bluuebunny/crossref_metadata_2025 huggingface dataset:
The dual GCGR/GLP‐1R agonist survodutide: Biomarkers and pharmacological profiling for clinical candidate selection
Authors: Thomas Leo , Martel Eric , Rist Wolfgang , Uphues Ingo , Hamprecht Dieter , Neubauer Heike , Augustin Robert
Published: April 2024

Aim

To describe the biomarker strategy that was applied to select survodutide (BI 456906), BI 456908 and BI 456897 from 19 dual glucagon receptor (GCGR)/ glucagon‐like peptide‐1 receptor (GLP‐1R) agonists for in‐depth pharmacological profiling, which led to the qualification of survodutide as the clinical development candidate.

Materials and Methods

Potencies to increase cyclic adenosine monophosphate (cAMP) were determined in Chinese hamster ovary (CHO)‐K1 cells stably expressing human GCGR and GLP‐1R. Agonism for endogenously expressed receptors was investigated in insulinoma cells (MIN6) for mouse GLP‐1R, and in rat primary hepatocytes for the GCGR. In vivo potencies to engage the GLP‐1R or GCGR were determined, measuring improvement in oral glucose tolerance (30 nmol/kg) and increase in plasma fibroblast growth factor‐21 (FGF21) and liver nicotinamide N‐methyltransferase (NNMT) mRNA expression (100 nmol/kg), respectively. Body weight‐ and glucose‐lowering efficacies were investigated in diet‐induced obese (DIO) mice and diabetic db/db mice, respectively.

Results

Upon acute dosing in lean mice, target engagement biomarkers for the GCGR and GLP‐1R demonstrated a significant correlation (Spearman correlation coefficient with p < 0.05) to the in vitro GCGR and GLP‐1R potencies for the 19 dual agonists investigated. Survodutide, BI 456908 and BI 456897 were selected for in‐depth pharmacological profiling based on the significant improvement in acute oral glucose tolerance achieved (area under the curve [AUC] of 54%, 57% and 60% vs. vehicle) that was comparable to semaglutide (AUC of 45% vs. vehicle), while showing different degrees of in vivo GCGR engagement, as determined by hepatic NNMT mRNA expression (increased by 15‐ to 17‐fold vs. vehicle) and plasma FGF21 concentrations (increased by up to sevenfold vs. vehicle). In DIO mice, survodutide (30 nmol/kg/once daily), BI 456908 (30 nmol/kg/once daily) and BI 456897 (10 nmol/kg/once daily) achieved a body weight‐lowering efficacy from baseline of 25%, 27% and 26%, respectively. In db/db mice, survodutide and BI 456908 (10 and 20 nmol/kg/once daily) significantly lowered glycated haemoglobin (0.4%–0.6%); no significant effect was observed for BI 456897 (3 and 7 nmol/kg/once daily).

Conclusions

Survodutide was selected as the clinical candidate based on its balanced dual GCGR/GLP‐1R pharmacology, engaging the GCGR for robust body weight‐lowering efficacy exceeding that of selective GLP‐1R agonists, while achieving antidiabetic efficacy that was comparable to selective GLP‐1R agonism. Survodutide is currently being investigated in Phase 3 clinical trials in people living with obesity.
Left atrial reservoir longitudinal strain and its incremental value to the left ventricular global longitudinal strain in predicting anthracycline‐induced cardiotoxicity
Authors: Li Zheng , Zhao Rui , Zhang Qunling , Shen Yihui , Shu Xianhong , Cheng Leilei
Published: April 2024

Background

Left ventricular global longitudinal strain (LVGLS) has been recommended by current guidelines for diagnosing anthracycline‐induced cardiotoxicity. However, little is known about the early changes in left atrial (LA) morphology and function in this population. Our study aimed to evaluate the potential usefulness of LA indices and their incremental value to LVGLS with three‐dimensional echocardiography (3DE) in the early detection of subclinical cardiotoxicity in patients with lymphoma receiving anthracycline.

Methods

A total of 80 patients with diffuse large B‐cell lymphoma who received six cycles of anthracycline‐based treatment were enrolled. Echocardiography was performed at baseline (T0), after four cycles (T1), and after the completion of six cycles of chemotherapy (T2). Left ventricular ejection fraction (LVEF), LVGLS, LA volumes, LA emptying fraction (LAEF), LA active emptying fraction (LAAEF), and LA reservoir longitudinal strain (LASr) were quantified with 3DE. Left atrioventricular global longitudinal strain (LAVGLS) was calculated as the sum of peak LASr and the absolute value of peak LVGLS (LAVGLS = LASr+|LVGLS|). LV cardiotoxicity was defined as a new LVEF reduction by ≥10 percentage points to an LVEF of ≤50%.

