Predicted genetic burden and frequency of phenotype-associated variants in the horse.

Disease-causing variants have been identified for less than 20% of suspected equine genetic diseases. Whole genome sequencing (WGS) allows rapid identification of rare disease causal variants. However, interpreting the clinical variant consequence is confounded by the number of predicted deleterious variants that healthy individuals carry (predicted genetic burden). Estimation of the predicted genetic burden and baseline frequencies of known deleterious or phenotype associated variants within and across the major horse breeds have not been performed. We used WGS of 605 horses across 48 breeds to identify 32,818,945 variants, demonstrate a high predicted genetic burden (median 730 variants/horse, interquartile range: 613-829), show breed differences in predicted genetic burden across 12 target breeds, and estimate the high frequencies of some previously reported disease variants. This large-scale variant catalog for a major and highly athletic domestic animal species will enhance its ability to serve as a model for human phenotypes and improves our ability to discover the bases for important equine phenotypes.

Identifying acute illness phenotypes via deep temporal interpolation and clustering network on physiologic signatures.

Using clustering analysis for early vital signs, unique patient phenotypes with distinct pathophysiological signatures and clinical outcomes may be revealed and support early clinical decision-making. Phenotyping using early vital signs has proven challenging, as vital signs are typically sampled sporadically. We proposed a novel, deep temporal interpolation and clustering network to simultaneously extract latent representations from irregularly sampled vital signs and derive phenotypes. Four distinct clusters were identified. Phenotype A (18%) had the greatest prevalence of comorbid disease with increased prevalence of prolonged respiratory insufficiency, acute kidney injury, sepsis, and long-term (3-year) mortality. Phenotypes B (33%) and C (31%) had a diffuse pattern of mild organ dysfunction. Phenotype B's favorable short-term clinical outcomes were tempered by the second highest rate of long-term mortality. Phenotype C had favorable clinical outcomes. Phenotype D (17%) exhibited early and persistent hypotension, high incidence of early surgery, and substantial biomarker incidence of inflammation. Despite early and severe illness, phenotype D had the second lowest long-term mortality. After comparing the sequential organ failure assessment scores, the clustering results did not simply provide a recapitulation of previous acuity assessments. This tool may impact triage decisions and have significant implications for clinical decision-support under time constraints and uncertainty.

Genomic wide association study and selective sweep analysis identify genes associated with improved yield under drought in Turkish winter wheat germplasm.

A panel comprising of 84 Turkish winter wheat landraces (LR) and 73 modern varieties (MV) was analyzed with genome wide association study (GWAS) to identify genes/genomic regions associated with increased yield under favorable and drought conditions. In addition, selective sweep analysis was conducted to detect signatures of selection in the winter wheat genome driving the differentiation between LR and MV, to gather an understanding of genomic regions linked to adaptation and yield improvement. The panel was genotyped with 25 K wheat SNP array and phenotyped for agronomic traits for two growing seasons (2018 and 2019) in Konya, Turkey. Year 2018 was treated as drought environment due to very low precipitation prior to heading whereas year 2019 was considered as a favorable season. GWAS conducted with SNPs and haplotype blocks using mixed linear model identified 18 genomic regions in the vicinities of known genes i.e., TaERF3-3A, TaERF3-3B, DEP1-5A, FRIZZY PANICLE-2D, TaSnRK23-1A, TaAGL6-A, TaARF12-2A, TaARF12-2B, WAPO1, TaSPL16-7D, TaTGW6-A1, KAT-2B, TaOGT1, TaSPL21-6B, TaSBEIb, trs1/WFZP-A, TaCwi-A1-2A and TaPIN1-7A associated with grain yield (GY) and yield related traits. Haplotype-based GWAS identified five haplotype blocks (H1A-42, H2A-71, H4A-48, H7B-123 and H7B-124), with the favorable haplotypes showing a yield increase of > 700 kg/ha in the drought season. SNP-based GWAS, detected only one larger effect genomic region on chromosome 7B, in common with haplotype-based GWAS. On an average, the percentage variation (PV) explained by haplotypes was 8.0% higher than PV explained by SNPs for all the investigated traits. Selective sweep analysis detected 39 signatures of selection between LR and MV of which 15 were within proximity of known functional genes controlling flowering (PRR-A1, PPR-D1, TaHd1-6B), GY and GY components (TaSus2-2B, TaGS2-B1, AG1-1A/WAG1-1A, DUO-A1, DUO-B1, AG2-3A/WAG2-3A, TaLAX1, TaSnRK210-4A, FBP, TaLAX1, TaPIL1 and AP3-1-7A/WPA3-7A) and 10 regions underlying various transcription factors and regulatory genes. The study outcomes contribute to utilization of LR in breeding winter wheat.

