bluuebunny/crossref_metadata_2025 huggingface dataset:
Single‐center study on SARS‐CoV‐2 infection in patients affected by CML: Vaccination status and bosutinib therapy as possible protective factors for hospitalization
Authors: Civettini Ivan , Antolini Laura , Brioschi Filippo , Zambrotta Giovanni Paolo Maria , Guglielmana Veronica , Gambacorti‐Passerini Carlo
Published: April 2023

Introduction

COVID‐19 pandemic had a considerable impact among haematological patients. On the other hand, the effect of this disease on patients (pts) affected by Chronic Myeloid Leukemia (CML) is not clearly defined.

Objectives

The primary objective of this study was to evaluate mortality‐hospitalization rates and possible protective factors for hospitalization in CML pts affected by COVID.

Methods

We collected data from CML patients followed at our institution whotested positive for SARS‐CoV‐2 infection. The following variables were assessed: demographical data, type of TKI therapy, vaccination status, presence of cardiovascular disease (CVD), period of infection, COVID‐19 presenting symptoms, severity and mortality. Data were collected retrospectively and then analysed in univariate and multivariate analysis.

Results

Out of a total of 325 CML pts treated at our institution, we recorded 72 SARS‐CoV‐2pts (22%) who tested positive with a SARS‐CoV‐2 PCR assay. Twenty two were infected in 2020 (30%), 16 patients in 2021 (22%) and 34 in 2022 (46%); with a hospitalization rate of 27%, 25% and 3% respectively. Of the 72 confirmed infections, 13 pts (18%; (CI) 10–28) were asymptomatic and 48 (66%; CI: 55–76) had mild symptoms. A total of 11 pts were admitted to hospital and 3 of these required ICU admission. No deaths were recorded. The probability of hospitalization was significantly reduced if patients were vaccinated (odds ratio OR 0.037 with CI: 0–0.33 p 0.002) or treated with Bosutinib (OR 0.06 with CI: 0–0.5 p 0.008).

Conclusion

In the present study, no significant increase in mortality was noted among patients with CML as compared to the general population inItaly. Vaccination and treatment with bosutinib were identified as baseline characteristics that were associated with a decreased risk of hospitalitazion resulting from COVID‐19 infection.
Prognostic assessment in patients operated for brain metastasis from systemic tumors
Authors: Grossenbacher Bettina , Lareida Anna , Moors Selina , Roth Patrick , Kulcsar Zsolt , Regli Luca , Le Rhun Emilie , Weller Michael , Wolpert Fabian
Published: April 2023

Background

Established models for prognostic assessment in patients with brain metastasis do not stratify for prior surgery. Here we tested the prognostic accuracy of the Graded Prognostic Assessment (GPA) score model in patients operated for BM and explored further prognostic factors.

Methods

We included 285 patients operated for brain metastasis at the University Hospital Zurich in the analysis. Information on patient characteristics, imaging, staging, peri‐ and postoperative complications and survival were extracted from the files and integrated into a multivariate Cox hazard model.

Results

The GPA score showed an association with outcome. We further identified residual tumor after surgery (p = 0.007, hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.1–2.3) steroid use (p = 0.021, HR 1.7, 95% CI 1.1–2.6) and number of extracranial metastasis sites (p = 0.009, HR 1.4, 95% CI 1.1–1.6) at the time of surgery as independent prognostic factors. A trend was observed for postoperative infection of the subarachnoid space (p = 0.102, HR 3.5, 95% CI 0.8–15.7).

Conclusions

We confirm the prognostic capacity of the GPA score in a cohort of operated patients with brain metastasis. However, extent of resection and steroid use provide additional aid for the prognostic assessment in these patients.
Knockdown of kinesin family member 4A inhibits cell proliferation, migration, and invasion while promoting apoptosis of urothelial bladder carcinoma cells
Authors: Zhang Chen , Wang Maoyu , Ying Yidie , Meng Fang , Gao Hongliang , Zeng Shuxiong , Zhu Yasheng , Liu Anwei , Zhang Zhensheng , Xu Chuanliang
Published: April 2023

Background

Kinesin family member 4A (KIF4A) is upregulated in a variety of cancers. However, its expression and potential downstream targets in urothelial bladder carcinoma (UBC) remain unclear.

