bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of vascular repair by tissue-engineered human acellular vessels or expanded polytetrafluoroethylene grafts in a porcine model of limb ischemia and reperfusion
Authors: Kirkton Robert D. , Watson J. Devin B. , Houston Robert , Prichard Heather L. , Niklason Laura E. , Rasmussen Todd E. 
Published: March 2023

BACKGROUND
This study evaluated performance of a tissue-engineered human acellular vessel (HAV) in a porcine model of acute vascular injury and ischemia. The HAV is an engineered blood vessel consisted of human vascular extracellular matrix proteins. Limb reperfusion and vascular outcomes of the HAV were compared with those from synthetic expanded polytetrafluoroethylene (ePTFE) grafts.

METHODS
Thirty-six pigs were randomly assigned to four treatment groups, receiving either the HAV or a PTFE graft following a hind limb ischemia period of either 0 or 6 hours. All grafts were 3-cm-long interposition 6-mm diameter grafts implanted within the right iliac artery. Animals were not immunosuppressed and followed for up to 28 days after surgery. Assessments performed preoperatively and postoperatively included evaluation of graft patency, hind limb function, and biochemical markers of tissue ischemia or reperfusion injury. Histological analysis was performed on explants to assess host cell responses.

RESULTS
Postoperative gait assessment and biochemical analysis confirmed that ischemia and reperfusion injury were caused by 6-hour ischemia, regardless of vascular graft type. Hind limb function and tissue damage biomarkers improved in all groups postoperatively. Final patency rates at postoperative day 28 were higher for HAV than for ePTFE graft in both the 0-hour (HAV, 85.7%; ePTFE, 66.7%) and 6-hour (HAV, 100%; ePTFE, 75%) ischemia groups, but these differences were not statistically significant. Histological analyses identified some intimal hyperplasia and host reactivity to the xenogeneic HAV and also to the synthetic ePTFE graft. Positive host integration and vascular cell infiltration were identified in HAV but not ePTFE explants.

CONCLUSION
Based on the functional performance and the histologic profile of explanted HAVs, this study supports further investigation to evaluate long-term performance of the HAV when used to repair traumatic vascular injuries.
Gordonia sputi -associated bloodstream infection in a renal transplant patient with chronic indwelling central venous catheter: a case report and literature review
Authors: Lo Calvin Ka-Fung , Broderick Conor , Stefanovic Aleksandra , Connors William , Murray Melanie 
Published: March 2023

Introduction: Although rare, human infections caused by Gordonia spp. have been reported especially within the immunocompromised population and those with long-term indwelling devices. We report a case of Gordonia spp. bacteremia in a renal transplant patient and present a literature review on microbiologic identification methods of this organism.
Case Presentation: A 62-year-old female renal transplant recipient admitted to hospital with a 2-month history of dry cough and fevers occurring weekly when receiving electrolyte replacement infusions via Groshong line. Over two weeks, blood cultures on multiple occasions repeatedly isolated a Gram-positive bacillus in aerobic bottle only, initially reported as Rhodococcus spp. by local microbiology laboratory. Chest computed tomography (CT) showed multiple ground-glass lung opacities suggestive of septic pulmonary emboli. As central line-associated blood stream infection was suspected, empiric antibiotics were initiated and the Groshong line was removed. The Gram-positive bacillus was later confirmed by reference laboratory as Gordonia sputi via 16S-rRNA sequencing. Vancomycin and ciprofloxacin for duration of six weeks was completed as targeted antimicrobial therapy. After treatment, she remained symptom-free with marked improvement on repeat CT chest imaging.
Conclusion: This case illustrates the challenges surrounding identification of Gordonia spp. and other aerobic actinomycetes.16S-rRNA gene sequencing may be a preferred identification method, especially when initial workup of a weakly acid-fast organism fails to identify or shows discrepant results using traditional diagnostic modalities.
OASIS: An interpretable, finite-sample valid alternative to Pearson’sX2for scientific discovery
Authors: Baharav Tavor Z. , Tse David , Salzman Julia 
Published: March 2023

