Excess natural-cause mortality in US counties and its association with reported COVID-19 deaths.

In the United States, estimates of excess deaths attributable to the COVID-19 pandemic have consistently surpassed reported COVID-19 death counts. Excess deaths reported to non-COVID-19 natural causes may represent unrecognized COVID-19 deaths, deaths caused by pandemic health care interruptions, and/or deaths from the pandemic's socioeconomic impacts. The geographic and temporal distribution of these deaths may help to evaluate which explanation is most plausible. We developed a Bayesian hierarchical model to produce monthly estimates of excess natural-cause mortality for US counties over the first 30 mo of the pandemic. From March 2020 through August 2022, 1,194,610 excess natural-cause deaths occurred nationally [90% PI (Posterior Interval): 1,046,000 to 1,340,204]. A total of 162,886 of these excess natural-cause deaths (90% PI: 14,276 to 308,480) were not reported to COVID-19. Overall, 15.8 excess deaths were reported to non-COVID-19 natural causes for every 100 reported COVID-19 deaths. This number was greater in nonmetropolitan counties (36.0 deaths), the West (Rocky Mountain states: 31.6 deaths; Pacific states: 25.5 deaths), and the South (East South Central states: 26.0 deaths; South Atlantic states: 25.0 deaths; West South Central states: 24.2 deaths). In contrast, reported COVID-19 death counts surpassed estimates of excess natural-cause deaths in metropolitan counties in the New England and Middle Atlantic states. Increases in reported COVID-19 deaths correlated temporally with increases in excess deaths reported to non-COVID-19 natural causes in the same and/or prior month. This suggests that many excess deaths reported to non-COVID-19 natural causes during the first 30 mo of the pandemic in the United States were unrecognized COVID-19 deaths.

Emerging opportunities for C3 inhibition in the eye.

The eye presents a unique opportunity for complement component 3 (C3) therapeutics. Drugs can be delivered directly to specific parts of the eye, and growing evidence has established a pivotal role for C3 in age-related macular degeneration (AMD). Emerging data show that C3 may be important to the pathophysiology of other eye diseases as well. This article will discuss the location of C3 expression in the eye as well as the preclinical and clinical data regarding C3's functions in AMD. We will provide a comprehensive review of developing C3 inhibitors for the eye, including the Phase 2 and 3 data for the C3 inhibitor pegcetacoplan as a treatment for the geographic atrophy of AMD. Developing evidence also points toward C3 as a therapeutic target for stages of AMD preceding geographic atrophy. We will also discuss data illuminating C3's relationship to other eye diseases, such as Stargardt disease, diabetic retinopathy, and glaucoma. In addition to being a converging point and centerpiece of the complement cascade, C3 has broad effects as a multifaceted controller of opsonophagocytosis, microglia/macrophage recruitment, and downstream terminal pathway activity. C3 is a crucial player in the pathophysiology of AMD but also seems to have importance in other diseases that are major causes of blindness. Directions for further investigation will be highlighted, as culminating evidence suggests that we may be approaching an era of C3 therapeutics for the eye.

Pathologic vs. protective roles of hypoxia-inducible factor 1 in RPE and photoreceptors in wet vs. dry age-related macular degeneration.

It has previously been reported that antioxidant vitamins can help reduce the risk of vision loss associated with progression to advanced age-related macular degeneration (AMD), a leading cause of visual impairment among the elderly. Nonetheless, how oxidative stress contributes to the development of choroidal neovascularization (CNV) in some AMD patients and geographic atrophy (GA) in others is poorly understood. Here, we provide evidence demonstrating that oxidative stress cooperates with hypoxia to synergistically stimulate the accumulation of hypoxia-inducible factor (HIF)-1α in the retinal pigment epithelium (RPE), resulting in increased expression of the HIF-1-dependent angiogenic mediators that promote CNV. HIF-1 inhibition blocked the expression of these angiogenic mediators and prevented CNV development in an animal model of ocular oxidative stress, demonstrating the pathological role of HIF-1 in response to oxidative stress stimulation in neovascular AMD. While human-induced pluripotent stem cell (hiPSC)-derived RPE monolayers exposed to chemical oxidants resulted in disorganization and disruption of their normal architecture, RPE cells proved remarkably resistant to oxidative stress. Conversely, equivalent doses of chemical oxidants resulted in apoptosis of hiPSC-derived retinal photoreceptors. Pharmacologic inhibition of HIF-1 in the mouse retina enhanced-while HIF-1 augmentation reduced-photoreceptor apoptosis in two mouse models for oxidative stress, consistent with a protective role for HIF-1 in photoreceptors in patients with advanced dry AMD. Collectively, these results suggest that in patients with AMD, increased expression of HIF-1α in RPE exposed to oxidative stress promotes the development of CNV, but inadequate HIF-1α expression in photoreceptors contributes to the development of GA.

