[Clinical phenotyping of severe Mycoplasma pneumoniae pneumonia in children].

Objective: To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods: This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children's Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results: Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions: Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.

Pyramiding of triple Clubroot resistance loci conferred superior resistance without negative effects on agronomic traits in Brassica napus.

Clubroot disease caused by Plasmodiophora brassicae is becoming a serious threat to rapeseed (Brassica napus) production worldwide. Breeding resistant varieties using CR (clubroot resistance) loci is the most promising solution. Using marker-assisted selection and speed-breeding technologies, we generated Brassica napus materials in homozygous or heterozygous states using CRA3.7, CRA08.1, and CRA3.2 loci in the elite parental line of the Zhongshuang11 background. We developed three elite lines with two CR loci in different combinations and one line with three CR loci at the homozygous state. In our study, we used six different clubroot strains (Xinmin, Lincang, Yuxi, Chengdu, Chongqing, and Jixi) which are categorized into three groups based on our screening results. The newly pyramided lines with two or more CR loci displayed better disease resistance than the parental lines carrying single CR loci. There is an obvious gene dosage effect between CR loci and disease resistance levels. For example, pyramided lines with triple CR loci in the homozygous state showed superior resistance for all pathogens tested. Moreover, CR loci in the homozygous state are better on disease resistance than the heterozygous state. More importantly, no negative effect was observed on agronomic traits for the presence of multiple CR loci in the same background. Overall, these data suggest that the pyramiding of triple clubroot resistance loci conferred superior resistance with no negative effects on agronomic traits in Brassica napus.

ARTN-GFRA3 axis induces epithelial-mesenchymal transition phenotypes, migration, and invasion of gastric cancer cells via KRAS signaling.

Neural invasion underlies the local spread of gastric cancer and is associated with poor prognosis. This process has been receiving increasing attention in recent years. However, the relationship between neural invasion and the malignant phenotypes of gastric cancer cells, as well as the molecular mechanism involved in this process, remain unclear. In this study, bioinformatics analysis was performed using a dataset obtained from The Cancer Genome Atlas-Stomach Adenocarcinoma. The results revealed that high expression of GDNF family receptor alpha 3 (GFRA3) was associated with a poor prognosis of patients with gastric cancer. GFRA3 is a receptor for artemin (ARTN), a glial cell line-derived neurotrophic factor (GDNF). This association was indicated by short overall/disease-free survival, as well as the presence of high-stage and high-grade disease. Gene set enrichment analysis showed that two cancer-associated pathways, namely KRAS signaling and epithelial-mesenchymal transition (EMT), were activated when GFRA3 was highly expressed in gastric cancer. Further studies confirmed that GFRA3 activated KRAS downstream signaling phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) or extracellular signal-regulated kinase (ERK) and induced EMT markers, as well as promoted the migration and invasion of gastric cancer cells. As a ligand of GFRA3, ARTN induced the EMT, migration, and invasion of gastric cancer cells via GFRA3. Notably, the effects of the ARTN-GFRA3 axis were attenuated by treatment with a KRAS inhibitor. The present findings indicated that, during the neural invasion of gastric cancer, ARTN-mediated activation of GFRA3 induces EMT phenotypes, migration, and invasion of gastric cancer cells via KRAS signaling.

[Analysis of the efficacy and safety of pulsed radiofrequency for the treatment of thoracic postherpetic neuralgia in elderly patients with different pain phenotypes].

