APPLICATIONS OF MULTIMODAL GENERATIVE ARTIFICIAL INTELLIGENCE IN A REAL-WORLD RETINA CLINIC SETTING.

PURPOSE: This study evaluates a large language model, Generative Pre-trained Transformer 4 with vision, for diagnosing vitreoretinal diseases in real-world ophthalmology settings. METHODS: A retrospective cross-sectional study at Bascom Palmer Eye Clinic, analyzing patient data from January 2010 to March 2023, assesses Generative Pre-trained Transformer 4 with vision's performance on retinal image analysis and International Classification of Diseases 10th revision coding across 2 patient groups: simpler cases (Group A) and complex cases (Group B) requiring more in-depth analysis. Diagnostic accuracy was assessed through open-ended questions and multiple-choice questions independently verified by three retina specialists. RESULTS: In 256 eyes from 143 patients, Generative Pre-trained Transformer 4-V demonstrated a 13.7% accuracy for open-ended questions and 31.3% for multiple-choice questions, with International Classification of Diseases 10th revision code accuracies at 5.5% and 31.3%, respectively. Accurately diagnosed posterior vitreous detachment, nonexudative age-related macular degeneration, and retinal detachment. International Classification of Diseases 10th revision coding was most accurate for nonexudative age-related macular degeneration, central retinal vein occlusion, and macular hole in OEQs, and for posterior vitreous detachment, nonexudative age-related macular degeneration, and retinal detachment in multiple-choice questions. No significant difference in diagnostic or coding accuracy was found in Groups A and B. CONCLUSION: Generative Pre-trained Transformer 4 with vision has potential in clinical care and record keeping, particularly with standardized questions. Its effectiveness in open-ended scenarios is limited, indicating a significant limitation in providing complex medical advice.

An experimental field study of inbreeding depression in an outcrossing invasive plant.

Inbreeding depression is likely to play an important role during biological invasion. But relatively few studies have investigated the fitness of selfed and outcrossed offspring in self-incompatible invasive plants in natural environments in their introduced range. Moreover, the majority of studies on inbreeding depression have investigated self-compatible species with mixed mating, and less is known about the intensity of inbreeding depression in outcrossing self-incompatible species. Here, we address these questions experimentally by comparing selfed and outcrossed progeny of purple loosestrife (Lythrum salicaria) over four growing seasons, including three under field conditions in a freshwater marsh in southern Ontario, Canada, a region where L. salicaria is highly invasive. The tristylous mating system of L. salicaria involves disassortative mating among floral morphs enforced by trimorphic incompatibility. However, owing to partial incompatibility, self-fertilized seed can be obtained by manual self-pollination thus facilitating comparisons of selfed and outcrossed progeny. We compared progeny with and without intraspecific competition from selfed or outcrossed neighbours and examined the influence of breeding treatment and competition on fitness correlates by measuring a range of life-history traits including: proportion of seeds germinating, days to germination, survival, proportion of plants flowering, time to flowering, vegetative mass, and inflorescence number and mass. We analysed data for each trait using functions from time series estimates of growth and two multiplicative estimates of fitness. We detected varying intensities of inbreeding depression for several traits in three of the four years of the experiment, including inflorescence mass and reproductive output. Cumulative inbreeding depression over four years averaged δ = 0.48 and 0.68, depending on the method used to estimate multiplicative fitness. The competition treatments did not significantly affect plant performance and the magnitude of inbreeding depression. Given the primarily outcrossing mating system of L. salicaria populations, the detection of inbreeding depression for several key life-history traits was as predicted by theory. Our results suggests that biparental inbreeding and low selfing in colonizing populations may have significant effects on demographic parameters such as population growth.

Phased Assembly of Neo-Sex Chromosomes Reveals Extensive Y Degeneration and Rapid Genome Evolution in Rumex hastatulus.