Epidemiology of nasopharyngeal carcinoma: current insights and future outlook.

Nasopharyngeal carcinoma (NPC) is characterised by its remarkable geographical and ethnic distribution. The interplay between genetic susceptibility, environmental exposures, and Epstein-Barr virus (EBV) infections is indicated in the development of NPC. Exposure to tobacco smoking, dietary factors, and inhalants has been associated with the risk of NPC. Genetic association studies have revealed NPC-associated susceptibility loci, including genes involved in immune responses, xenobiotic metabolism, genome maintenance, and cell cycle regulation. EBV exposure timing and strain variation might play a role in its carcinogenicity, although further investigations are required. Other factors including medical history and oral hygiene have been implicated in NPC. Prevention strategies, including primary prevention and secondary prevention through early detection, are vital in reducing mortality and morbidity of NPC. The current review discusses the global and regional distribution of NPC incidences, the risk factors associated with NPC, and the public health implications of these insights. Future investigations should consider international, large-scale prospective studies to elucidate the mechanisms underlying NPC pathogenesis and develop individualized interventions for NPC.

Mapping the Ecological Terrain of Stroke Prehospital Delay: A Nationwide Registry Study.

BACKGROUND: Delays in hospital presentation limit access to acute stroke treatments. While prior research has focused on patient-level factors, broader ecological and social determinants have not been well studied. We aimed to create a geospatial map of prehospital delay and examine the role of community-level social vulnerability. METHODS: We studied patients with ischemic stroke who arrived by emergency medical services in 2015 to 2017 from the American Heart Association Get With The Guidelines-Stroke registry. The primary outcome was time to hospital arrival after stroke (in minutes), beginning at last known well in most cases. Using Geographic Information System mapping, we displayed the geography of delay. We then used Cox proportional hazard models to study the relationship between community-level factors and arrival time (adjusted hazard ratios [aHR] <1.0 indicate delay). The primary exposure was the social vulnerability index (SVI), a metric of social vulnerability for every ZIP Code Tabulation Area ranging from 0.0 to 1.0. RESULTS: Of 750 336 patients, 149 145 met inclusion criteria. The mean age was 73 years, and 51% were female. The median time to hospital arrival was 140 minutes (Q1: 60 minutes, Q3: 458 minutes). The geospatial map revealed that many zones of delay overlapped with socially vulnerable areas (https://harvard-cga.maps.arcgis.com/apps/webappviewer/index.html?id=08f6e885c71b457f83cefc71013bcaa7). Cox models (aHR, 95% CI) confirmed that higher SVI, including quartiles 3 (aHR, 0.96 [95% CI, 0.93-0.98]) and 4 (aHR, 0.93 [95% CI, 0.91-0.95]), was associated with delay. Patients from SVI quartile 4 neighborhoods arrived 15.6 minutes [15-16.2] slower than patients from SVI quartile 1. Specific SVI themes associated with delay were a community's socioeconomic status (aHR, 0.80 [95% CI, 0.74-0.85]) and housing type and transportation (aHR, 0.89 [95% CI, 0.84-0.94]). CONCLUSIONS: This map of acute stroke presentation times shows areas with a high incidence of delay. Increased social vulnerability characterizes these areas. Such places should be systematically targeted to improve population-level stroke presentation times.

