bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost of Failure to Achieve Textbook Outcomes: Association of Insurance Type with Outcomes and Cumulative Cost for Inpatient Surgery
Authors: Jacobs Michael A , Kim Jeongsoo , Tetley Jasmine C , Schmidt Susanne , Brimhall Bradley B , Mika Virginia , Wang Chen-Pin , Manuel Laura S , Damien Paul , Shireman Paula K
Published: January 2023

BACKGROUND:

Surgical outcome/cost analyses typically focus on single outcomes and do not include encounters beyond the index hospitalization.

STUDY DESIGN:

This cohort study used NSQIP (2013-2019) data with electronic health record and cost data risk-adjusted for frailty, preoperative acute serious conditions (PASC), case status, and operative stress assessing cumulative costs of failure to achieve textbook outcomes defined as absence of 30-day Clavien-Dindo level III and IV complications, emergency department visits/observation stays (EDOS), and readmissions across insurance types (private, Medicare, Medicaid, uninsured). Return costs were defined as costs of all 30-day emergency department visits/observation stays and readmissions.

RESULTS:

Cases were performed on patients (private 1,506; Medicare 1,218; Medicaid 1,420; uninsured 2,178) with a mean age 52.3 years (SD 14.7) and 47.5% male. Medicaid and uninsured patients had higher odds of presenting with preoperative acute serious conditions (adjusted odds ratios 1.89 and 1.81, respectively) and undergoing urgent/emergent surgeries (adjusted odds ratios 2.23 and 3.02, respectively) vs private. Medicaid and uninsured patients had lower odds of textbook outcomes (adjusted odds ratios 0.53 and 0.78, respectively) and higher odds of emergency department visits/observation stays and readmissions vs private. Not achieving textbook outcomes was associated with a greater than 95.1% increase in cumulative costs. Medicaid patients had a relative increase of 23.1% in cumulative costs vs private, which was 18.2% after adjusting for urgent/emergent cases. Return costs were 37.5% and 65.8% higher for Medicaid and uninsured patients, respectively, vs private.

CONCUSIONS:

Higher costs for Medicaid patients were partially driven by increased presentation acuity (increased rates/odds of preoperative acute serious conditions and urgent/emergent surgeries) and higher rates of multiple emergency department visits/observation stays and readmission occurrences. Decreasing surgical costs/improving outcomes should focus on reducing urgent/emergent surgeries and improving postoperative care coordination, especially for Medicaid and uninsured populations.
Overtriage, Undertriage, and Value of Care after Major Surgery: An Automated, Explainable Deep Learning-Enabled Classification System
Authors: Loftus Tyler J , Ruppert Matthew M , Shickel Benjamin , Ozrazgat-Baslanti Tezcan , Balch Jeremy A , Hu Die , Javed Adnan , Madbak Firas , Skarupa David J , Guirgis Faheem , Efron Philip A , Tighe Patrick J , Hogan William R , Rashidi Parisa , Upchurch Gilbert R , Bihorac Azra
Published: January 2023

BACKGROUND:

In single-institution studies, overtriaging low-risk postoperative patients to ICUs has been associated with a low value of care; undertriaging high-risk postoperative patients to general wards has been associated with increased mortality and morbidity. This study tested the reproducibility of an automated postoperative triage classification system to generating an actionable, explainable decision support system.

STUDY DESIGN:

This longitudinal cohort study included adults undergoing inpatient surgery at two university hospitals. Triage classifications were generated by an explainable deep learning model using preoperative and intraoperative electronic health record features. Nearest neighbor algorithms identified risk-matched controls. Primary outcomes were mortality, morbidity, and value of care (inverted risk-adjusted mortality/total direct costs).

RESULTS:

Among 4,669 ICU admissions, 237 (5.1%) were overtriaged. Compared with 1,021 control ward admissions, overtriaged admissions had similar outcomes but higher costs ($15.9K [interquartile range $9.8K to $22.3K] vs $10.7K [$7.0K to $17.6K], p < 0.001) and lower value of care (0.2 [0.1 to 0.3] vs 1.5 [0.9 to 2.2], p < 0.001). Among 8,594 ward admissions, 1,029 (12.0%) were undertriaged. Compared with 2,498 control ICU admissions, undertriaged admissions had longer hospital length-of-stays (6.4 [3.4 to 12.4] vs 5.4 [2.6 to 10.4] days, p < 0.001); greater incidence of hospital mortality (1.7% vs 0.7%, p = 0.03), cardiac arrest (1.4% vs 0.5%, p = 0.04), and persistent acute kidney injury without renal recovery (5.2% vs 2.8%, p = 0.002); similar costs ($21.8K [$13.3K to $34.9K] vs $21.9K [$13.1K to $36.3K]); and lower value of care (0.8 [0.5 to 1.3] vs 1.2 [0.7 to 2.0], p < 0.001).

