Morphometric and carcass traits of indigenous chickens under the prevailing scavenging production system in Farta District of South Gondar Zone, Amhara, Ethiopia.

Schematic overview of primary biofilm formation, dispersion of primary biofilm-associated cells (PBACs), and development of secondary biofilms.Image 1.

A machine learning approach for analysis of genotypic and phenotypic variability in rice (Oryza Sativa L.) for drought stress screening

A systematic review and meta-analysis of cross-sectional mixture modeling applications to identify person-centered phenotypes of posttraumatic stress disorder.

Zymoseptoria tritici, the causal agent of Septoria tritici blotch (STB), poses a critical threat to wheat (Triticum aestivum L.) production in temperate Europe, underscoring the need for durable genetic resistance. Here, we screened 151 winter wheat varieties at the seedling stage using a mixed inoculum of five virulent isolates. Disease severity was quantified at 14, 21, and 28 days post-inoculation to calculate the area under the disease progress curve. We observed broad phenotypic variation, with higher susceptibility in Southern European germplasm. A genome-wide association study identified three significantly resistant loci: IWB5774 on chromosome 2D, and IWB72742 and IWB11406 on chromosome 1B. Functional annotation mapped these markers to high-priority candidate genes, including a TaBx3D-like protein, the endomembrane trafficking regulator WDR91, and NAP1, a nucleosome assembly factor involved in stress signaling. These findings provide robust molecular markers for breeding and nominate specific targets for functional validation of STB resistance mechanisms.

Roots play a pivotal role for plant performance, but they are difficult to access, which hampers quantitative measurements. Repeated imaging of rhizotrons, flat growth containers with a transparent side, has proven suitable to assess dynamics of root traits in indoor experiments. However, measuring hundreds of soil-grown plants with high temporal resolution remains a laborious challenge. We introduce a novel whole-plant phenotyping platform with a capacity of almost 900 rhizotrons, which we named GrowScreen-Rhizo 3. This platform was designed to image shoots and roots of individual plants simultaneously and derive digital proxy traits for biomass and growth. In addition, built-in weighing and watering stations deliver water use data for each rhizotron. To achieve the desired throughput (image all 896 plants once a day) a high degree of automatization and standardization was required. We realized a modular plant-to-sensor solution, using a fleet of automated guided vehicles (AGVs) to transport large rhizotrons (80 × 40 × 5 cm) to four measurement chambers for daily imaging, weighing, and watering. Simultaneous imaging of the root system with a high-resolution camera (116 μm per px) and the shoot from six different viewing angles allows to monitor plant growth with high spatial and temporal accuracy. First, we verified that moving plants to the measurement chambers did not significantly affect above- or belowground plant growth. Next, we measured phenotypic variation in root and shoot traits of 24 barley genotypes, parents of a nested association mapping population. Our analysis revealed that heritability of root traits such as root system depth and seminal root length was moderate to high (r2 = 0.52 and r2 = 0.93, respectively), enabling further assessment of increasing numbers of recombinant genotypes. The results demonstrate the suitability of GrowScreen-Rhizo 3 to phenotype a range of plant species characterized by various growth habits, including crop, niche, and wild plant species. We conclude that GrowScreen-Rhizo 3 will contribute significantly to the development of phenotyping pipelines for the identification of candidate genotypes with improved resource use efficiency and to pre-breeding processes of climate-resilient crops.