Mutation mapping of a variegated EMS tomato reveals an FtsH-like protein precursor potentially causing patches of four phenotype classes in the leaves with distinctive internal morphology.

BACKGROUND: Leaf variegation is an intriguing phenomenon observed in many plant species. However, questions remain on its mechanisms causing patterns of different colours. In this study, we describe a tomato plant detected in an M2 population of EMS mutagenised seeds, showing variegated leaves with sectors of dark green (DG), medium green (MG), light green (LG) hues, and white (WH). Cells and tissues of these classes, along with wild-type tomato plants, were studied by light, fluorescence, and transmission electron microscopy. We also measured chlorophyll a/b and carotene and quantified the variegation patterns with a machine-learning image analysis tool. We compared the genomes of pooled plants with wild-type-like and mutant phenotypes in a segregating F2 population to reveal candidate genes responsible for the variegation. RESULTS: A genetic test demonstrated a recessive nuclear mutation caused the variegated phenotype. Cross-sections displayed distinct anatomy of four-leaf phenotypes, suggesting a stepwise mesophyll degradation. DG sectors showed large spongy layers, MG presented intercellular spaces in palisade layers, and LG displayed deformed palisade cells. Electron photomicrographs of those mesophyll cells demonstrated a gradual breakdown of the chloroplasts. Chlorophyll a/b and carotene were proportionally reduced in the sectors with reduced green pigments, whereas white sectors have hardly any of these pigments. The colour segmentation system based on machine-learning image analysis was able to convert leaf variegation patterns into binary images for quantitative measurements. The bulk segregant analysis of pooled wild-type-like and variegated progeny enabled the identification of SNP and InDels via bioinformatic analysis. The mutation mapping bioinformatic pipeline revealed a region with three candidate genes in chromosome 4, of which the FtsH-like protein precursor (LOC100037730) carries an SNP that we consider the causal variegated phenotype mutation. Phylogenetic analysis shows the candidate is evolutionary closest to the Arabidopsis VAR1. The synonymous mutation created by the SNP generated a miRNA binding site, potentially disrupting the photoprotection mechanism and thylakoid development, resulting in leaf variegation. CONCLUSION: We described the histology, anatomy, physiology, and image analysis of four classes of cell layers and chloroplast degradation in a tomato plant with a variegated phenotype. The genomics and bioinformatics pipeline revealed a VAR1-related FtsH mutant, the first of its kind in tomato variegation phenotypes. The miRNA binding site of the mutated SNP opens the way to future studies on its epigenetic mechanism underlying the variegation.

VDR promotes pancreatic cancer progression in vivo by activating CCL20-mediated M2 polarization of tumor associated macrophage.

BACKGROUND: Activation of VDR pathway was a promising anti-tumor therapy strategy. However, numerous clinical studies have demonstrated the effect of activating VDR is limited, which indicates that VDR plays a complex role in vivos. METHODS: We analyzed the TCGA database to examine the association between VDR expression and immune cell infiltration in pancreatic adenocarcinoma (PAAD). Western blot, ELISA, ChIP, and dual-luciferase reporter assays were performed to determine the mechanism of VDR regulating CCL20. Migration assay and immunofluorescence were used to investigate the role of CCL20 in M2 macrophage polarization and recruitment. We employed multiplexed immunohistochemical staining and mouse models to validate the correlation of VDR on macrophages infiltration in PAAD. Flow cytometry analysis of M2/M1 ratio in subcutaneous graft tumors. RESULTS: VDR is extensively expressed in PAAD, and patients with elevated VDR levels exhibited a significantly reduced overall survival. VDR expression in PAAD tissues was associated with increased M2 macrophages infiltration. PAAD cells overexpressing VDR promote macrophages polarization towards M2 phenotype and recruitment in vitro and vivo. Mechanistically, VDR binds to the CCL20 promoter and up-regulates its transcription. The effects of polarization and recruitment on macrophages can be rescued by blocking CCL20. Finally, the relationship between VDR and M2 macrophages infiltration was evaluated using clinical cohort and subcutaneous graft tumors. A positive correlation was demonstrated between VDR/CCL20/CD163 in PAAD tissues and mouse models. CONCLUSION: High expression of VDR in PAAD promotes M2 macrophage polarization and recruitment through the secretion of CCL20, which activates tumor progression. This finding suggests that the combination of anti-macrophage therapy may improve the efficacy of VDR activation therapy in PAAD.