CONCLUSIONs:

Overtriage was associated with low value of care; undertriage was associated with both low value of care and increased mortality and morbidity. The proposed framework for generating automated postoperative triage classifications is reproducible.
Central Venous Waveform Analysis and Cardiac Output in a Porcine Model of Endotoxemic Hypotension and Resuscitation
Authors: Bergman Zachary R , Kiberenge Roy K , Mohammed Azmath , Bianco Richard W , Beilman Greg J , Brophy Colleen M , Hocking Kyle M , Alvis Bret D , Wise Eric S
Published: January 2023

BACKGROUND:

Cardiac output (CO) is a valuable proxy for perfusion, and governs volume responsiveness during resuscitation from distributive shock. The underappreciated venous system has nuanced physiology that confers valuable hemodynamic information. In this investigation, deconvolution of the central venous waveform by the fast Fourier transformation (FFT) algorithm is performed to assess its ability to constitute a CO surrogate in a porcine model of endotoxemia-induced distributive hypotension and resuscitation.

STUDY DESIGN:

Ten pigs were anesthetized, catheterized, and intubated. A lipopolysaccharides infusion protocol was used to precipitate low systemic vascular resistance hypotension. Four crystalloid boluses (10 cc/kg) were then given in succession, after which heart rate, mean arterial pressure, thermodilution-derived CO, central venous pressure (CVP), and the central venous waveform were collected, the last undergoing fast Fourier transformation analysis. The amplitude of the fundamental frequency of the central venous waveform’s cardiac wave (f0-CVP) was obtained. Heart rate, mean arterial pressure, CVP, f0-CVP, and CO were plotted over the course of the boluses to determine whether f0-CVP tracked with CO better than the vital signs, or than CVP itself.

RESULTS:

Distributive hypotension to a 25% mean arterial pressure decrement was achieved, with decreased systemic vascular resistance (mean 918 ± 227 [SD] dyne/s/cm-5vs 685 ± 180 dyne/s/cm-5; p = 0.038). Full hemodynamic parameters characterizing this model were reported. Slopes of linear regression lines of heart rate, mean arterial pressure, CVP, f0-CVP, and CO were –2.8, 1.7, 1.8, 0.40, and 0.35, respectively, demonstrating that f0-CVP values closely track with CO over the 4-bolus range.

CONCLUSIONS:

Fast Fourier transformation analysis of the central venous waveform may allow real-time assessment of CO during resuscitation from distributive hypotension, possibly offering a venous-based approach to clinical estimation of volume responsiveness.
Fibrolamellar Hepatocellular Carcinoma: Comprehensive Review of Diagnosis, Imaging, and Management
Authors: Aziz Hassan , Brown Zachary J , Panid Madani Seyedeh , Kamel Ihab R , Pawlik Timothy M
Published: January 2023

BACKGROUND:

Fibrolamellar hepatocellular carcinoma (FLC) is a rare malignancy that primarily affects patients in late adolescence and young adulthood. FLC tumors are characterized by their unique histologic features and a recently discovered genomic alteration, a chimeric fusion protein found in nearly all tumors. This review article provides the latest advancements in diagnosing, imaging, and managing FLC.

STUDY DESIGN:

A comprehensive systematic review was performed using MEDLINE/PubMed and Web of Science databases, with the end of search date being July 1, 2022, regarding FLC diagnosis, imaging, and management.

RESULTS:

Surgical resection remains the mainstay of therapy offering a chance for cure; however, given the incidence of metastatic disease at diagnosis and high rates of distant relapse, systemic therapies remain a crucial component of disease control. Unfortunately, few systemic therapies have demonstrated proven benefits. Consequently, recent efforts have galvanized around single-institute or small consortia–based studies specifically focused on enrolling patients with FLC or using agents with a biologic rationale.

CONCLUSIONS:

FLC has unique demographic, radiologic, and pathologic features. The rarity of these tumors, coupled with the only recent acknowledgment of the genomic abnormality, has likely led to disease underrecognition and deprioritization of collaborative efforts to establish an evidence-based standard of care. Despite R0 resection, most patients experience recurrence. However, surgical resection is feasible for many recurrences and is associated with good survival. The role of chemotherapy is evolving, and further research is required to define its role in managing this disease.
Promiscuous evolution of Group A Streptococcal M and M-like proteins
Authors: Frost Hannah R. , Guglielmini Julien , Duchêne Sebastian , Lacey Jake A. , Sanderson-Smith Martina , Steer Andrew C. , Walker Mark J. , Botteaux Anne , Davies Mark R. , Smeesters Pierre R.
Published: January 2023

Group A

Streptococcus

(GAS) M and M-like proteins are essential virulence factors and represent the primary epidemiological marker of this pathogen. Protein sequences encoding 1054 M, Mrp and Enn proteins, from 1668 GAS genomes, were analysed by SplitsTree4, partitioning around medoids and co-occurrence. The splits network and groups-based analysis of all M and M-like proteins revealed four large protein groupings, with multiple evolutionary histories as represented by multiple edges for most splits, leading to ‘M-family-groups’ (FG) of protein sequences: FG I, Mrp; FG II, M protein and Protein H; FG III, Enn; and FG IV, M protein. M and Enn proteins formed two groups with nine sub-groups and Mrp proteins formed four groups with ten sub-groups. Discrete co-occurrence of M and M-like proteins were identified suggesting that while dynamic, evolution may be constrained by a combination of functional and virulence attributes. At a granular level, four distinct family-groups of M, Enn and Mrp proteins are observable, with Mrp representing the most genetically distinct of the family-group of proteins. While M and Enn protein families generally group into three distinct family-groups, horizontal and vertical gene flow between distinct GAS strains is ongoing.
Predicting and quantifying coexistence outcomes between resident and invading species using trait and abundance data
Authors: Behm Jocelyn E. , Ellers Jacintha , Jesse Wendy A. M. , Tran Tyler J. , Helmus Matthew R.
Published: January 2023

