bluuebunny/crossref_metadata_2025_split huggingface dataset:
ntLink: A Toolkit for De Novo Genome Assembly Scaffolding and Mapping Using Long Reads
Authors: Coombe Lauren , Warren René L. , Wong Johnathan , Nikolic Vladimir , Birol Inanc 
Published: April 2023

AbstractWith the increasing affordability and accessibility of genome sequencing data, de novo genome assembly is an important first step to a wide variety of downstream studies and analyses. Therefore, bioinformatics tools that enable the generation of high‐quality genome assemblies in a computationally efficient manner are essential. Recent developments in long‐read sequencing technologies have greatly benefited genome assembly work, including scaffolding, by providing long‐range evidence that can aid in resolving the challenging repetitive regions of complex genomes. ntLink is a flexible and resource‐efficient genome scaffolding tool that utilizes long‐read sequencing data to improve upon draft genome assemblies built from any sequencing technologies, including the same long reads. Instead of using read alignments to identify candidate joins, ntLink utilizes minimizer‐based mappings to infer how input sequences should be ordered and oriented into scaffolds. Recent improvements to ntLink have added important features such as overlap detection, gap‐filling, and in‐code scaffolding iterations. Here, we present three basic protocols demonstrating how to use each of these new features to yield highly contiguous genome assemblies, while still maintaining ntLink's proven computational efficiency. Further, as we illustrate in the alternate protocols, the lightweight minimizer‐based mappings that enable ntLink scaffolding can also be utilized for other downstream applications, such as misassembly detection. With its modularity and multiple modes of execution, ntLink has broad benefit to the genomics community, from genome scaffolding and beyond. ntLink is an open‐source project and is freely available from https://github.com/bcgsc/ntLink. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: ntLink scaffolding using overlap detectionBasic Protocol 2: ntLink scaffolding with gap‐fillingBasic Protocol 3: Running in‐code iterations of ntLink scaffoldingAlternate Protocol 1: Generating long‐read to contig mappings with ntLinkAlternate Protocol 2: Using ntLink mappings for genome assembly correction with Tigmint‐longSupport Protocol: Installing ntLink
One‐Flask Synthesis of Cyclic Diguanosine Monophosphate (c‐di‐GMP)
Authors: Gaffney Barbara L. , Jones Roger A. 
Published: April 2023

AbstractThe bacterial signaling molecule cyclic diguanosine monophosphate (c‐di‐GMP) plays a key role in controlling biofilm formation and pathogenic virulence, among many other functions. It has widespread consequences for human health, and current research is actively exploring its molecular mechanisms. The convenient one‐flask, gram‐scale synthesis of c‐di‐GMP described here has facilitated these efforts and has been applied to a variety of analogs. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.
Bee diversity decreases rapidly with time since harvest in intensively managed conifer forests
Authors: Zitomer Rachel A. , Galbraith Sara M. , Betts Matthew G. , Moldenke Andrew R. , Progar Robert A. , Rivers James W. 
Published: April 2023

AbstractDespite widespread concerns about the anthropogenic drivers of global pollinator declines, little information is available about the impacts of land management practices on wild bees outside of agricultural systems, including in forests managed intensively for wood production. We assessed changes in wild bee communities with time since harvest in 60 intensively managed Douglas‐fir (Pseudotsuga menziesii) stands across a gradient in stand ages spanning a typical harvest rotation. We measured bee abundance, species richness, and alpha and beta diversity, as well as habitat characteristics (i.e., floral resources, nesting substrates, understory vegetation, and early seral forest in the surrounding landscape) during the spring and summer of 2018 and 2019. We found that bee abundance and species richness declined rapidly with stand age, decreasing by 61% and 48%, respectively, for every 5 years since timber harvest. Asymptotic estimates of Shannon and Simpson diversity were highest in stands 6–10 years post‐harvest and lowest after the forest canopy had closed, ~11 years post‐harvest. Bee communities in older stands were nested subsets of bee communities found in younger stands, indicating that changes were due to species loss rather than turnover as the stands aged. Bee abundance—but not species richness—was positively associated with floral resource density, and neither metric was associated with floral richness. The amount of early seral forest in the surrounding landscape seemed to enhance bee species richness in older, closed‐canopy stands, but otherwise had little effect. Changes in the relative abundance of bee species did not relate to bee functional characteristics such as sociality, diet breadth, or nesting substrate. Our study demonstrates that Douglas‐fir plantations develop diverse communities of wild bees shortly after harvest, but those communities erode rapidly over time as forest canopies close. Therefore, stand‐scale management activities that prolong the precanopy closure period and enhance floral resources during the initial stage of stand regeneration will provide the greatest opportunity to enhance bee diversity in landscapes dominated by intensively managed conifer forests.
Spatiotemporal variation in the competitive environment, with implications for how climate change may affect a species with parental care
Authors: Potticary Ahva L. , Otto Hans W. , McHugh Joseph V. , Moore Allen J. 
Published: April 2023