Phenotypes and outcome of diffuse pulmonary non-amyloid light chain deposition disease.

BACKGROUND: Light chain deposition disease (LCDD) is a very rare entity. Clinical manifestations of LCDD vary according to the organs involved. Data on pulmonary LCDD are scarce and limited to small series or case reports. This study aimed to describe the characteristics and outcome of diffuse pulmonary non-amyloid LCDD localized to the lungs. STUDY DESIGN AND METHODS: A multicenter retrospective cohort study was conducted. Clinical characteristics were collected, and chest CTs were centrally reviewed. The diagnosis of pulmonary non-amyloid LCDD was confirmed by immunohistochemistry. RESULTS: Thirty-one cases were identified (68% female), with a median age at diagnosis of 50 years (IQR 20). Baseline FEV1/FVC was < 0.70 in 45% of patients. Mean (± SD) FEV1 and DLCO were 86% ± 26.2 and 52% ± 23.9, respectively. CT revealed peculiar patterns of thin-walled cysts (58%) and thin-walled cystic bronchiectases (27%). Increased serum kappa light chain was found in 87% of patients. Histological analysis showed kappa light chain deposits in all patients, except one with lambda chain deposits. Median annual FEV1 decline was 127 ml (IQR 178) and median DLCO decline was 4.3% (IQR 4.3). Sixteen patients received immunomodulatory treatment or chemotherapy; serum light chain levels decreased in 9 cases (75%), without significant improvement in FEV1 (p = 0.173). Overall, 48% of patients underwent bilateral lung transplantation. Transplant-free survival at 5 and 10 years were 70% and 30%, respectively. An annual FEV1 decline greater than 127 ml/year was associated with increased risk of death or transplantation (p = 0.005). CONCLUSIONS: Diffuse pulmonary LCDD is characterised by female predominance, a peculiar imaging pattern with bronchiectasis and/or cysts, progressive airway obstruction and severe DLCO impairment, and poor outcome. Lung transplantation is a treatment of choice.

Pre-breeding of spontaneous Robertsonian translocations for density planting architecture by transferring Agropyron cristatum chromosome 1P into wheat.

KEY MESSAGE: We developed T1AL·1PS and T1AS·1PL Robertsonian translocations by breakage-fusion mechanism based on wheat-A. cristatum 1P(1A) substitution line with smaller leaf area, shorter plant height, and other excellent agronomic traits Agropyron cristatum, a wild relative of wheat, is a valuable germplasm resource for improving wheat genetic diversity and yield. Our previous study confirmed that the A. cristatum chromosome 1P carries alien genes that reduce plant height and leaf size in wheat. Here, we developed T1AL·1PS and T1AS·1PL Robertsonian translocations (RobTs) by breakage-fusion mechanism based on wheat-A. cristatum 1P (1A) substitution line II-3-1c. Combining molecular markers and cytological analysis, we identified 16 spontaneous RobTs from 911 F2 individuals derived from the cross of Jimai22 and II-3-1c. Fluorescence in situ hybridization (FISH) was applied to detect the fusion structures of the centromeres in wheat and A. cristatum chromosomes. Resequencing results indicated that the chromosomal junction point was located at the physical position of Triticum aestivum chromosome 1A (212.5 Mb) and A. cristatum chromosome 1P (230 Mb). Genomic in situ hybridization (GISH) in pollen mother cells showed that the produced translocation lines could form stable ring bivalent. Introducing chromosome 1PS translocation fragment into wheat significantly increased the number of fertile tillers, grain number per spike, and grain weight and reduced the flag leaf area. However, introducing chromosome 1PL translocation fragment into wheat significantly reduced flag leaf area and plant height with a negative effect on yield components. The pre-breeding of two spontaneous RobTs T1AL·1PS and T1AS·1PL was important for wheat architecture improvement.