Objective: To analyze the efficacy and safety of pulsed radiofrequency (PRF) for the treatment of thoracic postherpetic neuralgia (PHN) in elderly patients with different pain phenotypes. Methods: A total of 201 elderly thoracic PHN patients, including 110 males and 91 females aged (72.2±6.9) years who received high-voltage, long-duration PRF at the dorsal root ganglion at Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine from January 2020 to December 2022, were retrospectively included. The neuropathic pain symptom inventory (NPSI) was used to evaluate the five different pain phenotypes, which included superficial spontaneous pain, deep spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia, and to analyze the distribution of the five pain phenotypes. The numerical rating scale (NRS) and NPSI scores of all patients were compared before treatment and three months after treatment to evaluate the efficacy and safety of PRF for different pain phenotypes and pain phenotype combinations. Results: All patients had two or more pain phenotypes, and 50.2% (101/201) of the patients had five pain phenotypes at the same time. Compared with those before treatment, three months after treatment, the NPSI scores for superficial spontaneous pain, deep spontaneous pain, paroxysmal pain, evoked pain and paresthesia/dysesthesia decreased (all P<0.05), and the scores decreased byï¼»M（Q1，Q3）］3.0 (2.0, 4.0), 1.5 (0.5, 2.5), 3.0 (2.5, 4.0), 2.3 (1.0, 4.0), and 1.0 (0.5, 2.0) points, respectively, the differences were statistically significant (P<0.001). The decrease in the NPSI score in patients with paroxysmal pain was greater than that in patients with the other 4 pain phenotypes (all P<0.05). After treatment, the NRS score decreased by 4.0 (3.0, 5.0), 4.0 (3.0, 5.0), 4.0 (3.0, 5.0) and 5.0 (4.0, 6.0) points in patients with 2, 3, 4 and 5 pain phenotypes, respectively, and the difference was statistically significant (P<0.001). The decrease in the NRS score was greater in patients with a combination of 5 pain phenotypes than that in patients with a combination of 3 and 4 pain phenotypes (all P<0.05). No complications, such as pneumothorax, haematoma or infection, occurred in any of the patients during treatment. Conclusion: PRF has different therapeutic effects on PHN patients with different pain phenotypes, it has the best effect on paroxysmal pain, and the treatment is safe.

Temperatures above 37°C increase virulence of a convergent Klebsiella pneumoniae sequence type 307 strain.

Background: Convergence of Klebsiella pneumoniae (KP) pathotypes has been increasingly reported in recent years. These pathogens combine features of both multidrug-resistant and hypervirulent KP. However, clinically used indicators for hypervirulent KP identification, such as hypermucoviscosity, appear to be differentially expressed in convergent KP, potential outbreak clones are difficult to identify. We aimed to fill such knowledge gaps by investigating the temperature dependence of hypermucoviscosity and virulence in a convergent KP strain isolated during a clonal outbreak and belonging to the high-risk sequence type (ST)307. Methods: Hypermucoviscosity, biofilm formation, and mortality rates in Galleria mellonella larvae were examined at different temperatures (room temperature, 28°C, 37°C, 40°C and 42°C) and with various phenotypic experiments including electron microscopy. The underlying mechanisms of the phenotypic changes were explored via qPCR analysis to evaluate plasmid copy numbers, and transcriptomics. Results: Our results show a temperature-dependent switch above 37°C towards a hypermucoviscous phenotype, consistent with increased biofilm formation and in vivo mortality, possibly reflecting a bacterial response to fever-like conditions. Furthermore, we observed an increase in plasmid copy number for a hybrid plasmid harboring carbapenemase and rmpA genes. However, transcriptomic analysis revealed no changes in rmpA expression at higher temperatures, suggesting alternative regulatory pathways. Conclusion: This study not only elucidates the impact of elevated temperatures on hypermucoviscosity and virulence in convergent KP but also sheds light on previously unrecognized aspects of its adaptive behavior, underscoring its resilience to changing environments.

New immune phenotypes for treatment response in high-grade serous ovarian carcinoma patients.

