bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the definition and distribution of spring ephemeral wildflowers in eastern North America
Authors: Yancy Abby J. , Lee Benjamin R. , Kuebbing Sara E. , Neufeld Howard S. , Spicer Michelle Elise , Heberling J. Mason 
Published: October 2023

AbstractThe herbaceous layer accounts for the majority of plant biodiversity in eastern North American forests, encompassing substantial variation in life history strategy and function. One group of early season herbaceous understory species, colloquially referred to as “spring ephemeral wildflowers,” are of particular ecological and cultural importance. Despite this, little is known about the prevalence and biogeographic patterns of the spring ephemeral strategy. Here, we used georeferenced and dated observations from the Global Biodiversity Information Facility (GBIF) to define the phenological strategies of 559 herbaceous, vascular, understory plant species in eastern North America from a composite species list encompassing 16 site-level species lists ranging from Georgia to southern Canada. Specifically, we estimated activity periods from regional observations (primarily consisting of citizen scientist iNaturalist observations) and classified species as ephemeral if they completed all aboveground activity (including leafing, flowering, fruiting, and senescence) prior to an estimated date of canopy closure derived from remote-sensed data. We then evaluated the richness of these species at the landscape scale using estimates of biogeographic and environmental drivers aggregated for 100 km x 100 km grid cells. Importantly, our spatially-explicit approach defines each species’ spring ephemerality along a continuous scale (which we call the Ephemerality Index, EI) based on the proportion of its range in which it senesces before canopy closure (with EI = 0 indicating a species that is never ephemeral and EI = 1 indicating a species that is always ephemeral). We found that 18.4% (103 species) of understory wildflowers exhibited spring ephemerality in at least part of their range, with only 3.4% of all species exhibiting ephemeral behavior in all parts of their range. Ephemeral species had higher overall richness and composed a higher proportion of understory biodiversity in low-elevation areas with intermediate spring temperatures and elevated spring precipitation. Spring ephemerals peaked in both absolute species richness and relative proportion at mid latitudes. These biogeographic patterns deserve further study in other regions of the world and to uncover mechanisms behind these patterns. Using our new metric, our results demonstrate that the spring ephemeral strategy is not a discrete category, but rather a continuum that can vary across species’ ranges.
Ecological metabolomics of tropical tree communities across an elevational gradient: Implications for chemically-mediated biotic interactions and species diversity
Authors: Henderson David , Sedio Brian E. , Tello J. Sebastián , Cayola Leslie , Fuentes Alfredo F. , Alvestegui Belen , Muchhala Nathan , Myers Jonathan A. 
Published: October 2023

AbstractSeminal hypotheses in ecology and evolution postulate that stronger and more specialized biotic interactions contribute to higher species diversity at lower elevations and latitudes. Plant-chemical defenses mediate biotic interactions between plants and their natural enemies and provide a highly dimensional trait space in which chemically mediated niches may facilitate plant species coexistence. However, the role of chemically mediated biotic interactions in shaping plant communities remains largely untested across large-scale ecological gradients. To test this hypothesis, we used ecological metabolomics to quantify the chemical dissimilarity of foliar metabolomes among 473 tree species (906 unique species-plot combinations) in 16 tropical tree communities along an elevational gradient in Madidi National Park, Bolivia. We predicted that chemical dissimilarity among co-occurring tree species would be greater, and chemical phylogenetic signal lower, in communities with greater tree species richness and warmer, wetter, and less-seasonal climates, as pressure from natural enemies is likely to be greater in these locales. Further, we predicted that these relationships should be especially pronounced for secondary metabolites derived from biosynthetic pathways known to include anti-herbivore and antimicrobial defenses than for primary metabolites. We found that median chemical dissimilarity among tree species with respect to all metabolites and secondary metabolites increased with tree species richness, decreased with elevation, and increased along a principal component of climatic variation that reflected increasing temperature and precipitation and decreasing seasonality. In contrast, median chemical dissimilarity among tree species with respect to primary metabolites was unrelated to tree species richness, elevation, or the principal component of climatic variation. Furthermore, phylogenetic signal of secondary and primary metabolites decreased with tree species richness. Among tree communities in moist forests, phylogenetic signal of secondary metabolites also increased with elevation and decreased with the temperature and precipitation. Our results support the hypothesis that chemically mediated biotic interactions shape elevational diversity gradients by imposing stronger selection for interspecific divergence in plant chemical defenses in warmer, wetter, and more stable climates. Our study also illustrates the promise of ecological metabolomics in the study of biogeography, community ecology, and complex species interactions in high-diversity ecosystems.
Pharmacokinetics of Extended-release Buprenorphine (Ethiqa) in Female Yorkshire Swine (Sus scrofa domestica)
Authors: Stevey-Rindenow Lynlee M. , Saenz Marissa , La Vivian , Franklin Craig , Aycock-Williams Ari , Fueger Patrick T. 
Published: October 2023