Results

Fourteen (17.5%) patients developed LV cardiotoxicity at T2. LA volumes, LAEF, and LAAEF remained stable over time. Impairment of LASr (28.35 ± 5.03 vs. 25.04 ± 4.10, p < .001), LVGLS (–22.77 ± 2.45 vs. –20.44 ± 2.62, p < .001), and LAVGLS (51.12 ± 5.63 vs. 45.61 ± 5.22, p < .001) was observed by the end of the fourth cycle of chemotherapy (T1). Statistically significant declines in LVEF (61.30 ± 4.73 vs. 57.08 ± 5.83, p < .001) were only observed at T2. The relative decrease in LASr (ΔLASr), LVGLS (ΔLVGLS), and LAVGLS (ΔLAVGLS) from T0 to T1 were predictors of LV cardiotoxicity. A ΔLASr of >19.75% (sensitivity, 71.4%; specificity, 87.9%; area under the curve (AUC), .842; p < .001), a ΔLVGLS of >13.19% (sensitivity, 78.6%; specificity, 74.2%; AUC, .763; p < .001), and a ΔLAVGLS of >16.80% (sensitivity, 78.6%; specificity, 93.9%; AUC, .905; p < .001) predicted subsequent LV cardiotoxicity at T2, with the AUC of ΔLAVGLS significantly larger than that of ΔLVGLS (.905 vs. .763, p = .027). Compared to ΔLVGLS, ΔLAVGLS showed improved specificity (93.9% vs. 74.2%, p = .002) and maintained sensitivity in predicting LV cardiotoxicity.

Conclusions

LASr could predict anthracycline‐induced LV cardiotoxicity with excellent diagnostic performance. Incorporating LASr into LVGLS (LAVGLS) led to a significantly improved specificity and maintained sensitivity in predicting LV cardiotoxicity.
Developmental coordination disorder in preterm children: A systematic review and meta‐analysis
Authors: Panceri Carolina , Sbruzzi Graciele , Zanella Larissa W. , Wiltgen Andressa , Procianoy Renato S. , Silveira Rita C. , Valentini Nadia C.
Published: April 2024

This study aimed to review the prevalence of developmental coordination disorder (DCD) in individuals born preterm and systematically explore this prevalence according to gestational age and different assessment cut‐offs and compare it to full‐term peers. The eligibility criteria were observational and experimental studies reporting the prevalence of DCD in preterm individuals. A systematic search was performed in databases from inception until March 2022. Two independent reviewers performed the selection. Study quality assessment was performed using the checklists from Joanna Briggs Institute (JBI). Data analysis was performed on Excel and Review Manager Software 5.4. Among the 1774 studies identified, 32 matched the eligibility criteria. The pooled estimate rate of the DCD rate in preterm was 21% (95% confidence interval [CI] 17.8–24.3). The estimate rates were higher as gestational age decreased, and preterm children are two times more likely to have DCD than their full‐term peers risk ratio (RR) 2.2 (95% CI 1.77–2.79). The limitation was high heterogeneity between studies; the assessment tools, cut‐off points and age at assessment were diverse. This study provided evidence that preterm children are at higher risk for DCD than full‐term children, and the risks increased as gestational age decreased.
Against “silent” retractions in neuroscience
Authors: Teixeira da Silva Jaime A. , Daly Timothy
Published: April 2024

When an academic paper is published in a journal that assigns a digital object identifier (DOI) to papers, this is a de facto fait accompli. Corrections or retractions are supposed to follow a specific protocol, especially in journals that claim to follow the Committee on Publication Ethics (COPE) guidelines. In this paper, we highlight a case of a new, fully open access neuroscience journal that claims to be COPE‐compliant, yet has silently retracted two papers since all records, bibliometrics, and PDF files related to their existence have been deleted from the journal's website. Although this phenomenon does not seem to be common in the neurosciences, we consider that any opaque corrective measures in journals whose papers could be cited may negatively impact the wider neuroscience literature and community. Instead, we encourage transparency in retraction to promote truthfulness and trustworthiness.
Antiganglioside antibody frequency in routine clinical care settings
Authors: Giesche Niklas , Böhm‐Gonzalez Samuel Tobias , Kleiser Benedict , Kowarik Markus C. , Dubois Evelyn , Stransky Elke , Armbruster Marcel , Grimm Alexander , Marquetand Justus
Published: April 2024

Background and purpose

Antiganglioside antibodies (AGAs) might be involved in the etiopathogenesis of many neurological diseases, such as Miller–Fisher syndrome (MFS) and Guillain–Barré syndrome (GBS). Available comprehensive reference data regarding AGA positivity rates and cross‐responsiveness among AGAs (where one line immunoblot is positive for ≥1 AGA) during routine clinical care are scant.

Methods

In this 10‐year monocentric retrospective study, 3560 immunoglobulin (Ig) G and IgM line blots (GA Generic Assays' Anti‐Ganglioside Dot kit) obtained using cerebrospinal fluid (CSF) and serum samples from 1342 patients were analyzed for AGA positivity in terms of 14 diagnosis categories and AGA cross‐responsiveness.

Results

Of all 3560 line blots 158 (4.4%) and of all CSF samples 0.4% (4/924) CSF line blots were AGA positive. For serum IgG, blots with positivity rates higher than the standard deviation of 15.6% were associated with MFS (GD3, GD1a, GT1a and GQ1b) and acute motor axonal neuropathy (AMAN) (GM1, GD1a and GT1a). For serum IgM, blots with positivity rates higher than the standard deviation of 8.1% were associated with AMAN (GM2, GT1a and GQ1b), MFS (GM1, GT1a and GQ1b), multifocal motor neuropathy (MMN) (GM1, GM2 and GQ1b) and chronic inflammatory demyelinating polyneuropathy (CIDP) (GM1). Cross‐responsiveness was observed in 39.6% of all positive serum AGA.