Contingency tables, data represented as counts matrices, are ubiquitous across quantitative research and data-science applications. Existing statistical tests are insufficient however, as none are simultaneously computationally efficient and statistically valid for a finite number of observations. In this work, motivated by a recent application in reference-free genomic inference (1), we develop OASIS (Optimized Adaptive Statistic for Inferring Structure), a family of statistical tests for contingency tables. OASIS constructs a test-statistic which is linear in the normalized data matrix, providing closed form p-value bounds through classical concentration inequalities. In the process, OASIS provides a decomposition of the table, lending interpretability to its rejection of the null. We derive the asymptotic distribution of the OASIS test statistic, showing that these finitesample bounds correctly characterize the test statistic’s p-value up to a variance term. Experiments on genomic sequencing data highlight the power and interpretability of OASIS. The same method based on OASIS significance calls detects SARS-CoV-2 and Mycobacterium Tuberculosis strains de novo, which cannot be achieved with current approaches. We demonstrate in simulations that OASIS is robust to overdispersion, a common feature in genomic data like single cell RNA-sequencing, where under accepted noise models OASIS still provides good control of the false discovery rate, while Pearson’sX2test consistently rejects the null. Additionally, we show on synthetic data that OASIS is more powerful than Pearson’sX2test in certain regimes, including for some important two group alternatives, which we corroborate with approximate power calculations.Significance StatementContingency tables are pervasive across quantitative research and data-science applications. Existing statistical tests fall short, however; none provide robust, computationally efficient inference and control Type I error. In this work, motivated by a recent advance in reference-free inference for genomics, we propose a family of tests on contingency tables called OASIS. OASIS utilizes a linear test-statistic, enabling the computation of closed form p-value bounds, as well as a standard asymptotic normality result. OASIS provides a partitioning of the table for rejected hypotheses, lending interpretability to its rejection of the null. In genomic applications, OASIS performs reference-free and metadata-free variant detection in SARS-CoV-2 and M. Tuberculosis, and demonstrates robust performance for single cell RNA-sequencing, all tasks without existing solutions.
Mitigation of membrane morphology defects explain stability and orientational specificity of CLC dimers
Authors: Ozturk Tugba N. , Bernhardt Nathan , Schwartz Noah , Chadda Rahul , Robertson Janice L. , Faraldo-Gómez José D. 
Published: March 2023

AbstractMost membrane proteins are oligomers, but the physical forces explaining the stable association of these complexes inside the lipid bilayer are not well understood. The homodimeric antiporter CLC-ec1 highlights the puzzling nature of this reaction. This complex is thermodynamically stable even though it associates via a large hydrophobic protein-protein interface that appears well adapted to interact with the membrane interior. In a previous study, however, we discovered that when CLC-ec1 is dissociated, this interface introduces a morphological defect in the surrounding membrane, leading us to hypothesize association is driven by the elimination of this defect upon dimerization. This study tests this hypothetical mechanism directly and shows it is supported by molecular and physical models. First, using coarse-grained umbrella-sampling molecular simulations, we calculated the membrane contribution to the potential-of-mean-force for dimerization in a POPC bilayer. This shows the stable association of CLC subunits prior to formation of direct protein-protein contacts, but only via the native interface that presents the membrane defect, and not others. Single-molecule photobleaching experiments show that addition of short-chain DLPC lipids, known to alleviate the membrane defect, also shifts the association equilibrium from dimers to monomers. We explain this destabilizing effect through additional umbrella-sampling and alchemical free-energy simulations, which show DLPC enrichment of the defect diminishes the membrane contribution to the association free energy, as it improves the lipid-solvation energetics of the monomer but not the dimer. In summary, this study establishes a physical model that explains the stability and orientational specificity of CLC dimers in terms of membrane-mediated forces, rather than protein-protein interactions. We posit that cells might ubiquitously leverage morphological defects in the bilayer to drive organization of membrane proteins into functional complexes, and that cellular regulation of lipid composition can modulate this organizing effect.
Trends in mosquito species distribution modeling: insights for vector surveillance and disease control
Authors: Lippi Catherine A. , Mundis Stephanie J. , Sippy Rachel , Flenniken J. Matthew , Chaudhary Anusha , Hecht Gavriella , Carlson Colin J. , Ryan Sadie J. 
Published: March 2023

