Ablation of Inositol 1,4,5-Trisphosphate Receptor Type 2 (IP3R2) Fails to Modify Disease Progression in a Mouse Model of Spinocerebellar Ataxia Type 3.

Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease caused by an abnormal polyglutamine expansion within the ataxin-3 protein (ATXN3). This leads to neurodegeneration of specific brain and spinal cord regions, resulting in a progressive loss of motor function. Despite neuronal death, non-neuronal cells, including astrocytes, are also involved in SCA3 pathogenesis. Astrogliosis is a common pathological feature in SCA3 patients and animal models of the disease. However, the contribution of astrocytes to SCA3 is not clearly defined. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant IP3R in mediating astrocyte somatic calcium signals, and genetically ablation of IP3R2 has been widely used to study astrocyte function. Here, we aimed to investigate the relevance of IP3R2 in the onset and progression of SCA3. For this, we tested whether IP3R2 depletion and the consecutive suppression of global astrocytic calcium signalling would lead to marked changes in the behavioral phenotype of a SCA3 mouse model, the CMVMJD135 transgenic line. This was achieved by crossing IP3R2 null mice with the CMVMJD135 mouse model and performing a longitudinal behavioral characterization of these mice using well-established motor-related function tests. Our results demonstrate that IP3R2 deletion in astrocytes does not modify SCA3 progression.

Validity of the Paediatric Canadian Triage Acuity Scale in a Tertiary Hospital: An Analysis of Severity Markers' Variability.

With the increasing influx of patients and frequent overcrowding, the adoption of a valid triage system, capable of distinguishing patients who need urgent care, from those who can wait safely is paramount. Hence, the aim of this study is to evaluate the validity of the Paediatric Canadian Triage and Acuity Scale (PaedCTAS) in a Portuguese tertiary hospital. Furthermore, we aim to study the performance and appropriateness of the different surrogate severity markers to validate triage. This is a retrospective study considering all visits to the hospital's Paediatric Emergency Department (PED) between 2014 and 2019. This study considers cut-offs on all triage levels for dichotomization in order to calculate validity measures e.g. sensitivity, specificity and likelihood ratios, ROC curves; using hospital admission, admission to intensive care and the use of resources as outcomes/markers of severity. Over the study period there were 0.2% visits triaged as Level 1, 5.7% as Level 2, 39.4% as Level 3, 50.5% as Level 4, 4.2% as Level 5, from a total of 452,815 PED visits. The area under ROC curve was 0.96, 0.71, 0.76, 0.78, 0.59 for the surrogate markers: "Admitted to intensive care"; "Admitted to intermediate care"; "Admitted to hospital"; "Investigations performed in the PED" and "Uses PED resources", respectively. The association found between triage levels and the surrogate markers of severity suggests that the PedCTAS is highly valid. Different surrogate outcome markers convey different degrees of severity, hence different degrees of urgency. Therefore, the cut-offs to calculate validation measures and the thresholds of such measures should be chosen accordingly.

Comparison between concentration and type of intracellular cryoprotectants and the presence of sucrose for cryobanks of somatic cells derived from captive Pumas.

The loss of wild biodiversity has prompted the development of cryobanks, such as those of somatic cells. This is the reality of Pumas, wild felids of ecological importance that suffer from anthropogenic actions, population decline, and subsequent loss of genetic diversity. Somatic cell banks are a strategy for conserving population diversity. We compared different concentrations and types of intracellular cryoprotectants (dimethyl sulfoxide, DMSO; ethylene glycol, EG) associated with 0.2 M of sucrose (SUC) in the cryopreservation of the somatic cells of captive Pumas. The cells were cryopreserved by slow freezing with different solutions containing Dulbecco's modified Eagle's medium with 10% fetal bovine serum and varying concentrations of DMSO and EG in the absence or presence of SUC. The cells were analyzed for morphological characteristics, viability, proliferative activity, metabolic activity, and apoptosis levels. Cells maintained similar fusiform morphology before and after cryopreservation. There was no difference in viability, regardless of the reduction in the concentration and type of intracellular cryoprotectants and sucrose. Similarly, proliferative activity, metabolic activity, and apoptosis levels were not altered by the composition of the cryoprotectants. In summary, we demonstrate that reducing the concentration of DMSO or EG ensures adequate cryopreservation of Puma somatic cells, regardless of the presence of SUC.

Predator responses to prey camouflage strategies: a meta-analysis.