Conclusions

Testing for AGAs during routine clinical care rarely led to positive findings, both in serum and even less in CSF, except for the diagnoses AMAN, MFS, MMN and CIDP. Nonspecific findings found as cross‐responsiveness between different AGA samples occur frequently, impacting the positivity of most AGA subtypes.
Health care utilization of Hispanic/Latino veterans with epilepsy: A national population‐based study
Authors: Tantillo Gabriela B. , Sullivan‐Baca Erin , Rehman Rizwana , López María Raquel , Haneef Zulfi
Published: April 2024

Objective

Hispanic/Latino people with epilepsy are a growing population that has been understudied in clinical epilepsy research. U.S. veterans are at a higher risk of epilepsy due to greater exposures including traumatic brain injury. Hispanic/Latino Veterans with Epilepsy (HL‐VWEs) represent a growing population; however the treatment utilization patterns of this population have been vastly understudied.

Methods

HL‐VWE were identified from administrative databases during fiscal year 2019. Variables compared between Hispanic and non‐Hispanic VWEs included demographics, rurality, service era, utilization of clinical services/investigations, and service‐connected injury. Chi‐square and Student's t tests were used for comparisons.

Results

Among 56 556 VWEs, 3247 (5.7%) were HL. HL‐VWEs were younger (59.2 vs 63.2 years; p < .01) and more commonly urban‐dwelling (81.6% vs 63.2%, p < .01) compared to non–HL‐VWEs. They were also more likely to have served in recent missions such as the Persian Gulf War and post‐ 9/11 wars (p < .01). HL‐VWEs had a higher utilization of all neurology services examined including neurology clinic visits, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, electroencephalography (EEG), epilepsy monitoring, and comprehensive epilepsy care (p < .01 for all). HL‐VWEs were more likely to visit an emergency room or have seizure‐related hospitalizations (p < .01). HL‐VWEs were more likely to have a service‐connected disability greater or equal to 50% (p < .01).

Significance

This study is one of the largest cohorts examining HL‐VWEs. We found higher utilization of services in neurology, epilepsy, and neuroimaging by HL‐VWEs. HL‐VWE are younger, more commonly urban‐dwelling, and more likely to have served during recent combat periods and have higher amounts of service‐connected disability. Given that the proportion of Hispanic veterans is projected to rise over time, more research is needed to provide the best interventions and mitigate the long‐term impact of epilepsy on this diverse patient group.
Multi‐focal channel attention for medical image segmentation
Authors: Al Jowair Hamdan , Alsulaiman Mansour , Muhammad Ghulam
Published: April 2024

Medical image segmentation through the use of deep learning is becoming a trend targeting to automate disease detection and provide effective treatment. Traditionally huge manual efforts are associated with medical image processing by medical staff. The wide use of neural networks driven by the progressive advancement in computing power and the availability of training data provides instrumental means to automate medical image processing. A polyp refers to an abnormal growth that can occur in various parts of the body. While the majority of polyps are noncancerous or benign, there are instances where certain types can develop into cancer. Detecting and segmenting polyps is highly valuable for identifying early signs and potentially enabling more effective treatment of colon cancer. In this paper, we introduce a novel method for segmenting polyp images. The proposed method utilizes convolutional neural networks (CNNs) and employs an enhanced attention mechanism. To cater to a more granular attention view, this paper enhances the Convolutional Block Attention Module by introducing the multi‐focal channel attention (MFCA) concept, which we call MFCA. In the proposed MFCA channel attention, focal attention spots allow us to consider scattered areas of interest more effectively. To evaluate the effectiveness of the proposed method, multiple experiments are conducted on five well‐known benchmark datasets for polyp image segmentation: Kvasir, CVC‐Clinic DB, CVC‐Colon DB, CVC‐T, and ETIS‐Larib. Various testing scenarios are examined, including the impact of two focal attention spots and four focal attention spots. The experimental results demonstrated that the proposed method achieved superior performance compared to previous state‐of‐the‐art techniques on two of the benchmark datasets, and ranked second on a third dataset.
2D and 3D characterization of oxidation‐fatigue mechanisms in an advanced Ni‐based superalloy: Effects of microstructure and elevated temperature
Authors: Kim Donghyuk , Jiang Rong , Reed Philippa A. S.
Published: April 2024

The effects of varying γ′ size and grain boundary carbide distribution at elevated temperatures on the fatigue behavior of turbine disk alloy RR1000 were examined through combining 2D and 3D imaging characterization. The fatigue crack growth rate at 725°C is higher than at 650°C due to enhanced oxidation damage at higher temperature, dominated by an intergranular fracture mode. This is more marked with longer dwell time (linked to diffusion time) and when carbides have formed continuously at grain boundaries. The fatigue crack path was characterized by X‐ray CT scan to present the complex 3D crack propagation morphology. It is noted that a discontinuous crack path and uncracked ligaments can be discerned ahead of the crack tip particularly in the microstructure where carbides are continuously formed at grain boundaries. This is linked to embrittled zones ahead of the crack tip formed during longer dwell times at the maximum stress during cycling at elevated temperature.
Trade credit and corporate digital transformation: The role of managerial ability
Authors: Wang Liukai , Wang Caiting , Yarovaya Larisa , Huang Heshu
Published: April 2024

We examine whether managerial ability affects the relationship between corporate digital transformation and trade credit. To measure digital transformation, we perform a textual analysis of companies’ annual reports using a customized Chinese dictionary containing digital transformation keywords based on national policy documents and academic literature. Using 10,554 observations from 2509 A‐shares listed companies in China, we show that corporate digital transformation has significantly impacted trade credit. Managerial ability enhances the relationship between digital transformation and received trade credit but does not change the impact between digital transformation and provided trade credit. A battery of robustness tests confirms the findings.
Shaded streams with permeable watersheds provide naturally resilient fish habitat refugia during heatwaves
Authors: Kelly Seán , Kelly Fiona L.
Published: April 2024