AbstractSpecies distribution modeling (SDM) has become an increasingly common approach to explore questions about ecology, geography, outbreak risk, and global change as they relate to infectious disease vectors. Here, we conducted a systematic review of the scientific literature, screening 563 abstracts and identifying 204 studies that used SDMs to produce distribution estimates for mosquito species. While the number of studies employing SDM methods has increased markedly over the past decade, the overwhelming majority used a single method (MaxEnt) and focused on human infectious disease vectors or their close relatives. The majority of regional models were developed for areas in Africa and Asia, while more localized modeling efforts were most common for North America and Europe. Findings from this study highlight gaps in taxonomic, geographic, and methodological foci of current SDM literature for mosquitoes that can guide future efforts to study the geography of mosquito-borne disease risk.
Coupling enzymatic activity and gating in an ancient TRPM chanzyme and its molecular evolution
Authors: Huang Yihe , Lü Wei , Du Juan 
Published: March 2023

AbstractThe canonical ion channels gated by chemical ligands use the free energy of agonist binding to open the channel pore, returning to a closed state upon agonist departure. A unique class of ion channels, known as channel-enzymes (chanzymes), possess additional enzymatic activity that is directly or indirectly linked to their channel function. Here we investigated a TRPM2 chanzyme from choanoflagellates, an evolutionary ancestor of all metazoan TRPM channels, which integrates two seemingly incompatible functions into a single peptide: a channel module activated by ADP ribose (ADPR) with high open probability and an enzyme module (NUDT9-H domain) consuming ADPR at a remarkably slow rate. Using time-resolved cryo- electron microscopy (cryo-EM), we captured a complete series of structural snapshots of the gating and catalytic cycles, revealing the coupling mechanism between channel gating and enzymatic activity. Our results showed that the slow kinetics of the NUDT9-H enzyme module confers a novel self-regulatory mechanism, whereby the enzyme module modulates channel gating in a binary manner. Binding of ADPR to NUDT9-H first triggers tetramerization of the enzyme modules, promoting channel opening, while the subsequent hydrolysis reaction reduces local ADPR availability, inducing channel closure. This coupling enables the ion-conducting pore to alternate rapidly between open and closed states, avoiding Mg2+and Ca2+overload. We further demonstrated how the NUDT9-H domain has evolved from a structurally semi-independent ADPR hydrolase module in early species TRPM2 to a fully integrated component of a gating ring essential for channel activation in advanced species TRPM2. Our study demonstrated an example of how organisms can adapt to their environments at the molecular level.
ITNR: Inversion Transformer-based Neural Ranking for Cancer Drug Recommendations
Authors: Sotudian Shahabeddin , Paschalidis Ioannis Ch. 
Published: March 2023

ABSTRACTPersonalized drug response prediction is an approach for tailoring effective therapeutic strategies for patients based on their tumors’ genomic characterization. The current study introduces a new listwise Learning-to-rank (LTR) model called Inversion Transformer-based Neural Ranking (ITNR). ITNR utilizes genomic features and a transformer architecture to decipher functional relationships and construct models that can predict patient-specific drug responses. Our experiments were conducted on three major drug response data sets, showing that ITNR reliably and consistently outperforms state-of-the-art LTR models.HighlightsThe proposed framework is a transformer-based model to predict drug responses using RNAseq gene expression profile, drug descriptors and drug fingerprints.ITNR utilizes a Context-Aware-Transformer architecture as its scoring function that ensures the modeling of inter-item dependencies.We introduced a novel loss function using the concept of Inversion and Approximate Permutation matrices.Our computational results indicated that our method leads to substantially improved performance when compared to the baseline methods across all performance metrics, which can lead to selecting highly effective personalized treatment.
Pulmonary maternal immune activation does not extend through the placenta but leads to fetal metabolic adaptation
Authors: Hansen Signe Schmidt Kjølner , Krautz Robert , Rago Daria , Havelund Jesper , Færgeman Nils J. , Prézelin Audrey , Rivière Julie , Couturier-Tarrade Anne , Akimov Vyacheslav , Blagoev Blagoy , Elfving Betina , Stigliani Arnaud , Vogel Ulla Birgitte , Khodosevich Konstantin , Hougaard Karin Sørig , Sandelin Albin 
Published: March 2023