Time-series point clouds have emerged as an effective approach for precise, continuous crop monitoring and quantitative growth analysis. This study constructed a spatiotime-series point cloud dataset containing four species and eleven plant varieties, exploring crop organ instance segmentation, phenotypic parameter extraction, growth quantification, and canopy photosynthesis assessment. A skeleton-based framework for organ-level instance segmentation and time-series analysis is proposed, demonstrating robust performance across all four crops. To fully utilize the time-series data, a novel time-series leaf matching method was introduced, achieving a matching accuracy, defined as the proportion of correctly matched leaves, of over 0.823 for all species. By integrating the matching results with phenotypic parameter extraction, time-series phenotypic data were generated, and a phenotypic variation rate was defined as a suitable metric for quantifying crop growth. Furthermore, these results were integrated into a canopy photosynthesis model to derive key time-series photosynthetic metrics, including photosynthetic rate, absorbed light quantity, light energy utilization efficiency, and each crop organ's contribution to photosynthesis. These metrics provide insights into the crop’s growth patterns and photosynthetic strategy. This study offers refined quantitative analysis of crop morphology and photosynthetic parameters through time-series point cloud segmentation, contributing valuable data for advancing plant biology research and enhancing the understanding of crop growth dynamics. • Skeleton-guided 3D segmentation and tracking: Developed a robust method for organ-level point cloud segmentation and time-series matching, enabling accurate monitoring of crop development. • Leaf-scale growth and photosynthesis quantification: Established a pipeline to track leaf-level growth and compute key photosynthetic traits, including photosynthetic rate, absorbed light, and light use efficiency. • Phenotypic Variation Rate (PVR): Proposed a new metric to quantify dynamic changes in 3D plant structure, enhancing the analysis of growth patterns across time.

Cryptococcus gattii is an environmental yeast capable of causing severe infections in immunocompetent hosts. Its virulence mechanisms remain less characterized than those of C. neoformans. This study aimed to evaluate the expression of major virulence factors and the immunomodulatory potential of eight C. gattii strains representing five genotypes and multiple sequence types (STs). Virulence traits-including capsule thickness, melanin and laccase production, phospholipase, hemolysin, urease, and DNase activities-were assessed using standardized in vitro assays. In vivo pathogenicity was evaluated in Galleria mellonella, and macrophage responses were analyzed via nitric oxide (NO) production and cytokine gene expression in J774.A1 cells. Capsule and melanin production varied significantly across strains, with VGI/ST106 and VGII/ST7 showing the highest levels, respectively. VGIV/ST336, VGI/ST106, and VGVI/ST556 induced greater larval mortality than the reference C. neoformans strain (VNI/ST5), while VGII strains exhibited ST-dependent virulence. Most strains inhibited NO production in macrophages, except VGI/ST106, which enhanced it. Cytokine expression remained low in the absence of inflammatory priming. These findings reveal substantial phenotypic variability in virulence and immune modulation among C. gattii strains. Further investigation into strain-specific host interactions may helpthe development of targeted antifungal strategies and improve clinical management of cryptococcosis.

Imprinting disorders are caused by epigenetic alterations leading to abnormal gene expression from imprinted loci. Pseudohypoparathyroidism type 1B is characterized by methylation defects at the GNAS locus, affecting hormone responsiveness. Monozygotic twins discordant for imprinting disorders provide a unique opportunity to investigate the timing, maintenance, and tissue-specific distribution of epimutations and their relation to clinical expression. Most previous studies focus on infants, where fetal blood chimerism may influence epigenetic profiles, but data in adolescents remain scarce. We studied adolescent monozygotic twin sisters presenting clinical and biochemical discordance for pseudohypoparathyroidism type 1B. Both twins exhibited an identical, partial methylation defect at the GNAS locus in peripheral blood, consistent with a postzygotic epigenetic alteration occurring before embryonic splitting. Exclusion of known genetic causes, including uniparental disomy and structural variants, and absence of multilocus imprinting disturbances or maternal-effect gene mutations, were confirmed through comprehensive genomic and methylation analyses. The affected twin showed involvement of methylation abnormalities across all three germ layers derived tissues, whereas the unaffected twin presented very mild or absent defects in some tissues, possibly explaining the phenotypic divergence. The persistent concordance of partial methylation defects in blood despite phenotypic discordance suggests stable early epimutations maintained in hematopoietic progenitors, while tissue-specific mosaicism and differential methylation maintenance across organs critical to disease expression contribute to clinical differences. Advanced long-read sequencing demonstrated sensitivity for detecting partial and mosaic methylation patterns, rather than just complete alterations. This study underscores the complexity of epigenetic mosaicism in imprinting disorders, highlighting that early postzygotic partial epimutations may yield identical blood methylation profiles but divergent tissue distributions, leading to discordant clinical phenotypes in monozygotic twins. The adolescent age of our subjects challenges the fetal blood chimerism explanation for methylation concordance and emphasizes the importance of multi-tissue evaluation and sensitive molecular assays. These findings have important implications for diagnosis, monitoring, and genetic counseling in imprinting disorders, advocating for integrated approaches to assess epigenetic heterogeneity and phenotypic variability.