A major challenge in invasion ecology is determining which introduced species pose a threat to resident species through competitive displacement. Here, we provide a statistical framework rooted in coexistence theory to calculate coexistence outcomes – including competitive displacement – between resident and invading species. Advantageously, our framework uses readily available trait and abundance data rather than the demographic data traditionally used in coexistence theory applications which is often difficult to collect for most species. Our framework provides methods forpredictingdisplacement that has yet to manifest in incipient invasions, and forquantifyingdisplacement in ongoing invasions. We apply this framework to the native and introduced gecko species on Curaçao and predict the displacement of all three native species by introduced species and quantify that the displacement of one native species is already underway. Our results affirm that trait and abundance data are suitable proxies to reasonably predict and quantify coexistence outcomes.
Data-driven characterization of Preterm Birth through intramodal Diffusion MRI
Authors: Trò Rosella , Roascio Monica , Tortora Domenico , Severino Mariasavina , Rossi Andrea , Garyfallidis Eleftherios , Arnulfo Gabriele , Fato Marco Massimo , Fadnavis Shreyas
Published: January 2023

Preterm birth still represents a concrete emergency to be managed and addressed globally. Since cerebral white matter injury is the major form of brain impairment in survivors of premature birth, the identification of reliable, non-invasive markers of altered white matter development is of utmost importance in diagnostics. Diffusion MRI has recently emerged as a valuable tool to investigate these kinds of alterations. In this work, rather than focusing on a single MRI modality, we worked on a compound of beyond-DTI High Angular Resolution Diffusion Imaging (HARDI) techniques in a group of 46 preterm babies studied on a 3T scanner at term equivalent age and in 23 control neonates born at term. After extracting relevant derived parameters, we examined discriminative patterns of preterm birth through (i) a traditional voxel-wise statistical method such as the Tract-Based Spatial Statistics approach (TBSS); (ii) an advanced Machine Learning approach such as the Support Vector Machine (SVM) classification; (iii) establishing the degree of association between the two methods in voting white matter most discriminating areas. Finally, we applied a multi-set Canonical Correlation Analysis (CCA) in search for sources of linked alterations across modalities. TBSS analysis showed significant differences between preterm and term cohorts in several white matter areas for multiple HARDI features. SVM classification performed on skeletonized HARDI measures produced satisfactory accuracy rates, especially as for highly informative parameters about fibers’ directionality. Assessment of the degree of overlap between the relevant measures identified by the two methods exhibited a good, though parameter-dependent rate of agreement. Finally, CCA analysis identified joint changes precisely for those features exhibiting less correspondence between TBSS and SVM. Our results suggest that a data-driven intramodal imaging approach is crucial to extract deep and complementary information that cannot be extracted from a single modality.
Bayesian areal disaggregation regression to predict wildlife distribution and relative density with low-resolution data
Authors: Murphy Kilian J , Ciuti Simone , Burkitt Tim , Morera-Pujol Virginia
Published: January 2023

For species of conservation concern and human-wildlife conflict, it is imperative that spatial population data are available to design adaptive-management strategies and be prepared to meet challenges such as land use and climate change, disease outbreaks, and invasive species spread. This can be difficult, perhaps impossible, if spatially explicit wildlife data are not available. Low-resolution areal counts, however, are common in wildlife monitoring, i.e., number of animals reported for a region, usually corresponding to administrative subdivisions, e.g., region, province, county, departments, or cantons. Bayesian areal disaggregation regression is a solution to exploit areal counts and provide conservation biologists with high-resolution species distribution predictive models. This method originated in epidemiology but lacks experimentation in ecology. It provides a plethora of applications to change the way we collect and analyse data for wildlife populations. Based on high-resolution environmental rasters, the disaggregation method disaggregates the number of individuals observed in a region and distributes them at the pixel level (e.g., 5×5 km or finer resolution), therefore converting the low-resolution data into high-resolution distribution and indices of relative density. In our demonstrative study, we disaggregated areal count data from hunting bag returns to disentangle the changing distribution and population dynamics of three deer species (red, sika and fallow) in Ireland from 2000 to 2018. We show an application of Bayesian areal disaggregation regression method and document marked increases in relative population density and extensive range expansion for each of the three deer species across Ireland. We challenged our disaggregated model predictions by correlating them with independent deer surveys carried out in field sites and alternative deer distribution models built using presence-only and presence-absence data. Finding high correlation with both independent datasets, we highlighted the accurate ability of Bayesian areal disaggregation regression to capture fine scale spatial patterns of animal distribution. This study opens new scenarios for wildlife managers and conservation biologists to reliably use regional count data disregarded so far in species distribution modelling. Thus, representing a step forward in our ability to monitor wildlife population and meet challenges in our changing world.

