bluuebunny/crossref_metadata_2025 huggingface dataset:
VARP binds SNX27 to promote endosomal supercomplex formation on membranes
Authors: Chandra Mintu , Kendall Amy , Ford Marijn , Jackson Lauren Parker
Published: July 2024

Multiple essential membrane trafficking pathways converge at endosomes to maintain cellular homeostasis by sorting critical transmembrane cargo proteins to the plasma membrane or the trans-Golgi network (TGN). The Retromer heterotrimer (VPS26/VPS35/VPS29 subunits) binds multiple sorting nexin (SNX) proteins on endosomal membranes, but molecular mechanisms regarding formation and regulation of metazoan SNX/Retromer complexes have been elusive. Here, we combine biochemical and biophysical approaches with AlphaFold2 Multimer modeling to identify a direct interaction between the VARP N-terminus and SNX27 PDZ domain. VARP and SNX27 interact with high nanomolar affinity using the binding pocket established for PDZ binding motif (PDZbm) cargo. Specific point mutations in VARP abrogate the interaction in vitro. We further establish a full biochemical reconstitution system using purified mammalian proteins to directly and systematically test whether multiple endosomal coat complexes are recruited to membranes to generate tubules. We successfully use purified coat components to demonstrate which combinations of Retromer with SNX27, ESCPE-1 (SNX2/SNX6), or both complexes can remodel membranes containing physiological cargo motifs and phospholipid composition. SNX27, alone and with Retromer, induces tubule formation in the presence of PI(3)P and PDZ cargo motifs. ESCPE-1 deforms membranes enriched with Folch I and CI-MPR cargo motifs, but surprisingly does not recruit Retromer. Finally, we find VARP is required to reconstitute a proposed endosomal supercomplex containing SNX27, ESCPE-1, and Retromer on PI(3)P-enriched membranes. These data suggest VARP functions as a key regulator in metazoans to promote cargo sorting out of endosomes.
Immunometabolic Blood Biomarkers of Developmental Trajectories of Depressive Symptoms: Findings From the ALSPAC Birth Cohort
Authors: Tsang Ruby S. M. , Stow Daniel , Kwong Alex S. F. , Donnelly Nicholas A. , Fraser Holly , Barroso Inês A. , Holmans Peter A. , Owen Michael J. , Wood Megan L. ,   LINC Consortium, van den Bree Marianne B. M. , Timpson Nicholas J. , Khandaker Golam M.
Published: July 2024

Studies of longitudinal trends of depressive symptoms in young people could provide insight into aetiologic mechanism, heterogeneity and origin of common cardiometabolic comorbidities for depression. Depression is associated with immunological and metabolic alterations, but immunometabolic characteristics of developmental trajectories of depressive symptoms remain unclear. Using depressive symptoms scores measured on 10 occasions between ages 10 and 25 years in the Avon Longitudinal Study of Parents and Children (n=7302), we identified four distinct trajectories: low-stable (70% of the sample), adolescent-limited (13%), adulthood-onset (10%) and adolescent-persistent (7%). We examined associations of these trajectories with: i) anthropometric, cardiometabolic and psychiatric phenotypes using multivariable regression (n=1709-3410); ii) 67 blood immunological proteins and 57 metabolomic features using empirical Bayes moderated linear models (n=2059 and n=2240 respectively); and iii) 28 blood cell counts and biochemical measures using multivariable regression (n=2256). Relative to the low-stable group, risk of depression and anxiety in adulthood was higher for all other groups, especially in the adolescent-persistent (ORdepression=22.80, 95% CI 15.25-34.37; ORGAD=19.32, 95% CI 12.86-29.22) and adulthood-onset (ORdepression=7.68, 95% CI 5.31-11.17; ORGAD=5.39, 95% CI 3.65-7.94) groups. The three depression-related trajectories vary in their immunometabolic profile, with evidence of little or no alterations in the adolescent-limited group. The adulthood-onset group shows widespread classical immunometabolic changes (e.g., increased immune cell counts and insulin resistance), while the adolescent-persistent group is characterised by higher BMI both in childhood and adulthood with few other immunometabolic changes. These findings point to distinct mechanisms and intervention opportunities for adverse cardiometabolic profile in different groups of young people with depression.
Wavelength scaling and multicolor operation of a plasma-driven attosecond x-ray source via harmonic generation
Authors: Hessami Rafi , Morgan Jenny , Robles River , Larsen Kirk A. , Marinelli Agostino , Emma Claudio
Published: July 2024