Methods

Expression data of KIF4A in UBC and noncancerous tissues were downloaded from the GEPIA database. Cell proliferation, migration, invasion, and apoptosis of T24 and 5637 UBC cells were examined using wound healing, transwell, colony formation, CCK‐8, and flow cytometry assays. KIF4A and potential downstream genes were analyzed using qRT‐PCR, western blot analysis, and immunohistochemistry.

Results

In UBC samples, KIF4A expression was significantly higher than in corresponding noncancerous samples. UBC patients with high KIF4A expression had poor cancer‐specific survival and overall survival. Knockdown of KIF4A significantly inhibited proliferation and promoted apoptosis of UBC cells, accompanied by dephosphorylation of AKT and increased the protein level of proapoptotic factors. Additionally, knockdown of KIF4A reduced migration and invasion of UBC cells whereas overexpression of KIF4A exhibited opposite effects, along with altered protein level in epithelial‐mesenchymal transition‐related genes. Furthermore, overexpression of YAP1 promoted KIF4A expression whereas knockdown of YAP1 suppressed KIF4A expression in UBC cells. Alternatively, KIF4A knockdown reduced YAP1 nuclear protein level whereas KIF4A overexpression suppressed YAP1 phosphorylation and facilitated YAP1 nuclear translocation.

Conclusions

KIF4A upregulation correlates with poor prognosis of UBC. Knockdown of KIF4A inhibits proliferation, migration, and invasion of UBC cells while inducing apoptosis possibly through dephosphorylation of AKT, changes in EMT‐related genes, and interaction with YAP1.
Investigation on the Anticancer and Antibacterial Mechanism of Thiazoline/Imidazoline Derived Palladium(II) Complexes
Authors: Mahanty Susobhan , Sudharsan Murugesan , Suresh Devarajan , Rathinasamy Krishnan
Published: April 2023

Biological activities of a series of palladium(II) complexes (M1–M9) bearing N∩N, N∩S, and N∩O chelating ligands are reported. The palladium complexes were tested for their cytotoxic properties against human cervical cancer (HeLa) cells and antibacterial activity against Gm+ve and Gm–ve bacteria. Among the palladium complexes studied (M1‐M9), the complex M5, M8, and M9 were found to be more effective in inhibiting the proliferation of HeLa cells. Hence, these complexes were further investigated for their potential role in cellular damage and apoptosis. DCFDA staining, Rhodamine 123 staining and DNA cleavage assay revealed that complex M5, M8 and M9 induced apoptotic cell death in HeLa cells through ROS generation, DNA damage and mitochondrial depolarization. Computational and titration studies also indicated strong electrostatic interaction with DNA groove. Most of the complexes exhibited good antibacterial activity against both Gm+ve and Gm−ve bacteria. The antibacterial activity of the compounds could not be correlated with their anticancer activity indicating a differential mechanism at their effective concentrations. The detailed study on the antibacterial mechanism of the most potent complex M7 revealed that it exerted its antibacterial activity by inhibiting the function of FtsZ and perturbing the localization of the Z‐ring at the mid cell.
Synthesis of 1,6/7‐(NO2)2‐Perylenediimide and 1,6/7‐(NH2)2‐Perylenediimide as Regioisomerically Pure Materials**
Authors: Gapin Adèle , David Arthur H. G. , Allain Magali , Masson Dorian , Alévêque Olivier , Ave Thomas , Le Bras Laura , Hudhomme Piétrick , Goujon Antoine
Published: April 2023