Hypertrophic cardiomyopathy (HCM) is frequently associated with mutations in cardiac myosin binding protein C (cMyBP-C; MYBPC3) and cMyBP-C haploinsufficiency. Previously we discovered burst-like transcription of MYBPC3 and unequal amounts of wild type cMyBP-C from cardiomyocyte to cardiomyocyte in HCM-patient's myocardium. The present study introduces human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying the patient-specific heterozygous MYBPC3 c.927-2A > G mutation and the respective isogenic control to examine in long-term culture whether comparable pathophysiological features exist in vitro. We generated a human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) model harboring the patient-specific MYBPC3 c.927-2A > G splice-site mutation. An isogenic control line was used for direct comparison. We assessed cMyBP-C protein expression, transcriptional dynamics, contractile function, and calcium handling, and compared the cellular phenotype to heart tissue from the HCM patient with the same mutation. cMyBP-C haploinsufficiency in MYBPC3c.927-2A> G-hiPSC-CMs was confirmed by Western blot. Immunostaining showed myofibrillar disarray and an increasing proportion of cMyBP-C-negative CMs over time for mutant hiPSC-CMs, closely mirrored the variable cMyBP-C protein expression observed in HCM-patient's myocardium. RNA-FISH revealed variable MYBPC3 transcription from cell to cell, likely contributing to cMyBP-C expression heterogeneity. Twitch shortening velocity slowed over time while Ca²⁺ transient kinetics accelerated in mutant hiPSC-CMs. Transcriptomic analysis revealed dysregulation of pathways associated with contraction, calcium handling, and HCM. This study presents a validated hiPSC-based model of MYBPC3-associated HCM that captures the variability in protein expression and functional phenotype observed in patient heart tissue. Our findings support the relevance of single-cell transcriptional variability in HCM pathogenesis and highlight the utility of this model for future studies.

Alterations in metabolite concentrations often serve as direct drivers of phenotypic variation or disease onset. The changes in metabolite concentrations are directly dependent on the enzymatic reaction rates. However, spatially resolved imaging of the absolute metabolic enzymatic reaction rate (also known as metabolic flux) remains a critical unmet challenge in systems biology. We developed spatially quantitative kinetic flux profiling (SQ-KFP), a framework for quantitatively imaging the metabolic reaction rate, which has the potential for broad application to plant and animal tissues. This approach firstly realized the integration of quantitative flux analysis with mass spectrometry imaging, by generating isotope labeling data with coupled temporal and spatial resolution via image registration. SQ-KFP imaged the backward reaction rate of fumarase (vFUM) with spatial resolution as a proof-of-concept, revealing different reaction rate densities in petiole-lamina junctions and spatial decoupling between the metabolic reaction rate, metabolite concentration, and isotopic enrichment in leaves of Oxalis corymbosa and Medicago lupulina (validated by various detection methods). These results demonstrate that neither metabolite concentrations nor isotopic labeling values can substitute for reaction rates. Our method provides quantitative imaging of metabolic reaction rates and enables spatial flux analysis across diverse tissues and organisms.