The generation of high-power coherent soft x-ray pulses of sub-100 as duration and 10 nm wavelength using beams from a GeV energy plasma wakefield accelerator has been recently investigated in Emma []. As a future upgrade to this concept, this contribution investigates scaling to shorter x-ray wavelengths by cascading undulators tuned to higher harmonics of the fundamental. We present two simulation studies for plasma-driven attosecond harmonic generation schemes with final photon wavelengths of 2 and 0.40 nm. We demonstrate in these schemes that using undulators with retuned fundamental frequencies can produce GW-scale pulses of sub-nm radiation with tens of attosecond-scale pulse lengths, an order of magnitude shorter than current state-of-the-art attosecond x-ray free electron lasers (XFELs). This multipulse multicolor operation will be broadly applicable to attosecond pump-probe experiments.

Published by the American Physical Society
2024
Direct evidence from high-field magnetotransport for a dramatic change of quasiparticle character in van der Waals ferromagnet
Fe3−xGeTe2
Authors: Vaidya S. , Coak M. J. , Mayoh D. A. , Lees M. R. , Balakrishnan G. , Singleton J. , Goddard P. A.
Published: July 2024

Magnetometry and magnetoresistance (MR) data taken on the van der Waals ferromagnet Fe3−xGeTe2 (FGT) reveal three distinct contributions to the MR: a linear negative component, a contribution from closed Fermi-surface orbits, and an enhancement proportional to the square of the applied magnetic field which is linked to a noncoplanar spin arrangement. Contrary to earlier studies on FGT, by accounting for the field dependence of the anomalous Hall effect, we find that the ordinary Hall coefficient decreases markedly below 80 K, indicating a significant change in character of the electrons and holes on the Fermi-surface at this temperature. The resulting altered ground state eventually causes the Hall coefficient to reverse sign at 35 K. Our Hall data support the proposal that Kondo-lattice behavior develops in this d-electron material below 80 K. Additional evidence comes from the negative linear component of the MR, which arises from electron-magnon scattering with an atypical temperature dependence attributable to the onset of Kondo screening.

Published by the American Physical Society
2024
Bis(ethylenediammonium) μ-ethylenediaminetetraacetato-1κ3
O,N,O′:2κ3
O′′,N′,O′′′-bis[trioxidomolybdate(VI)] tetrahydrate
Authors: Yaffa Lamine , Seye Dame , Kama Antoine Blaise , Toure Assane , Diop Cheikh Abdoul Khadir
Published: July 2024

The title compound, (C2H10N2)2[(C10H12N2O8)(MoO3)2]·4H2O, which crystallizes in the monoclinic C2/c space group, was obtained by mixing molybdenum oxide, ethylenediamine and ethylenediaminetetraacetic acid (H4edta) in a 2:4:1 ratio. The complex anion contains two MoO3 units bridged by an edta4− anion. The midpoint of the central C—C bond of the edta4− anion is located on a crystallographic inversion centre. The independent Mo atom is tridentately coordinated by a nitrogen atom and two carboxylate groups of the edta4− ligand, together with the three oxo ligands, producing a distorted octahedral coordination environment. In the three-dimensional supramolecular crystal structure, the dinuclear anions, the organoammonium counter-ions and the solvent water molecules are linked by N—H...Ow, N—H...Oedta and O—H...O hydrogen bonds.
IPO underpricing: a comparative analysis of risk factor disclosures in the financial and non-financial sectors
Authors: Bhullar Pritpal Singh , Grover Krishan Lal , Tiwari Ranjit
Published: July 2024

Purpose

This study aims to identify mutually exclusive risk categories and determine whether these categories effectively capture the potential impact of risk disclosures on the initial returns of initial public offerings (IPOs) in the financial and non-financial sectors.

Design/methodology/approach

Data were collected from 131 Indian IPO prospectuses (104 non-financial and 27 financial) issued between 2015 and 2021. Content analysis was performed to identify mutually exclusive risk categories, and the effects of these categories on initial IPO returns were assessed by regression analysis

Findings

The findings revealed that risk factor disclosures have a significant impact on underpricing, but not all risk factors are relevant. In the current study, in the financial sector, IPO underpricing was mostly driven by technological and competitive risk factors. In the non-financial sector, underpricing was predominantly influenced by operating risk and compliance risk factors.