Geographic Distribution of Rabies Virus and Genomic Sequence Alignment of Wild and Vaccine Strains, Kenya.

Rabies, a viral disease that causes lethal encephalitis, kills ≈59,000 persons worldwide annually, despite availability of effective countermeasures. Rabies is endemic in Kenya and is mainly transmitted to humans through bites from rabid domestic dogs. We analyzed 164 brain stems collected from rabid animals in western and eastern Kenya and evaluated the phylogenetic relationships of rabies virus (RABV) from the 2 regions. We also analyzed RABV genomes for potential amino acid changes in the vaccine antigenic sites of nucleoprotein and glycoprotein compared with RABV vaccine strains commonly used in Kenya. We found that RABV genomes from eastern Kenya overwhelmingly clustered with the Africa-1b subclade and RABV from western Kenya clustered with Africa-1a. We noted minimal amino acid variances between the wild and vaccine virus strains. These data confirm minimal viral migration between the 2 regions and that rabies endemicity is the result of limited vaccine coverage rather than limited efficacy.

Concurrent Clade I and Clade II Monkeypox Virus Circulation, Cameroon, 1979-2022.

During 1979-2022, Cameroon recorded 32 laboratory-confirmed mpox cases among 137 suspected mpox cases identified by the national surveillance network. The highest positivity rate occurred in 2022, indicating potential mpox re-emergence in Cameroon. Both clade I (n = 12) and clade II (n = 18) monkeypox virus (MPXV) were reported, a unique feature of mpox in Cameroon. The overall case-fatality ratio of 2.2% was associated with clade II. We found mpox occurred only in the forested southern part of the country, and MPXV phylogeographic structure revealed a clear geographic separation among concurrent circulating clades. Clade I originated from eastern regions close to neighboring mpox-endemic countries in Central Africa; clade II was prevalent in western regions close to West Africa. Our findings suggest that MPXV re-emerged after a 30-year lapse and might arise from different viral reservoirs unique to ecosystems in eastern and western rainforests of Cameroon.

Geographic, sex and socioeconomic disparities in esophageal cancer incidence in China: A population-based study.

Geographic and sex differences in esophageal cancer have been reported in China, but data are lacking at the local level. We aimed to investigate geographic and sex disparities in esophageal cancer incidence among Chinese counties and whether county-level socioeconomic status was associated with these variations. We obtained esophageal cancer data from 2015 to 2017 for 782 counties from population-based cancer registries in China. We calculated age-standardized incidence rates and male-to-female incidence rate ratios (IRRs) by county. We performed hotspot analysis to identify geographical clusters. We used negative binomial regression models to analyze the association between incidence rates and county-level socioeconomic factors. There were significant geographic disparities in esophageal cancer incidence, with 8.1 times higher rate in the 90th-percentile county than in the 10th-percentile county (23.7 vs 2.9 per 100 000 person-years). Clusters of elevated rates were prominent across north-central China. Nationally, men had 2.9 times higher incidence of esophageal cancer than women. By county, the male-to-female IRRs ranged from 1.1 to 21.1. Clusters of high male-to-female IRRs were observed in northeast China. Rurality (IRR 1.16, 95% CI 1.10-1.22), per capita gross domestic product (IRR 0.95, 0.92-0.98) and percentage of people with a high school diploma (IRR 0.86, 0.84-0.87) in a county were significantly associated with esophageal cancer incidence. The male-to-female IRRs were higher in counties with higher socioeconomic status. Substantial differences in incidence rates and sex ratios of esophageal cancer exist between Chinese counties, and county-level socioeconomic status was associated with these variations. These findings may inform interventions to reduce these disparities.

Spatial Patterning of Spontaneous and Medically Indicated Preterm Birth in Philadelphia.

