Repeat polymorphisms underlie top genetic risk loci for glaucoma and colorectal cancer.

Many regions in the human genome vary in length among individuals due to variable numbers of tandem repeats (VNTRs). To assess the phenotypic impact of VNTRs genome-wide, we applied a statistical imputation approach to estimate the lengths of 9,561 autosomal VNTR loci in 418,136 unrelated UK Biobank participants and 838 GTEx participants. Association and statistical fine-mapping analyses identified 58 VNTRs that appeared to influence a complex trait in UK Biobank, 18 of which also appeared to modulate expression or splicing of a nearby gene. Non-coding VNTRs at TMCO1 and EIF3H appeared to generate the largest known contributions of common human genetic variation to risk of glaucoma and colorectal cancer, respectively. Each of these two VNTRs associated with a >2-fold range of risk across individuals. These results reveal a substantial and previously unappreciated role of non-coding VNTRs in human health and gene regulation.

The Eukaryotic CO2-Concentrating Organelle Is Liquid-like and Exhibits Dynamic Reorganization.

Approximately 30%-40% of global CO2 fixation occurs inside a non-membrane-bound organelle called the pyrenoid, which is found within the chloroplasts of most eukaryotic algae. The pyrenoid matrix is densely packed with the CO2-fixing enzyme Rubisco and is thought to be a crystalline or amorphous solid. Here, we show that the pyrenoid matrix of the unicellular alga Chlamydomonas reinhardtii is not crystalline but behaves as a liquid that dissolves and condenses during cell division. Furthermore, we show that new pyrenoids are formed both by fission and de novo assembly. Our modeling predicts the existence of a "magic number" effect associated with special, highly stable heterocomplexes that influences phase separation in liquid-like organelles. This view of the pyrenoid matrix as a phase-separated compartment provides a paradigm for understanding its structure, biogenesis, and regulation. More broadly, our findings expand our understanding of the principles that govern the architecture and inheritance of liquid-like organelles.

Association neurons in the crow telencephalon link visual signs to numerical values.

Many animals can associate signs with numerical values and use these signs in a goal-directed way during task performance. However, the neuronal basis of this semantic association has only rarely been investigated, and so far only in primates. How mechanisms of number associations are implemented in the distinctly evolved brains of other animal taxa such as birds is currently unknown. Here, we explored this semantic number-sign mapping by recording single-neuron activity in the crows' nidopallium caudolaterale (NCL), a brain structure critically involved in avian numerical cognition. Crows were trained to associate visual shapes with varying numbers of items in a number production task. The responses of many NCL neurons during stimulus presentation reflected the numerical values associated with visual shapes in a behaviorally relevant way. Consistent with the crow's better behavioral performance with signs, neuronal representations of numerical values extracted from shapes were more selective compared to those from dot arrays. The existence of number association neurons in crows points to a phylogenetic preadaptation of the brains of cognitively advanced vertebrates to link visual shapes with numerical meaning.

Hill-Chao numbers allow decomposing gamma multifunctionality into alpha and beta components.

Biodiversity-ecosystem functioning (BEF) research has provided strong evidence and mechanistic underpinnings to support positive effects of biodiversity on ecosystem functioning, from single to multiple functions. This research has provided knowledge gained mainly at the local alpha scale (i.e. within ecosystems), but the increasing homogenization of landscapes in the Anthropocene has raised the potential that declining biodiversity at the beta (across ecosystems) and gamma scales is likely to also impact ecosystem functioning. Drawing on biodiversity theory, we propose a new statistical framework based on Hill-Chao numbers. The framework allows decomposition of multifunctionality at gamma scales into alpha and beta components, a critical but hitherto missing tool in BEF research; it also allows weighting of individual ecosystem functions. Through the proposed decomposition, new BEF results for beta and gamma scales are discovered. Our novel approach is applicable across ecosystems and connects local- and landscape-scale BEF assessments from experiments to natural settings.

Twenty years of big plant genera.