Research limitations/implications

The limitations of this study include the use of sentence-based context analysis, which does not assess the quality of risk disclosures. The statistical data reduction technique used to generate mutually exclusive risk categories may also be a limitation.

Practical implications

This research has the potential to assist companies in standardizing the disclosure of risks within IPO prospectuses. The insights gained can inform market regulators in designing policies aimed at aiding investors in formulating investment strategies, ultimately enhancing transparency and clarity regarding information disclosure. Moreover, the findings offer valuable guidance to investors in selecting IPOs aligned with their risk tolerance levels.

Social implications

From a societal perspective, this study represents advancements by guiding regulators towards developing and regulating standardized, mutually exclusive risk factors. Such measures can aid investors in enhancing their decision-making perspectives regarding IPOs, promoting a more informed and confident investment environment.

Originality/value

This study is a pioneering attempt to address knowledge gaps by identifying distinct categories of risk disclosures in IPO prospectuses and examining their potential influence on IPO underpricing in the financial and non-financial sectors in India.
A study of rare-earth magnet profiles for torque ripple improvement of axial flux permanent magnet machine
Authors: Ali Salman , Qadeer Neelam , Ciprini Luca , Marignetti Fabrizio
Published: July 2024

Purpose

The purpose of this study is to reduce the cogging torque in axial flux permanent magnet (AFPM) machine using optimal magnet shape.

Design/methodology/approach

This study analyzes different magnet shapes for AFPM machine performance enhancement. Three-dimensional (3D) finite element analysis is performed to see the effects of pole shaping on the cogging torque of the AFPM machine.

Findings

The magnetic pole shape has a significant effect on cogging torque and overall efficiency. The conventional model has the highest torque whereas the conventional skewing affected cogging torque positively and significantly reduced the cogging torque. The combination of skewing the pole along with face curving is more effective and decreases the cogging torque from 3.88 Nm to 1.5 Nm.

Originality/value

Rare-earth magnets are the most expensive and important part of AFPM machines. Shape and volume optimization of rare-earth magnets is crucial for the performance of AFPM machines. The research aims to analyze the different permanent magnet designs for performance improvement of the AFPM machine. Conventional flat top trapezoidal, curved-top and skewed-magnet shapes are analyzed and the performance of the AFPM machine is compared with different magnet shapes. Curved-top shape and skewed magnet significantly reduce the cogging torque. Furthermore, a combination of curved-top shape and skew magnet shape is proposed to reduce the cogging torque further and improve the AFPM machine’s overall performance. Newly proposed magnet profile gives skewed curve magnet shapes which reduce the cogging torque further. 3D finite element analysis has been used to analyze the single-sided AFPM with all four different magnet shapes. The research focuses on single-sided AFPM machines, but the results are also valid for double-sided AFPM machines and can be extended to other topologies of AFPM machines.
An adaptive multi-output Gaussian process surrogate model for large-scale parameter estimation problems
Authors: Lyu Xiaolong , Huang Dan , Wu Liwei , Chen Ding
Published: July 2024

Purpose

Parameter estimation in complex engineering structures typically necessitates repeated calculations using simulation models, leading to significant computational costs. This paper aims to introduce an adaptive multi-output Gaussian process (MOGP) surrogate model for parameter estimation in time-consuming models.

Design/methodology/approach

The MOGP surrogate model is established to replace the computationally expensive finite element method (FEM) analysis during the estimation process. We propose a novel adaptive sampling method for MOGP inspired by the traditional expected improvement (EI) method, aiming to reduce the number of required sample points for building the surrogate model. Two mathematical examples and an application in the back analysis of a concrete arch dam are tested to demonstrate the effectiveness of the proposed method.

Findings

The numerical results show that the proposed method requires a relatively small number of sample points to achieve accurate estimates. The proposed adaptive sampling method combined with the MOGP surrogate model shows an obvious advantage in parameter estimation problems involving expensive-to-evaluate models, particularly those with high-dimensional output.

Originality/value

A novel adaptive sampling method for establishing the MOGP surrogate model is proposed to accelerate the procedure of solving large-scale parameter estimation problems. This modified adaptive sampling method, based on the traditional EI method, is better suited for multi-output problems, making it highly valuable for numerous practical engineering applications.
Exploring the critical success factors of virtual reality adoption in the hotel industry
Authors: Lodhi Rab Nawaz , Asif Muhammad , Del Gesso Carla , Cobanoglu Cihan
Published: July 2024

Purpose

This qualitative study aims to investigate the critical success factors (CSFs) driving the adoption of virtual reality (VR) in the hospitality industry, shedding light on key determinants for successful implementation.