Open data statement

Data used in the study has been publicly archived for reproducibility.

Data archive DOI: 10.6084/m9.figshare.21890505
Sustainability of seed harvesting in wild plant populations: an insight from a global database of matrix population models
Authors: Bucharova Anna , Bossdorf Oliver , Scheepens J. F. , Salguero-Gómez Roberto
Published: January 2023

Seed harvesting from wild plant populations is key for ecological restoration, but may threaten the persistence of source populations. Consequently, several countries have set guidelines limiting the proportions of harvestable seeds. However, these guidelines are so far inconsistent, and they lack a solid empirical basis. Here, we use high-resolution data from 298 plant species to model the demographic consequences of seed harvesting. We find that the current guidelines do not protect populations of annuals and short-lived perennials, while they are overly restrictive for long-lived plants. We show that the maximum possible fraction of seed production – what can be harvested without compromising the long-term persistence of populations – is strongly related to the generation time of the target species. When harvesting every year, this safe seed fraction ranges from 80% in long-lived species to 2% in most annuals. Less frequent seed harvesting substantially increases the safe seed fraction: In the most vulnerable annual species, it is safe to harvest 5%, 10% or 30% of population seed production when harvesting every two, five or ten years, respectively. Our results provide a quantitative basis for seed harvesting legislations worldwide, based on species’ generation time and harvesting regime.

Significance

The UN Decade on Ecosystem Restoration, 2021-2030, foresees upscaling restoration, and the demand for native seed is skyrocketing. Seeds for restoring native vegetation are often harvested in wild, but too intensive harvest can threaten the donor populations. Existing guidelines that set limits to wild seed harvest are mostly based on expert opinions, yet they commonly lack empirical basis and vary among regions in one order of magnitude. We show that the current guidelines urgently need to be reformulated, because they are overly restrictive in long-lived species, while they do not protect annual plants from extinction. Using matrix population models of nearly 300 plant species, we provide a quantitative basis for a new seed harvesting legislation world-wide.
Knowledge “installed” diffusion model predicts the geometry of actin cytoskeleton from cell morphology
Authors: Li Honghan , Liu Shiyou , Deguchi Shinji , Matsunaga Daiki
Published: January 2023

Cells exhibit various morphological characteristics due to their physiological activities, and changes in cell morphology are inherently accompanied by the assembly and disassembly of the actin cytoskeleton. Stress fibers are a prominent component of the actin-based intracellular structure and are highly involved in numerous physiological processes, e.g., mechanotransduction and maintenance of cell morphology. Although it is widely accepted that variations in cell geometry interact with the distribution and localization of stress fibers, it remains unclear if there are underlying geometric principles between the cell morphology and actin cytoskeleton. Here we present a machine learning system, which uses the diffusion model, that can convert the cell shape to the distribution of stress fibers. By training with corresponding datasets of cell shape and stress fibers, our system learns the conversion to generate the stress fiber images from its corresponding cell shape. The predicted stress fiber distribution has good agreement with the experimental data, and the overlap region of predicted and experimentally observed stress fibers reaches 79.3 ±12.4%. We then found some unknown natures such as a linear relation relationship between the stress fiber length and cell area. With this “installed” conversion relation between cellular morphology and corresponding stress fibers’ localization, our system could perform virtual experiments that provide a visual map showing the probability of stress fiber distribution from the virtual cell shape. Our system provides a powerful approach to seek further hidden geometric principles between the cell morphologies and actin cytoskeletons.
Between a rock and a hard place: Effects of land-use change on rock-dwelling animals of lateritic plateaus in the northern Western Ghats
Authors: Jithin Vijayan , Rane Manali , Watve Aparna , Giri Varad B. , Naniwadekar Rohit
Published: January 2023

Open natural ecosystems like lateritic plateaus, are undergoing rapid transformation with very poor understanding of these impacts on the threatened and endemic biodiversity. The unprotected, low-elevation lateritic plateaus of the northern Western Ghats are case to the point, as they have high endemicity but remain unprotected under Indian law. We aimed to understand the impact of the conversion of the natural lateritic plateaus to agroforestry and paddy cultivation on biodiversity. We compared the prevalence of two species of endemic herpetofauna of the northern Western Ghats (Gegeneophis seschachariandHemidactylus albofasciatus) and a widespread snake (Echis carinatus) and the composition of other rock-dwelling animals across 12 undisturbed plateau sites and 10 sites each in agroforestry plantations and abandoned paddies on plateaus using time-constrained searches. We had 5738 encounters with 38 different animal species/groups. We found that the abundance of large rocks, which were the most-preferred size class of rocks by animals, was higher in abandoned paddy compared to plateaus and orchards. However, the prevalence ofH. albofasciatusandE. carinatuswas highest on undisturbed plateaus. Contrastingly, the prevalence ofG. seshachariwas significantly higher in abandoned paddy than undisturbed plateau or orchards. Non-metric multi-dimensional analysis showed that the assemblage of rock-dwelling fauna differed significantly across the three land-use types. Despite being adapted to persist in extremely variable climates on lateritic plateaus, we find that multiple species/groups are vulnerable to land-use change. However,G. seshachariand a few other taxa appear to benefit from certain kinds of land-use change, highlighting the context-specificity in species responses. While multiple studies have determined the impacts of forest conversion to other land-uses, this is one of the first studies to determine the impacts of the conversion of rocky outcrops, thereby highlighting the conservation value of habitats that are often classified as wastelands.
Reverse chemical ecology approach for sustainable palm tree protection against invasive palm weevils
Authors: Antony Binu , Montagné Nicolas , Comte Arthur , Mfarrej Sara , Jakše Jernej , Capoduro Rémi , Shelke Rajan , Cali Khasim , AlSaleh Mohammed Ali , Persaud Krishna , Pain Arnab , Jacquin-Joly Emmanuelle
Published: January 2023