Plasmids, particularly those of the IncHI2 type, are key drivers of multidrug resistance in Salmonella. However, the fitness costs imposed by multidrug-resistant (MDR) IncHI2 plasmids across different serovars and the underlying mechanisms remain poorly understood. Here, we report that carriage of the MDR IncHI2 plasmid pMDRHI2 imposes a fitness cost that varies in magnitude across Salmonella hosts. This phenotypic variation is accompanied by serovar-specific differences in both transcriptional and metabolic reprogramming. Notably, despite this heterogeneity, plasmid carriage consistently perturbed the expression of chromosomal loci involved in propanediol utilization (pdu), ethanolamine utilization (eut) and sulphur and glycerophospholipid metabolism, though in a strain-dependent manner. Integrative transcriptomic and metabolomic analyses revealed that the fitness costs are linked to distinct metabolic lesions in a serovar-specific manner. Exogenous metabolite supplementation further confirmed that these lesions – such as dysregulated propanoate metabolism or impaired redox homeostasis – underlie the observed fitness costs. Collectively, these findings demonstrate that the fitness burden imposed by MDR IncHI2 plasmid carriage is dictated by serovar-specific host factors and arises from plasmid-mediated remodelling of central metabolic pathways.

Pseudomonas aeruginosa is a major cause of acute nosocomial infections, as well as chronic respiratory infections associated with cystic fibrosis (CF). In chronic lung infections, P. aeruginosa populations typically exhibit extensive phenotypic variation, a trait linked to their need to undergo pathoadaptive mutations to counteract host-derived selective pressures. In this study, two clonally related P. aeruginosa isolates, SCPA07 and SCPA08, were identified to coexist in a single bronchoalveolar lavage fluid (BALF) sample from a patient with bacterial pneumonia. Whole-genome sequencing (WGS) was conducted to characterize their genetic background, as well as antimicrobial resistance and virulence gene profiles. A comprehensive analysis of phylogenetic relationships and comparative genomic features of the two isolates was conducted using a panel of bioinformatics tools. Their antimicrobial resistance mechanisms were elucidated via gene sequence analysis and quantitative reverse-transcription PCR (qRT-PCR). A series of phenotypic experiments, including growth, biofilm formation, environmental stress, and virulence assays, and others were performed to characterize their phenotypic traits. Antimicrobial susceptibility assay showed that both strains were carbapenem-non-susceptible (defined as intermediate or resistant according to the Clinical and Laboratory Standards Institute (CLSI) guidelines). Genomic analysis revealed that they are 'hypermutator' strains and harbor both the exoS and exoU virulence genes, indicating an increased propensity for persistent host infection and high virulence potential. Both strains harbored mutations in oprD, and exhibited elevated expression of AmpC β-lactamase and the efflux pump MexB, which most likely contributed to their non-susceptibility to carbapenems. Despite harboring nucleotide variations at only ten genetic loci, these two strains exhibited distinct phenotypic traits: SCPA07 showed rapid growth, strong biofilm formation, high virulence, and growth advantages under iron limitation and serum stress; in contrast, its variant SCPA08 had slow growth, poor motility, reduced pyocyanin production, low virulence, and increased tolerance to the host antimicrobials human cathelicidin LL-37 and hydrogen peroxide (H2O2). These phenotypic variations are proposed to be primarily driven by genetic mutations affecting the O-antigen biosynthesis, iron utilization, Porin D, and other determinants. This study elucidates the divergent adaptive evolutionary strategies of a single exoS+/exoU+ P. aeruginosa clone within the host during bacterial pneumonia, as well as their critical role in shaping the bacterium's virulence and adaptability, which sheds light on the within-host evolution dynamics of P. aeruginosa populations during their pathogenesis and persistence in the lung.