Streamflow, dissolved oxygen, and water temperature underpin stream fish habitat suitability, so climate change could cause widespread habitat deterioration. Identifying stream characteristics that mediate habitat resilience to heatwaves will allow conservation effort prioritisation. Here, a set of readily applied metrics were used to assess hydrological and oxythermal responses of neighbouring salmonid streams, with distinctive geologies, soil‐types, and localised riparian shading, to periods of anomalously warm conditions. During heatwaves, low flows, warm‐water temperatures, and diel oxygen variability, associated with biogenic production and respiration, predominated. In a low‐shade stream lacking significant catchment water storage, high daytime (>22°C) and night‐time (>19°C) water temperatures and low early morning O2 concentrations (<5 mg L−1) accumulated oxythermal stress for salmonids throughout summer. A stream with localised shading and a higher proportion of underlying aquifers and permeable soils throughout its watershed experienced considerably less cumulative oxythermal stress (O2 > 6 mg L−1; temperatures <19°C), whilst slower release of subsurface water bolstered base flows during dry spells. Our findings support conservation of shaded streams with permeable watersheds characterised by higher soil infiltration rates and aquifer storage capacity as salmonid sanctuaries under a warmer, drier summer climate. Preventing water quality and hydromorphological deterioration are paramount for safeguarding their role as climate refugia.
Incidence of hyperkalemia in anuric hemodialysis patients treated with sacubitril/valsartan
Authors: Li Xiaofan , Ma Fei , Wang Yan , Zhao Haidan , Gao Jianjun
Published: April 2024

Introduction

Sacubitril/valsartan is increasingly used in hemodialysis patients due to its cardioprotective benefits. However, its impact on serum potassium levels in anuric patients undergoing hemodialysis remains controversial.

Methods

We conducted a retrospective data from patients undergoing hemodialysis at two dialysis centers. A total of 71 out of 332 patients receiving hemodialysis treatment were enrolled. Mean serum potassium (mean value of 6–8 determinations), peak serum potassium (maximum K value observed during follow‐up observations), and other biochemical parameters were recorded at baseline and during the follow‐up period.

Findings

After 6 months of follow‐up, mean serum potassium increased from 4.84 ± 0.45 mmol/L at baseline to 5.07 ± 0.46 mmol/L at 3 months and 5.04 ± 0.46 mmol/L at 6 months (p < 0.001). Notably, no significant group differences were found in peak serum potassium concentrations between baseline and 6 months after sacubitril/valsartan therapy (5.69 ± 0.56 vs. 5.75 ± 0.41, p = 0.419). Prior to starting sacubitril/valsartan treatment, none of the patients had severe hyperkalemia; however, after 3 and 6 months of sacubitril/valsartan therapy, two (2.80%) and three (4.20%) patients experienced severe hyperkalemia, respectively; however, this difference was not statistically significant. Additionally, there was a significant reduction in blood pressure; however, serum sodium, bicarbonate, and Kt/V values did not change significantly during either period.

Discussion

Sacubitril/valsartan therapy is associated with an increase in serum potassium levels in anuric hemodialysis patients. Nevertheless, the proportion of patients with severe hyperkalemia did not increase significantly. This suggests that the use of sacubitril/valsartan in anuric patients on hemodialysis is relatively safe.
The application of targeted RNA sequencing for the analysis of fusion genes, gene mutations, IKZF1 intragenic deletion, and CRLF2 overexpression in acute lymphoblastic leukemia
Authors: Zhang Zhenyu , Jing Yu , Chen Bin , Zhang Hong , Liu Tuo , Dong Shuran , Zhang Lei , Yan Xiaoyan , Yang Shaobin , Chen Long , Lin Yani , Ru Kun
Published: March 2024

Introduction

Acute lymphoblastic leukemia (ALL) is characterized by highly genetic heterogeneity, owing to recurrent fusion genes, gene mutations, intragenic deletion, and gene overexpression, which poses significant challenges in clinical detection. RNA sequencing (RNA‐seq) is a powerful tool for detecting multiple genetic abnormalities, especially cryptic gene rearrangements, in a single test.

Methods

Sixty samples (B‐ALL, n = 49; T‐ALL, n = 9; mixed phenotype acute leukemia (MPAL), n = 2) and 20 controls were analyzed by targeted RNA‐seq panel of 507 genes developed by our lab. Of these, 16 patients were simultaneously analyzed for gene mutations at the DNA level using a next‐generation sequencing panel of 51 genes. Fusion genes, CRLF2 expression, and IKZF1 intragenic deletion were also detected by reverse transcription‐polymerase chain reaction (RT‐PCR). Karyotype analysis was performed using the R‐banding and G‐banding technique on bone marrow cells after 24 hours of culture. Partial fusion genes were analyzed using fluorescence in situ hybridization (FISH).

Results

Compared with the results of Karyotype analysis, FISH, and RT‐PCR, the detection rate of fusion genes by targeted RNA‐seq increased from 48.3% to 58.3%, and six unexpected fusion genes were discovered, along with one rare isoform of IKZF1 intragenic deletion (IK10). The DNA sequencing analysis of 16 ALL patients revealed that 96.2% (25/26) of gene mutations identified at the DNA level were also detectable at the RNA level, except for one mutation with a low variant allele fraction. The detection of CRLF2 overexpression exhibited complete concordance between RT‐PCR and RNA‐seq.