The use of perylenediimide (PDI) building blocks in materials for organic electronic is of considerable interest. This popular n‐type organic semiconductor is tuned by introducing peripheral groups in their ortho and bay positions. Such modifications radically alter their optoelectronic properties. In this article, we describe an efficient method to afford regioisomerically pure 1,6/7‐(NO2)2‐ and (NH2)2‐PDIs employing two key steps: the selective crystallization of 1,6‐(NO2)2‐perylene‐3,4,9,10‐tetracarboxy tetrabutylester and the nitration of regiopure 1,7‐Br2‐PDI with silver nitrite. The optoelectronic properties of the resulting regioisomerically pure dinitro, diamino‐PDIs and bisazacoronenediimides (BACDs) are reported and demonstrate the need to separate both regioisomers of such n‐type organic semiconductors for their inclusion in advanced optoelectronic devices. For the first time, the two regioisomers of the same PDI starting material are available on the multigram scale, which will stimulate the exploration of regioisomerism/properties relationship for this family of dyes.
Efficient and Low‐Impact Acetalization Reactions in Deep Eutectic Solvents
Authors: Arnodo Davide , Meazzo Carolina , Baldino Salvatore , Blangetti Marco , Prandi Cristina
Published: April 2023

The synthesis of acetals in acidic natural deep eutectic solvents (NADES), in which the solvent itself participates in the catalytic promotion of the reaction, is reported herein. The reaction is performed under feasible conditions, open air, without the need of external additives, catalysts or water‐removing techniques, and it is wide in scope. The products are easily recovered, and the reaction medium is fully recycled and reused without weakening of its catalytic activity after 10 times. Remarkably, the entire process has been realized on gram scale.
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

With 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 detection

Basic Protocol 2: ntLink scaffolding with gap‐filling

Basic Protocol 3: Running in‐code iterations of ntLink scaffolding

Alternate Protocol 1: Generating long‐read to contig mappings with ntLink

Alternate Protocol 2: Using ntLink mappings for genome assembly correction with Tigmint‐long

Support Protocol: Installing ntLink
One‐Flask Synthesis of Cyclic Diguanosine Monophosphate (c‐di‐GMP)
Authors: Gaffney Barbara L. , Jones Roger A.
Published: April 2023

The 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

Despite 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

Burying 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

In 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

Climate 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

Aims

Given 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 results

The 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.

Conclusions

Our 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

Aims

The 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 results

A 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).

Conclusions

Empagliflozin 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

Aims

The 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 results

A 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).

Conclusions

In 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

Aims

The 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 results

The 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.

Conclusions

The 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

Nowadays, 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.

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Preparation and flocculation effect of copper ion imprinted chitosan flocculant
Authors: Feng Ying , Xie Yuju , Li Qixue , Zhao Mengjie , Cui Qian , Zhang Jianwei , Dong Xin
Published: April 2023

A copper ion imprinted chitosan flocculant (Cu2+@CTS) was synthesized by the molecular imprinting technique to improve the flocculation selectivity of chitosan to heavy metal ions. The effects of the amount of crosslinking agent, crosslinking time, temperature on the properties of the material were systematically investigated. Under the optimum preparation conditions, the flocculation rate and removal rate of Cu2+@CTS were 98.26% and 88.4%, respectively, 2.85 and 3.86 times higher than that of the unprinted chitosan flocculant. On this basis, the flocculation selectivity of Cu2+@CTS to Cu2+ in the presence of Zn2+, Ni2+ and other competitive ions was further explored. The experimental results indicated the removal rate of Cu2+ by Cu2+@CTS was as high as 70%–85%, which was 2.2–2.7 times that of other ions, while the removal rate of three metal ions by non‐imprinted chitosan flocculants was less than 35%. This study provided a reference for improving the selectivity of chitosan‐based flocculant to Cu2+.
Neurocysticercosis and epilepsy: Imaging and clinical characteristics
Authors: Rodríguez‐Leyva Ildefonso , Cantú‐Flores Karla , Domínguez‐Frausto Arturo , Vaudano Anna Elisabetta , Archer John , Bernhardt Boris , Caciagli Lorenzo , Cendes Fernando , Chinvarun Yotin , Federico Paolo , Gaillard William D. , Kobayashi Eliane , Ogbole Godwin , Rampp Stefan , Wang Irene , Wang Shuang , Concha Luis
Published: April 2023