AbstractDespite the use of swine as a large animal translational surgical model, precise dosing regimens for commonly used analgesics such as buprenorphine, are currently lacking in this species. A newly available extended-release formulation of buprenorphine (XRB, Ethiqa) is FDA-indexed and approved for use in mice and rats; however, no studies have examined the efficacy and pharmacokinetic parameters of XRB in swine. The goal of this study was to determine the pharmacokinetics of the newly available XRB in swine. We hypothesized that after a single subcutaneous administration of XRB in adult swine, buprenorphine plasma concentrations would be at or above the therapeutic threshold of 0.1 ng/mL and that local injection side effects would be minimal. XRB was administered once, subcutaneously to two separate cohorts of adult female Yorkshire swine at low and high doses (0.2 and 0.4 mg/kg, respectively; n = 3 and 2). Blood was collected from an indwelling jugular catheter prior to and after XRB administration (13 total time points). Individual animal data indicated all animals reached therapeutic buprenorphine plasma concentrations by 8 h post administration. Average plasma buprenorphine levels for both the low- and high-dose cohorts reached therapeutic concentrations starting at 1.5 h after XRB administration and were maintained above therapeutic concentrations throughout the 96-h study period. In the low-dose cohort, the average half-life was 212.6 ± 107.1 h, whereas the half-lives in the high-dose cohort was 63.8 and 48.9 h. As expected, histology of XRB subcutaneous sites revealed mild injection site reactions characterized by granulomatous inflammation with intralesional cholesterol cleft formation. These results support our hypothesis and indicate that all animals maintained therapeutic plasma buprenorphine levels beginning at 8 h and maintaining past 96 h. Thus, XRB at either dose provide therapeutic levels of plasma buprenorphine and therefore its use should be further explored in swine.
Rewiring native post-transcriptional carbon regulators to build multi-layered genetic circuits and optimize engineered microbes for bioproduction
Authors: Simmons Trevor R. , Partipilo Gina , Stankes Anna C. , Srivastava Rashmi , Buchser Ryan , Chiu Darian , Keitz Benjamin K. , Contreras Lydia M. 
Published: October 2023