Despite advances in surgical and therapeutic approaches, high-grade serous ovarian carcinoma (HGSOC) prognosis remains poor. Surgery is an indispensable component of therapeutic protocols, as removal of all visible tumor lesions (cytoreduction) profoundly improves the overall survival. Enhanced predictive tools for assessing cytoreduction are essential to optimize therapeutic precision. Patients' immune status broadly reflects the tumor cell biological behavior and the patient responses to disease and treatment. Serum cytokine profiling is a sensitive measure of immune adaption and deviation, yet its integration into treatment paradigms is underexplored. This study is part of the IMPACT trial (NCT03378297) and aimed to characterize immune responses before and during primary treatment for HGSOC to identify biomarkers for treatment selection and prognosis. Longitudinal serum samples from 22 patients were collected from diagnosis until response evaluation. Patients underwent primary cytoreductive surgery or neoadjuvant chemotherapy (NACT) based on laparoscopy scoring. Twenty-seven serum cytokines analyzed by Bio-Plex 200, revealed two immune phenotypes at diagnosis: Immune High with marked higher serum cytokine levels than Immune Low. The immune phenotypes reflected the laparoscopy scoring and allocation to surgical treatment. The five Immune High patients undergoing primary cytoreductive surgery exhibited immune mobilization and extended progression-free survival, compared to the Immune Low patients undergoing the same treatment. Both laparoscopy and cytoreductive surgery induced substantial and transient changes in serum cytokines, with upregulation of the inflammatory cytokine IL-6 and downregulation of the multifunctional cytokines IP-10, Eotaxin, IL-4, and IL-7. Over the study period, cytokine levels uniformly decreased in all patients, leading to the elimination of the initial immune phenotypes regardless of treatment choice. This study reveals distinct pre-treatment immune phenotypes in HGSOC patients that might be informative for treatment stratification and prognosis. This potential novel biomarker holds promise as a foundation for improved assessment of treatment responses in patients with HGSOC. ClinicalTrials.gov Identifier: NCT03378297.

Detailed phenotyping reveals diverse and highly skewed neutrophil subsets in both the blood and airways during active tuberculosis infection.

Introduction: Neutrophils play a complex and important role in the immunopathology of TB. Data suggest they are protective during early infection but become a main driver of immunopathology if infection progresses to active disease. Neutrophils are now recognized to exist in functionally diverse states, but little work has been done on how neutrophil states or subsets are skewed in TB disease. Methods: To address this, we carried out comprehensive phenotyping by flow cytometry of neutrophils in the blood and airways of individuals with active pulmonary TB with and without HIV co-infection recruited in Durban, South Africa. Results: Active TB was associated with a profound skewing of neutrophils in the blood toward phenotypes associated with activation and apoptosis, reduced phagocytosis, reverse transmigration, and immune regulation. This skewing was also apparently in airway neutrophils, particularly the regulatory subsets expressing PDL-1 and LOX-1. HIV co-infection did not impact neutrophil subsets in the blood but was associated with a phenotypic change in the airways and a reduction in key neutrophil functional proteins cathelicidin and arginase 1. Discussion: Active TB is associated with profound skewing of blood and airway neutrophils and suggests multiple mechanisms by which neutrophils may exacerbate the immunopathology of TB. These data indicate potential avenues for reducing neutrophil-mediated lung pathology at the point of diagnosis.

Label-free morpho-molecular phenotyping of living cancer cells by combined Raman spectroscopy and phase tomography.

Accurate, rapid and non-invasive cancer cell phenotyping is a pressing concern across the life sciences, as standard immuno-chemical imaging and omics require extended sample manipulation. Here we combine Raman micro-spectroscopy and phase tomography to achieve label-free morpho-molecular profiling of human colon cancer cells, following the adenoma, carcinoma, and metastasis disease progression, in living and unperturbed conditions. We describe how to decode and interpret quantitative chemical and co-registered morphological cell traits from Raman fingerprint spectra and refractive index tomograms. Our multimodal imaging strategy rapidly distinguishes cancer phenotypes, limiting observations to a low number of pristine cells in culture. This synergistic dataset allows us to study independent or correlated information in spectral and tomographic maps, and how it benefits cell type inference. This method is a valuable asset in biomedical research, particularly when biological material is in short supply, and it holds the potential for non-invasive monitoring of cancer progression in living organisms.