Although numerous studies about camouflage have been conducted in the last few decades, there is still a significant gap in our knowledge about the magnitude of protective value of different camouflage strategies in prey detection and survival. Furthermore, the functional significance of several camouflage strategies remains controversial. Here we carried out a comprehensive meta-analysis including comparisons of different camouflage strategies as well as predator and prey types, considering two response variables: mean predator search time (ST) (63 studies) and predator attack rate (AR) of camouflaged prey (28 studies). Overall, camouflage increased the predator ST by 62.56% and decreased the AR of prey by 27.34%. Masquerade was the camouflage strategy that most increased predator ST (295.43%). Background matching and disruptive coloration did not differ from each other. Motion camouflage did not increase ST but decreases AR on prey. We found no evidence that eyespot increases ST and decreases AR by predators. The different types of predators did not differ from each other, but caterpillars were the type of prey that most influenced the magnitude of camouflage's effect. We highlight the potential evolutionary mechanisms that led camouflage to be a highly effective anti-predatory adaptation, as well as potential discrepancies or redundancies among strategies, predator and prey types.

Impact of multiple selective breeding programs on genetic diversity in soybean germplasm.

KEY MESSAGE: Independent soybean breeding programs shape genetic diversity from unimproved germplasm to modern cultivars in similar ways, but distinct breeding populations retain unique genetic variation, preserving additional diversity. From the domestication of wild soybean (Glycine soja Sieb. & Zucc.), over 3,000 years ago, to the modern soybean (Glycine max L. Merr) cultivars that provide much of the world's oil and protein, soybean populations have undergone fundamental changes. We evaluated the molecular impact of breeding and selection using 391 soybean accessions including US cultivars and their progenitors from the USDA Soybean Germplasm Collection (CGP), plus two new populations specifically developed to increase genetic diversity and high yield in two alternative gene pools: one derived from exotic G. max germplasm (AGP) and one derived from G. soja (SGP). Reduction in nucleotide genetic diversity (π) was observed with selection within gene pools, but artificial selection in the AGP maintained more diversity than in the CGP. The highest FST levels were seen between ancestral and elite lines in all gene pools, but specific nucleotide-level patterns varied between gene pools. Population structure analyses support that independent selection resulted in high-yielding elite lines with similar allelic compositions in the AGP and CGP. SGP, however, produced elite progeny that were well differentiated from, but lower yielding than, CGP elites. Both the AGP and SGP retained a significant number of private alleles that are absent in CGP. We conclude that the genomic diversity shaped by multiple selective breeding programs can result in gene pools of highly productive elite lines with similar allelic compositions in a genome-wide perspective. Breeding programs with different ancestral lines, however, can retain private alleles representing unique genetic diversity.

Inflammation and physical dysfunction: responses to moderate intensity exercise in chronic kidney disease.

BACKGROUND: People with chronic kidney disease (CKD) experience skeletal muscle wasting, reduced levels of physical function and performance, and chronic systemic inflammation. While it is known that a relationship exists between inflammation and muscle wasting, the association between inflammation and physical function or performance in CKD has not been well studied. Exercise has anti-inflammatory effects, but little is known regarding the effect of moderate intensity exercise. This study aimed to (i) compare systemic and intramuscular inflammation between CKD stage G3b-5 and non-CKD controls; (ii) establish whether a relationship exists between physical performance, exercise capacity and inflammation in CKD; (iii) determine changes in systemic and intramuscular inflammation following 12 weeks of exercise; and (iv) investigate whether improving inflammatory status via training contributes to improvements in physical performance and muscle mass. METHODS: This is a secondary analysis of previously collected data. CKD patients stages G3b-5 (n = 84, n = 43 males) and non-CKD controls (n = 26, n = 17 males) underwent tests of physical performance, exercise capacity, muscle strength and muscle size. In addition, a subgroup of CKD participants underwent 12 weeks of exercise training, randomized to aerobic (AE, n = 21) or combined (CE, n = 20) training. Plasma and intramuscular inflammation and myostatin were measured at rest and following exercise. RESULTS: Tumour necrosis factor-α was negatively associated with lower $^{^{^{.}}}{\rm V}$O2Peak (P = 0.01), Rectus femoris-cross sectional area (P = 0.002) and incremental shuttle walk test performance (P < 0.001). Interleukin-6 was negatively associated with sit-to-stand 60 performances (P = 0.006) and hand grip strength (P = 0.001). Unaccustomed exercise created an intramuscular inflammatory response that was attenuated following 12 weeks of training. Exercise training did not reduce systemic inflammation, but AE training did significantly reduce mature myostatin levels (P = 0.02). Changes in inflammation were not associated with changes in physical performance. CONCLUSIONS: Systemic inflammation may contribute to reduced physical function in CKD. Twelve weeks of exercise training was unable to reduce the level of chronic systemic inflammation in these patients, but did reduce plasma myostatin concentrations. Further research is required to further investigate this.