AbstractAs the bioprocessing and synthetic biology spaces rapidly expand, post-transcriptional regulation is emerging as driver for maximizing signal response rate and for minimizing cost per protein within cells. Designing robust post-transcriptional control systems that have precise tunability and can achieve diverse regulatory outcomes are paramount to advance the field. Herein, we develop a new approach for engineered post-transcriptional control in bacteria by rewiring a native regulatory system inEscherichia coli, the Carbon Storage Regulatory (Csr) Network, to create tunable, complex genetic circuits. First, by co-opting native components of the Csr Network to regulate translation of a target mRNA transcript, we establish a Csr-regulated Buffer Gate. Next, by rationally engineering the interactions between our synthetic construct and the native components of the Csr Network, we expand our original design into a genetic toolbox of 12 Buffer Gates that achieve precise tunability across a 10-fold range of target gene expression. Subsequently, to further regulatory capabilities using this approach, we develop a Csr-regulated NOT Gate through engineering a Csr-activated sequence into our synthetic constructs. We then build upon the Csr Buffer and Not Gates to create post-transcriptional dual input Boolean OR, NOR, AND and NAND Logic Gates, as well as a genetic pulse circuit. As a third step, we demonstrate portability of our Csr-regulated Buffer Gates into three industrially relevant bacteria by recapitulating Buffer Gate activity simply by leveraging the conserved homologous Csr Network in each species. Lastly, as a demonstration of downstream application, we apply our system to a proof-of-concept synthetic mevalonate pathway. Using our engineered constructs, we optimize mevalonate production inE.coli resulting in a three-fold increase in production relative to a transcriptionally controlled mevalonate pathway. As a whole, we establish a novel approach to rewire post-transcriptional regulatory networks for complex bacterial computation that can be utilized for efficient bioproduction in engineered microbes.
Non-linear phylogenetic regression using regularized kernels
Authors: Rosas-Puchuri Ulises , Santaquiteria Aintzane , Khanmohammadi Sina , Solís-Lemus Claudia , Betancur-R Ricardo 
Published: October 2023

AbstractPhylogenetic regression is a type of Generalized Least Squares (GLS) method that incorporates a covariance matrix based on the evolutionary relationships between species (i.e., phylogenetic relationships). While this method has found widespread use in hypothesis testing via comparative phylogenetic methods, such as phylogenetic ANOVA, its ability to account for non-linear relationships has received little attention.To address this issue, we utilized GLS in a high-dimensional feature space, employing linear combinations of transformed data to account for non-linearity, a common approach in kernel regression. We analyzed two biological datasets using both Radial Basis Function (RBF) and linear kernel transformations. The first dataset contained morphometric data, while the second dataset comprised discrete trait data and diversification rates as labels. Hyperparameter tuning of the model was achieved through cross-validation rounds in the training set.In the tested biological datasets, regularized kernels reduced the error rate (as measured by RMSE) by around 20% compared to linear-based regression when data did not exhibit linear relationships. In simulated datasets, the error rate decreased almost exponentially with the level of non-linearity.These results show that introducing kernels into phylogenetic regression analysis presents a novel and promising tool for complementing phylogenetic comparative methods. We have integrated this method into Python package named phyloKRR, which is freely available at:https://github.com/Ulises-Rosas/phylokrr.
Assessment of Deep Learning-Based Triage Application for Acute Ischemic Stroke on Brain MRI in the Emergency Room
Authors: Kim Jimin , Oh Se Won , Kim Jee Young , Meyer Heiko , Huwer Stefan , Zhao Gengyan , Han Dongyeob 
Published: October 2023

AbstractBackgroundsTo improve the outcomes of acute ischemic stroke (AIS) patients, a well-organized triage system is essential in the emergency room (ER). This study aimed to assess the detection performance of a deep learning triage research application for AIS that was newly developed based on brain MRI in the ER.MethodsThis retrospective study consecutively enrolled 831 brain MRIs including mandatory diffusion-weighted image (DWI) performed in the ER of our institution from April to October 2021. MRIs were analyzed with this triage research application as the index test and results were compared with the gold standard of three neuroradiologists. We evaluated sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), and maximum F1 score for this application. We also compared changes in its detection performance with and without the addition of optional sequences, which were T1- and T2-weighted images.Results831 individuals (mean age, 64 years ± 16; 399 men, 432 women) were enrolled and 201 were positive for AIS. The application showed detection performance as follows; sensitivity, 90%; specificity, 89%; AUROC, 0.95 (95% confidence interval, 0.93-0.96); AUPRC, 0.91 (95% confidence interval, 0.86-0.94); and maximum F1 score, 0.86. The addition of optional sequences led to inferior performance compared to the mandatory sequence alone for detecting AIS.ConclusionsThe triage research application accurately detected AIS in a real-world ER with no additional benefits to its detection performance with optional sequences. Therefore, the triage research application can potentially help clinicians detect AIS in the ER sufficiently/adequately with only mandatory DWI.
Absence of Care Among Community-Living Older Persons with Dementia and Functional Limitations: A Cross-National Analysis of Population Survey from 22 Countries
Authors: Lin Zhuoer , Qian Yuting , Gill Thomas M. , Hou Xiaohui , Chen Shanquan , Chen Xi 
Published: October 2023