The reverse chemical ecology approach facilitates sustainable plant protection by identifying odorant receptors (ORs) tuned to odorants, especially the volatile molecules emitted from host plants that insects use for detection. A few studies have explored such an approach to develop sustainable pest management programs, especially in host-specialized insect species. We revealed the molecular mechanism of host plant detection of a destructive, invasive insect pest of palm trees (Arecaceae), the Asian palm weevil (Rhynchophorus ferrugineus), by deorphanizing an OR (RferOR2) tuned to several palm-emitted odors. We found that RferOR2 responded explicitly to several ecologically relevant palm-emitted odors and significantly to palm esters when transgenically expressed inDrosophilaolfactory neurons. We mapped RferOR2 expression in theR. ferrugineusgenome and found that odor specificity is likely to develop equally in both sexes. We inferred that the semiochemicals that attract palm weevils to a palm tree might aid in weevil control efforts by improving attraction, enticing many palm weevils to the traps. We demonstrate that including synthetic palm volatiles in pheromone-based mass trapping has a synergistic effect on pheromones, resulting in significantly increased weevil catches. We proved that insect OR deorphanization could aid in the identification of novel behaviorally active volatiles for inclusion in pest management. These results suggest that targeting RferOR2 may help design receptor antagonists that can interfere with weevil host-searching behavior in sustainable pest management applications.

Significance

Asian and South American palm weevils are tremendously important agricultural pests primarily adapted to palm trees and cause severe destruction, threatening sustainable palm cultivation worldwide. The host plant selection of these weevils is mainly attributed to functional specialization of odorant receptors that detect palm-derived volatiles. We unraveled the intricacies of weevil–palm tree communication by deorphanizing an odorant receptor tuned to natural palm-emitted odors. We used palm ester volatiles, which produced a significant response in the functional studies, and proved their synergistic effect on the pheromone coinciding with increased weevil catches in the field. We revealed that insect odorant receptor deorphanization could help identify novel behaviorally active volatiles (reverse chemical ecology) for sustainable palm protection.
An Open-Source Platform for Head-Fixed Operant and Consummatory Behavior
Authors: Gordon-Fennell Adam , Barbakh Joumana M. , Utley MacKenzie , Singh Shreya , Bazzino Paula , Gowrishankar Raajaram , Bruchas Michael R. , Roitman Mitchell F. , Stuber Garret D.
Published: January 2023

Head-fixed behavioral experiments in rodents permit unparalleled experimental control, precise measurement of behavior, and concurrent modulation and measurement of neural activity. Here we present OHRBETS (Open-Source Head-fixed Rodent Behavioral Experimental Training System; pronounced ‘Orbitz’), a low-cost, open-source ecosystem of hardware and software to flexibly pursue the neural basis of a variety of motivated behaviors. Head-fixed mice tested with OHRBETS displayed operant conditioning for caloric reward that replicates core behavioral phenotypes observed during freely moving conditions. OHRBETS also permits for optogenetic intracranial self-stimulation under positive or negative operant conditioning procedures and real-time place preference behavior, like that observed in freely moving assays. In a multi-spout brief-access consumption task, mice displayed licking as a function of concentration of sucrose, quinine, and sodium chloride, with licking modulated by homeostatic or circadian influences. Finally, to highlight the functionality of OHRBETS, we measured mesolimbic dopamine signals during the multi-spout brief-access task that display strong correlations with relative solution value and magnitude of consumption. All designs, programs, and instructions are provided freely online. This customizable ecosystem enables replicable operant and consummatory behaviors and can be incorporated with methods to perturb and record neural dynamicsin vivo.

Impact Statement

A customizable open-source hardware and software ecosystem for conducting diverse head-fixed behavioral experiments in mice.
Building modern coexistence theory from the ground up: the role of community assembly
Authors: Spaak Jurg W. , Schreiber Sebastian J.
Published: January 2023

Modern coexistence theory (MCT) is one of the leading methods to understand species coexistence. It uses invasion growth rates – the average, per-capita growth rate of a rare species – to identify when and why species coexist. Despite significant advances in dissecting coexistence mechanisms when coexistence occurs, MCT relies on a “mutual invasibility” condition designed for two species communities, but poorly defined for species rich communities. Here, we review well-known issues with this component of MCT and propose a solution based on recent mathematical advances. We propose a clear framework for expanding MCT to species rich communities and for understanding invasion resistance as well as coexistence, especially for communities which could not be analyzed with MCT so far. Using two data-driven community models from the literature, we illustrate the utility of our framework and highlight the opportunities for bridging the fields of community assembly and species coexistence.