Design/methodology/approach

Drawing on a diverse set of interviews conducted in Italy, Pakistan, the USA and Turkey, this study uses thematic analysis facilitated by NVivo 12 to comprehensively explore and identify the CSFs influencing VR adoption within the global hospitality industry.

Findings

This study identifies distinct CSFs at various phases of VR adoption in the hospitality industry. Preimplementation emphasizes budget planning and stakeholder engagement, implementation highlights safety training and feedback mechanisms and postimplementation underscores the importance of innovation, feedback utilization and maintenance for sustained success. These findings offer a strategic roadmap for VR integration in hospitality.

Practical implications

The study informs hospitality industry stakeholders of crucial success factors for VR adoption, thereby guiding strategic decision-making. Sustained VR integration success is ensured by emphasizing budget planning, stakeholder engagement, safety training, feedback mechanisms and postimplementation innovation.

Originality/value

To the best of the authors’ knowledge, this groundbreaking research is the first in-depth investigation into CSFs for the adoption of VR in the hospitality industry. This research advances our understanding of and provides fresh guidance for effective VR integration by revealing novel insights into the key variables at various deployment phases.
Structural characterization and hypoglycemic effect of polysaccharides of Polygonatum sibiricum
Authors: Wang Xin , Yang Mengyuan , Shen Ying , Zhang Yipeng , Xiu Weiye , Yu Shiyou , Ma Yongqiang
Published: July 2024

Polygonatum sibiricum polysaccharide (PSP) was extracted and purified from raw material obtained from P. sibiricum. The structural features of PSP were investigated by Congo red, circular dichroism spectrum, high‐performance gel permeation chromatography, scanning electron microscope, atomic force microscope, ultraviolet spectroscopy, and Fourier transform infrared spectroscopy analysis. In vitro simulations were conducted to investigate the kinetics of PSP enzyme inhibition. Moreover, a type II diabetes mouse model (T2DM) with streptozotocin‐induced insulin resistance was established, and the indexes of lipid quadruple, insulin resistance index, oral glucose tolerance (OGTT), organ index, and pancreatic morphology of model mice were measured. The results showed that PSP mainly consists of monosaccharides, such as mannose, glucose, galactose, xylose, and arabinose. It also has a β‐glycosidic bond of a pyranose ring and an irregular reticulated aggregated structure with a triple helix. In vitro enzyme inhibition assays revealed that PSP acts as a reversible competitive inhibitor of α‐glucosidase and α‐amylase. Furthermore, PSP was found to reduce insulin resistance index, increase OGTT and serum insulin levels, decrease free fatty acid content to improve lipid metabolism, and lower glycated serum protein content to enhance glucose metabolism in T2DM mice, thereby leading to a reduction in blood glucose concentration. Additionally, PSP exhibited reparative effects on the damaged liver tissue cells and pancreatic tissue in T2DM mice. The experiment results provide a preliminary basis for the therapeutic mechanism of PSP about type II diabetes and a theoretical reference for application in food and pharmaceutical development.
Myeloid ectopic viral integration site 2 accelerates the progression of Alzheimer's disease
Authors: Cui Yuting , Zhang Xiaomin , Liu Jing , Hou Yuli , Song Qiao , Cao Min , Zhang Jingjing , Wang Xiaoling , Liu Congcong , Wang Peichang , Wang Yaqi
Published: July 2024

Amyloid plaques, a major pathological hallmark of Alzheimer's disease (AD), are caused by an imbalance between the amyloidogenic and non‐amyloidogenic pathways of amyloid precursor protein (APP). BACE1 cleavage of APP is the rate‐limiting step for amyloid‐β production and plaque formation in AD. Although the alteration of BACE1 expression in AD has been investigated, the underlying mechanisms remain unknown. In this study, we determined MEIS2 was notably elevated in AD models and AD patients. Alterations in the expression of MEIS2 can modulate the levels of BACE1. MEIS2 downregulation improved the learning and memory retention of AD mice and decreased the number of amyloid plaques. MEIS2 binds to the BACE1 promoter, positively regulates BACE1 expression, and accelerates APP amyloid degradation in vitro. Therefore, our findings suggest that MEIS2 might be a critical transcription factor in AD, since it regulates BACE1 expression and accelerates BACE1‐mediated APP amyloidogenic cleavage. MEIS2 is a promising early intervention target for AD treatment.
Corporate Bond Market Reaction to the Mandatory ESG Disclosure Act: Is Sustainium Sustainable?*
Authors: Lee Jung Hwa , Choi Daewoung , Choi Hoyong , Han Seung Hun
Published: July 2024