Preterm birth (PTB) remains a key public health issue that disproportionately affects Black individuals. Since spontaneous PTB (sPTB) and medically indicated PTB (mPTB) may have different causes and interventions, we quantified racial disparities for sPTB and mPTB, and we characterized the geographic patterning of these phenotypes, overall and according to race/ethnicity. We examined a pregnancy cohort of 83,952 singleton births at 2 Philadelphia hospitals from 2008-2020, and classified each PTB as sPTB or mPTB. We used binomial regression to quantify the magnitude of racial disparities between non-Hispanic Black and non-Hispanic White individuals, then generated small area estimates by applying a Bayesian model that accounts for small numbers and smooths estimates of PTB risk by borrowing information from neighboring areas. Racial disparities in both sPTB and mPTB were significant (relative risk of sPTB = 1.83, 95% confidence interval: 1.70, 1.98; relative risk of mPTB = 2.20, 95% confidence interval: 2.00, 2.42). The disparity was 20% greater in mPTB than sPTB. There was substantial geographic variation in PTB, sPTB, and mPTB risks and racial disparity. Our findings underscore the importance of distinguishing PTB phenotypes within the context of public health and preventive medicine. Future work should consider social and environmental exposures that may explain geographic differences in PTB risk and disparities.

Association of travel time, patient characteristics, and hospital quality with patient mobility for breast cancer surgery: A national population-based study.

BACKGROUND: This national study investigated hospital quality and patient factors associated with treatment location for breast cancer surgery. METHODS: By using linked administrative data sets from the English National Health Service, the authors identified all women diagnosed between January 2, 2016, and December 31, 2018, who underwent breast-conserving surgery (BCS) or a mastectomy with or without immediate breast reconstruction. The extent to which patients bypassed their nearest hospital was investigated using a geographic information system (ArcGIS). Conditional logistic regressions were used to estimate the impact of travel time, hospital quality, and patient characteristics. RESULTS: 22,622 Of 69,153 patients undergoing BCS, 22,622 (32.7%) bypassed their nearest hospital; and, of 23,536 patients undergoing mastectomy, 7179 (30.5%) bypassed their nearest hospital. Women who were younger, without comorbidities, or from rural areas were more likely to travel to more distant hospitals (p < .05). Patients undergoing BCS (odds ratio [OR], 1.85; 95% confidence interval [CI], 1.36-2.50) or mastectomy (OR, 1.52; 95% CI, 1.14-2.02) were more likely to be treated at specialist breast reconstruction centers despite not undergoing the procedure. Patients receiving mastectomy and immediate breast reconstruction were more likely to travel to hospitals employing surgeons who had a media reputation (OR, 2.41; 95% CI, 1.28-4.52). Patients undergoing BCS were less likely to travel to hospitals with shorter surgical waiting times (OR, 0.65; 95% CI, 0.46-0.92). The authors did not observe a significant impact for research activity, hospital quality rating, breast re-excision rates, or the status as a multidisciplinary cancer center. CONCLUSIONS: Patient choice policies may drive inequalities in the health care system without improving patient outcomes.

Spinocerebellar ataxia type 10 and Huntington disease-like 2 in Venezuela: Further evidence of two different ancestral founder effects.

INTRODUCTION: The American continent populations have a wide genetic diversity, as a product of the admixture of three ethnic groups: Amerindian, European, and African Sub-Saharan. Spinocerebellar ataxia type 10 (SCA10) and Huntington disease-like 2 (HDL2) have very ancient ancestral origins but are restricted to two populations: Amerindian and African Sub-Saharan, respectively. This study aimed to investigate the genetic epidemiological features of these diseases in Venezuela. METHODS: In-phase haplotypes with the expanded alleles were established in seven unrelated index cases diagnosed with SCA10 and in 11 unrelated index cases diagnosed with HDL2. The origins of remote ancestors were recorded. RESULTS: The geographic origin of the ancestors showed grouping in clusters. SCA10 had a minimal general prevalence of 1:256,174 families in the country, but within the identified geographic clusters, the prevalence ranged from 5 per 100,000 to 43 per 100,000 families. HDL2 had a general prevalence of 1:163,016 families, however, within the clusters, the prevalence ranged from 31 per 100,000 to 60 per 100,000 families. The locus-specific haplotype shared by all families worldwide, including the Venezuelans, supports a single old ancestral origin in each case. CONCLUSION: Knowing the genetic ancestry and geographic origins of patients in Ibero-American mixed populations could have significant diagnostic implications; thus, both diseases in Venezuela should always be first explored in patients with a suggestive phenotype and ancestors coming from the same known geographic clusters.