Y chromosomes are thought to undergo progressive degeneration due to stepwise loss of recombination and subsequent reduction in selection efficiency. However, the timescales and evolutionary forces driving degeneration remain unclear. To investigate the evolution of sex chromosomes on multiple timescales, we generated a high-quality phased genome assembly of the massive older (<10 MYA) and neo (<200,000 yr) sex chromosomes in the XYY cytotype of the dioecious plant Rumex hastatulus and a hermaphroditic outgroup Rumex salicifolius. Our assemblies, supported by fluorescence in situ hybridization, confirmed that the neo-sex chromosomes were formed by two key events: an X-autosome fusion and a reciprocal translocation between the homologous autosome and the Y chromosome. The enormous sex-linked regions of the X (296 Mb) and two Y chromosomes (503 Mb) both evolved from large repeat-rich genomic regions with low recombination; however, the complete loss of recombination on the Y still led to over 30% gene loss and major rearrangements. In the older sex-linked region, there has been a significant increase in transposable element abundance, even into and near genes. In the neo-sex-linked regions, we observed evidence of extensive rearrangements without gene degeneration and loss. Overall, we inferred significant degeneration during the first 10 million years of Y chromosome evolution but not on very short timescales. Our results indicate that even when sex chromosomes emerge from repetitive regions of already-low recombination, the complete loss of recombination on the Y chromosome still leads to a substantial increase in repetitive element content and gene degeneration.

Parallel evolution of morphological and genomic selfing syndromes accompany the breakdown of heterostyly.

Evolutionary transitions from outcrossing to selfing in flowering plants have convergent morphological and genomic signatures and can involve parallel evolution within related lineages. Adaptive evolution of morphological traits is often assumed to evolve faster than nonadaptive features of the genomic selfing syndrome. We investigated phenotypic and genomic changes associated with transitions from distyly to homostyly in the Primula oreodoxa complex. We determined whether the transition to selfing occurred more than once and investigated stages in the evolution of morphological and genomic selfing syndromes using 22 floral traits and both nuclear and plastid genomic data from 25 populations. Two independent transitions were detected representing an earlier and a more recently derived selfing lineage. The older lineage exhibited classic features of the morphological and genomic selfing syndrome. Although features of both selfing syndromes were less developed in the younger selfing lineage, they exhibited parallel development with the older selfing lineage. This finding contrasts with the prediction that some genomic changes should lag behind adaptive changes to morphological traits. Our findings highlight the value of comparative studies on the timing and extent of transitions from outcrossing to selfing between related lineages for investigating the tempo of morphological and molecular evolution.

Haplotype-resolved genome assembly provides insights into the evolution of S-locus supergene in distylous Nymphoides indica.

Distyly has evolved independently in numerous animal-pollinated angiosperm lineages. Understanding of its molecular basis has been restricted to a few species, primarily Primula. Here, we investigate the genetic architecture of the single diallelic locus (S-locus) supergene, a linkage group of functionally associated genes, and explore how it may have evolved in distylous Nymphoides indica, a lineage of flowering plants not previously investigated. We assembled haplotype-resolved genomes, used read-coverage-based genome-wide association study (rb-GWAS) to locate the S-locus supergene, co-expression network analysis to explore gene networks underpinning the development of distyly, and comparative genomic analyses to investigate the origins of the S-locus supergene. We identified three linked candidate S-locus genes - NinBAS1, NinKHZ2, and NinS1 - that were only evident in the short-styled morph and were hemizygous. Co-expression network analysis suggested that brassinosteroids contribute to dimorphic sex organs in the short-styled morph. Comparative genomic analyses indicated that the S-locus supergene likely evolved via stepwise duplications and has been affected by transposable element activities. Our study provides novel insight into the structure, regulation, and evolution of the supergene governing distyly in N. indica. It also provides high-quality genomic resources for future research on the molecular mechanisms underlying the striking evolutionary convergence in form and function across heterostylous taxa.

A new type of cell related to organ movement for selfing in plants.

Many plants employ osmotic and hydrostatic pressure to generate movement for survival, but little is known about the cellular mechanisms involved. Here, we report a new cell type in angiosperms termed 'contractile cells' in the stigmas of the flowering plant Chirita pumila with a much-expanded rough endoplasmic reticulum (RER). Cryo-scanning electron microscopy and transmission electron microscopy analyses revealed that the RER is continuously distributed throughout the entirety of cells, confirmed by endoplasmic reticulum (ER)-specific fluorescent labeling, and is distinct from the common feature of plant ER. The RER is water-sensitive and extremely elongated with water absorption. We show that the contractile cells drive circadian stigma closing-bending movements in response to day-to-night moisture changes. RNA-seq analyses demonstrated that contractile cells have distinct molecular components. Furthermore, multiple microstructural changes in stigma movements convert an anti-selfing structure into a device promoting selfing-a unique cellular mechanism of reproductive adaptation for uncertain pollination environments.