We investigate the primary and secondary market reactions of US corporate bonds to the mandatory Environmental, Social, and Governance (ESG) Disclosure Act of 2021 (hereafter, the ESG Disclosure Act). We compare ESG bonds with non‐ESG bonds through a yield spread analysis for the primary market and a bond event study for the secondary market, assessing the impact on a sustainable premium (“sustainium”) following the enactment. Sustainium disappears from the primary market after the ESG Disclosure Act. Abnormal corporate bond returns in the secondary market are negative, and the impact on the sustainium is not economically different from zero. We also find that long‐term corporate bonds are more vulnerable to the ESG Disclosure Act. These findings indicate that investors should assess ESG bonds according to long‐term horizons if the sustainium is expected to persist.
Children with eosinophilic esophagitis non‐responsive to combination therapy have distinct esophageal transcriptomic and microbiome profile
Authors: Hiremath Girish , Choksi Yash , Correa Hernan , Jacobse Justin , Das Suman R. , Ma Siyuan , Goettel Jeremy A. , Rajagopala Seesandra V.
Published: July 2024

Background

A combination of proton‐pump inhibitors (PPI) and topical steroids (TS) is used to treat children with eosinophilic esophagitis (EoE). However, a subset of children do not respond to this combination therapy. We aimed to identify the esophageal transcriptional, cell composition, and microbial differences between the non‐responders (EoE‐PPI‐TSnr; n = 7) and responders (EoE‐PPI‐TSr; n = 7) to the combination therapy for EoE and controls (n = 9) using metatranscriptomics.

Methods

Differential gene expression analysis was used to identify transcriptional differences, validated using the EoE diagnostic panel (EDP). Deconvolution analysis was performed to identify differences in their cell type composition. Microbiome analysis was conducted from esophageal biopsies RNAseq data, and microbial abundance was correlated with esophageal gene expression.

Results

In all, 3164 upregulated and 3154 downregulated genes distinguished EoE‐PPI‐TSnr from EoE‐PPI‐TSr. Eosinophilic inflammatory response, cytokine signaling, and collagen formation pathways were significantly upregulated in EoE‐PPI‐TSnr. There was a 56% overlap in dysregulated genes between EoE‐PPI‐TSnr and EDP, with a perfect agreement in the directionality of modulation. Eosinophils, dendritic cells (DCs), immature DCs, megakaryocytic‐erythroid progenitors, and T helper type 1 cells were significantly higher in EoE‐PPI‐TSnr. There was no significant difference in microbiome diversity. The relative abundance of Fusobacterium sp. and Acinetobacter sp. notably differed in EoE‐PPI‐TSnr and correlated with the key pathways.

Conclusion

Our results provide critical insights into the molecular, cellular, and microbial factors associated with the lack of response to PPI and TS combination therapy in children with EoE. This study advances our understanding of the pathobiology of EoE while guiding personalized treatment strategies.
Adjunctive therapy with an oral H2S donor provides additional therapeutic benefit beyond SGLT2 inhibition in cardiometabolic heart failure with preserved ejection fraction
Authors: Doiron Jake E. , Xia Huijing , Yu Xiaoman , Nevins Alexandra R. , LaPenna Kyle B. , Sharp Thomas E. , Goodchild Traci T. , Allerton Timothy D. , Elgazzaz Mona , Lazartigues Eric , Shah Sanjiv J. , Li Zhen , Lefer David J.
Published: July 2024

Background and Purpose

Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a potent therapy for heart failure with preserved ejection fraction (HFpEF). Hydrogen sulphide (H2S), a well‐studied cardioprotective agent, could be beneficial in HFpEF. SGLT2i monotherapy and combination therapy involving an SGLT2i and H2S donor in two preclinical models of cardiometabolic HFpEF was investigated.