In 2004, David Frodin published a landmark review of the history and concepts of big plant genera. Two decades of taxonomic activity have taken place since, coinciding with a revolution in phylogenetics and taxonomic bioinformatics. Here we use data from the World Flora Online (WFO) to provide an updated list of big (more than 500 species) and megadiverse (more than 1000 species) flowering plant genera and highlight changes since 2004. The number of big genera has increased from 57 to 86; today one of every four plant species is classified as a member of a big genus, with 14% in just 28 megadiverse genera. Most (71%) of the growth in big genera since 2000 is the result of new species description, not generic re-circumscription. More than 15% of all currently accepted flowering plant species described in the last two decades are in big genera, suggesting that groups previously considered intractable are now being actively studied taxonomically. Despite this rapid growth in big genera, they remain a significant yet understudied proportion of plant diversity. They represent a significant proportion of global plant diversity and should remain a priority not only for taxonomy but for understanding global diversity patterns and plant evolution in general.

Meta-analysis of the Microbial Diversity Cultured in Bioreactors Simulating the Gut Microbiome.

Understanding the intricate ecological interactions within the gut microbiome and unravelling its impact on human health is a challenging task. Bioreactors are valuable tools that have contributed to our understanding of gut microbial ecology. However, there is a lack of studies describing and comparing the microbial diversity cultivated in these models. This knowledge is crucial for refining current models to reflect the gastrointestinal microbiome accurately. In this study, we analysed the microbial diversity of 1512 samples from 18 studies available in public repositories that employed cultures performed in batches and various bioreactor models to cultivate faecal microbiota. Community structure comparison between samples using t-distributed stochastic neighbour embedding and the Hellinger distance revealed a high variation between projects. The main driver of these differences was the inter-individual variation between the donor faecal inocula. Moreover, there was no overlap in the structure of the microbial communities between studies using the same bioreactor platform. In addition, α-diversity analysis using Hill numbers showed that highly complex bioreactors did not exhibit higher diversities than simpler designs. However, analyses of five projects in which the samples from the faecal inoculum were also provided revealed an amplicon sequence variants enrichment in bioreactors compared to the inoculum. Finally, a comparative analysis of the taxonomy of the families detected in the projects and the GMRepo database revealed bacterial families exclusively found in the bioreactor models. These findings highlight the potential of bioreactors to enrich low-abundance microorganisms from faecal samples, contributing to uncovering the gut microbial "dark matter".

How many species of algae are there? A reprise. Four kingdoms, 14 phyla, 63 classes and still growing.

To date (1 November 2023), the online database AlgaeBase has documented 50,589 species of living algae and 10,556 fossil species here referred to four kingdoms (Eubacteria, Chromista, Plantae, and Protozoa), 14 phyla, and 63 classes. The algae are the third most speciose grouping of plant-like organisms after the flowering plants (≈382,000 species) and fungi (≈170,000 species, including lichens) but are the least well defined of all the botanical groupings. Priority is given to phyla and class names that are familiar to phycologists and that are nomenclaturally valid. The most species-rich phylum is the Heterokontophyta to which 18 classes are referred with 21,052 living species and which is dominated by the diatoms in three classes with 18,673 species (16,427 living; 2239 fossil). The next most species-rich phyla are the red algae (7276 living), the green algae (6851 living), the blue-green algae (Cyanobacteria, 5723 living), the charophytes (4950 living, including the Charophyceae, 511 species living, and the Zygnematophyceae, 4335 living species), Dinoflagellata (2956 living, including the Dinophyceae, 2828 extant), and haptophytes (Haptophyta 1722 species, 517 living).

Building integrated number sense in adults and children: Comparing fractions-only training with cross-notation number line training.

Mounting evidence points to the predictive power of cross-notation rational number understanding (e.g., 2/5 vs. 0.25) relative to within-notation understanding (e.g., 2/5 vs. 1/4) in predicting math outcomes. Although correlational in nature, these studies suggest that number sense training emphasizing integrating across notations may have more positive outcomes than a within-notation focus. However, this idea has not been empirically tested. Thus, across two studies with undergraduate students (N = 183 and N = 181), we investigated the effects of a number line training program using a cross-notation approach (one that focused on connections among fractions, decimals, and percentages) and a within-notation approach (one that focused on fraction magnitude representation only). Both number line approaches produced positive effects, but those of the cross-notation approach were larger for fraction magnitude estimation and cross-notation comparison accuracy. In a third study (N = 63), we adapted the cross-notation number line training for use in place of typical classroom warm-up activities for middle school students. Similar to the results with undergraduate students, the cross-notation training program yielded positive benefits for middle school students over a typical warm-up activity (fraction arithmetic practice). Together, these results suggest the importance of an integrated approach to teaching rational number notations, an approach that appears to be uncommon in current curricula.