ABSTRACTBackgroundThe provision of long-term care for persons living with dementia (PLWD) who have functional limitations is a significant global public health challenge. However, there is limited evidence on the patterns of care received by PLWD across countries and regions. This study aimed to examine the global trends in the absence of care for PLWD with functional limitations and identify potential sociodemographic disparities.MethodsWe used harmonized longitudinal survey data from four Health and Retirement Global Family of Studies that surveyed community-living persons aged 50 and older in the United States, England, 18 European countries and Israel, and China. The analysis focused on persons who reported functional limitations and developed dementia during the study periods (2012-2018). Functional limitations were assessed using activities of daily living (ADL) and instrumental activities of daily living (IADL). Absence of care was evaluated as the proportion of PLWD receiving no care for their ADL/IADL limitations.ResultsAt least 20% of PLWD in both developed and developing countries received no care for their functional limitations, and this absence of care remained stable over time. The absence of care was notable for both ADL and IADL limitations, as well as for informal and formal care. Moreover, substantial disparities were observed, with less-educated individuals and those living alone experiencing greater absence of formal and informal care, respectively. These patterns and trends were consistent across all countries and regions studied.Discussion and ImplicationsThe findings underscore the pressing need to ensure basic care provision for persons with dementia and functional limitations, especially for those who are less educated or living alone. Policymakers should prioritize addressing these disparities and improving care provision for this population worldwide.
Predicting response and resistance to immune checkpoint blockade and surgery in melanoma patients
Authors: Mestrallet Guillaume 
Published: October 2023

AbstractMelanoma remains a formidable clinical challenge, claiming the lives of 60,000 patients annually. Current therapeutic modalities encompass surgical intervention and immune checkpoint inhibitors (ICB). Nevertheless, the efficacy of ICB varies, necessitating the need to anticipate response and resistance outcomes, while also considering alternative approaches, such as surgical interventions coupled with autologous skin grafts. In pursuit of these objectives, we conducted a comprehensive analysis involving seven melanoma patient cohorts subjected to four distinct ICB treatments. Remarkably, our findings revealed varying response rates: 29% for Nivolumab, 43% for Pembrolizumab, 20% for Ipilimumab, and an encouraging 62.5% for the combination of Pembrolizumab and Ipilimumab. This underscores the superior clinical outcomes associated with anti-PD1+anti-CTLA4 therapy. Intriguingly, responders to Pembrolizumab and Ipilimumab exhibited distinct immunological characteristics, characterized by an augmentation in Th1 and M1 macrophages, alongside a reduction in CD4+ T cell infiltration. This phenomenon coincided with the upregulation of antigen presentation genes (HLA, CD80), heightened pro-inflammatory cytokine production (CCL5, CXCL9, CXCL10), and enhanced T cell responses. Furthermore, based on these response profiles, we have developed predictive software to forecast individual patient responses to available checkpoint inhibitor combinations. This innovative tool also facilitates precise calculations for the extent of melanoma resection required during surgery, graft sizing, and the determination of the necessary autologous skin cell resources. In conclusion, our approach advocates for tailored therapies, leveraging patient-specific attributes and computational predictions to enhance clinical outcomes following immunotherapy and surgical interventions. This strategy holds promise for advancing melanoma treatment paradigms.
Impact of cardiac rehabilitation and treatment compliance after ST-segment elevation myocardial infarction (STEMI) in France, the STOP SCA+ study
Authors: Laurent Emeline , Godillon Lucile , Tassi Marc-Florent , Marcollet Pierre , Chassaing Stéphan , Decomis Marie , Bezin Julien , Laure Christophe , Angoulvant Denis , Range Grégoire , Grammatico-Guillon Leslie 
Published: October 2023