AbstractBurying beetles of the genus Nicrophorus have become a model for studying the evolution of complex parental care in laboratory studies. Nicrophorus species depend on small vertebrate carcasses to breed, which they process and provision to their begging offspring. However, vertebrate carcasses are highly sought after by a wide variety of species and so competition is expected to be critical to the evolution of parental care. Despite this, the competitive environment for Nicrophorus is rarely characterized in the wild and remains a missing factor in laboratory studies. Here, we performed a systematic sampling of Nicrophorus orbicollis living near the southern extent of their range at Whitehall Forest in Clarke County, Georgia, USA. We determined the density of N. orbicollis and other necrophilous species that may affect the availability of this breeding resource through interference or exploitation competition. In addition, we characterize body size, a key trait involved in competitive ability, for all Nicrophorus species at Whitehall Forest throughout the season. Finally, we compare our findings to other published natural history data for Nicrophorines. We document a significantly longer active season than was observed 20 years previously at Whitehall Forest for both N. orbicollis and Nicrophorus tomentosus, potentially due to climate change. As expected, the adult body size of N. orbicollis was larger than N. tomentosus, the only other Nicrophorus species that was captured in 2022 at Whitehall Forest. The other most prevalent insects captured included species in the families Staphylinidae, Histeridae, Scarabaeidae, and Elateridae, which may act as competitors or predators of Nicrophorus young. Together, our results indicate significant variation in intra‐ and interspecific competition relative to populations within the N. orbicollis range. These findings suggest that the competitive environment shows extensive spatiotemporal variation, providing the basis to make predictions for how ecology may influence parenting in this species.
Consistent microbial and nutrient resource island patterns during monsoon rain in a Chihuahuan Desert bajada shrubland
Authors: Darrouzet‐Nardi Anthony , Asaff Isabel Siles , Mauritz Marguerite , Roman Kathleen , Keats Eleanor , Tweedie Craig E. , McLaren Jennie R. 
Published: April 2023

AbstractIn dryland soils, spatiotemporal variation in surface soils (0–10 cm) plays an important role in the function of the “critical zone” that extends from canopy to groundwater. Understanding connections between soil microbes and biogeochemical cycling in surface soils requires repeated multivariate measurements of nutrients, microbial abundance, and microbial function. We examined these processes in resource islands and interspaces over a two‐month period at a Chihuahuan Desert bajada shrubland site. We collected soil in Prosopis glandulosa (honey mesquite), Larrea tridentata (creosote bush), and unvegetated (interspace) areas to measure soil nutrient concentrations, microbial biomass, and potential soil enzyme activity. We monitored the dynamics of these belowground processes as soil conditions dried and then rewetted due to rainfall. Most measured variables, including inorganic nutrients, microbial biomass, and soil enzyme activities, were greater under shrubs during both wet and dry periods, with the highest magnitudes under mesquite followed by creosote bush and then interspace. One exception was nitrate, which was highly variable and did not show resource island patterns. Temporally, rainfall pulses were associated with substantial changes in soil nutrient concentrations, though resource island patterns remained consistent during all phases of the soil moisture pulse. Microbial biomass was more consistent than nutrients, decreasing only when soils were driest. Potential enzyme activities were even more consistent and did not decline in dry periods, potentially helping to stimulate observed pulses in CO2 efflux following rain events observed at a co‐located eddy flux tower. These results indicate a critical zone with organic matter cycling patterns consistently elevated in shrub resource islands (which varied by shrub species), high decomposition potential that limits soil organic matter accumulation across the landscape, and nitrate fluxes that are decoupled from the organic matter pathways.
Climate envelope modeling for ocelot conservation planning: peering inside the black box
Authors: Lehnen Sarah E. , Lombardi Jason V. 
Published: April 2023