A cross-cultural comparison of finger-based and symbolic number representations.

The current study examined predictions from embodied cognition for effects of finger counting on number processing. Although finger counting is spontaneous and nearly universal, counting habits reflect learning and culture. European cultures use a sub-base-five system, requiring a full hand plus additional fingers to express numbers exceeding 5. Chinese culture requires only one hand to express such numbers. We investigated the differential impact of early-acquired finger-based number representations on adult symbolic number processing. In total, 53 European and 56 Chinese adults performed two versions of the magnitude classification task, where numbers were presented either as Arabic symbols or as finger configurations consistent with respective cultural finger-counting habits. Participants classified numbers as smaller/larger than 5 with horizontally aligned buttons. Finger-based size and distance effects were larger in Chinese compared with Europeans. These differences did not, however, induce reliably different symbol processing signatures. This dissociation challenges the idea that sensory and motor habits shape our conceptual representations and implies notation-specific processing patterns.

Children's estimates of equivalent rational number magnitudes are not equal: Evidence from fractions, decimals, percentages, and whole numbers.

Integration of rational number knowledge with prior whole number knowledge has been theorized as critical for mathematical success. Fractions, decimals, and percentages are generally assumed to differ in difficulty based on the degree to which their structure is perceptually similar to whole numbers. Specifically, percentages are viewed as most similar to whole numbers with their fixed unstated denominator of 100. Decimals are often assumed to be easier than fractions because their place-value structure is an extension of the base-ten system for whole numbers, unlike fractions, which have a bipartite structure (i.e., a/b). However, there has been no comprehensive investigation of how fraction, decimal, and percentage knowledge compares with whole number knowledge. To assess understanding of the four notations, we measured within-participants number line estimation of equivalent fractions and decimals with shorter string lengths (e.g., 8/10 and 0.8) and longer string lengths (e.g., 80/100 and 0.80), percentages (e.g., 80%), and proportionally equivalent whole numbers on a 0-100 scale (e.g., 80.0). Middle school students (N = 65; 33 female) generally underestimated all formats relative to their actual values (whole numbers: 3% below; percentages: 2%; decimals: 17%; fractions: 5%). Shorter string-length decimals and fractions were estimated as smaller than equivalent longer string-length equivalents. Overall, percentages were estimated similarly to corresponding whole numbers, fractions had modest string-length effects, and decimals were the most underestimated, especially for single-digit decimals. These results highlight the strengths and weaknesses of children's understanding of each notation's magnitudes and challenge the assumption that decimals are easier than fractions.

Place-value and physical size converge in automatic processing of multi-digit numbers.

Previous research has shown that multi-digit number processing is modulated by both place-value and physical size of the digits. By pitting place-value against physical size, the present study examined whether one of the attributes had a greater impact on the automatic processing of multi-digit numbers. In three experiments, participants were presented with two-digit number pairs that appeared in frames. They were instructed to select the larger frame while ignoring the numbers within the frames. Importantly, we manipulated the physical size of the digits (i.e., both decade/unit digits were physically larger) within the frames, the unit-decade compatibility (i.e., the relationship between the numerical values of both decade and unit digits was consistent or inconsistent), and the congruity between the numerical values of the decade digits and the frames' physical size (i.e., decade-value-frame-size congruity). In Experiment 1, where all pairs were unit-decade compatible, a decade-value-frame-size congruity effect emerged for pairs with physically larger decade, but not unit, digits. However, when adding unit-decade incompatible pairs (Experiments 2-3), in unit-decade compatible pairs, there was a decade-value-frame-size congruity effect regardless of the digits' physical size. In contrast, in unit-decade incompatible pairs, there was no decade-value-frame-size congruity effect, even when the physically larger digit (i.e., unit) contradicted the place-value information, presumably due to the cancellation of the opposing influences of the digits' physical sizes their place-values. Overall, these findings suggest that place-value and physical size are intertwined in the Hindu-Arabic numerical system and are processed as one.