The ILAE Neuroimaging Task Force aimed to publish educational case reports highlighting basic aspects related to neuroimaging in epilepsy consistent with the educational mission of the ILAE. Neurocysticercosis (NCC) is highly endemic in resource‐limited countries and increasingly more often seen in non‐endemic regions due to migration. Cysts with larva of the tapeworm Taenia solium lodge in the brain and cause several neurological conditions, of which seizures are the most common. There is great heterogeneity in the clinical presentation of neurocysticercosis because cysts vary in number, larval stage, and location among patients. We here present two illustrative cases with different clinical features to highlight the varying severity of symptoms secondary to this parasitic infestation. We also present several examples of imaging characteristics of the disease at various stages, which emphasize the central role of neuroimaging in the diagnosis of neurocysticercosis.
Seismic risk scenario for the historical centre of castelpoto in Southern Italy
Authors: Formisano Antonio , Chieffo Nicola , Asteris Panagiotis G. , Lourenço Paulo B.
Published: April 2023

The study proposed a seismic vulnerability methodology applied to the historical centre of Castelpoto, located in the province of Benevento (Southern Italy). The seismic vulnerability of the examined aggregates was examined using an index‐based procedure specifically developed for structural masonry compounds. The structural details and specific characteristics of building aggregates are crucial in determining the seismic vulnerability of buildings in urban environments. Parameters such as the plan configuration, size, and layout of buildings, including the thickness, height of the masonry walls and the connections among different components of the construction, were appropriately considered, since all might have an impact on their seismic performance. Furthermore, the type of masonry, the strength and composition of the mortar, as well as the quality of constructions, can also contribute to the global seismic performance of buildings. These structural parameters, collected in the used form, were correlated to the Masonry Quality Index (MQI) to provide an exhaustive assessment of the capacity (in‐plane and out‐of‐plane mechanisms) of the bearing elements towards seismic loads. Secondly, the susceptibility to damage of the existing building stock was evaluated by applying a parametric simulation of damage scenarios adopting an appropriate Intensity Prediction Equation (IPE). To this purpose, fault models were acquired from the Database of Individual Seismogenic Sources (DISS) and the considered IPE was validated according to the Italian Macroseismic Database (DBMI). Thus, the proposed research aims to highlight how an accurate assessment of masonry strength is crucial during the inspection phase to optimise the prediction of the expected damage scenario allowing for effective risk mitigation in urbanised contexts.
Default return spread: A powerful predictor of crude oil price returns
Authors: Han Qingxiang , He Mengxi , Zhang Yaojie , Umar Muhammad
Published: April 2023

This paper uses the default return spread (DFR) to predict crude oil price returns over the period January 1986 through December 2020. Results of in‐sample and out‐of‐sample analyses show that the DFR can predict oil price returns and significantly outperform the benchmark and other competing variables. In an asset allocation exercise, a mean–variance investor can obtain considerable certainty equivalent return (CER) gains based on the return forecasts of DFR relative to the benchmark. We also perform a series of robustness tests to confirm our previous conclusion. We further investigate the source of the DFR's predictive ability from oil market sentiment, in which we provide some theoretical basis to explain.
Hydrocarbon dominant migration direction and accumulation mode in Qijiang area, Sichuan Basin, China
Authors: Cheng Xiaoyun , Ding Wenlong , Li Yuntao , Liu Tianshun , Shi Siyu
Published: April 2023