Conclusion

The utilization of RNA‐seq enables the identification of clinically significant genetic abnormalities that may go undetected through conventional detection methods. Its robust analytical performance might bring great application value for clinical diagnosis, prognosis, and therapy in ALL.
Coinfection of Influenza A and B and Human OC43 Coronavirus in Normal Human Bronchial Epithelial Cells
Authors: Kim JungHyun , Hickerson Brady T. , Ilyushina Natalia A.
Published: April 2024

Background

Influenza viruses and seasonal coronaviruses are pathogens transmitted via an airborne route that can cause respiratory diseases in humans that have similar symptoms such as fever, cough, and pneumonia. These two viruses can infect similar human tissues, such as the respiratory tract and nasal, bronchial, and alveolar epithelial cells. Influenza virus and seasonal coronavirus coinfections are poorly understood.

Methods

Here, we coinfected normal human bronchial epithelial (NHBE) cells with influenza A/California/04/09 (IAV) or B/Victoria/504/2000 (IBV) strains and the seasonal human beta‐coronavirus OC43 and evaluated viral replication capacities. We also examined changes in the expression of various cytokines/chemokines by qPCR and Luminex assay.

Results

We observed that the replication of IAV and IBV was not affected by coinfection with OC43. However, coinfection reduced OC43 titers (~3‐fold) compared with infection with OC43 alone. Select cytokine/chemokine expression was increased in coinfected cells compared with all single infections with greater differences seen between coinfected cells and cells infected with OC43 alone compared with IAV‐ or IBV‐infected cells. In addition, IL‐8 and IL‐1RA showed the highest expression among a panel of 22 cytokines by Luminex.

Conclusions

As the rate of influenza and seasonal coronavirus coinfection continue to increase, our findings may help set guidelines for the treatments of the individuals coinfected with both viruses.
Foam structure–derived strong and tough alumina ceramics with fine grains and transgranular fracture
Authors: Zhao Shihui , Qiao Jianli , Sang Guolong , Xi Xiaoqing , Yang Jinlong
Published: April 2024

Controlling the preparation process is essential to ensure the quality of the ceramics. Previous research on the ceramic process concentrated on a certain part of powder synthesis, forming, or sintering. Herein, we propose a novel process, foam precursor–derived Al2O3 ceramics, to realize particle rearrangement, assembly, and sintering and find that this method has a marvelous influence on the microstructure and mechanical properties. Alumina foams prepared by the particle‐stabilized foam method are used as ceramic precursors, and after pre‐sintering, crash, and hot pressing, foam precursor–derived Al2O3 ceramics can be obtained. It has fine grains (1/5 of the traditional process) and uniform grain size without any additional sintering aid, realized by the high grain growth exponent of foams. Ultrahigh dislocation density (∼1010 mm−2) is discovered in (0 0 0 1) plane of foam precursor–derived ceramics, comparable to the dislocation density of high‐entropy ceramics. Besides, transgranular fracture mode is observed in the ceramics prepared by the new method rather than the intergranular fracture in the control group, and the comprehensive mechanical properties are promoted accordingly. The unusual microstructure and fracture mode caused by the foam precursor process reveal the influence of the microstructure such as dislocation and grain boundary on the fracture behavior of ceramics, which is less considered in conventional research. This preparation process may be applied in the preparation of other high‐performance ceramics.
Effect of iron acceptor doping and calcium donor doping in potassium sodium niobate‐based lead‐free piezoceramics
Authors: Azadeh Maryam , Zhao Changhao , Pawadi Apoorva , Gao Shuang , Frömling Till
Published: April 2024

Lead‐free potassium sodium niobate (KNN) ferroelectrics have emerged as promising alternatives to lead‐based materials due to their reduced toxicity and sometimes enhanced properties. The opportunity to modify the ferroelectric properties by doping, nevertheless, differs from lead‐based ceramics. A much lower impact with increasing dopant concentration was observed. This study systematically investigates the differences in defect chemistry of Na0.475K0.475Li0.065Nb0.92Ta0.08O3 ceramics through iron (Fe) acceptor doping and calcium (Ca) donor doping at varying concentrations. From the defect chemical point of view, it becomes evident that the impact of intrinsic defects on the electrical properties exceeds the effect of extrinsic defects induced by doping. The performance of the donor‐doped (Ca2+) ceramics closely resembles that of undoped KNN. Thus, hardly any change in ferroelectric properties and conductivity is observed. For the Fe‐doped samples, the conductivity and its contribution to the dielectric loss increased, which is not to the benefit of an application as a ferroelectric. Therefore, the concepts of “softening” and “hardening” of ferroelectric properties by doping are incompatible with regularly sintered KNN ceramics.
Microscopic effect of iron dosage on the stability of Fe‐doped ettringite
Authors: Bouibes Amine , Laanaiya Majdouline , Lacarrière Laurie
Published: April 2024