AbstractClimate envelope models have been used to evaluate the predicted impacts of climate change on species of concern and can be a useful planning tool in determining the long‐term suitability of current habitat and potential introduction sites. However, due to model complexity, these models have generally been seen as “black boxes” when it comes to understanding why they make the predictions they do. In this study, we examined current potential ocelot (Leopardus pardalis) habitat using publicly available ocelot records and CHELSA bioclimatic variables combined in an ensemble model approach. We then predicted future potential ocelot habitat under three different emission scenarios using five climate models produced at a 30 arcsec grid cell size. To better understand what was driving model predictions, we used a variety of model interpretability approaches, including variable importance values, Shapley additive explanations, interaction detection, and a local surrogate model. These approaches revealed that ocelot potential habitat was associated with at least 233 mm of precipitation during the warmest quarter (BIO18) and at least 146 mm of precipitation during the wettest month (BIO13). Shapley additive explanations, applied to four protected areas across the species range, were valuable for understanding which climatic predictors drove predicted ocelot habitat at a local scale, with the protected areas with the highest predicted values having consistently more precipitation and higher temperatures. These tools are model agnostic and can be used to assess model predictions for biological validity and to further understand potential underlying relationships. As climate change shifts species range distributions, species distribution models and the tools to interpret them may become increasingly valuable, particularly on the leading edge of range expansion.
IGFBP7 and left ventricular mass regression: a sub‐analysis of the EMPA‐HEART CardioLink‐6 randomized clinical trial
Authors: Puar Pankaj , Mistry Nikhil , Connelly Kim A. , Yan Andrew T. , Quan Adrian , Teoh Hwee , Pan Yi , Verma Raj , Hess David A. , Verma Subodh , Mazer C. David 
Published: April 2023

AbstractAimsGiven recent suggestions that serum levels of insulin‐like growth factor‐binding protein 7 (IGFBP7) may identify patients who derive greater cardiorenal benefits from treatment with sodium‐glucose transport 2 inhibitors (SGLT2i), this exploratory sub‐analysis of the EMPA‐HEART CardioLink‐6 randomized controlled trial evaluated the association between serum levels of IGFBP7 and empagliflozin‐mediated left ventricular mass regression.Methods and resultsThe EMPA‐HEART CardioLink‐6 trial used gold‐standard cardiac magnetic resonance imaging to detect change in left ventricular mass indexed to body surface area (LVMi) following 6 months of treatment with empagliflozin or matching placebo in 97 patients with type 2 diabetes and coronary artery disease. Serum samples were collected at baseline and analysed for IGFBP7 using an enzyme‐linked immunosorbent assay. A multivariate linear regression model was used to assess the association between IGFBP7 and baseline LVMi. A linear model adjusting for baseline differences in LVMi was used to test the relationship between baseline IGFBP7 level, change in LVMi over 6 months, and treatment arm. Of the 97 patients enrolled, 74 had complete covariate data and were included in our analysis. No association between baseline IGFBP7 and baseline LVMi was found [baseline LVMi: 0.14 g/m2 (95% CI: −0.29 g/m2 to 0.57 g/m2) per 1 ng/mL higher baseline IGFBP7]. In addition, no difference between patients treated with empagliflozin versus matching placebo was found when evaluating the association between serum IGFBP7, 6 month change in LVMi, and treatment arm [empagliflozin 6 month change in LVMi: 0.25 g/m2 (95% CI: −0.17 g/m2 to 0.67 g/m2) per 1 ng/mL higher IGFBP7 vs. matching placebo 6 month change in LVMi: 0.07 g/m2 (95% CI: −0.21 g/m2 to 0.35 g/m2) per 1 ng/mL higher IGFBP7; Pinteraction = 0.49]. Additional sensitivity analysis assessing IGFBP7 as a categorical variable (above/below the median) showed no significant association between IGFBP7, 6 month change in LVMi, and treatment arm.ConclusionsOur study provides insight into the generalizability of IGFBP7 as a surrogate marker of cardiac remodelling in patients with type 2 diabetes and coronary artery disease. Our results suggest that SGLT2i‐mediated reverse cardiac remodelling may be independent of IGFBP7 levels. Further investigations evaluating the association between IGFBP7 and SGLT2i are suggested to understand if and how IGFBP7 levels may modulate benefits received from SLGT2i.
Baseline neutrophil‐to‐lymphocyte ratio and efficacy of SGLT2 inhibition with empagliflozin on cardiac remodelling
Authors: Verma Raj , Moroney Michael , Hibino Makoto , Mazer Cyril David , Connelly Kim A. , Yan Andrew T. , Quan Adrian , Teoh Hwee , Verma Subodh , Puar Pankaj 
Published: April 2023