Application of artificial neural networks to classify Avena fatua and Avena sterilis based on seed traits: insights from European Avena populations primarily from the Balkan Region.

BACKGROUND: Avena fatua and A. sterilis are challenging to distinguish due to their strong similarities. However, Artificial Neural Networks (ANN) can effectively extract patterns and identify these species. We measured seed traits of Avena species from 122 locations across the Balkans and from some populations from southern, western, and central Europe (total over 22 000 seeds). The inputs for the ANN model included seed mass, size, color, hairiness, and placement of the awn attachment on the lemma. RESULTS: The ANN model achieved high classification accuracy for A. fatua and A. sterilis (R2 > 0.99, RASE < 0.0003) with no misclassification. Incorporating geographic coordinates as inputs also resulted in successful classification (R2 > 0.99, RASE < 0.000001) with no misclassification. This highlights the significant influence of geographic coordinates on the occurrence of Avena species. The models revealed hidden relationships between morphological traits that are not easily detectable through traditional statistical methods. For example, seed color can be partially predicted by other seed traits combined with geographic coordinates. When comparing the two species, A. fatua predominantly had the lemma attachment point in the upper half, while A. sterilis had it in the lower half. A. sterilis exhibited slightly longer seeds and hairs than A. fatua, while seed hairiness and mass were similar in both species. A. fatua populations primarily had brown, light brown, and black colors, while A. sterilis populations had black, brown, and yellow colors. CONCLUSIONS: Distinguishing A. fatua from A. sterilis based solely on individual characteristics is challenging due to their shared traits and considerable variability of traits within each species. However, it is possible to classify these species by combining multiple seed traits. This approach also has significant potential for exploring relationships among different traits that are typically difficult to assess using conventional methods.

Expanding community case management of malaria to all ages can improve universal access to malaria diagnosis and treatment: results from a cluster randomized trial in Madagascar.

BACKGROUND: Global progress on malaria control has stalled recently, partly due to challenges in universal access to malaria diagnosis and treatment. Community health workers (CHWs) can play a key role in improving access to malaria care for children under 5 years (CU5), but national policies rarely permit them to treat older individuals. We conducted a two-arm cluster randomized trial in rural Madagascar to assess the impact of expanding malaria community case management (mCCM) to all ages on health care access and use. METHODS: Thirty health centers and their associated CHWs in Farafangana District were randomized 1:1 to mCCM for all ages (intervention) or mCCM for CU5 only (control). Both arms were supported with CHW trainings on malaria case management, community sensitization on free malaria care, monthly supervision of CHWs, and reinforcement of the malaria supply chain. Cross-sectional household surveys in approximately 1600 households were conducted at baseline (Nov-Dec 2019) and endline (Nov-Dec 2021). Monthly data were collected from health center and CHW registers for 36 months (2019-2021). Intervention impact was assessed via difference-in-differences analyses for survey data and interrupted time-series analyses for health system data. RESULTS: Rates of care-seeking for fever and malaria diagnosis nearly tripled in both arms (from less than 25% to over 60%), driven mostly by increases in CHW care. Age-expanded mCCM yielded additional improvements for individuals over 5 years in the intervention arm (rate ratio for RDTs done in 6-13-year-olds, RRRDT6-13 years = 1.65; 95% CIs 1.45-1.87), but increases were significant only in health system data analyses. Age-expanded mCCM was associated with larger increases for populations living further from health centers (RRRDT6-13 years = 1.21 per km; 95% CIs 1.19-1.23). CONCLUSIONS: Expanding mCCM to all ages can improve universal access to malaria diagnosis and treatment. In addition, strengthening supply chain systems can achieve significant improvements even in the absence of age-expanded mCCM. TRIAL REGISTRATION: The trial was registered at the Pan-African Clinical Trials Registry (#PACTR202001907367187).