A comprehensive phenotypic and genotypic evaluation of Spanish groundnuts from diverse crosses to identify superior and stable donors for fresh seed dormancy.

Breeding high yielding groundnut cultivars with 2-3 weeks of fresh seed dormancy, particularly in Spanish-type cultivars, enhances the sustainability of agriculture in groundnuts. In this context, we conducted a comprehensive phenotypic and genotypic evaluation of advanced breeding lines developed in the genetic background of Spanish types. By employing multi-phenotyping and marker data, we identified PBS 15044, 16004, 16013, 16015, 16016, 16017, 16020, 16021, 16026, 16031, 16035, 16037, 16038, 16039, 16041, and 16042 with 2-3 weeks dormancy (> 90%).The various parametric and non-parametric estimates identified the stable fresh dormant genotypes with one or more superior economic trait. PBS 16021, 15044, 16038, and 16039 identified with high hundred pod weight (HPW) were also reported having high intensity of dormancy (> 90% for up to 3 weeks); PBS 15044, 16016, PBS 16038 and PBS 16039 with high hundred kernel weight (HKW) also reported with up to 3 weeks fresh seed dormancy; and PBS 16013, 16031, and 16038 with up to 3 weeks fresh seed dormancy had high shelling percentage (SP). They can be used to develop lines with the desired level of dormancy, and high yields, by designing appropriate breeding strategies.

Male and female contributions to diversity among birdwing butterfly images.

Machine learning (ML) newly enables tests for higher inter-species diversity in visible phenotype (disparity) among males versus females, predictions made from Darwinian sexual selection versus Wallacean natural selection, respectively. Here, we use ML to quantify variation across a sample of > 16,000 dorsal and ventral photographs of the sexually dimorphic birdwing butterflies (Lepidoptera: Papilionidae). Validation of image embedding distances, learnt by a triplet-trained, deep convolutional neural network, shows ML can be used for automated reconstruction of phenotypic evolution achieving measures of phylogenetic congruence to genetic species trees within a range sampled among genetic trees themselves. Quantification of sexual disparity difference (male versus female embedding distance), shows sexually and phylogenetically variable inter-species disparity. Ornithoptera exemplify high embedded male image disparity, diversification of selective optima in fitted multi-peak OU models and accelerated divergence, with cases of extreme divergence in allopatry and sympatry. However, genus Troides shows inverted patterns, including comparatively static male embedded phenotype, and higher female than male disparity - though within an inferred selective regime common to these females. Birdwing shapes and colour patterns that are most phenotypically distinctive in ML similarity are generally those of males. However, either sex can contribute majoritively to observed phenotypic diversity among species.

High resolution mapping of a novel non-transgressive hybrid susceptibility locus in barley exploited by P. teres f. maculata.

Hybrid genotypes can provide significant yield gains over conventional inbred varieties due to heterosis or hybrid vigor. However, hybrids can also display unintended negative attributes or phenotypes such as extreme pathogen susceptibility. The necrotrophic pathogen Pyrenophora teres f. maculata (Ptm) causes spot form net blotch, which has caused significant yield losses to barley worldwide. Here, we report on a non-transgressive hybrid susceptibility locus in barley identified between the three parental lines CI5791, Tifang and Golden Promise that are resistant to Ptm isolate 13IM.3. However, F2 progeny from CI5791 × Tifang and CI5791 × Golden Promise crosses exhibited extreme susceptibility. The susceptible phenotype segregated in a ratio of 1 resistant:1 susceptible representing a genetic segregation ratio of 1 parental (res):2 heterozygous (sus):1 parental (res) suggesting a single hybrid susceptibility locus. Genetic mapping using a total of 715 CI5791 × Tifang F2 individuals (1430 recombinant gametes) and 149 targeted SNPs delimited the hybrid susceptibility locus designated Susceptibility to Pyrenophora teres 2 (Spt2) to an ~ 198 kb region on chromosome 5H of the Morex V3 reference assembly. This single locus was independently mapped with 83 CI5791 × Golden Promise F2 individuals (166 recombinant gametes) and 180 genome wide SNPs that colocalized to the same Spt2 locus. The CI5791 genome was sequenced using PacBio Continuous Long Read technology and comparative analysis between CI5791 and the publicly available Golden Promise genome assembly determined that the delimited region contained a single high confidence Spt2 candidate gene predicted to encode a pentatricopeptide repeat-containing protein.