Statement of authorship: Studied conceived jointly by JWS and SJS. JWS and SJS wrote the manuscript together. JWS wrote the python code and SJS wrote R code.

Data accessibility: All computer code used in this manuscript will be made publicly available on figshare.

Niche and fitness differences | Storage effect | Coexistence
Evidence of Lactate Shuttling in the Human Brain using Hyperpolarized13C-MRI
Authors: Uthayakumar Biranavan , Soliman Hany , Chen Albert P. , Bragagnolo Nadia , Endre Ruby , Perks William J. , Ma Nathan , Heyn Chris , Cunningham Charles H.
Published: January 2023

Purpose

To test the hypothesis that lactate shuttling contributes to the13C-lactate and13C-bicarbonate signal observed in the awake human brain using hyperpolarized13C MRI.

Methods

Healthy human volunteers (n = 6) were scanned twice using hyperpolarized13C-MRI, with reduced radiofrequency saturation of13C-lactate on one set of scans.13C-lactate,13C-bicarbonate, and13C-pyruvate signals for 132 brain regions across each set of scans were compared using a clustered Wilcoxon sum rank test.

Results

Reduced13C-lactate radiofrequency saturation resulted in a significantly greater13C-bicarbonate signal (p= 0.04). These changes were observed across the majority of brain regions.

Conclusion

Radiofrequency saturation of13C-lactate leads to a decrease in13C-bicarbonate signal, demonstrating that the13C-lactate generated from the injected13C-pyruvate is being converted back to13C-pyruvate and oxidized throughout the human brain.
Anchoring the mean generation time in the SEIR to mitigate biases in ℜ0estimates due to uncertainty in the distribution of the epidemiological delays
Authors: Andrade Jair , Duggan Jim
Published: January 2023

The basic reproduction number,ℜ0, is of paramount importance in the study of infectious disease dynamics. Primarily,ℜ0serves as an indicator of the transmission potential of an emerging infectious disease and the effort required to control the invading pathogen. However, its estimates from compartmental models are strongly conditioned by assumptions in the model structure, such as the distributions of the latent and infectious periods (epidemiological delays). To further complicate matters, models with dissimilar delay structures produce equivalent incidence dynamics. Following a simulation study, we reveal that the nature of such equivalency stems from a linear relationship betweenℜ0and the mean generation time, along with adjustments to other parameters in the model. Leveraging this knowledge, we propose and successfully test an alternative parameterisation of the SEIR model that produces accurateℜ0estimates regardless of the distribution of the epidemiological delays, at the expense of biases in other quantities deemed of lesser importance. We further explore this approach’s robustness by testing various transmissibility levels, generation times, and data fidelity (overdispersion). Finally, we apply the proposed approach to data from the 1918 influenza pandemic. We anticipate that this work will mitigate biases in estimatingℜ0.
Retinal ganglion cells undergo cell type–specific functional changes in a biophysically detailed model of retinal degeneration
Authors: Xu Aiwen , Beyeler Michael
Published: January 2023

Understanding the retina in health and disease is a key issue for neuroscience and neuroengineering applications such as retinal prostheses. During degeneration, the retinal network undergoes complex and multi-stage neuroanatomical alterations, which drastically impact the retinal ganglion cell (RGC) response and are of clinical importance. Here we present a biophysically detailedin silicomodel of retinal degeneration that simulates the network-level response to both light and electrical stimulation as a function of disease progression. The model is not only able to reproduce common findings about RGC activity in the degenerated retina, such as hyperactivity and increased electrical thresholds, but also offers testable predictions about the underlying neuroanatomical mechanisms. Overall, our findings demonstrate how biophysical changes associated with retinal degeneration affect retinal responses to both light and electrical stimulation, which may further our understanding of visual processing in the retina as well as inform the design and application of retinal prostheses.
Shared patterns of population genomic variation and phenotypic response across rapid range expansions in two invasive lady beetle species
Authors: Jones Angela G. , Obrycki John. J. , Sethuraman Arun , Weisrock David W.
Published: January 2023

Non-native lady beetle species have often been introduced, with variable success, into North America for biological control of aphids, scales, whiteflies, and other agricultural pests. Two predatory lady beetle species,Propylea quatuordecimpunctataandHippodamia variegata, both originating from Eurasia, were first discovered near Montreal, Quebec, in North America in 1968 and 1984, respectively, and have since expanded into northeastern North America and the midwestern United States. In this study, we estimate the range-wide population structure, establishment and range-expansion, and recent evolutionary history of these species of non-native lady beetles using reduced representation genotyping-by-sequencing via ddRADseq. In addition, we quantified the responses to a key abiotic factor, photoperiod, that regulates adult reproductive diapause in these two species and may influence their latitudinal distribution and spread in North America. Our analyses detect (1) non-significant genetic differentiation and divergence among North American populations, (2) evidence of reduced contemporary gene flow within the continental US, (3) significant phenotypic differences in diapause induction despite genetic similarities across sampled populations.
Transfer learning in heterogeneous drug-target interaction predictions using federated boosting
Authors: Sándor Dániel , Antal Péter
Published: January 2023