AbstractIntroductionAcute ST elevation myocardial infarction (STEMI) is one frequent and serious presentation of acute coronary syndrome. The STOP SCA+ study aimed to identify factors associated with negative outcomes one year after STEMI, particularly the impact of rehabilitation care and compliance.MethodsPatients>18 years old hospitalized for STEMI management in five interventional cardiac centers in one French region (2.5 million inhabitants), between 2014 and 2018, were included. After a probabilistic matching with the National Health Insurance database (SNDS, 96% matching), compliance for cardiac tri-therapy was studied: aspirin, P2Y12 inhibitor statin. Factors associated with poor outcomes (ischemic complications, death) were analyzed using Cox modelling and those for the compliance by logistic regression.Results3,768 patients were included, with 84% of primary percutaneous coronary intervention. At one year, 3,362 were prescribed a tri-therapy (89.2%) among whom 53% were compliant; 2,478 patients went to cardiac rehabilitation (65.8%). Death occurred in 130 patients and/or ischemic complication in 194 (total poor outcome 8.0%). Compliance was not associated with complications over the year (HR 1.16 [0.86-1.57]), while the absence of cardiac rehabilitation was (2.31 [1.73-3.08]). Additionally, cardiac rehabilitation was associated with compliance (OR 1.55 [1.34-1.79]).DiscussionSTEMI clinical evolution at one year is mainly favorable. Pejorative outcomes were scarce, and appeared to be related to patients’ characteristics, initial STEMI presentation, and no access to rehabilitation. Compliance part in patient health outcome will need further modelling to accurately study its impact. Matching clinical and medico-administrative databases proved to be relevant for assessing outcomes at a large scale.Key learning pointsWhat is already knownAlthough the compliance with a cardiac treatment and cardiac rehabilitation immediately after a myocardial infarction are key factors for improving the prognosis, less is known about compliance maintenance at one year.What this study addsAt one year, few poor outcomes occurred and were not associated with compliance to the cardiac tri-therapy, while they were associated with the absence of cardiac rehabilitation.Matching two complementary clinical and medico-administrative databases proved to be reliable for assessing outcomes on a large scale (4,000 individuals over 5 years).
An ultrasensitive genetically encoded voltage indicator uncovers the electrical activity of non-excitable cells
Authors: Rühl Philipp , Nair Anagha G. , Gawande Namrata , Dehiwalage Sassrika N.C.W. , Münster Lukas , Schönherr Roland , Heinemann Stefan H. 
Published: October 2023

AbstractGenetically encoded voltage indicators (GEVIs) are powerful, non-invasive tools for recording action potentials in excitable cells. However, most animal cell types are non-excitable, and yet variations in the membrane potential are biologically relevant in these cells as well. Resolving such small voltage signals demands GEVIs with exceptionally high sensitivity. In this study, we applied structure-guided engineering to the GEVI ASAP3 to generate rEstus, a sensor with optimized brightness, voltage sensitivity, and voltage range. rEstus is most sensitive in the resting voltage range of non-excitable cells, exhibits a 3.6-fold improvement in fast voltage spike detection, and allows for absolute voltage calibration at the single-cell level. Using rEstus, we resolved endogenous voltage fluctuations in several non-excitable cell types and demonstrate that correlation analysis of these optically recorded fluctuations provides an easy, non-invasive, real-time readout of electrical gap-junction coupling. Our work provides greatly enhanced tools and methods for the non-invasive study of electrical signaling in excitable and non-excitable cells.