Twenty-year survival following lung transplantation.

Background: Lung transplantation median survival has seen improvements due to recognition of short-term survival factors but continues to trail behind other solid organs due to limited understanding of long-term survivorship. Given the creation of the United Network for Organ Sharing (UNOS) database in 1986, it was difficult to accrue data on long-term survivors until recently. This study characterizes factors impacting lung transplant survival beyond 20 years, conditional to 1-year survival. Methods: Lung transplant recipients listed in UNOS from 1987 to 2002 who survived to 1 post-transplant year were reviewed. Kaplan-Meier and adjusted Cox regression analyses were performed at 20 and 10 years to identify risk factors associated with long-term outcomes independent of their short-term effects. Results: A total of 6,172 recipients were analyzed, including 472 (7.6%) recipients who lived 20+ years. Factors associated with increased likelihood of 20-year survival were female-to-female gender match, recipient age 25-44, waitlist time >1 year, human leukocyte antigen (HLA) mismatch level 3, and donor cause of death: head trauma. Factors associated with decreased 20-year survival included recipient age ≥55, chronic obstructive pulmonary disease/emphysema (COPD/E) diagnosis, donor smoking history >20 pack-years, unilateral transplant, blood groups O&AB, recipient glomerular filtration rate (GFR) <10 mL/min, and donor GFR 20-29 mL/min. Conclusions: This is the first study identifying factors associated with multiple-decade survival following lung transplant in the United States. Despite its challenges, long-term survival is possible and more likely in younger females in good waitlist condition without COPD/E who receive a bilateral allograft from a non-smoking, gender-matched donor of minimal HLA mismatch. Further analysis of the molecular and immunologic implications of these conditions are warranted.

Selecting DCD Recipients Using Predictive Indices.

Donation after circulatory death (DCD) allografts might represent one of the largest untapped sources of liver allografts. Our aim was to identify independent recipient risk factors that predict mortality in DCD allograft recipients to preselect optimal candidates for successful transplantation. Furthermore, we compared the application of our newly constructed DCD Recipient Selector Index (RSI) score to previously developed models to determine superiority in predicting recipient survival. Methods: Using the Organ Procurement and Transplantation Network database, we performed univariate and multivariate retrospective analyses on 4228 DCD liver allograft recipients. Results: We identified 8 significant factors and incorporated them into the weighted RSI to predict 3-mo survival following DCD liver transplantation with a C-statistic of 0.6971. The most significant recipient risk factors were recipient serum sodium levels >150 mEq/L at transplant, recipient albumin <2.0 g/dL at transplant, and a history of portal vein thrombosis. Because Model for End-Stage Liver Disease (MELD) score components were included as individual predictors, the DCD RSI predicts survival independently of MELD. Upon comparison with 3 previous recipient risk scores-Balance of Risk, Renal Risk Index, Patient-Survival Outcomes Following Liver Transplantation-the DCD RSI was determined to be superior at selecting optimal candidates pre-DCD transplantation, yielding a C-statistic of 0.6971. Conclusions: After verifying the performance of predictive indices for selection of DCD recipients, the DCD RSI is best used to preselect patients for optimized outcomes after DCD transplantation. This can increase utilization of DCD donors by improving outcomes.

Diverse mating consequences of the evolutionary breakdown of the sexual polymorphism heterostyly.