Probabilistic human health risk assessment of PCDD/Fs near municipal solid-waste incinerator using Monte Carlo analysis coupled with triangular fuzzy numbers.

PCDD/Fs are dioxins produced by waste incineration and pose risks to human health. We aimed to detail the health risks of airborne and soil PCDD/Fs near a municipal solid-waste incinerator (MSWI) for the surrounding population and develop a new model that improves upon existing methods. Thus, we conducted field sampling and then investigated a MSWI in the Pearl River Delta (2016-2018). Our results showed that the carcinogenic and non-carcinogenic risk values of PCDD/Fs exposed to residents in nearby areas were acceptable, with hazard index (HI) values lower than 1.0 and a total carcinogenic risk lower than 1.0E-6. Notably, the results raised concerns regarding higher non-carcinogenic risks in children than in adults. Comparative analysis of the frequency accumulation diagram, accumulated probability risk, and the absolute value of error (δ) between the 95% confidence interval (CI) and the 90% CI of the Monte Carlo stochastic simulation-triangular fuzzy number (MCSS-TFN) and the MCSS model, respectively, demonstrated that the MCSS-TFN exhibited less uncertainty than the MCSS model, regardless of the health risk value of PCDD/Fs in ambient air or in soil. This observation underscores the superiority of the MCSS-TFN model over other models in assessing the health risks associated with PCDD/Fs in situations with limited data. Our new method overcomes the limited dataset size and high uncertainty in assessing the health risks of dioxin substances, providing a more comprehensive understanding of their associated health risks than MCSS models.

Estimating global numbers of fishes caught from the wild annually from 2000 to 2019.

Finfishes are caught from the wild for food, feed (often in the form of fishmeal and oil) and bait. According to the Food and Agriculture Organisation of the United Nations (FAO), between 74 and 83 million tonnes (averaging 77 million tonnes) were caught annually in 2000-2019. Although fishes are now widely recognised as sentient beings, capture is still quantified as biomass rather than number of individuals (in contrast to wild-caught marine mammals and crocodiles; and farmed mammals and birds). Here, we estimate global numbers of wild-caught finfishes using FAO capture production (landing) tonnages (2000-2019 data) and estimates of mean individual weight at capture, based on internet-sourced capture and market weights. We estimate that between 1,100 and 2,200 billion (1.1-2.2 × 1012), or 1.1-2.2 trillion, wild finfishes were caught annually, on average, during 2000-2019. Anchoveta (Engraulis ringens) comprised 28%, by estimate midpoint. Estimated numbers in 2019, totalling 980-1,900 billion, were lower due to reduced anchoveta landings, but still represented 87.5% of vertebrate numbers killed for food or feed, as obtained or estimated from FAO data. These figures exclude unrecorded capture such as illegal fishing, discards and ghost fishing. Estimated finfish numbers used for reduction to fishmeal and oil represented 56% of the total 2010 estimate (1,000-1,900 billion), by midpoint. It is recommended that the FAO reports fish capture numbers. The welfare of wild-caught fishes, which is generally very poor during and after capture, should be addressed as part of sustainable utilisation of aquatic resources.

Relaxivity Enhancement of Hybrid Micelles via Modulation of Water Coordination Numbers for Magnetic Resonance Lymphography.

Considerable efforts have been made to develop nanoparticle-based magnetic resonance contrast agents (CAs) with high relaxivity. The prolonged rotational correlation time (τR) induced relaxivity enhancement is commonly recognized, while the effect of the water coordination numbers (q) on the relaxivity of nanoparticle-based CAs gets less attention. Herein, we first investigated the relationship between T1 relaxivity (r1) and q in manganese-based hybrid micellar CAs and proposed a strategy to enhance the relaxivity by increasing q. Hybrid micelles with different ratios of amphiphilic manganese complex (MnL) and DSPE-PEG2000 were prepared, whose q values were evaluated by Oxygen-17-NMR spectroscopy. Micelles with lower manganese doping density exhibit increased q and enhanced relaxivity, corroborating the conception. In vivo sentinel lymph node (SLN) imaging demonstrates that DSPE-PEG/MnL micelles could differentiate metastatic SLN from inflammatory LN. Our strategy makes it feasible for relaxivity enhancement by modulating q, providing new approaches for the structural design of high-performance hybrid micellar CAs.