The high‐quality hydrocarbon source rocks developed in the Longtan Formation of the Qijiang area and the good reservoir capacity of the overlying dolomite of the Jialingjiang Formation indicate that the area has great exploration potential. To clarify the hydrocarbon migration and accumulation characteristics of the area, the fluid potential of the Longtan Formation in the Qijiang area in the Early Jurassic was determined. The direction of the maximum negative gradient of the fluid potential indicates the direction of the primary migration of hydrocarbons, and the structural ridge theory is used to analyse the direction of the secondary migration of hydrocarbons. The results show that the fluid potential of the hydrocarbon source rocks of the Longtan Formation in the Early Jurassic is characterized by the alternate distribution of high potential zones and low‐potential zones. The central syncline, eastern syncline and western syncline are drainage zones and high potential zones, while the Shiyougou structural belt and Fo'er Ya structural belt are supply zones and low‐potential zones. The oil and gas fluids migrate from the east–west direction to the anticlinal zone for the primary migration; the structural ridge controls the secondary migration of oil and gas in the low‐potential area along the north–south direction, resulting in a zonal distribution of oil and gas traps along the structural ridge. By combining fluid potential and structural ridge characteristics to determine the dominant direction of primary and secondary hydrocarbon migration, a model of hydrocarbon migration and accumulation in the Qijiang area is developed, which provides an important basis for finding hydrocarbon reservoirs.
A zircon classification scheme for sedimentary provenance analysis using radiation damage
Authors: Shi Guanzhong , Shen Chuanbo , Wauschkuhn Bastian , Härtel Birk , Ratschbacher Lothar , Xia Bin , Ge Xiang , Zeng Xiaowei , Fu Hongyang
Published: April 2023

Detrital single‐grain zircon U–Pb geochronology is a powerful tool for provenance studies if information on the source rocks is available. This paper proposes a new source‐rock classification tool that uses the degree of annealing of radiation damage in detrital zircon; the annealing is expressed by the relationship between the width (full‐width at half‐maximum; FWHM) of the v3[SiO4] Raman band at ~1008 cm−1 and the calculated α‐dose. The host rocks of the zircons are classified into three types according to their emplacement process and/or thermal history: volcanic and rapidly cooled plutonic and high‐grade metamorphic rocks (type 1); rocks with hydrothermal zircons (type 2); slowly cooled igneous and metamorphic rocks (type 3). We construct a naive Bayes prediction model by training it with a collection of zircons of known types. The unknown zircons are assigned a probability of derivation from a specific host‐rock type. This classification scheme is best used as an accessory tool in provenance studies that apply detrital zircon U–Pb geochronology.
Late Cretaceous stratigraphic division in the northwestern Songliao Basin, Northeast China: Evidence from palaeontology and palaeomagnetism
Authors: Wang Wendong , He Fubing , Guo Hongyu , Xu Jianxin , Zhao Jiaqi , Chen Hongpeng , Chen Yang , Zhou Long , Wang Zhenjie , Zhou Zhiguang
Published: April 2023

This paper combines new palaeomagnetic studies, palaeontological dating, and sedimentary analyses to propose a modified stratigraphic classification scheme in the northwestern Songliao Basin, which is of great significance for stratigraphic correlation, sedimentation analysis, basinal subsidence, and oil and gas exploration. New palaeontological and palaeomagnetic evidence redefined a group of semi‐consolidated lacustrine strata, buried beneath the Quaternary Yaluhe Formation on the Western Slope of the Songliao Basin, as Late Cretaceous, not the Middle Pleistocene. The chronostratigraphic framework re‐evaluates its stratigraphic age as late Coniacian to early Campanian (Late Cretaceous), between 83 and 85 Ma. Sedimentation research from 17 boreholes on the Western Slope of the Songliao Basin displays that the semi‐consolidated strata successively experienced lacustrine and delta facies deposits. Comparison of this new stratigraphy with the Late Cretaceous sequences on the adjacent Central Depression of the Songliao Basin reveals significant variations in lithology and palynological assemblages. Three new palynological assemblages are also reported from the Late Cretaceous sequences of the Songliao Basin.
Identifying hydrologic signatures associated with streamflow depletion caused by groundwater pumping
Authors: Lapides Dana A. , Zipper Sam , Hammond John C.
Published: April 2023