AbstractAimsThe neutrophil‐to‐lymphocyte ratio (NLR) is a marker of systemic inflammation and plays a critical role in the assessment and prognosis in patients with heart failure. The EMPA‐HEART CardioLink‐6 trial demonstrated that patients with type 2 diabetes (T2D) and coronary artery disease (CAD) treated with a sodium–glucose transport protein 2 inhibitor for 6 months experienced regression in left ventricular mass. Given this, we evaluated the relationship of baseline NLR and cardiac reverse remodelling in the entire cohort of this trial.Methods and resultsA total of 97 individuals were randomized to receive empagliflozin (10 mg/day) or placebo for 6 months. The primary outcome of the trial was change in left ventricular mass indexed to body surface area (LVMi) from baseline to 6 months as measured by cardiac magnetic resonance imaging. In our analysis, the cohort was stratified above and below an NLR level of 2. To assess the treatment effect on the 6 month change in NLR, we used a linear model adjusting for baseline differences in NLR [analysis of covariance (ANCOVA)] that included an interaction term between the baseline NLR and treatment. To assess the treatment effect on the 6 month change in LVMi in each of the subgroups divided by baseline NLR, we used an ANCOVA adjusting for baseline differences in LVMi that included an interaction term between the subgroups and treatment. The results of the regression models were summarized as adjusted differences with two‐sided 95% confidence intervals (CIs). Patients who exhibited an elevated baseline NLR demonstrated higher LVMi and left ventricular end‐diastolic volume indexed to body surface area than those with a lower NLR. In patients with an NLR < 2 and NLR ≥ 2, the adjusted difference in LVMi between the empagliflozin‐ and placebo‐treated patients was −2.98 g/m2 (95% CI: −6.18 to 0.22 g/m2) (P value = 0.067) and −4.43 g/m2 (95% CI: −8.50 to −1.11 g/m2), respectively (Pinteraction = 0.60).ConclusionsEmpagliflozin treatment is associated with consistent reductions in LVMi in patients with T2D and CAD independent of baseline NLR.
Impact of diabetes duration on left ventricular mass regression with empagliflozin
Authors: Moroney Michael , Verma Raj , Hibino Makoto , Mazer C. David , Connelly Kim A. , Yan Andrew T. , Quan Adrian , Teoh Hwee , Verma Subodh , Puar Pankaj 
Published: April 2023

AbstractAimsThe duration of type 2 diabetes mellitus (T2DM) is an important determinant of diabetes severity. The EMPA‐HEART CardioLink‐6 trial reported significant left ventricular (LV) mass indexed to body surface area (LVMi) regression in patients treated with the sodium‐glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin for 6 months. This exploratory sub‐analysis of the same trial investigated the association between T2DM duration and LVMi regression.Methods and resultsA total of 97 individuals with T2DM and coronary artery disease (CAD) were randomly assigned to receive empagliflozin 10 mg daily or placebo. LVMi was measured at the baseline and 6 month visit using cardiac magnetic resonance imaging. The study population was divided into those with a baseline T2DM duration <10 years (n = 40) or ≥10 years (n = 57). A linear model adjusting for baseline values in each of the subgroups (ANCOVA) was used to assess the treatment effect of 6 month change in LVMi, LV end systolic volume indexed to body surface area, LV end diastolic volume indexed to body surface area and LV ejection fraction. Patients in the T2DM duration <10 years group (38 males [95.0%], median age 63 [IQR: 55 years to 70 years]) had a median T2DM duration of 4 years (IQR: 2.0 years to 7.0 years). Those in the T2DM duration ≥10 years group (52 males [91.2%], median age 65 [IQR: 57 years to 71 years]) had a median duration of 15 years (IQR: 12 years to 20 years). There was no significant difference in baseline LVMi according to T2DM duration (median 62 g/m2 [IQR: 53.1 g/m2 to 70.0 g/m2] for T2DM duration <10 years; median 57.5 g/m2 [IQR: 52.1 g/m2 to 66.2 g/m2] for T2DM duration ≥10 years; P = 0.11). Empagliflozin was associated with reductions in LVMi irrespective of duration of T2DM above and below 10 years (T2DM duration <10 years group, mean adjusted difference −2.90 g/m2 [95% CI: −6.64 g/m2 to 0.84 g/m2]; T2DM duration ≥10 years group, mean adjusted difference −3.69 g/m2 [95% CI: −0.14 g/m2 to −7.24 g/m2]; Pinteraction = 0.07).ConclusionsIn the EMPA‐HEART CardioLink‐6 trial, empagliflozin treatment was associated with reductions in LVMi in people with T2DM and CAD irrespective of the duration of diabetes assessed categorically above and below 10 years.
The win ratio method in heart failure trials: lessons learnt from EMPULSE
Authors: Pocock Stuart J. , Ferreira João Pedro , Collier Timothy J. , Angermann Christiane E. , Biegus Jan , Collins Sean P. , Kosiborod Mikhail , Nassif Michael E. , Ponikowski Piotr , Psotka Mitchell A. , Teerlink John R. , Tromp Jasper , Gregson John , Blatchford Jonathan P. , Zeller Cordula , Voors Adriaan A. 
Published: April 2023