Whole-genome duplication (WGD) is widespread in plants, yet the extent to which it yields predictable phenotypic outcomes remains unclear. Here, we show that the phenotypic consequences of genome doubling in a duckweed model system, Spirodela polyrhiza, are highly repeatable and largely deterministic. We previously generated three independent colchicine-induced autotetraploids from each of nine globally distributed diploid genotypes and now quantified growth and morphology across a salt gradient. In benign conditions, diploids grew faster, whereas tetraploids had larger, thicker fronds. As salinity increased, the diploid growth advantage diminished, and tetraploids frequently matched or exceeded diploid growth rates. By partitioning the components of variance in growth in our experimental design, we found that ploidy per se explained a comparable amount of phenotypic variation in growth and substantially more variation in salt tolerance than the genotypic background, with evidence of rare within-genotype stochastic differences between tetraploids. These results indicate that the shifts in morphology and stress tolerance from genome doubling are predictable and can match the phenotypic effect from genetic sequence diversity.

Exploiting natural variation to uncouple yield from nitrogen (N) input is essential for sustainable oilseed rape production. Here, we screened 505 accessions and discovered a 10-fold gradient in chlorate (ClO₃⁻) sensitivity that mirrors genotypic differences in nitrogen use efficiency (NUE). Chlorate-sensitive genotypes (CSG) exhibited 35% higher ¹⁵NO₃⁻ influx, 40%-62% greater root glutamine synthetase (GS) activity, and almost twice the seed yield of chlorate-insensitive genotypes (CIG) under high-N supply, whereas nitrate (NO₃⁻) reductase activity was unchanged. Chemical inhibition of GS using L-methionine-S-sulfoximine (MSX) resulted in the loss of ClO₃⁻ sensitivity, mechanistically linking assimilation flux to the observed phenotypic variation. Root proteomic analysis identified differentially abundant proteins between CSG and CIG and showed that BnaA02.GLN1;2 (a cytosolic GS1 homologue) was a hub protein with higher abundance in CSG. Overexpression of BnaA02.GLN1;2 enhanced rapeseed chlorate sensitivity under sufficient NO₃⁻ supply, promoted seedling growth, and enhanced both NO₃⁻ uptake and assimilation. Mature transgenic plants produced more pods and higher yields under normal N conditions while simultaneously reducing seed erucic acid and glucosinolate concentrations. Genome-wide association study mapped a major quantitative trait locus on chromosome A02, with BnaA02.GLN1;2 as the causal gene. Eleven single-nucleotide polymorphisms (SNPs) classified BnaA02.GLN1;2 into three haplotypes: BnaA02.GLN1;2Hap1 showed higher gene expression level, GS activity and shoot N content than BnaA02.GLN1;2Hap3. Our findings reposition GS1 as a key regulator that coordinates NO₃⁻ uptake and assimilation and establish BnaA02.GLN1;2Hap1 as a breeding-ready target to develop high-yield, low-input rapeseed.

SLC26A4 is a major causative gene for hereditary hearing loss, its mutation spectrum shows pronounced population specificity. In Chinese populations, patients predominantly carry biallelic mutations, and compound heterozygous genotypes are prevalent, which results in a wide spectrum of auditory phenotypes. However, how different alleles interact within these contexts to shape phenotypic variability remains poorly understood. We employed cellular and mouse models to explore the allele-specific mechanisms associated with two novel mutations, a frameshift mutation and a missense mutation, in compound heterozygous that share the same splice-site pathogenic allele. In vitro, wild-type (WT) and mutant (c.574delC, c.1211C>A) SLC26A4 constructs were expressed in HeLa cells to assess pendrin localization. Both mutations reduced membrane enrichment and increased intracellular retention. In vivo, compound heterozygous knock-in mouse models (Slc26a4c.574delC/c.919-2A>G and Slc26a4c.1211C>A/c.919-2A>G) were generated using CRISPR/Cas9. The auditory function and cochlear pathology were investigated. Both compound mutants exhibited elevated ABR thresholds, with more severe hearing loss in Slc26a4c.574delC/c.919-2A>G mice. Correspondingly, these mice showed marked hair cell disruption, stereociliary loss, and cochlear structural abnormalities, whereas the Slc26a4c.1211C>A/c.919-2A>G mice displayed milder changes. Transcriptomic profiling examined by bulk RNA-sequencing revealed broader differential expression in Slc26a4c.574delC/c.919-2A>G mice, enriched in structural and developmental pathways, while the missense model showed predominantly immune-related signatures. Our findings demonstrate that allele-specific functional divergence in compound heterozygous SLC26A4 mutations leads to distinct auditory dysfunction, cochlear pathology, and transcriptional programs. These findings provide mechanistic insight into the phenotypic heterogeneity of hearing loss and may indicate future allele-specific interventions or therapeutic strategies.