ABSTRACTMaternal immune system activation (MIA) during pregnancy can disrupt the fetal environment, causing postnatal susceptibility to disorders. How the placenta and the fetus respond to acute MIA over time is unknown. Here, we characterized the response to acute maternal pulmonary inflammation across time in maternal and fetal organs using multi-omics. Unlike maternal organs which mounted strong innate immune responses, the placenta upregulated tissue-integrity genes, likely to prevent fetal exposure to infections, and downregulated growth-associated genes. Subsequently, the placenta upregulated biosynthesis and endoplasmic reticulum stress genes in order to return to homeostasis. These responses likely protected the fetus, since we observed no immune response in fetal liver. Instead, likely due to nutrient depletion, the fetal liver displayed metabolic adaptations, including increases in lipids containing docosahexaenoic acid, crucial for fetal brain development. Our study shows, for the first time, the integrated temporal response to pulmonary MIA across maternal and fetal organs.
funspace: an R package to build, analyze and plot functional trait spaces
Authors: Carmona Carlos P. , Pavanetto Nicola , Puglielli Giacomo 
Published: March 2023

SummaryFunctional trait space analyses are pivotal to define species’ ecological strategies across the tree of life. Yet, there is no single application that streamlines the many sometimes-troublesome steps needed to build and analyze functional trait spaces.To fill this gap, we proposefunspace, an R package to easily handle bivariate and multivariate (PCA-based) functional trait space analyses. The six functions that constitute the package can be grouped in three modules: ‘Building and exploring’, ‘Mapping’, and ‘Plotting’.The building and exploring module defines the main features of a functional trait space (e.g., functional diversity metrics) by leveraging kernel density-based methods. The mapping module uses general additive models to map how a target variable distributes within a trait space. The plotting module provides many options for creating flexible and high-quality figures representing the outputs obtained from previous modules. We provide a worked example to demonstrate a completefunspaceworkflow.funspacewill provide researchers working with functional traits across the tree of life with an indispensable asset to easily explore: (i) the main features of any functional trait space, (ii) the relationship between a functional trait space and any other biological or non-biological factor that might contribute to shaping species’ functional diversity.
Functional convergence underground? The scale-dependency of community assembly processes in European cave spiders
Authors: Mammola Stefano , Graco-Roza Caio , Ballarin Francesco , Hesselberg Thomas , Isaia Marco , Lunghi Enrico , Mouron Samuel , Pavlek Martina , Tolve Marco , Cardoso Pedro 
Published: March 2023

AbstractUnderstanding how species assemble into communities is a central tenet in ecology. One of the most elusive questions is the relative contribution of environmental filtering versus limiting similarity. Important advances in this area have been achieved by looking at communities through a functional lens (i.e., the traits they express), so as to derive principles valid across species pools. Yet, even using traitsin lieuof taxonomy, the issue remains controversial because i) environmental filtering and limiting similarity often act simultaneously in shaping communities; and ii) their effect is scale-dependent. We exploited the experimental arena offered by caves, island-like natural laboratories characterized by largely constant environmental gradients and a limited diversity of species and interactions. Leveraging uniquely available data on distribution and traits for European cave spiders, we tested explicit hypotheses about variations in community assembly rules across ecological gradients and scales. We demonstrate that environmental filtering and limiting similarity shape cave communities acting on trait evolution in opposing directions. These effects are strongly scale dependent, varying along multiple environmental gradients. Conversely, the effect of geography on trait composition is weak, indicating that trait turnover in space happens primarily by substitution of species pursuing similar functions due to strong environmental filters. Our findings reconcile contrasted views about the relative importance of the two main mechanisms shaping patterns of biodiversity, and provide a conceptual foundation to account for scaling effects in the study of community assembly.
Optimized two-color single-molecule tracking of fast-diffusing membrane receptors
Authors: Spagnolo Chiara Schirripa , Moscardini Aldo , Amodeo Rosy , Beltram Fabio , Luin Stefano 
Published: March 2023