One significant aspect that affects the performance of high‐ferrite cement is the incorporation of iron (Fe) atoms and its stabilization into the cement phases. However, the influence of Fe doping on the stability of key phases, particularly on the ettringite, remains largely unexplored requiring deeper insights into the fundamental mechanisms. The present study explored the stability of Fe‐doped AFt structure based on density functional theory calculations at different Fe dosage. The obtained results showed that the stability of AFt structure decreases by increasing Fe dosage, which is in good agreement with the previous experimental observations. The incorporation of Fe into ettringite induced a series of changes in AFt structural and electronic properties. Bond order analysis underscored stronger covalent Fe–O bonds compared to Al–O, further emphasizing changes in the material's bonding network. Notably, density of states (DOS) analysis highlights the emergence of new occupied states near the Fermi level, primarily contributed by Fe and O atoms. This increased DOS, coupled with higher electron mobility, correlates with a reduction in material stability, as observed through shifts in bonding interactions and alterations in the bonding network. These findings point toward a complex interplay of factors, including altered bonding characteristics, increased electron mobility, and changes in the electronic structure, contributing to the observed instability of Fe‐doped ettringite.
Controllable hierarchical Bi2MoO6 spheres with ferroelectric polarization enhanced photocatalytic efficiency
Authors: Hui Kezhen , Zhou Aoqi , Dai Fanqi , Zhang Weichen , Wang Xinxin , Zhao Peiyao , Li Wei , Li Qian , Li Longtu , Guo Limin , Wang Xiaohui
Published: April 2024

The fast recombination of photogenerated electrons and holes remains a major issue in hindering photocatalytic efficiency. Apart from traditional methods, such as rare metal deposition and element doping, the introduction of a built‐in electric field has been proven an efficient way in recent years. Ferroelectrics, which possess spontaneous polarization and associated polarization electric fields, are attracting more attention as photocatalysts. In this study, Bi2MoO6 spheres with different hierarchical upper nanostructures are synthesized through a one‐pot hydrothermal method. With this porous structure and the intrinsic ferroelectricity, BMO spheres present excellent physisorption and photodegradation ability toward dye molecules. After corona poling treatment, the ferroelectric field of the BMO samples was enhanced, and the recombination of charges was suppressed, leading to an obvious increase in photocatalytic rate. The origin BMO‐5 can reach a total degradation of RhB in 20 min, and the polarized BMO‐5 (BMO‐5P) can remove all RhB molecules instantly through the physisorption process. Apart from BMO‐5, other samples also present excellent catalytic behavior. Origin BMO‐2 can fully degrade the RhB in 40 min, and the degradation time of polarized BMO‐2P is 30 min. The hierarchical structure and internal polarized electric field endow BMO spheres with outstanding adsorption purification and photodegradation ability and provide a new comprehensive strategy for the catalyst design.
Using learning analytics to measure self‐regulated learning: A systematic review of empirical studies in higher education
Authors: Alhazbi Saleh , Al‐ali Afnan , Tabassum Aliya , Al‐Ali Abdulla , Al‐Emadi Ahmed , Khattab Tamer , Hasan Mahmood A.
Published: March 2024

Background

Measuring students' self‐regulation skills is essential to understand how they approach their learning tasks in order to identify areas where they might need additional support. Traditionally, self‐report questionnaires and think aloud protocols have been used to measure self‐regulated learning skills (SRL). However, these methods are based on students' interpretation, so they are prone to potential inaccuracy. Recently, there has been a growing interest in utilizing learning analytics (LA) to capture students' self‐regulated learning (SRL) by extracting indicators from their online trace data.

Objectives

This paper aims to identify the indicators and metrics employed by previous studies to measure SRL in higher education. Additionally, the study examined how these measurements were validated.

Methods

Following the protocol of Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA), this study conducted an analysis of 25 articles, published between 2015 and 2022, and sourced from major databases.

Results and Conclusions

The results showed that previous research used a variety of indicators to capture learners' SRL. Most of these indicators are related to time management skills, such as indicators of engagement, regularity, and anti‐procrastination. Furthermore, the study found that the majority of the reviewed studies did not validate the proposed measurements based on any theoretical models. This highlights the importance of fostering closer collaboration between learning analytics and learning science to ensure the extracted indicators accurately represent students' learning processes. Moreover, this collaboration can enhance the validity and reliability of data‐driven approaches, ultimately leading to more meaningful and impactful educational interventions.
Ancestry and genetic structure of resident and anadromous rainbow trout (Oncorhynchus mykiss) in Argentina
Authors: Lázari Carolina , Riva‐Rossi Carla , Ciancio Javier , Pascual Miguel , Clemento Anthony J. , Pearse Devon E. , Garza John Carlos
Published: April 2024

Since the first introduction from North America more than a century ago, rainbow trout (Oncorhynchus mykiss) have rapidly established self‐sustaining populations in major river basins of Patagonia. Many generations later, only the freshwater resident life history is expressed in the Chubut and Negro rivers of northern Argentinian Patagonia, whereas both the resident and anadromous life histories are found in the Santa Cruz River of southern Argentina. Despite previous studies that have tried to identify the sources of these introduced populations, uncertainty still exists. Here we combined data from many single‐nucleotide polymorphisms and microsatellite loci in O. mykiss populations from Argentina and North America to evaluate putative source populations, gene flow between Argentinian river basins, and genetic diversity differences between Argentinian and North American populations. We found that populations from northern and southern Patagonia are highly differentiated and have limited gene flow between them. Phylogeographic analysis also confirmed that they have separate origins, with the northern populations most closely related to the domesticated rainbow trout strains that are raised worldwide and the Santa Cruz River populations most closely related to North American populations from California and Oregon that have an anadromous component. In addition, fish with different life histories in the Santa Cruz River were found to constitute a single interbreeding population. No evidence was found of reduced genetic variation in introduced rainbow trout, suggesting multiple contributing sources. In spite of these advances in understanding, significant questions remain regarding the origins and evolution of the introduced O. mykiss in Patagonia.
Development and optimization of a mechanized jackfruit processing unit for enhanced efficiency and commercial viability
Authors: Shidenur Hareesh , Mathew Santhi Mary , Sagarika Nukasani , Warrier Aswin S. , Harikrishnan M. P. , Pandiselvam R. , Kothakota Anjineyulu
Published: April 2024