Genetic and phenotypic diversification in a widespread fish, the Sailfin Molly (Poecilia latipinna).

Widespread species often experience significant environmental clines over the area they naturally occupy. We investigated a widespread livebearing fish, the Sailfin molly (Poecilia latipinna) combining genetic, life-history, and environmental data, asking how structured populations are. Sailfin mollies can be found in coastal freshwater and brackish habitats from roughly Tampico, Veracruz in Mexico to Wilmington, North Carolina, in the USA. In addition, they are found inland on the Florida peninsula. Using microsatellite DNA, we genotyped 168 individuals from 18 populations covering most of the natural range of the Sailfin molly. We further determined standard life-history parameters for both males and females for these populations. Finally, we measured biotic and abiotic parameters in the field. We found six distinct genetic clusters based on microsatellite data, with very strong indication of isolation by distance. However, we also found significant numbers of migrants between adjacent populations. Despite genetic structuring we did not find evidence of cryptic speciation. The genetic clusters and the migration patterns do not match paleodrainages. Life histories vary between populations but not in a way that is easy to interpret. We suggest a role of humans in migration in the sailfin molly, for example in the form of a ship channel that connects southern Texas with Louisiana which might be a conduit for fish migration.

Taxonomic and phenotypic analysis of bifidobacteria isolated from IBD patients as potential probiotic strains.

BACKGROUND: Inflammatory Bowel Diseases (IBD) are a major public health issue with unclear aetiology. Changes in the composition and functionality of the intestinal microbiota are associated with these pathologies, including the depletion of strict anaerobes such as Feacalibacterium prausnitzii. Less evidence is observed for depletion in other anaerobes, among which bifidobacteria. This study characterized the taxonomic and functional diversity of bifidobacteria isolated from the human intestinal microbiota in active and non-active IBD patients by a culturomics approach and evaluated if these bifidobacteria might be used as probiotics for gut health. RESULTS: A total of 341 bifidobacteria were isolated from the intestinal microbiota of IBD patients (52 Crohn's disease and 26 ulcerative colitis patients), with a high proportion of Bifidobacterium dentium strains (28% of isolated bifidobacteria). In ulcerative colitis, the major species identified was B. dentium (39% of isolated bifidobacteria), in active and non-active ulcerative colitis. In Crohn's disease, B. adolescentis was the major species isolated from non-active patients (40%), while similar amounts of B. dentium and B. adolescentis were found in active Crohn's disease patients. The relative abundance of B. dentium was increased with age, both in Crohn's disease and ulcerative colitis and active and non-active IBD patients. Antibacterial capacities of bifidobacteria isolated from non-active ulcerative colitis against Escherichia coli LF82 and Salmonella enterica ATCC 14028 were observed more often compared to strains isolated from active ulcerative colitis. Finally, B. longum were retained as strains with the highest probiotic potential as they were the major strains presenting exopolysaccharide synthesis, antibacterial activity, and anti-inflammatory capacities. Antimicrobial activity and EPS synthesis were further correlated to the presence of antimicrobial and EPS gene clusters by in silico analysis. CONCLUSIONS: Different bifidobacterial taxonomic profiles were identified in the microbiota of IBD patients. The most abundant species were B. dentium, mainly associated to the microbiota of ulcerative colitis patients and B. adolescentis, in the intestinal microbiota of Crohn's disease patients. Additionally, the relative abundance of B. dentium significantly increased with age. Furthermore, this study evidenced that bifidobacteria with probiotic potential (antipathogenic activity, exopolysaccharide production and anti-inflammatory activity), especially B. longum strains, can be isolated from the intestinal microbiota of both active and non-active Crohn's disease and ulcerative colitis patients.