In multitask federated learning, when small amounts of data are available, it can be harder to achieve proper predictive performance, especially if the clients’ tasks are different. However, task heterogeneity is common in modern Drug-Target interaction (DTI) prediction problems. As the data available for DTI tasks are sparse, it can be challenging for clients to synchronize the tasks used for training. In our method, we used boosting to enhance transfer in the multitask scenario and adapted it to a federated environment, allowing clients to train models without having to agree on the output dimensions. Boosting uses adaptive weighting of the data to train an ensemble of predictors. Weighting data boosting can induce the selection of important tasks when shaping a model’s latent representation. This way boosting contributes to the weighting of tasks on a client level and enhances transfer, while traditional federated algorithms can be used on a global level. We evaluate our results extensively on the tyrosine kinase assays of the KIBA data set to get a clear picture of connections between boosting federated learning and transfer learning.
Cryptochromes and UBP12/13 deubiquitinases antagonistically regulate DNA damage response in Arabidopsis
Authors: Hu Yuzhao , Rosado Daniele , Lindbäck Louise N. , Micko Julie , Pedmale Ullas V.
Published: January 2023

Cryptochromes (CRYs) are evolutionarily conserved blue-light receptors that evolved from bacterial photolyases that repair damaged DNA. Today, CRYs have lost their ability to repair damaged DNA; however, prior reports suggest that human CRYs can respond to DNA damage. Currently, the role of CRYs in the DNA damage response (DDR) is lacking, especially in plants. Therefore, we evaluated the role of plant CRYs in DDR along with UBP12/13 deubiquitinases, which interact with and regulate the CRY2 protein. We found thatcry1cry2was hypersensitive, whileubp12ubp13was hyposensitive to UVC-induced DNA damage. Elevated UV-induced cyclobutane pyrimidine dimers (CPDs) and the lack of DNA repair protein RAD51 accumulation incry1cry2plants indicate that CRYs are required for DNA repair. On the contrary, CPD levels diminished and RAD51 protein levels elevated in plants lacking UBP12 and UBP13, indicating their role in DDR repression. Temporal transcriptomic analysis revealed that DDR-induced transcriptional responses were subdued incry1cry2, but elevated inubp12ubp13compared to WT. Through transcriptional modeling of the timecourse transcriptome, we found that genes quickly induced by UVC (15 min) are targets of CAMTA 1-3 transcription factors, which we found are required for DDR. This transcriptional regulation seems, however, diminished in thecry1cry2mutant, indicating that CAMTAs are required for CRY2-mediated DDR. Furthermore, we observed enhanced CRY2-UBP13 interaction and formation of CRY2 nuclear speckles under UVC, suggesting that UVC activates CRY2 similarly to blue light. Together, our data reveal the temporal dynamics of the transcriptional events underlying UVC-induced genotoxicity and expand our knowledge of the role of CRY and UBP12/13 in DDR.
Impaired polyamine metabolism causes behavioral and neuroanatomical defects in a novel mouse model of Snyder-Robinson Syndrome
Authors: Akinyele Oluwaseun , Munir Anushe , Johnson Marie A. , Perez Megan S. , Gao Yuan , Foley Jackson R. , Wu Yijen , Murray-Stewart Tracy , Casero Robert A. , Bayir Hulya , Kemaladewi Dwi U.
Published: January 2023

Polyamines (putrescine, spermidine, and spermine) are essential molecules for normal cellular functions and are subject to strict metabolic regulation. Mutations in the gene encoding spermine synthase (SMS) lead to accumulation of spermidine in an X-linked recessive disorder known as Snyder-Robinson syndrome (SRS). Presently, no treatments exist for this rare disease that manifests with a spectrum of symptoms including intellectual disability, developmental delay, thin habitus, and low muscle tone. The development of therapeutic interventions for SRS will require a suitable disease-specific animal model that recapitulates many of the abnormalities observed in patients.

Here, we characterize the molecular, behavioral, and neuroanatomical features of a mouse model with a missense mutation inSmsgene that results in a glycine-to-serine substitution at position 56 (G56S) of the SMS protein. Mice harboring this mutation exhibit a complete loss of SMS protein and elevated spermidine/spermine ratio in skeletal muscles and the brain. In addition, the G56S mice demonstrate increased anxiety, impaired learning, and decreased explorative behavior in fear conditioning, Morris water maze, and open field tests, respectively. Furthermore, these mice failed to gain weight over time and exhibit abnormalities in brain structure and bone density. Transcriptomic analysis of the cerebral cortex revealed downregulation of genes associated with mitochondrial oxidative phosphorylation and ribosomal protein synthesis. Our findings also revealed impaired mitochondrial bioenergetics in fibroblasts isolated from the G56S mice, indicating a correlation between these processes in the affected mice. Collectively, our findings establish the first in-depth characterization of an SRS preclinical mouse model that identifies cellular processes that could be targeted for future therapeutic development.
Receptive field sizes and neuronal encoding bandwidth are constrained by axonal conduction delays
Authors: Hladnik Tim , Grewe Jan
Published: January 2023