AbstractSingle particle tracking (SPT) combined with total internal reflection fluorescence (TIRF) microscopy is an outstanding approach to decipher crucial molecular mechanisms on the cell membrane at the nanometric scale. In multicolor configurations it can even be the ideal tool to investigate interactions, but this is hindered by a number of experimental challenges. We systematically and quantitatively analyze the impact of all the necessary sub-elements of any SPT-TIRF setup on signal-to-noise ratio, especially in dynamic studies using minimally-invasive dyes for biomolecule labeling. We show that the dominant limiting factor is the autofluorescence originating from the commonly-used optical glass. We identify and test a different material and show a significant improvement of signal-to-noise ratio in a multichannel TIRF configuration employing the new glass covers. We also address the problem of photobleaching of fluorescent probes by presenting effective approaches suited to a multicolor implementation that requires simultaneous stabilization of multiple dyes. We apply the developed protocol to the analysis of p75 receptors labeled by two fluorophores on the membrane of living cells. Our strategy yields reliable, simultaneous two-color SPT, even for fast-diffusing receptors, enabling this study under conditions not accessible with standard experimental configurations. We argue that the present protocol can pave the way for multicolor super-resolved localization and tracking of single molecules by TIRF microscopy, much expanding the potential of SPT.
Cell type-specific and disease-associated eQTL in the human lung
Authors: Natri Heini M , Del Azodi Christina B , Peter Lance , Taylor Chase J , Chugh Sagrika , Kendle Robert , Chung Mei-i , Flaherty David K , Matlock Brittany K , Calvi Carla L , Blackwell Timothy S , Ware Lorraine B , Bacchetta Matthew , Walia Rajat , Shaver Ciara M , Kropski Jonathan A , McCarthy Davis J , Banovich Nicholas E 
Published: March 2023

AbstractCommon genetic variants confer substantial risk for chronic lung diseases, including pulmonary fibrosis (PF). Defining the genetic control of gene expression in a cell-type-specific and context-dependent manner is critical for understanding the mechanisms through which genetic variation influences complex traits and disease pathobiology. To this end, we performed single-cell RNA-sequencing of lung tissue from 67 PF and 49 unaffected donors. Employing a pseudo-bulk approach, we mapped expression quantitative trait loci (eQTL) across 38 cell types, observing both shared and cell type-specific regulatory effects. Further, we identified disease-interaction eQTL and demonstrated that this class of associations is more likely to be cell-type specific and linked to cellular dysregulation in PF. Finally, we connected PF risk variants to their regulatory targets in disease-relevant cell types. These results indicate that cellular context determines the impact of genetic variation on gene expression, and implicates context-specific eQTL as key regulators of lung homeostasis and disease.
How total mRNA influences cell growth
Authors: Calabrese Ludovico , Ciandrini Luca , Lagomarsino Marco Cosentino 
Published: March 2023

AbstractExperimental observations tracing back to the 1960s imply that ribosome quantities play a prominent role in determining a cell’s growth. Nevertheless, in biologically relevant scenarios, growth can also be influenced by the levels of mRNA and RNA polymerase. Here, we construct a quantitative model of biosynthesis providing testable scenarios for these situations. The model explores a theoretically-motivated regime where RNA polymerases compete for genes and ribosomes for transcripts, and gives general expressions relating growth rate, mRNA concentrations, ribosome and RNA polymerase levels. On general grounds, the model predicts how the fraction of ribosomes in the proteome depends on total mRNA concentration, and inspects an underexplored regime in which the trade-off between transcript levels and ribosome abundances sets the cellular growth rate. In particular, we show that the model predicts and clarifies three important experimental observations, in budding yeast andE. colibacteria: (i) that the growth-rate cost of unneeded protein expression can be affected by mRNA levels, (ii) that resource optimization leads to decreasing trends in mRNA levels at slow growth, and (iii) that ribosome allocation may increase, stay constant, or decrease, in response to transcription-inhibiting antibiotics. Since the data indicate that a regime of joint limitation may apply in physiological conditions and not only to perturbations, we speculate that this regime is likely self-imposed.