Malignancy and mass-forming phenotypes of IgG4-related disease: a challenging diagnosis.

Mass-forming phenotypes of IgG4-related disease (IgG4-RD) mimic malignancy and histological confirmation can be challenging. A woman in her 70s with HIV infection presented with painless obstructive jaundice and weight loss. Magnetic resonance imaging was suggestive of unresectable cholangiocarcinoma. Tumour markers and serum IgG4 were normal. Percutaneous liver biopsy was consistent with IgG4-RD inflammatory pseudotumour, with complete response to glucocorticoid therapy. Two years later, a new episode of obstructive jaundice occurred, with CT showing a solid lesion in the head of the pancreas with double duct sign and encasement of the portal vein. Re-induction therapy was tried without response. Fine-needle biopsy was consistent with pancreatic cancer. Supportive care was offered and the patient died 8 months later, with no signs of disease progression on subsequent imaging. We discuss the challenges of IgG4-RD diagnosis and treatment and the differential diagnosis between mass-forming phenotypes and malignancy, highlighting the difficulties in managing such patients.

Unraveling the genetic tapestry of pediatric sarcomeric cardiomyopathies and masquerading phenocopies in Jordan.

Pediatric cardiomyopathies are mostly attributed to variants in sarcomere-related genes. Unfortunately, the genetic architecture of pediatric cardiomyopathies has never been previously studied in Jordan. We sought to uncover the genetic landscape of 14 patients from nine families with several subtypes of pediatric cardiomyopathies in Jordan using Exome sequencing (ES). Our investigation identified pathogenic and likely pathogenic variants in seven out of nine families (77.8%), clustering in sarcomere-related genes. Surprisingly, phenocopies of sarcomere-related hypertrophic cardiomyopathies were evident in probands with glycogen storage disorder and mitochondrial-related disease. Our study underscored the significance of streamlining ES or expanding cardiomyopathy-related gene panels to identify plausible phenocopies of sarcomere-related cardiomyopathies. Our findings also pointed out the need for genetic testing in patients with cardiomyopathy and their at-risk family members. This can potentially lead to better management strategies, enabling early interventions, and ultimately enhancing their prognosis. Finally, our findings provide an initial contribution to the currently absent knowledge about the molecular underpinnings of cardiomyopathies in Jordan.

Exploring self-reported visual function and vision-related anxiety in patients with RPGR-associated retinal degeneration.

Variants in the retinitis pigmentosa GTPase regulator (RPGR) gene are responsible for the majority of X-linked retinitis pigmentosa cases, which not only affects male patients but also some heterozygous females. Vision-related disability and anxiety of patients with RPGR-associated retinal degeneration have never been explored before. This study aimed to evaluate self-reported visual function and vision-related anxiety in a Portuguese cohort of male and female patients with RPGR-associated retinal degeneration using two validated patient-reported outcome measures. Cross-sectional data of thirty-two genetically-tested patients was examined, including scores of the Michigan retinal degeneration questionnaire (MRDQ) and Michigan vision-related anxiety questionnaire. Patients were classified according to retinal phenotypes in males (M), females with male phenotype (FM), and females with radial or focal pattern. Both M and FM revealed higher rod-function and cone-function anxiety scores (p < 0.017). Most MRDQ disability scores were higher in M and FM (p < 0.004). Overall, positive correlations (p < 0.004) were found between every MRDQ domain and both anxiety scores. In RPGR-associated retinal degeneration, males and females with male phenotype show similar levels of increased vision-related anxiety and disability. Every MRDQ visual function domain showed a strong correlation with anxiety scores.