Reproductive systems of flowering plants are evolutionarily fluid, with mating patterns changing in response to shifts in abiotic conditions, pollination systems, and population characteristics. Changes in mating should be particularly evident in species with sexual polymorphisms that become ecologically destabilized, promoting transitions to alternative reproductive systems. Here, we decompose female mating portfolios (incidence of selfing, outcross mate number, and intermorph mating) in eight populations of Primula oreodoxa, a self-compatible insect-pollinated herb. This species is ancestrally distylous, with populations subdivided into two floral morphs that usually mate with each other (disassortative mating). Stages in the breakdown of polymorphism also occur, including "mixed" populations of distylous and homostylous (self-pollinating) morphs and purely homostylous populations. Population morph ratios vary with elevation in association with differences in pollinator availability, providing an unusual opportunity to investigate changes in mating patterns accompanying transitions in reproductive systems. Unexpectedly, individuals mostly outcrossed randomly, with substantial disassortative mating in at most two distylous populations. As predicted, mixed populations had higher selfing rates than distylous populations, within mixed populations, homostyles selfed almost twice as much as the distylous morphs, and homostylous populations exhibited the highest selfing rates. Populations with homostyles outcrossed with fewer mates and mate number varied negatively with population selfing rates. These differences indicate maintenance of distyly at low elevation, transition to monomorphic selfing at high elevation, and uncertain, possibly variable fates at intermediate elevation. By quantifying the earliest changes in mating that initiate reproductive transitions, our study highlights the key role of mating in promoting evolutionary divergence.

Genomic evidence supports the genetic convergence of a supergene controlling the distylous floral syndrome.

Heterostyly, a plant sexual polymorphism controlled by the S-locus supergene, has evolved numerous times among angiosperm lineages and represents a classic example of convergent evolution in form and function. Determining whether underlying molecular convergence occurs could provide insights on constraints to floral evolution. Here, we investigated S-locus genes in distylous Gelsemium (Gelsemiaceae) to determine whether there is evidence of molecular convergence with unrelated distylous species. We used several approaches, including anatomical measurements of sex-organ development and transcriptome and whole-genome sequencing, to identify components of the S-locus supergene. We also performed evolutionary analysis with candidate S-locus genes and compared them with those reported in Primula and Turnera. The candidate S-locus supergene of Gelsemium contained four genes, of which three appear to have originated from gene duplication events within Gelsemiaceae. The style-length genes GeCYP in Gelsemium and CYP734A50 in Primula likely arose from duplication of the same gene, CYP734A1. Three out of four S-locus genes in Gelsemium elegans were hemizygous, as previously reported in Primula and Turnera. We provide genomic evidence on the genetic convergence of the supergene underlying distyly among distantly related angiosperm lineages and help to illuminate the genetic architecture involved in the evolution of heterostyly.

Genetic variation and clonal diversity in floating aquatic plants: Comparative genomic analysis of water hyacinth species in their native range.

Many eukaryotic organisms reproduce by sexual and asexual reproduction. Genetic diversity in populations can be strongly dependent on the relative importance of these two reproductive modes. Here, we compare the amounts and patterns of genetic diversity in related water hyacinths that differ in their propensity for clonal propagation - highly clonal Eichhornia crassipes and moderately clonal E. azurea (Pontederiaceae). Our comparisons involved genotype-by-sequencing (GBS) of 137 E. crassipes ramets from 60 locations (193,495 nucleotide sites) and 118 E. azurea ramets from 53 locations (198,343 nucleotide sites) among six hydrological basins in central South America, the native range of both species. We predicted that because of more prolific clonal propagation, E. crassipes would exhibit lower clonal diversity than E. azurea. This prediction was supported by all measures of clonal diversity that we examined. Eichhornia crassipes also had a larger excess of heterozygotes at variant sites, another signature of clonality. However, genome-wide heterozygosity was not significantly different between the species. Eichhornia crassipes had weaker spatial genetic structure and lower levels of differentiation among hydrological basins than E. azurea, probably because of higher clonality and more extensive dispersal of its free-floating life form. Our findings for E. crassipes contrast with earlier studies from the invasive range which have reported very low levels of clonal diversity and extensive geographic areas of genetic uniformity.

Do Patients with Autoimmune Conditions Have Less Access to Liver Transplantation despite Superior Outcomes?