Groundwater pumping can reduce streamflow in nearby waterways (‘streamflow depletion’), a process which must be accounted for in integrated management of surface and groundwater resources. However, causal identification of streamflow depletion from hydrographs alone is challenging because pumping impacts are masked by other drivers of hydrologic variability. To identify potential indicators of streamflow depletion, we used synthetic hydrographs and an analytical streamflow depletion model to assess potential pumping impacts on specific hydrograph characteristics (‘hydrologic signatures’) for 215 streamgages spanning the conterminous United States (CONUS). We found that streamflow depletion commonly impacts signatures associated with seasonal and annual low flows and low flow recessions. The largest impacts occurred during dry years, suggesting streamflow depletion may be evident in dry years even where impacts are unmeasurable in wet years. Random forest models indicated that streamflow depletion could significantly impact Annual, Summer, and Fall signatures in most streams. Our finding that multiple hydrologic signatures are consistently responsive to streamflow depletion across CONUS suggests that the underlying hydrological processes linking pumping to streamflow reductions are consistent across diverse settings, information that will aid in identifying indicators of streamflow depletion from streamflow hydrographs.
Hydrological response of a headwater catchment in Southeast Brazil—Threshold patterns of stormflow response
Authors: Chittolina Mariane , da Rocha Humberto Ribeiro , Domingues Leonardo Moreno , de Araújo Lobo Gré
Published: April 2023

Headwater catchments are essential water sources for sustaining low flow in downstream rivers. The montane region of Serra da Mantiqueira in Southeast Brazil is the largest water supplier for the densely populated area of São Paulo, where we investigated the hydrological response of a subtropical catchment and four of its sub‐catchments. We discussed the relationships between rainfall, streamflow, baseflow, stormflow, soil moisture, and water table depth using high‐frequency field observations over 4 years. Baseflow accounted for most of the streamflow during the dry season and for half of streamflow in the wet season. In contrast, the variations in soil moisture were dampened, with increases in the early wet season preceding the increase in streamflow and decreases in the late wet season following the decrease in streamflow. The mean runoff coefficient and baseflow index varied from 23% to 37% and from 62% to 75% across the catchments, respectively. At the event scale, all catchments had a pronounced threshold behaviour, where stormflow increased sharply when event precipitation reached ≃10 mm, soil moisture reached ≃51% and water table depth decreased to ≃135 cm. The event stormflow coefficient was highly variable, with a maximum of 25%. The temporally integrated stormflow coefficient was low for conditions below a soil moisture threshold (≃3%–10%) and high above a soil moisture threshold (≃8%–15%). Our estimates of flows and threshold behaviours were consistent across the various study catchments, improving our understanding of runoff generation at a catchment scale. This information should help improve the management of water resources focused on water and food security in a context of climate change.
An empirical investigation of the relationship between real exchange rate and innovation: Evidence from China
Authors: Wen Jun , Usman Muhammad Ahmad
Published: April 2023

The aims of this study is to investigate the relationship between real exchange rate and innovation in China for the period spanning from 1985 to 2020 using an annual time series data collected from different sources. The study employs autoregressive distributed lag bound test and other econometrics techniques to analyse the short‐run and long‐run relationship among the variables. The findings of the study reveal the existence of short‐run and long‐run relationship between real exchange rate (undervalued RMB) and technological innovation. Furthermore, real exchange rate (undervalued RMB) has positive effect on innovation while real exchange rate volatility is negatively affect innovation. Based on the above empirical findings, the study suggests some policy implications which are considered important for fostering rapid and sustainable economic growth.