ABSTRACTAimsThe EMPULSE trial evaluated the clinical benefit of empagliflozin versus placebo using the stratified win ratio approach in 530 patients with acute heart failure (HF) after initial stabilization. We aim to elucidate how this method works and what it means, thereby giving guidance for use of the win ratio in future trials.Methods and resultsThe primary trial outcome is a hierarchical composite of death, number of HF events, time to first HF event, or a ≥5‐point difference in Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score change at 90 days. In an overall (unstratified) analysis we show how comparison of all 265 x 265 patients pairs contribute to ‘wins’ for empagliflozin and placebo at all four levels of the hierarchy, leading to an unstratified win ratio of 1.38 (95% confidence interval [CI] 1.11–1.71; p = 0.0036). How such a win ratio should (and should not) be interpreted is then described. The more complex primary analysis using a stratified win ratio is then presented in detail leading to a very similar overall result. Win ratios for de novo acute HF and decompensated chronic HF patients were 1.29 and 1.39, respectively, their weighted combination yielding an overall stratified win ratio of 1.36 (95% CI 1.09–1.68) (p = 0.0054). Alternative ways of including HF events and KCCQ scores in the clinical hierarchy are presented, leading to recommendations for their use in future trials. Specifically, inclusion of both number of HF events and time‐to‐first HF event appears an unnecessary complication. Also, the use of a 5‐point margin for KCCQ score paired comparisons is not statistically necessary.ConclusionsThe EMPULSE trial findings illustrate how deaths, clinical events and patient‐reported outcomes can be integrated into a win ratio analysis strategy that yields clinically meaningful findings of patient benefit. This has implications for future trial designs that recognize the clinical priorities of patient evaluation and the need for efficient progress towards approval of new treatments.
Enabling high‐performance 4.6 V LiCoO2 in a wide temperature range via a synergetic strategy
Authors: Ren Jincan , Tang Yu , Li Weibao , He Dong , Zhu He , Wang Xingyu , Lan Si , Yin Zijia , Yang Tingting , Bai Zhaowen , Ren Yang , Xiao Xiangheng , Liu Qi 
Published: April 2023

AbstractNowadays, LiCoO2 has dominated the cathode technology of lithium‐ion batteries (LIBs) for 3C digital devices, but the sluggish electrochemical kinetics and severe structure destruction limit its further application under extreme temperatures. Herein, we design a synergetic strategy including La, Mg co‐doping and LiAlO2@Al2O3 surface coating. Typically, the La3+ increases the interlayer distance and significantly enhances the ionic conductivity, the Mg2+ improves electronic conductivity, and the LiAlO2@Al2O3 coating layer improves the interfacial charge transfer and suppresses the polarization. The co‐modified LiCoO2 (CM‐LCO) shows excellent temperature adaptability with remarkable electrochemical performance in a wide temperature range (−40–70°C). Remarkably, the CM‐LCO also exhibits excellent cycle stability and high‐rate performance at extreme temperatures. The synergistic effects of this co‐modification strategy are demonstrated by investigating the electrochemical reaction kinetics and structure evolution of CM‐LCO. This work proposes a promising strategy for the application of the high‐voltage LCO in a wide temperature range.image