A High-Throughput Approach for Photosynthesis Studies in a Brassicaceae Panel.

The study of natural variations in photosynthesis in the Brassicaceae family offers the possibility of identifying mechanisms to enhance photosynthetic efficiency in crop plants. Indeed, this family, and particularly its tribe Brassiceae, has been shown to harbor species that have a higher-than-expected photosynthetic efficiency, possibly as a result of a complex evolutionary history. Over the past two decades, methods have been developed to measure photosynthetic efficiency based on chlorophyll fluorescence. Chlorophyll fluorescence measurements are performed with special cameras, such as the FluorCams, which can be included in robotic systems to create high-throughput phenotyping platforms. While these platforms have so far demonstrated high efficiency in measuring small model species like Arabidopsis thaliana, they have the drawback of limited adaptability to accommodate different plant sizes. As a result, the range of species that can be analyzed is restricted. This chapter presents our approach to analyze the photosynthetic parameters: ϕPSII and Fv/Fm for a panel of Brassicaceae species, including a high-photosynthesis species, Hirschfeldia incana, and the adaptations to the phenotyping platform that are required to accommodate this varied group of plants.

Physiotyping of Plants and Modeling the Soil Plant Atmospheric Continuum (SPAC).

This chapter presents a holistic and quantitative approach to the carbon cycle in plant systems biology. It includes (rapid) phenotyping and monitoring of physiological key interactions of plants with its respective soil and atmospheric environment (soil plant atmospheric continuum-SPAC). The approach aims at qualifying and quantifying key components of this microhabitat as influenced by a single plant or a local group of plants in order to contribute to a flux-based modelling approach. The toolset consists of plant biometry, gas exchange, metabolomics, ionomics, root exudate characterization as well as soil biological and physical-chemical characterization. The results are presented as a basic interaction and input-output model aka conceptual system model employing H. T. Odum-style plots based on empirical data.

Methods for Functional Physiological Phenotyping and High-Order Data Quantification.

This chapter presents the application of Plantarray, a high-throughput platform commercially available for noninvasive monitoring of plant functional physiology phenotyping (FPP). The platform continuously measures water flux in the soil-plant-atmosphere for each plant in dynamic environments. To better interpret the massive phenotypic data acquired with FPP, several quantitative analysis methods were demonstrated for various types of data. Simple mathematical models were utilized to fit characteristic parameters of plant transpiration response to drought stress. Additionally, ecophysiological models were employed to quantify the sensitivity of transpiration to radiation and vapor pressure deficit (VPD) as component traits and predict more complex higher-order traits. The established protocols provide a tangible tool for integrating FPP and model analysis to address complex traits.

An Overview of High-Throughput Crop Phenotyping: Platform, Image Analysis, Data Mining, and Data Management.

In this chapter, we explore the application of high-throughput crop phenotyping facilities for phenotype data acquisition and the extraction of significant information from the collected data through image processing and data mining methods. Additionally, the construction and outlook of crop phenotype databases are introduced and the need for global cooperation and data sharing is emphasized. High-throughput crop phenotyping significantly improves accuracy and efficiency compared to traditional measurements, making significant contributions to overcoming bottlenecks in the phenotyping field and advancing crop genetics.

QTL Mapping Using RIL Population.

Genetic maps are an excellent tool for the analysis of important traits, the development of which is the result of the combined expression of several genes, enabling the genomic localization of the factors determining them. Such features, characterized by a normal distribution of values, are referred to as quantitative or polygenic. The analysis of their genetic background using a chromosome map is called the mapping of quantitative traits loci (QTL). QTL analysis is a statistical method of determining the genetic association of phenotypic data (trait measurements) with genotypic data (DNA markers assigned to linkage groups).There are numerous tools developed for QTL mapping. This chapter introduces Windows QTL Cartographer with Composite Interval Mapping (CIM) method, which estimates the QTL position by combining interval mapping with multiple regression. The genotypic and phenotypic data used in the exemplary QTL mapping procedure were obtained for the recombinant inbred line (RIL) population of rye. Plant height, assessed in three seasons, was the exemplary trait under study.