The jackfruit is the largest edible fruit but remains underutilized due to challenges such as sticky latex, labor‐intensive peeling/coring, and lack of mechanization. This study developed and evaluated a jackfruit peeling, coring, and cutting machine to enhance processing efficiency. Performance was modeled using response surface methodology (RSM) and artificial neural network (ANN). Three jackfruit sizes (small, medium, and large) and three machine speeds (90, 120, and 150 RPM) were evaluated for peeling time (26.1–50.3 s), peeling efficiency (71.6%–85.3%), coring time (15.5–29.9 s), coring efficiency (74.7%–96.0%), and bulb wastage (6.2%–17.6%). RSM showed high model adequacy (R2 ≥ 0.97) and ANN confirmed prediction reliability (R2 = 0.81–0.99; mean square error = 4.4–44.9). Increasing fruit size significantly increased peeling and coring times but decreased efficiencies. Machine speeds caused minor variations. Optimized conditions of 120 RPM fruit holder speed and 150 RPM corer speed gave maximum desirability (0.869). The machine had a payback period of 2 years and benefit–cost ratio of 2.32 versus 2.66 for manual peeling/coring. The mechanized jackfruit processing will promote enhanced utilization of this nutritious fruit.

Practical applications

The mechanized jackfruit peeling‐coring‐cutting machine developed in this study has significant practical utility. By enabling efficient and rapid processing of jackfruits, the machine can help tap the underutilized potential of this highly nutritious and functionally beneficial fruit. The optimized machine parameters allow jackfruit processing industries to achieve higher throughput with reduced wastage, thereby boosting productivity and profits. Additionally, the mechanization facilitates value‐addition by enabling jackfruit utilization in various processed products like chips, flour, jam, etc. Further, the machine helps create livelihood opportunities in jackfruit value chains, as it reduces drudgery and enhances process efficiency as compared to manual methods. The simple fabrication and operation also enable adoption by farmer‐producer organizations, self‐help groups, and community‐based jackfruit processing enterprises. Overall, the mechanized solution provides an impetus for sustainable utilization of jackfruit, while also addressing issues like food loss, nutrition security, income support, and women empowerment. The practical insights on machine performance modeling using response surface methodology and artificial neural network approaches further facilitate quality improvements in equipment design.
The effect of the combined addition of copper, lithium and sulphur on the formation of Portland cement clinker
Authors: Staněk Theodor , Rybová Alexandra , Boháč Martin , Bartoníčková Eva , Palovčík Jakub
Published: April 2024

Both copper and lithium act as strong fluxes and lower the temperature of the clinker melt formation. Sulphur promotes the stabilisation of more hydraulically active modification of alite M1. It is expected that this combination could produce an alite clinker at significantly lower temperatures with high quality technological parameters. In this paper, the effect of combined oxides of copper, lithium and sulphur addition on the phase composition and clinker structure of Portland cement was investigated. The reference raw meal was prepared from common cement raw materials. Each of the mentioned oxides was added to the reference raw meal in two different concentrations, and 8 combinations were prepared. Chemically pure compounds (NH4)2SO4, CuO and Li2CO3 were used as a source of these oxides. The raw meals were burned to equilibrium at 1450°C. Their phase composition was determined by X‐ray diffraction analysis, the microstructure was monitored by optical microscopy, and the microchemistry of the clinker phases was observed by electron microscopy with EDS analysis. It was found that in samples with high lithium or copper content, there is an increase in belite and free lime at the expense of alite. The combination of Cu + Li has the most negative effect, followed by Li alone and Cu alone. The higher SO3 content slightly offsets this negative effect.
Pharmacokinetics of intraarticular liposomal amphotericin B in goats (Capra aegagrus hircus)
Authors: Smith Joe S. , Malla Grace D. , Garcia Jessica D. , Gebert Jessica E. , Noll Charlene V. , Mulon Pierre‐Yves , Knych Heather K.
Published: April 2024

Lameness is a significant welfare concern in goats. Amphotericin B is used via intraarticular (IA) administration in models to study experimentally induced lameness in large animals. The main objective of this study was to estimate plasma pharmacokinetic (PK) parameters for amphotericin B in goats after a single IA administration. Liposomal amphotericin B was administered to ten Kiko‐cross goats at a dose of 10 mg total (range: 0.34–0.51 mg/kg) via IA administration into the right hind lateral distal interphalangeal joint. Plasma samples were collected over 96 h. Amphotericin B concentrations were measured via liquid chromatography/mass spectrometry (LC–MS/MS). A non‐compartmental analysis was used to derive PK parameters. Following single IA administration, maximum plasma concentration was estimated at 54.6 ± 16.5 ng/mL, and time to maximum concentration ranged from 6 to 12 h. Elimination half‐life was estimated at 30.9 ± 16.5 h, and mean residence time was 45.1 ± 10.4 h. The volume of distribution after IA administration was 13.3 ± 9.4 L/kg. The area under the curve was 1481 ± 761 h*ng/mL. The achieved maximum concentration was less than the observed concentrations for other species and routes of administration. Further research is needed into the pharmacodynamics of IA liposomal amphotericin B in goats to determine specific research strategies.
Liver stiffness predicts progression to liver‐related events in patients with chronic liver disease – A cohort study of 14 414 patients
Authors: Hegmar Hannes , Wester Axel , Aleman Soo , Backman Jens , Degerman Erik , Ekvall Håkan , Lund Katarina , Lundgren Åsa , Nasr Patrik , Shahnavaz Afshin , Vessby Johan , Westin Johan , Önnerhag Kristina , Hagström Hannes
Published: April 2024