Dissolved organic matter (DOM) is independently stratified in thermally stratified water bodies.

Thermal stratification often occurs in deep-water bodies, including oceans, lakes, and reservoirs. Dissolved organic matter (DOM) plays a critical role in regulating the dynamics of aquatic food webs and water quality in aquatic ecosystems. In the past, thermal stratification boundaries have been sometimes used exclusively to analyze the vertical distribution of DOM in thermally stratified water bodies. However, the validity of this practice has been challenged. Currently, there is limited understanding of the formation mechanism and stratification of the vertical distribution of DOM in thermally stratified water bodies, which hinders the analysis of the interactions between DOM and vertical aquatic ecological factors. To address this gap, we conducted a comprehensive study to extensively collect the vertical distribution of DOM in thermally stratified water bodies and identify the primary factors influencing this distribution. We found that DOM was independently stratified in thermally stratified water bodies (including two cases in unstratified water bodies), and that the formation mechanisms and statuses of DOM stratification were different from those of thermal stratification. The boundaries and numbers of DOM stratification were generally inconsistent with those of thermal stratification. Therefore, it is more accurate to divide DOM into different layers according to its own vertical profile, and analyze DOM characteristics of each layer based on its own stratification instead of thermal stratification. This study sheds light on the relationship between DOM and thermal stratification and provides a novel approach for analyzing DOM vertical distribution characteristics and their impact on aquatic ecosystems. This finding also holds significant implications for the design and implementation of environmental management programs aimed at preserving the health and functionality of aquatic ecosystems.

Entropy of the Canonical Occupancy (Macro) State in the Quantum Measurement Theory.

The paper analyzes the probability distribution of the occupancy numbers and the entropy of a system at the equilibrium composed by an arbitrary number of non-interacting bosons. The probability distribution is obtained through two approaches: one involves tracing out the environment from a bosonic eigenstate of the combined environment and system of interest (the empirical approach), while the other involves tracing out the environment from the mixed state of the combined environment and system of interest (the Bayesian approach). In the thermodynamic limit, the two coincide and are equal to the multinomial distribution. Furthermore, the paper proposes to identify the physical entropy of the bosonic system with the Shannon entropy of the occupancy numbers, fixing certain contradictions that arise in the classical analysis of thermodynamic entropy. Finally, by leveraging an information-theoretic inequality between the entropy of the multinomial distribution and the entropy of the multivariate hypergeometric distribution, Bayesianism of information theory and empiricism of statistical mechanics are integrated into a common "infomechanical" framework.

The role of pharmacies in the implementation of vaccination cover- age in Italy. Insights from the preliminary data of the Lombardy Region.

Introduction: The administration of vaccines in pharmacies was not allowed in Italy until 2021. During the COVID-19 pandemic, legislative innovations were introduced that now allow qualified pharmacists to administer anti-flu and anti-COVID-19 vaccines after completing specific training. Methods: The article provides an overview of legislation concerning vaccinations in Italian pharmacies, followed by a description of the vaccinations carried out by pharmacies participating in the regional vaccination campaign from 2021 to 2023. The study relies on data extracted from the Lombardy Region's database on vaccine administration in pharmacies. Furthermore, innovative vaccination practices from the Marche Region were also taken into consideration. Study Design: Observational Study. Results: Lombardy became the Italian pioneer region in extensively incorporating pharmacy-based vaccinations, starting in 2021. This initiative reached its zenith with 46% of anti-COVID vaccines and 17% of flu vaccines administered within the first six weeks of the autumn 2023 campaign. Pharmacies played a crucial role in meeting the targets outlined in the Italian National Vaccine Prevention Plan for 2023-25. As part of an experimental program, the Marche Region has further expanded pharmacy-based vaccinations, now including anti-zoster and anti-pneumococcus vaccines for the 2023-24 campaign. Conclusions: The promising outcomes observed in Lombardy and the ongoing experimental efforts in the Marche are encouraging steps toward achieving vaccination coverage targets, albeit still falling below the objectives set by the National Vaccination Plan for 2023-25. The widespread presence of pharmacies throughout the territory makes them well-suited as support structures for vaccination campaigns, especially in reaching the adult, the elderly, and the vulnerable populations.