Phenotypic and Genotypic Methods for the Identification and Quantification of Cyanobacteria in Lake Water.

Early monitoring of Microcystis, a cyanobacterium that produces microcystin, is paramount in order to confirm the presence of Microcystis spp. Both phenotypic and genotypic methods have been used. The phenotypic methods provide the presence of the microcystis but do not confirm its species type and toxin produced. Additionally, phenotypic methods cannot differentiate toxigenic from non-toxigenic Microcystis. Therefore, the current protocol also describes genetic methods based on PCR to detect toxigenic Microcystis spp. based on microcystin synthetase E (mcy E) gene and 16-23S RNA genes for species-specific identification, which can effectively comprehend distinct lineages and discrimination of potential complexity of microcystin populations. The presence of these microcystin toxins in blood, in most cases, indicates contamination of drinking water by cyanobacteria. The methods presented herein are used to identify microcystin toxins in drinking water and blood.

4R-cembranoid suppresses glial cells inflammatory phenotypes and prevents hippocampal neuronal loss in LPS-treated mice.

Chronic neuroinflammation has been implicated in neurodegenerative disease pathogenesis. A key feature of neuroinflammation is neuronal loss and glial activation, including microglia and astrocytes. 4R-cembranoid (4R) is a natural compound that inhibits hippocampal pro-inflammatory cytokines and increases memory function in mice. We used the lipopolysaccharide (LPS) injection model to study the effect of 4R on neuronal density and microglia and astrocyte activation. C57BL/6J wild-type mice were injected with LPS (5 mg/kg) and 2 h later received either 4R (6 mg/kg) or vehicle. Mice were sacrificed after 72 h for analysis of brain pathology. Confocal images of brain sections immunostained for microglial, astrocyte, and neuronal markers were used to quantify cellular hippocampal phenotypes and neurons. Hippocampal lysates were used to measure the expression levels of neuronal nuclear protein (NeuN), inducible nitrous oxide synthase (iNOS), arginase-1, thrombospondin-1 (THBS1), glial cell-derived neurotrophic factor (GDNF), and orosomucoid-2 (ORM2) by western blot. iNOS and arginase-1 are widely used protein markers of pro- and anti-inflammatory microglia, respectively. GDNF promotes neuronal survival, and ORM2 and THBS1 are astrocytic proteins that regulate synaptic plasticity and inhibit microglial activation. 4R administration significantly reduced neuronal loss and the number of pro-inflammatory microglia 72 h after LPS injection. It also decreased the expression of the pro-inflammatory protein iNOS while increasing arginase-1 expression, supporting its anti-inflammatory role. The protein expression of THBS1, GDNF, and ORM2 was increased by 4R. Our data show that 4R preserves the integrity of hippocampal neurons against LPS-induced neuroinflammation in mice.

Trans-eQTL mapping in gene sets identifies network effects of genetic variants.

Nearly all trait-associated variants identified in genome-wide association studies (GWASs) are noncoding. The cis regulatory effects of these variants have been extensively characterized, but how they affect gene regulation in trans has been the subject of fewer studies because of the difficulty in detecting trans-expression quantitative loci (eQTLs). We developed trans-PCO for detecting trans effects of genetic variants on gene networks. Our simulations demonstrate that trans-PCO substantially outperforms existing trans-eQTL mapping methods. We applied trans-PCO to two gene expression datasets from whole blood, DGN (N = 913) and eQTLGen (N = 31,684), and identified 14,985 high-quality trans-eSNP-module pairs associated with 197 co-expression gene modules and biological processes. We performed colocalization analyses between GWAS loci of 46 complex traits and the trans-eQTLs. We demonstrated that the identified trans effects can help us understand how trait-associated variants affect gene regulatory networks and biological pathways.