Predicting fluid responsiveness in patients with acute respiratory distress syndrome (ARDS) remains a clinical challenge. While dynamic indices such as pulse pressure variation (PPV), stroke volume variation (SVV), and functional tests like passive leg raising (PLR), end-expiratory occlusion test (EEOT), and tidal volume challenge (VTC) are widely used in critical care, their reliability in ARDS-characterized by altered lung mechanics and heterogeneous pathophysiology-has not been clearly established. To systematically map the available evidence on predictors of fluid responsiveness in ARDS, including their performance under different ventilatory settings, the use of extracorporeal support, and the influence of respiratory mechanics and phenotypic variability. A scoping review was conducted following PRISMA-ScR and Arksey & O'Malley guidelines. A systematic search of PubMed, Embase, Web of Science, and Cochrane Library was performed from January 1999 to October 2024. Studies were included if they evaluated any fluid responsiveness predictor in adult ARDS patients and reported performance metrics such as sensitivity, specificity, or area under the curve (AUC). Data were extracted in duplicate and synthesized narratively. Ten studies were included. PPV was the most frequently evaluated predictor, followed by SVV, EEOT, VTC, and PLR. Only two studies assessed patients in the prone position, and two included patients supported with veno-venous extracorporeal membrane oxygenation (VV-ECMO). No study included spontaneously breathing patients or stratified results by ARDS phenotype. Diagnostic performance varied substantially across clinical contexts. Unadjusted PPV showed inconsistent diagnostic performance, particularly in patients with low respiratory system compliance or under prone positioning, whereas adjusted PPV, defined as PPV normalized to respiratory mechanics (e.g., driving pressure, transpulmonary pressure, respiratory system compliance, and chest wall elastance), demonstrated improved diagnostic performance in selected cohorts. Overall, predictor performance was highly dependent on ventilatory strategy, extracorporeal support, and validation methodology. The diagnostic performance of fluid responsiveness predictors in ARDS is highly variable and context-dependent, influenced by ventilatory strategy, respiratory mechanics, extracorporeal support, and methodological heterogeneity. Important evidence gaps persist, particularly in prone ventilation, VV-ECMO, and spontaneously breathing patients. Future studies should integrate measures of fluid tolerance and stratify patients by ARDS phenotype to support individualized fluid management strategies.

Objective: Primary lateral sclerosis (PLS) is a rare upper motor neuron disorder within the motor neuron disease spectrum. Data from Latin America remains limited. We aimed to characterize clinical phenotypes, non-motor features, and prognostic markers in a systematically adjudicated Brazilian PLS cohort. Methods: In this retrospective multicenter study, we analyzed the data of 81 patients meeting the Turner 2020 criteria for probable/definite PLS at SARAH Network Hospitals (2007–2023). Clinical phenotyping, neurophysiology, C9orf72 testing, and survival analyses were conducted. Results: The participants’ median age at onset was 54 years (interquartile range 46–62); 53% of them were men. The onset distribution was as follows: lower limb 65%, bulbar 22%, and upper limb 11%. Extrapyramidal signs (7%) identified high-risk patients with fourfold increased mortality (relative risk [RR] 4.2, p = 0.013) and sixfold increased cognitive impairment (RR 6.3, p = 0.007). Eight patients (9.9%) exhibited hemiparetic presentations, with two meeting the definite Mills syndrome criteria; seven patients progressed to generalized PLS. Non-motor features were common: pseudobulbar affect (51%), urinary urgency (57%), and cognitive impairment (11%). Family history was observed in 10% and C9orf72 expansion in 3%, with intrafamilial phenotypic variability. Five-year survival was excellent (98%) without onset-site effect (hazard ratio 0.80, p = 0.697). Two patients maintained isolated corticobulbar syndrome for 50–71 months. Conclusions: This first Latin American PLS cohort demonstrates clinical characteristics comparable to those reported in international studies. Extrapyramidal signs emerged as a high-risk marker. Hemiparetic presentations appear transitional, and non-motor manifestations support PLS as a multisystem disorder.