Orthotopic liver transplantation (OLT) is a lifesaving therapy for patients with irreversible liver damage caused by autoimmune liver diseases (AutoD) including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Currently, it is unclear how access to transplantation differs among patients with various etiologies of liver disease. Our aim is to evaluate the likelihood of transplant and the long-term patient and graft survival after OLT for each etiology for transplantation from 2000 to 2021. We conducted a large retrospective study of United Network for Organ Sharing (UNOS) liver transplant patients in five 4-year eras with five cohorts: AutoD (PBC, PSC, AIH cirrhosis), alcohol-related liver disease (ALD), hepatocellular carcinoma (HCC), viral hepatitis, and nonalcoholic steatohepatitis (NASH). We conducted a multivariate analysis for probability of transplant. Intent-to-treat (ITT) analysis was performed to assess the 10-year survival differences for each listing diagnosis while accounting for both waitlist and post-transplant survival. Across all eras, autoimmune conditions had a lower adjusted probability of transplant of 0.92 (0.92, 0.93) compared to ALD 0.97 (0.97, 0.97), HCC 1.08 (1.07, 1.08), viral hepatitis 0.99 (0.99, 0.99), and NASH 0.99 (0.99, 1.00). Patients with AutoD had significantly better post-transplant patient and graft survival than ALD, HCC, viral hepatitis, and NASH in each and across all eras (p-values all < 0.001). Patients with AutoD had superior ITT survival (p-value < 0.001, log rank test). In addition, the waitlist survival for patients with AutoD compared to other listing diagnoses was improved with the exception of ALD, which showed no significant difference (p-value = 0.1056, log rank test). Despite a superior 10-year graft and patient survival in patients transplanted for AutoD, patients with AutoD have a significantly lower probability of receiving a liver transplant compared to those transplanted for HCC, ALD, viral hepatitis, and NASH. Patients with AutoD may benefit from improved liver allocation while maintaining superior waitlist and post-transplant survival. Decreased access in spite of appropriate outcomes for patients poses a significant risk for increased morbidity for patients with AutoD.

Effects of the neo-X chromosome on genomic signatures of hybridization in Rumex hastatulus.

Natural hybrid zones provide opportunities for studies of the evolution of reproductive isolation in wild populations. Although recent investigations have found that the formation of neo-sex chromosomes is associated with reproductive isolation, the mechanisms remain unclear in most cases. Here, we assess the contemporary structure of gene flow in the contact zone between largely allopatric cytotypes of the dioecious plant Rumex hastatulus, a species with evidence of sex chromosome turn-over. Males to the west of the Mississippi river, USA, have an X and a single Y chromosome, whereas populations to the east of the river have undergone a chromosomal rearrangement giving rise to a larger X and two Y chromosomes. Using reduced-representation sequencing, we provide evidence that hybrids form readily and survive multiple backcross generations in the field, demonstrating the potential for ongoing gene flow between the cytotypes. Cline analysis of each chromosome separately captured no signals of difference in cline shape between chromosomes. However, principal component regression revealed a significant increase in the contribution of individual SNPs to inter-cytotype differentiation on the neo-X chromosome, but no correlation with recombination rate. Cline analysis revealed that the only SNPs with significantly steeper clines than the genome average were located on the neo-X. Our data are consistent with a role for neo-sex chromosomes in reproductive isolation between R. hastatulus cytotypes. Our investigation highlights the importance of studying plant hybrid zones for understanding the evolution of sex chromosomes.

Global analysis of floral longevity reveals latitudinal gradients and biotic and abiotic correlates.

The length of time a flower remains open and functional - floral longevity - governs important reproductive processes influencing pollination and mating and varies considerably among angiosperm species. However, little is known about large-scale biogeographic patterns and the correlates of floral longevity. Using published data on floral longevity from 818 angiosperm species in 134 families and 472 locations world-wide, we present the first global quantification of the latitudinal pattern of floral longevity and the relationships between floral longevity and a range of biotic and abiotic factors. Floral longevity exhibited a significant phylogenetic signal and was longer at higher latitudes in both northern and southern hemispheres, even after accounting for elevation. This latitudinal variation was associated with several biotic and abiotic variables. The mean temperature of the flowering season had the highest predictive power for floral longevity, followed by pollen number per flower. Surprisingly, compatibility status, flower size, pollination mode, and growth form had no significant effects on flower longevity. Our results suggest that physiological processes associated with floral maintenance play a key role in explaining latitudinal variation in floral longevity across global ecosystems, with potential implications for floral longevity under global climate change and species distributions.

Contrasting patterns of genetic diversity and differentiation across the continental disjunct range of a sexually polymorphic aquatic plant.