Natural variation in the Tn1a promoter regulates tillering in rice.

Rice tillering is an important agronomic trait that influences plant architecture and ultimately affects yield. This can be genetically improved by mining favourable variations in genes associated with tillering. Based on a previous study on dynamic tiller number, we cloned the gene Tiller number 1a (Tn1a), which encodes a membrane-localised protein containing the C2 domain that negatively regulates tillering in rice. A 272 bp insertion/deletion at 387 bp upstream of the start codon in the Tn1a promoter confers a differential transcriptional response and results in a change in tiller number. Moreover, the TCP family transcription factors Tb2 and TCP21 repress the Tn1a promoter activity by binding to the TCP recognition site within the 272 bp indel. In addition, we identified that Tn1a may affect the intracellular K+ content by interacting with a cation-chloride cotransporter (OsCCC1), thereby affecting the expression of downstream tillering-related genes. The Tn1a+272 bp allele, associated with high tillering, might have been preferably preserved in rice varieties in potassium-poor regions during domestication. The discovery of Tn1a is of great significance for further elucidating the genetic basis of tillering characteristics in rice and provides a new and favourable allele for promoting the geographic adaptation of rice to soil potassium.

KLFDAPC: a supervised machine learning approach for spatial genetic structure analysis.

Geographic patterns of human genetic variation provide important insights into human evolution and disease. A commonly used tool to detect and describe them is principal component analysis (PCA) or the supervised linear discriminant analysis of principal components (DAPC). However, genetic features produced from both approaches could fail to correctly characterize population structure for complex scenarios involving admixture. In this study, we introduce Kernel Local Fisher Discriminant Analysis of Principal Components (KLFDAPC), a supervised non-linear approach for inferring individual geographic genetic structure that could rectify the limitations of these approaches by preserving the multimodal space of samples. We tested the power of KLFDAPC to infer population structure and to predict individual geographic origin using neural networks. Simulation results showed that KLFDAPC has higher discriminatory power than PCA and DAPC. The application of our method to empirical European and East Asian genome-wide genetic datasets indicated that the first two reduced features of KLFDAPC correctly recapitulated the geography of individuals and significantly improved the accuracy of predicting individual geographic origin when compared to PCA and DAPC. Therefore, KLFDAPC can be useful for geographic ancestry inference, design of genome scans and correction for spatial stratification in GWAS that link genes to adaptation or disease susceptibility.

Global, Regional and National Burden of Paediatric Atopic Dermatitis: A Trend and Geographic Inequalities Analysis.

BACKGROUND: Atopic dermatitis (AD) is a common chronic skin disorder in children. We aimed to investigate trends and regional disparities of burden in paediatric AD at global, regional and national levels, and to explore potential associated factors. METHODS: Based on data from Global Burden of Disease study 2019, we assessed trends in burden of AD aged <19 years from 1990 to 2019, including prevalent and incident cases, age-standardised prevalence and age-standardised incidence. For potential associated factors, correlations of above trends and indexes of socio-economic status (sociodemographic index, SDI) and health service coverage (universal health coverage index, UHCI) were evaluated. We conducted decomposition analysis to understand the net contribution of population-level factors and their contribution proportions on changes of prevalent and incident cases, including age structure, population change and epidemiological change. RESULTS: Global prevalent and incident cases of paediatric AD increased by about 5.7 and 0.7 million between 1990 and 2019, respectively. Global age-standardised prevalence and incidence decreased by -0.17% (-0.19% to -0.16%) and -0.12% (-0.13% to -0.11%) per year from 1990 to 2019, respectively. Regionally, the highest increase of prevalent and incident cases was in low SDI region (by 96.77% and 84.85%); the highest decrease of age-standardised prevalence and incidence was in high SDI regions (by -0.20% and -0.27% per year). The correlation analyses identified significant negative correlations between trends and SDI and UHCI. Population change was a major driver of case rise; epidemiological change and age structure showed negative impact of case rise. Regional disparities in contribution of three population-level factors were seen, including net contribution direction (positive or negative) and contribution proportion levels. CONCLUSION: Global paediatric AD case numbers increased, primarily due to population growth. Prevalence and incidence decreased slightly. Geographic inequalities were seen. Developing region-specific strategies targeting potential factors is essential to reduce paediatric AD burden.