Primary care doctors retirements in the context of an ageing population in Italy.

Background: Ongoing shortages in primary care doctors/primary care paediatricians and increasing healthcare needs due to ageing of the population represent a great challenge for healthcare providers, managers, and policymakers. To support planning of primary healthcare resource allocation we analyzed the geographic distribution of primary care doctors/primary care paediatricians across Italian regions, accounting for area-specific number and age of the population. Additionally, we estimated the number of primary care doctors/primary care paediatricians expected to retire over the next 25 years, with a focus on the next five years. Study design: Ecological study. Methods: We gathered the list of Italian general practitioners and primary care paediatricians and combined them with the data from the National Federation of Medical Doctors, Surgeons and Dentists. Using data from the National Institutes of Statistics, we calculated the average number of patients per doctor for each region using the number of residents above and under 14 years of age for general practitioners and primary care paediatricians respectively. We also calculated the number of residents over-65 and over-75 years of age per general practitioner, as elderly patients typically have higher healthcare needs. Results: On average the number of patients per general practitioner was 1,447 (SD: 190), while for paediatricians it was 1,139 (SD: 241), with six regions above the threshold of 1,500 patients per general practitioner and only one region under the threshold of 880 patients per paediatrician. We estimated that on average 2,228 general practitioners and 444 paediatricians are going to retire each year for the next five years, reaching more than 70% among the current workforce for some southern regions. The number of elderly patients per general practitioner varies substantially between regions, with two regions having >15% more patients aged over 65 years compared to the expected number. Conclusions: over 65 years compared to the expected number. Conclusions. The study highlighted that some regions do not currently have the required primary care workforce, and the expec-ted retirements and the ageing of the population will exacerbate the pressure on the already over-stretched healthcare services. A response from healthcare administrations and policymakers is urgently required to allow equitable access to quality primary care across the country.

Modulating Ionic Transport and Interface Chemistry via Surface-Modified Silica Carrier in Nano Colloid Electrolyte for Stable Cycling of Li-Metal Batteries.

Tailoring the Li+ microenvironment is crucial for achieving fast ionic transfer and a mechanically reinforced solid-electrolyte interphase (SEI), which administers the stable cycling of Li-metal batteries (LMBs). Apart from traditional salt/solvent compositional tuning, this study presents the simultaneous modulation of Li+ transport and SEI chemistry using a citric acid (CA)-modified silica-based colloidal electrolyte (C-SCE). CA-tethered silica (CA-SiO2 ) can render more active sites for attracting complex anions, leading to further dissociation of Li+ from the anions, resulting in a high Li+ transference number (≈0.75). Intermolecular hydrogen bonds between solvent molecules and CA-SiO2 and their migration also act as nano-carrier for delivering additives and anions toward the Li surface, reinforcing the SEI via the co-implantation of SiO2 and fluorinated components. Notably, C-SCE demonstrated Li dendrite suppression and improved cycling stability of LMBs compared with the CA-free SiO2 colloidal electrolyte, hinting that the surface properties of the nanoparticles have a huge impact on the dendrite-inhibiting role of nano colloidal electrolytes.

Angular reproduction numbers improve estimates of transmissibility when disease generation times are misspecified or time-varying.

We introduce the angular reproduction number Ω, which measures time-varying changes in epidemic transmissibility resulting from variations in both the effective reproduction number R, and generation time distribution w. Predominant approaches for tracking pathogen spread infer either R or the epidemic growth rate r. However, R is biased by mismatches between the assumed and true w, while r is difficult to interpret in terms of the individual-level branching process underpinning transmission. R and r may also disagree on the relative transmissibility of epidemics or variants (i.e. rA > rB does not imply RA > RB for variants A and B). We find that Ω responds meaningfully to mismatches and time-variations in w while mostly maintaining the interpretability of R. We prove that Ω > 1 implies R > 1 and that Ω agrees with r on the relative transmissibility of pathogens. Estimating Ω is no more difficult than inferring R, uses existing software, and requires no generation time measurements. These advantages come at the expense of selecting one free parameter. We propose Ω as complementary statistic to R and r that improves transmissibility estimates when w is misspecified or time-varying and better reflects the impact of interventions, when those interventions concurrently change R and w or alter the relative risk of co-circulating pathogens.