Background & Aims

Liver stiffness measurement (LSM) by vibration‐controlled transient elastography (VCTE) is a non‐invasive diagnostic biomarker of liver fibrosis. It is uncertain if LSM can predict risk for future liver‐related outcomes in large, heterogenous populations.

Methods

This Swedish multi‐centre cohort study included patients (n = 14 414) from 16 sites who underwent LSM by VCTE between 2008 and 2020. Outcomes were ascertained from national registers. We investigated progression to cirrhosis with portal hypertension or hepatocellular carcinoma (HCC), separately. Cox regression was used to obtain hazard ratios (HRs). Harrel's C‐index was used to measure discrimination of VCTE.

Results

Included patients had a median age of 46 (interquartile range 34–57), median LSM of 5.9 kPa (4.6–8.0), 59% were male, and the majority had hepatitis C (50.1%). During a median follow‐up of 5.9 (4.3–8.0) years, 402 patients (2.7%) developed cirrhosis with portal hypertension. In patients with an LSM ≥25 kPa, 28.7% developed cirrhosis with portal hypertension within 5 years of follow‐up, while only .6% of patients with an LSM <10 kPa did. This translated to a HR of 48.3 (95% confidence interval = 37.6–62.0). VCTE had a high discriminative ability, with C‐indices above .80 for most liver diseases, including .82 for MASLD. Similar findings were seen for incident HCC.

Conclusions

Increased LSM by VCTE was associated with an increased risk of progression to both cirrhosis with portal hypertension, and to HCC, and had a high discriminative ability across different aetiologies of chronic liver diseases. These results support the use of VCTE to guide follow‐up and treatment decisions.
Signals of selection and ancestry in independently feral Gallus gallus populations
Authors: Gering E. , Johnsson M. , Theunissen D. , Martin Cerezo M. L. , Steep A. , Getty T. , Henriksen R. , Wright D.
Published: March 2024

Recent work indicates that feralisation is not a simple reversal of domestication, and therefore raises questions about the predictability of evolution across replicated feral populations. In the present study we compare genes and traits of two independently established feral populations of chickens (Gallus gallus) that inhabit archipelagos within the Pacific and Atlantic regions to test for evolutionary parallelism and/or divergence. We find that feral populations from each region are genetically closer to one another than other domestic breeds, despite their geographical isolation and divergent colonisation histories. Next, we used genome scans to identify genomic regions selected during feralisation (selective sweeps) in two independently feral populations from Bermuda and Hawaii. Three selective sweep regions (each identified by multiple detection methods) were shared between feral populations, and this overlap is inconsistent with a null model in which selection targets are randomly distributed throughout the genome. In the case of the Bermudian population, many of the genes present within the selective sweeps were either not annotated or of unknown function. Of the nine genes that were identifiable, five were related to behaviour, with the remaining genes involved in bone metabolism, eye development and the immune system. Our findings suggest that a subset of feralisation loci (i.e. genomic targets of recent selection in feral populations) are shared across independently established populations, raising the possibility that feralisation involves some degree of parallelism or convergence and the potential for a shared feralisation ‘syndrome’.
The prevalence of copy number increase at multiallelic copy number variants associated with cave colonization
Authors: Pokrovac Ivan , Rohner Nicolas , Pezer Željka
Published: April 2024

Copy number variation is a common contributor to phenotypic diversity, yet its involvement in ecological adaptation is not easily discerned. Instances of parallelly evolving populations of the same species in a similar environment marked by strong selective pressures present opportunities to study the role of copy number variants (CNVs) in adaptation. By identifying CNVs that repeatedly occur in multiple populations of the derived ecotype and are not (or are rarely) present in the populations of the ancestral ecotype, the association of such CNVs with adaptation to the novel environment can be inferred. We used this paradigm to identify CNVs associated with recurrent adaptation of the Mexican tetra (Astyanax mexicanus) to cave environment. Using a read‐depth approach, we detected CNVs from previously re‐sequenced genomes of 44 individuals belonging to two ancestral surfaces and three derived cave populations. We identified 102 genes and 292 genomic regions that repeatedly diverge in copy number between the two ecotypes and occupy 0.8% of the reference genome. Functional analysis revealed their association with processes previously recognized to be relevant for adaptation, such as vision, immunity, oxygen consumption, metabolism, and neural function and we propose that these variants have been selected for in the cave or surface waters. The majority of the ecotype‐divergent CNVs are multiallelic and display copy number increases in cavefish compared to surface fish. Our findings suggest that multiallelic CNVs – including gene duplications – and divergence in copy number provide a fast route to produce novel phenotypes associated with adaptation to subterranean life.