Breed of origin analysis in genome-wide association studies: enhancing SNP-based insights into production traits in a commercial Brangus population.

BACKGROUND: Carcass weight (HCW) and marbling (MARB) are critical for meat quality and market value in beef cattle. In composite breeds like Brangus, which meld the genetics of Angus and Brahman, SNP-based analyses have illuminated some genetic influences on these traits, but they fall short in fully capturing the nuanced effects of breed of origin alleles (BOA) on these traits. Focus on the impacts of BOA on phenotypic features within Brangus populations can result in a more profound understanding of the specific influences of Angus and Brahman genetics. Moreover, the consideration of BOA becomes particularly significant when evaluating dominance effects contributing to heterosis in crossbred populations. BOA provides a more comprehensive measure of heterosis due to its ability to differentiate the distinct genetic contributions originating from each parent breed. This detailed understanding of genetic effects is essential for making informed breeding decisions to optimize the benefits of heterosis in composite breeds like Brangus. OBJECTIVE: This study aims to identify quantitative trait loci (QTL) influencing HCW and MARB by utilizing SNP and BOA information, incorporating additive, dominance, and overdominance effects within a multi-generational Brangus commercial herd. METHODS: We analyzed phenotypic data from 1,066 genotyped Brangus steers. BOA inference was performed using LAMP-LD software using Angus and Brahman reference sets. SNP-based and BOA-based GWAS were then conducted considering additive, dominance, and overdominance models. RESULTS: The study identified numerous QTLs for HCW and MARB. A notable QTL for HCW was associated to the SGCB gene, pivotal for muscle growth, and was identified solely in the BOA GWAS. Several BOA GWAS QTLs exhibited a dominance effect underscoring their importance in estimating heterosis. CONCLUSIONS: Our findings demonstrate that SNP-based methods may not detect all genetic variation affecting economically important traits in composite breeds. BOA inclusion in genomic evaluations is crucial for identifying genetic regions contributing to trait variation and for understanding the dominance value underpinning heterosis. By considering BOA, we gain a deeper understanding of genetic interactions and heterosis, which is integral to advancing breeding programs. The incorporation of BOA is recommended for comprehensive genomic evaluations to optimize trait improvements in crossbred cattle populations.

Diagnosis of cystic fibrosis: a high heterogeneity of symptoms and genotypes in a Brazil population.

INTRODUCTION: In highly multiracial populations with inadequate newborn screening, knowledge of the various phenotypic presentations of Cystic Fibrosis (CF) can help reach an early diagnosis. This study aims to describe phenotypes and genotypes at the time of CF diagnosis in a state in the Northeast Region of Brazil. METHODS: Retrospective cross-sectional study. Clinical data were extracted from the medical records of CF patients. Clinical, laboratory, and genotypic characteristics were described for patients admitted to a tertiary referral center between 2007 and 2021. RESULTS: Fifty-eight (58) patients were included in the study, 53.5% of whom were diagnosed through clinical suspicion. The median age at diagnosis was 4.7 months (IQR: 1.5-14.8 months). Five patients had false-negative results in the newborn screening. Faltering growth was the most frequent clinical manifestation. Bronchiectasis and a history of pneumonia predominated in those older than ten, while thinness, underweight, and electrolyte imbalances were more frequent in children under two. Sequencing of the CFTR gene identified 27 genotypes, with at least one class I-III variant in all patients, and nine variants that are rare, previously undescribed, or have uncertain significance (619delA, T12991, K162Q, 3195del6, 1678del > T, 124del123bp, 3121-3113 A > T). The most frequent alleles were p.Phe508del, p.Gly542*, p.Arg334Trp, and p.Ser549Arg. CONCLUSIONS: Malnutrition and electrolyte imbalances were the most frequent phenotypes for children < 2 years and were associated with genotypes including 2 class I-III variants. Rare and previously undescribed variants were identified. The p.Gly542*, p.Arg334Trp, and p.Ser549Arg alleles were among the most frequent variants in this population.