Geographic Disparities in Availability of General and Specialized Pediatricians in the United States and Prevalence of Childhood Neurodevelopmental Disorders.

General pediatricians and those specialized in developmental-behavioral and neurodevelopmental disabilities support children with neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). We identified substantial geographic disparities in pediatrician availability (eg, urban > rural areas), as well as regions with low pediatrician access but high ASD/ADHD prevalence estimates (eg, the US Southeast).

Plant diversity darkspots for global collection priorities.

More than 15% of all vascular plant species may remain scientifically undescribed, and many of the > 350 000 described species have no or few geographic records documenting their distribution. Identifying and understanding taxonomic and geographic knowledge shortfalls is key to prioritising future collection and conservation efforts. Using extensive data for 343 523 vascular plant species and time-to-event analyses, we conducted multiple tests related to plant taxonomic and geographic data shortfalls, and identified 33 global diversity darkspots (those 'botanical countries' predicted to contain most undescribed and not yet recorded species). We defined priority regions for future collection according to several socio-economic and environmental scenarios. Most plant diversity darkspots are found within global biodiversity hotspots, with the exception of New Guinea. We identify Colombia, Myanmar, New Guinea, Peru, Philippines and Turkey as global collection priorities under all environmental and socio-economic conditions considered. Our study provides a flexible framework to help accelerate the documentation of global plant diversity for the implementation of conservation actions. As digitisation of the world's herbaria progresses, collection and conservation priorities may soon be identifiable at finer scales.

The global distribution of angiosperm genome size is shaped by climate.

Angiosperms, which inhabit diverse environments across all continents, exhibit significant variation in genome sizes, making them an excellent model system for examining hypotheses about the global distribution of genome size. These include the previously proposed large genome constraint, mutational hazard, polyploidy-mediated, and climate-mediated hypotheses. We compiled the largest genome size dataset to date, encompassing 16 017 (> 5% of known) angiosperm species, and analyzed genome size distribution using a comprehensive geographic distribution dataset for all angiosperms. We observed that angiosperms with large range sizes generally had small genomes, supporting the large genome constraint hypothesis. Climate was shown to exert a strong influence on genome size distribution along the global latitudinal gradient, while the frequency of polyploidy and the type of growth form had negligible effects. In contrast to the unimodal patterns along the global latitudinal gradient shown by plant size traits and polyploid proportions, the increase in angiosperm genome size from the equator to 40-50°N/S is probably mediated by different (mostly climatic) mechanisms than the decrease in genome sizes observed from 40 to 50°N northward. Our analysis suggests that the global distribution of genome sizes in angiosperms is mainly shaped by climatically mediated purifying selection, genetic drift, relaxed selection, and environmental filtering.

Symbiont plasticity as a driver of plant success.

We discuss which plant species are likely to become winners, that is achieve the highest global abundance, in changing landscapes, and whether plant-associated microbes play a determining role. Reduction and fragmentation of natural habitats in historic landscapes have led to the emergence of patchy, hybrid landscapes, and novel landscapes where anthropogenic ecosystems prevail. In patchy landscapes, species with broad niches are favoured. Plasticity in the degree of association with symbiotic microbes may contribute to broader plant niches and optimization of symbiosis costs and benefits, by downregulating symbiosis when it is unnecessary and upregulating it when it is beneficial. Plasticity can also be expressed as the switch from one type of mutualism to another, for example from nutritive to defensive mutualism with increasing soil fertility and the associated increase in parasite load. Upon dispersal, wide mutualistic partner receptivity is another facet of symbiont plasticity that becomes beneficial, because plants are not limited by the availability of specialist partners when arriving at new locations. Thus, under conditions of global change, symbiont plasticity allows plants to optimize the activity of mutualistic relationships, potentially allowing them to become winners by maximizing geographic occupancy and local abundance.