Resistance phenotype and virulence potential of Leclercia adecarboxylata strains isolated from different sources.

Introduction. Leclercia adecarboxylata is a member of Enterobacterales, often considered an opportunistic pathogen. Recent reports have highlighted L. adecarboxylata as an emerging pathogen harbouring virulence and resistance determinants.Gap statement. Little information exists on virulence and resistance determinants in L. adecarboxylata strains isolated from environmental, food, and clinical samples.Aim. To determine the presence of resistance and virulence determinants and plasmid features in L. adecarboxylata strains isolated from environmental, food, and clinical samples, as well as their phylogenetic relationship.Results. All strains tested showed resistance to ß-lactams and quinolones but were sensitive to aminoglycosides and nitrofurans. However, even though fosfomycin resistance is considered a characteristic trait of L. adecarboxylata, the resistance phenotype was only observed in 50 % of the strains; bla TEM was the most prevalent BLEE gene (70 %), while the quinolone qnrB gene was observed in 60 % of the strains. Virulence genes were differentially observed in the strains, with adhesion-related genes being the most abundant, followed by toxin genes. Finally, all strains carried one to seven plasmid bands ranging from 7 to 125 kbps and harboured several plasmid addiction systems, such as ParDE, VagCD, and CcdAB in 80 % of the strains.Conclusions. L. adecarboxylata is an important emerging pathogen that may harbour resistance and virulence genes. Additionally, it has mobilizable genetic elements that may contribute to the dissemination of genetic determinants to other bacterial genera.

Long COVID exhibits clinically distinct phenotypes at 3-6 months post-SARS-CoV-2 infection: results from the P4O2 consortium.

BACKGROUND: Four months after SARS-CoV-2 infection, 22%-50% of COVID-19 patients still experience complaints. Long COVID is a heterogeneous disease and finding subtypes could aid in optimising and developing treatment for the individual patient. METHODS: Data were collected from 95 patients in the P4O2 COVID-19 cohort at 3-6 months after infection. Unsupervised hierarchical clustering was performed on patient characteristics, characteristics from acute SARS-CoV-2 infection, long COVID symptom data, lung function and questionnaires describing the impact and severity of long COVID. To assess robustness, partitioning around medoids was used as alternative clustering. RESULTS: Three distinct clusters of patients with long COVID were revealed. Cluster 1 (44%) represented predominantly female patients (93%) with pre-existing asthma and suffered from a median of four symptom categories, including fatigue and respiratory and neurological symptoms. They showed a milder SARS-CoV-2 infection. Cluster 2 (38%) consisted of predominantly male patients (83%) with cardiovascular disease (CVD) and suffered from a median of three symptom categories, most commonly respiratory and neurological symptoms. This cluster also showed a significantly lower forced expiratory volume within 1 s and diffusion capacity of the lung for carbon monoxide. Cluster 3 (18%) was predominantly male (88%) with pre-existing CVD and diabetes. This cluster showed the mildest long COVID, and suffered from symptoms in a median of one symptom category. CONCLUSIONS: Long COVID patients can be clustered into three distinct phenotypes based on their clinical presentation and easily obtainable information. These clusters show distinction in patient characteristics, lung function, long COVID severity and acute SARS-CoV-2 infection severity. This clustering can help in selecting the most beneficial monitoring and/or treatment strategies for patients suffering from long COVID. Follow-up research is needed to reveal the underlying molecular mechanisms implicated in the different phenotypes and determine the efficacy of treatment.

Are the ICHD-3 criteria for headache attributed to idiopathic intracranial hypertension valid? Headache phenotyping and field-testing in newly diagnosed idiopathic intracranial hypertension.