Klinefelter syndrome (KS) is characterized by marked phenotypic heterogeneity that might be influenced by genetic modifiers, including androgen receptor (AR) repeat length (CAGn and GGCn). The clinical relevance of these repeat lengths in patients with KS before testosterone replacement therapy (TRT) remains unclear. To investigate the association between AR repeat length and anthropometric, hormonal, metabolic, and reproductive parameters in a well-characterized cohort of untreated adult patients with KS. In this cross-sectional single-center study, 214 men with classical 47, XXY karyotype were evaluated prior to TRT. Clinical, biochemical, and reproductive parameters were analyzed according to AR CAGn and GGCn repeat length. Nonparametric tests, multivariable linear and logistic regression models, and interaction terms between CAGn and GGCn were tested. Standardized beta coefficients were used to compare the relative contribution of AR repeat length with major clinical determinants. In unadjusted analyses, CAG repeat length was associated with estradiol concentrations, whereas GGC repeat length showed associations with hematocrit, platelet count, and total cholesterol. However, most associations were characterized by small effect sizes and did not persist after multivariable adjustment for possible confounders (age, BMI, and total testosterone levels). Moreover, AR repeat length was not associated with sperm retrieval rate. Standardized beta analyses demonstrated that testosterone levels, BMI, and age accounted for the largest proportion of phenotypic variability, whereas CAGn and GGCn repeat length had minimal roles. In untreated patients with KS, AR repeat length (CAGn and GGCn) appears to have a limited clinical impact compared with classical endocrine and metabolic determinants. These findings suggest that phenotypic variability in KS might be primarily driven by chromosomal aneuploidy and primary testicular dysfunction rather than AR repeat length.

Asthma is one of the commonest noncommunicable diseases worldwide. Poor clinical outcomes have been reported in asthma amongst ethnic minority groups (EMGs) and reasons are likely to be multifactorial. There is a suggestion that underlying disease may behave differently amongst EMGs, alongside other factors including deprivation, cultural, religious, social, literacy, patient beliefs, healthcare access, treatment adherence, alongside greater burden of multimorbidity. Multimorbidity (presence of ≥ 2 long-term health conditions) in asthma is increasingly known to contribute to greater asthma burden, with differences in multimorbidity burden and patterns seen across ethnicities with a tight association with deprivation. Earlier onset of multimorbidity with relatively reduced survival has been reported amongst EMG patients, particularly those from a deprived background compared to White patients. Data regarding asthma, multimorbidity and ethnicity are scant, but emerging data suggest that multimorbidity is heterogenous, and that ethnic background is associated with variations in asthma outcomes and multimorbidity phenotypes. What is currently lacking is population-based research with a joined-up interrogation of primary care and secondary care databases to determine the prevalence and patterns of T2 and non T2 multimorbidity in asthma amongst EMGs, and analysis of patterns of associations and link to socio-demographic variables and clinical outcomes. Deeper insight into views of EMG patients and their carers regarding lived experiences of asthma and multimorbidity management, as well as those of healthcare professionals is needed, to allow development of culturally tailored resources. These studies are likely to shape a holistic culturally tailored multidimensional and an equitable approach to management of asthma with multimorbidity amongst EMGs.