BACKGROUND AND AIMS: Reproductive systems enabling opportunities for self-fertilization influence population genetic structure and play a key role in colonization and genetic differentiation during range expansion. Because of their well-developed powers of dispersal, aquatic plants often have widespread disjunct geographical distributions, providing opportunities to investigate the role of reproductive systems in structuring genetic variation between parts of the range that differ in migration history and ecology. METHODS: We compared reproductive systems and spatial genetic structure of the freshwater aquatic macrophyte Sagittaria latifolia between disjunct western and eastern ranges of North America (NA). Populations of this species are most commonly either monoecious or dioecious. We examined chloroplast DNA haplotype variation to test the hypothesis that the western range of this species represents a secondary colonization from the east, and evaluated the roles of reproductive system differences and geography in structuring contemporary patterns of genetic variation at 11 polymorphic SSR (simple sequence repeat) loci. KEY RESULTS: Chloroplast haplotyping revealed a single haplotype in western NA compared to numerous haplotypes in eastern NA, consistent with a genetic bottleneck during westward migration. Estimates of genetic diversity in eastern NA populations differed significantly between reproductive systems, but this pattern was not evident in the western range. Eastern populations could be reliably assigned to genetic clusters based on their reproductive systems, whereas western populations clustered primarily by geographical location. CONCLUSIONS: The sparser distribution of aquatic habitats in the drier western range of S. latifolia, combined with secondary colonization of this region, probably cause the lower genetic diversity and increased differentiation among populations, possibly overriding the effects of reproductive system evident in the eastern portion of the range. Our findings demonstrate that the complex interplay between migratory history, reproductive systems and habitat availability plays an important role in structuring spatial patterns of genetic variation in disjunct plant populations.

Recombination landscape dimorphism and sex chromosome evolution in the dioecious plant Rumex hastatulus.

There is growing evidence from diverse taxa for sex differences in the genomic landscape of recombination, but the causes and consequences of these differences remain poorly understood. Strong recombination landscape dimorphism between the sexes could have important implications for the dynamics of sex chromosome evolution because low recombination in the heterogametic sex can favour the spread of sexually antagonistic alleles. Here, we present a sex-specific linkage map and revised genome assembly of Rumex hastatulus and provide the first evidence and characterization of sex differences in recombination landscape in a dioecious plant. We present data on significant sex differences in recombination, with regions of very low recombination in males covering over half of the genome. This pattern is evident on both sex chromosomes and autosomes, suggesting that pre-existing differences in recombination may have contributed to sex chromosome formation and divergence. Our analysis of segregation distortion suggests that haploid selection due to pollen competition occurs disproportionately in regions with low male recombination. We hypothesize that sex differences in the recombination landscape have contributed to the formation of a large heteromorphic pair of sex chromosomes in R. hastatulus, but more comparative analyses of recombination will be important to investigate this hypothesis further. This article is part of the theme issue 'Sex determination and sex chromosome evolution in land plants'.

The impact of diabetes on young transplant recipients: An American perspective.

Despite advancements in diabetic care, diabetic kidney transplant recipients have significantly worse outcomes than non-diabetics. AIM: Our study aims to demonstrate the impact of diabetes, types I and II, on American young adults (18-40 years old) requiring kidney transplantation. METHODS: Using the United Network for Organ Sharing database, we conducted a population cohort study that included all first-time, kidney-only transplant recipients during 2002-2019, ages 18-40 years old. Patients were grouped according to indication for transplant. Primary outcomes were cumulative all-cause mortality and death-censored graft failure. Death-censored graft failure and patient survival at 1, 5, and 10 years were calculated via the Kaplan-Meier method. Multivariate Cox regression was used to assess for potential confounders. RESULTS: Of 42 466 transplant recipients, 3418 (8.1%) had end-stage kidney disease associated with diabetes. At each time-point, cumulative mortality was higher in diabetics compared to patients with non-diabetic causes of renal failure. Conversely, cumulative graft failure was similar between the groups. Adjusted hazard ratios for all-cause mortality and graft failure in diabetics were 2.99 (95% CI 2.67-3.35; p < .01) and 0.98 (95% CI 0.92-1.05, p < .01), respectively. CONCLUSION: Diabetes mellitus in young adult kidney transplant recipients is associated with a nearly three-fold increase in mortality, reflecting a relatively vulnerable patient population. Identifying the underlying causes of poor outcomes in this population should be a priority for future study.