Torquetenovirus viral load is associated with anti-spike antibody response in SARS-CoV-2 mRNA BNT162b2 vaccinated kidney transplant patients.

INTRODUCTION: Kidney transplant patients (KT) are at high risk for severe COVID-19 and presented attenuated antibody responses to vaccination when compared to immunocompetent individuals. Torquetenovirus (TTV) has recently gained attention as a potential surrogate marker of the net state of immunosuppression. We evaluated the association between pre-vaccination TTV viral load and anti-spike total antibody response to SARS-CoV-2 vaccination in KT. MATERIAL AND METHODS: The 114 adult KT recipients enrolled in this prospective single-center cohort study received two doses of SARS-CoV-2 mRNA BNT162b2 vaccine. Serum samples were collected immediately before vaccination at the days when patients received both the first (T0) and the second dose (T1) and 16-45 days after the second dose (T2). Primary endpoint was the development of anti-spike total antibodies after vaccination. Demographic, clinical, and laboratorial parameters were compared between patients with and without detectable SARS-CoV-2 antibodies at T2. RESULTS: Ninety-nine patients (86.8%) were naïve for SARS-CoV-2 before vaccination. Fifty-six (56.6%) patients developed anti-spike total antibodies at T2. The use of mTOR inhibitors was associated with a favorable response (p = .005); conversely, mycophenolic acid (MPA) was associated with a negative response (p = .006). In a multivariable model, the presence of TTV at T0 ≥ 3.36 log10 cp/ml was associated with unfavorable vaccine response (OR: 5.40; 95% CI: 1.47-19.80; p = .011), after adjusting for age and eGFR at T0. CONCLUSIONS: Higher TTV viral loads before vaccination are associated with reduced anti-spike total antibody response in SARS-CoV-2 mRNA BNT162b2 vaccinated KT patients. The association between TTV viral load and vaccine response may be an added-value in the optimization of vaccination regimens in KT.

Multisource and temporal variability in Portuguese hospital administrative datasets: Data quality implications.

BACKGROUND: Unexpected variability across healthcare datasets may indicate data quality issues and thereby affect the credibility of these data for reutilization. No gold-standard reference dataset or methods for variability assessment are usually available for these datasets. In this study, we aim to describe the process of discovering data quality implications by applying a set of methods for assessing variability between sources and over time in a large hospital database. METHODS: We described and applied a set of multisource and temporal variability assessment methods in a large Portuguese hospitalization database, in which variation in condition-specific hospitalization ratios derived from clinically coded data were assessed between hospitals (sources) and over time. We identified condition-specific admissions using the Clinical Classification Software (CCS), developed by the Agency of Health Care Research and Quality. A Statistical Process Control (SPC) approach based on funnel plots of condition-specific standardized hospitalization ratios (SHR) was used to assess multisource variability, whereas temporal heat maps and Information-Geometric Temporal (IGT) plots were used to assess temporal variability by displaying temporal abrupt changes in data distributions. Results were presented for the 15 most common inpatient conditions (CCS) in Portugal. MAIN FINDINGS: Funnel plot assessment allowed the detection of several outlying hospitals whose SHRs were much lower or higher than expected. Adjusting SHR for hospital characteristics, beyond age and sex, considerably affected the degree of multisource variability for most diseases. Overall, probability distributions changed over time for most diseases, although heterogeneously. Abrupt temporal changes in data distributions for acute myocardial infarction and congestive heart failure coincided with the periods comprising the transition to the International Classification of Diseases, 10th revision, Clinical Modification, whereas changes in the Diagnosis-Related Groups software seem to have driven changes in data distributions for both acute myocardial infarction and liveborn admissions. The analysis of heat maps also allowed the detection of several discontinuities at hospital level over time, in some cases also coinciding with the aforementioned factors. CONCLUSIONS: This paper described the successful application of a set of reproducible, generalizable and systematic methods for variability assessment, including visualization tools that can be useful for detecting abnormal patterns in healthcare data, also addressing some limitations of common approaches. The presented method for multisource variability assessment is based on SPC, which is an advantage considering the lack of gold standard for such process. Properly controlling for hospital characteristics and differences in case-mix for estimating SHR is critical for isolating data quality-related variability among data sources. The use of IGT plots provides an advantage over common methods for temporal variability assessment due its suitability for multitype and multimodal data, which are common characteristics of healthcare data. The novelty of this work is the use of a set of methods to discover new data quality insights in healthcare data.