Studies on population coding implicitly assume that spikes from the presynaptic population arrive simultaneously at the integrating neuron. In natural neuronal populations, this is usually not the case — neuronal signalling takes time and neuronal populations cover a certain space. The spread of spike arrival times depends on population size, cell density and axonal conduction velocity. We here analyze the consequences of population size and axonal conduction delays on the stimulus encoding performance in the electrosensory system of the electric fishApteronotus leptorhynchus. We experimentally locate p-type electroreceptor afferents along the rostro-caudal body axis and relate locations to neurophysiological response properties. In an information-theoretical approach we analyze the coding performance in homogeneous and heterogeneous populations. As expected, the amount of information increases with population size and, on average, heterogeneous populations encode better than the average same-size homogeneous population if conduction delays are compensated for. The spread of neuronal conduction delays within a receptive field strongly degrades encoding of high-frequency stimulus components. Receptive field sizes typically found in the electrosensory lateral line lobe ofA. leptorhynchusappear to be a good compromise between the spread of conduction delays and encoding performance. The limitations imposed by finite axonal conduction velocity are relevant for any converging network as is shown by model populations of LIF neurons. The bandwidth of natural stimuli and the maximum meaningful population sizes are constrained by conduction delays and may thus impact the optimal design of nervous systems.

Author summary

Reading out the activity of a population of neurons can yield a more complete picture of the stimulus space. Generally, increasing population sizes increases the amount of information. This applies to homogeneous populations of similarly tuned neurons as well as heterogeneous populations. So far studies on population coding assumed the information to reach the integrating neuron simultanously. But neurons are neither disembodied nor does neuronal signalling happen instantaneously; populations cover a certain space and axonal conduction takes time. The interplay of encoding bandwidth, receptive field respectively population size and axonal conduction velocity has not been addressed before. Our results from the electrosensory system and of model simulations show that stimulus dynamics, receptive field sizes, and conduction velocity have to be factored in when we want to understand the design of nervous systems.
LDL Receptor-Related Protein 5 is a Selective Transporter for Unesterified Polyunsaturated Fatty Acids
Authors: Tang Wenwen , Luan Yi , Yuan Qianying , Li Ao , Chen Song , Menacherry Stanley , Young Lawrence , Wu Dianqing
Published: January 2023

Polyunsaturated fatty acids (PUFAs), which cannot be synthesized by animals and must be supplied from the diet, have been strongly associated with human health. However, the mechanisms for their accretion and actions remain poorly understood. Here, we show that LDL receptor-related protein 5 (LRP5), but not its homolog LRP6, selectively transports unesterified PUFAs into a number of cell types. The LDLa ligand-binding repeats of LRP5 directly bind to PUFAs and are required for PUFA transport. LRP5 transports PUFAs via internalization to intracellular compartments including lysosomes, and n-3 PUFAs depends on this transport mechanism to inhibit mTORC1. This LRP5-mediated PUFA transport mechanism suppresses neutrophil extracellular trap formation in neutrophils and protects mice from myocardial injury during ischemia-reperfusion. Thus, this study reveals a previously unknown and biologically important mechanism for PUFA transport and mTORC1 regulation.
Loss or Gain of Function? Effects of Ion Channel Mutations on Neuronal Firing Depend on the Cell Type
Authors: Koch Nils A. , Sonnenberg Lukas , Hedrich Ulrike B.S. , Lauxmann Stephan , Benda Jan
Published: January 2023

Clinically relevant mutations to voltage-gated ion channels, called channelopathies, alter ion channel function, properties of ionic current and neuronal firing. The effects of ion channel mutations are routinely assessed and characterized as loss of function (LOF) or gain of function (GOF) at the level of ionic currents. Emerging personalized medicine approaches based on LOF/GOF characterization have limited therapeutic success. Potential reasons are that the translation from this binary characterization to neuronal firing especially when considering different neuronal cell types is currently not well understood. Here we investigate the impact of neuronal cell type on the firing outcome of ion channel mutations with simulations of a diverse collection of neuron models. We systematically analyzed the effects of changes in ion current properties on firing in different neuronal types. Additionally, we simulated the effects of mutations in theKCNA1gene encoding the KV1.1 potassium channel subtype associated with episodic ataxia type 1 (EA1). These simulations revealed that the outcome of a given change in ion channel properties on neuronal excitability is cell-type dependent. As a result, cell-type specific effects are vital to a full understanding of the effects of channelopathies on neuronal excitability and present an opportunity to further the efficacy and precision of personalized medicine approaches.

Significance Statement

Although the genetic nature of ion channel mutations as well as their effects on the biophysical properties of an ion channel are routinely assessed experimentally, determination of their role in altering neuronal firing is more difficult. In particular, cell-type dependency of ion channel mutations on firing has been observed experimentally, and should be accounted for. In this context, computational modelling bridges this gap and demonstrates that the cell type in which a mutation occurs is an important determinant in the effects of neuronal firing. As a result, classification of ion channel mutations as loss or gain of function is useful to describe the ionic current but should not be blindly extend to classification at the level of neuronal firing.