BACKGROUND: Headache burden is substantial in idiopathic intracranial hypertension. The classification of idiopathic intracranial hypertension headache by the International Classification of Headache Disorders (ICHD) is an important tool for research and clinical purposes. METHODS: We phenotyped headaches and tested sensitivity and specificity of the ICHD-3 criteria for idiopathic intracranial hypertension headache in a prospective cohort of patients suspected of idiopathic intracranial hypertension at two tertiary headache centers. RESULTS: Sensitivity was 93% and specificity was 100% of ICHD-3 criteria for idiopathic intracranial hypertension-related headache validated in idiopathic intracranial hypertension (n = 140) and patients in whom idiopathic intracranial hypertension was suspected but disproven (n = 103). The phenotype of new/worsened headaches related to idiopathic intracranial hypertension suspicion was equally migraine-like (p = 0.76) and tension-type-like (p = 0.08). Lumbar puncture opening pressure was higher (p < 0.0001) and pulsatile tinnitus more frequent (p < 0.0001) in idiopathic intracranial hypertension patients, but neither improved the applicability of the headache criteria, nor did papilledema. CONCLUSION: Headache phenotype is not distinct in idiopathic intracranial hypertension. ICHD-3 criteria for idiopathic intracranial hypertension headache are sensitive and specific, but simplicity can be improved without compromising accuracy. We propose that a new or worsened headache temporally related to active idiopathic intracranial hypertension is a sufficient criterion for idiopathic intracranial hypertension headache regardless of headache phenotype or accompanying symptoms, and that elements of idiopathic intracranial hypertension diagnostics (papilledema and opening pressure) be segregated from headache criteria.Trial Registration: ClinicalTrials.gov Identifier: NCT04032379.

Genetic parameters, genetic trends and correlated responses of growth traits considering maternal ability in Nelore cattle.

The growth of Nelore cattle was analysed considering the following performance parameters; the effect of the calving order of cows on the phenotypic expression of birth weight (BW), average daily gain from birth to weaning (BWG), and weaning weight (WW), the estimated genetic parameters for the traits, including the covariance components between direct and maternal genetic effects. Genetic trends and correlated responses were also obtained for the studied traits. The calving order of cows, as well as other fixed effects used to obtain the adjusted phenotypic means, were statistically significant (p < 0.001) for studied traits. Direct heritability was estimated at 0.24 ± 0.01 (BW), 0.15 ± 0.01 (BWG), and 0.18 ± 0.01 (WW), while maternal heritability was 0.06 ± 0.01 (BW), 0.12 ± 0.01 (BWG), and 0.11 ± 0.01 (WW). The correlations between direct and maternal effects within the same trait were negligible. Moderate to higher direct genetic correlations (ranging from 0.54 ± 0.04 to 0.98 ± 0.01) and maternal genetic correlations (ranging from 0.34 ± 0.09 to 0.99 ± 0.002) were estimated between the studied traits. Unlike direct genetic effects, there was no significant change in maternal genetic effects over time (p > 0.05). These results indicated the need for revising selection indexes for enhancing maternal ability. Correlated responses were generally lower compared to direct responses, except for BWG. The selection for BWG, considering the maternal genetic effect, would be more efficient to improve maternal ability of the cows for pre-weaning growth in relation to selection for WW. Our results found that direct genetic merit improves pre-weaning weight and this trait can be incorporated into the breeding goal as reflected in the WW.

Diagnostic yield of the chromosomal microarray analysis in turkish patients with unexplained development delay/intellectual disability(ID), autism spectrum disorders and/or multiple congenital anomalies and new clinical findings.

BACKGROUND: Chromosomal microarray analysis is an essential tool for copy number variants detection in patients with unexplained developmental delay/intellectual disability, autism spectrum disorders, and multiple congenital anomalies. The study aims to determine the clinical significance of chromosomal microarray analysis in this patient group. Another crucial aspect is the evaluation of copy number variants detected in terms of the diagnosis of patients. METHODS AND RESULTS: A Chromosomal microarray analysis was was conducted on a total of 1227 patients and phenotype-associated etiological diagnosis was established in 135 patients. Phenotype-associated copy number variants were detected in 11% of patients. Among these, 77 patients 77 (57%, 77/135) were diagnosed with well-recognized genetic syndromes and phenotype-associated copy number variants were found in 58 patients (42.9%, 58/135). The study was designed to collect data of patients in Kocaeli Derince Training and Research Hospital retrospectively. In our study, we examined 135 cases with clinically significant copy number variability among all patients. CONCLUSIONS: In this study, chromosomal microarray analysis revealed pathogenic de novo copy number variants with new clinical features. Chromosomal microarray analysis in the Turkish population has been reported in the largest patient cohort to date.