Experimental Approach

Nine‐week‐old C57BL/6N mice received L‐NAME and a 60% high fat diet for five weeks. Mice were then randomized to either control, SGLT2i monotherapy or SGLT2i and H2S donor, SG1002, for five additional weeks. Ten‐week‐old ZSF1 obese rats were randomized to control, SGLT2i or SGLT2i and SG1002 for 8 weeks. SG1002 monotherapy was investigated in additional animals. Cardiac function (echocardiography and haemodynamics), exercise capacity, glucose handling and multiorgan pathology were monitored during experimental protocols.

Key Results

SGLT2i treatment improved E/e′ ratio and treadmill exercise in both models. Combination therapy afforded increases in cardiovascular sulphur bioavailability that coincided with improved left end‐diastolic function (E/e′ ratio), exercise capacity, metabolic state, cardiorenal fibrosis, and hepatic steatosis. Follow‐up studies with SG1002 monotherapy revealed improvements in diastolic function, exercise capacity and multiorgan histopathology.

Conclusions and Implications

SGLT2i monotherapy remediated pathological complications exhibited by two well‐established HFpEF models. Adjunctive H2S therapy resulted in further improvements of cardiometabolic perturbations beyond SGLT2i monotherapy. Follow‐up SG1002 monotherapy studies inferred an improved phenotype with combination therapy beyond either monotherapy. These data demonstrate the differing effects of SGLT2i and H2S therapy while also revealing the superior efficacy of the combination therapy in cardiometabolic HFpEF.
Arbidol, an antiviral drug, identified as a sodium channel blocker with anticonvulsant activity
Authors: Li Min , Jin Yuchen , Wu Jun , Zhao Miao , Yu Kexin , Yu Haibo
Published: July 2024

Background and purpose

Sodium channel blockers (SCBs) have traditionally been utilized as anti‐seizure medications by primarily targeting the inactivation process. In a drug discovery project aiming at finding potential anticonvulsants, we have identified arbidol, originally an antiviral drug, as a potent SCB. In order to evaluate its anticonvulsant potential, we have thoroughly examined its biophysical properties as well as its effects on animal seizure models.

Experimental approach

Patch clamp recording was used to investigate the electrophysiological properties of arbidol, as well as the binding and unbinding kinetics of arbidol, carbamazepine and lacosamide. Furthermore, we evaluated the anticonvulsant effects of arbidol using three different seizure models in male mice.

Key results

Arbidol effectively suppressed neuronal epileptiform activity by blocking sodium channels. Arbidol demonstrated a distinct mode of action by interacting with both the fast and slow inactivation of Nav1.2 channels compared with carbamazepine and lacosamide. A kinetic study suggested that the binding and unbinding rates might be associated with the specific characteristics of these three drugs. Arbidol targeted the classical binding site of local anaesthetics, effectively inhibited the gain‐of‐function effects of Nav1.2 epileptic mutations and exhibited varying degrees of anticonvulsant effects in the maximal electroshock model and subcutaneous pentylenetetrazol model but had no effect in the pilocarpine‐induced status epilepticus model.

Conclusions and implications

Arbidol shows promising potential as an anticonvulsant agent, providing a unique mode of action that sets it apart from existing SCBs.
Multifaceted interactions between cancer cells and glial cells in brain metastasis
Authors: Ishibashi Kojiro , Hirata Eishu
Published: July 2024

Cancer brain metastasis has a poor prognosis, is commonly observed in clinical practice, and the number of cases is increasing as overall cancer survival improves. However, experiments in mouse models have shown that brain metastasis itself is an inefficient process. One reason for this inefficiency is the brain microenvironment, which differs significantly from that of other organs, making it difficult for cancer cells to adapt. The brain microenvironment consists of unique resident cell types such as neurons, oligodendrocytes, astrocytes, and microglia. Accumulating evidence over the past decades suggests that the interactions between cancer cells and glial cells can positively or negatively influence the development of brain metastasis. Nevertheless, elucidating the complex interactions between cancer cells and glial cells remains challenging, in part due to the limitations of existing experimental models for glial cell culture. In this review, we first provide an overview of glial cell culture methods and then examine recent discoveries regarding the interactions between brain metastatic cancer cells and the surrounding glial cells, with a special focus on astrocytes and microglia. Finally, we discuss future perspectives for understanding the multifaceted interactions between cancer cells and glial cells for the treatment of metastatic brain tumors.
Metabolism score and machine learning models for the prediction of esophageal squamous cell carcinoma progression
Authors: Chen Lu , Zhang WenXin , Shi Huanying , Zhu Yongjun , Chen Haifei , Wu Zimei , Zhong Mingkang , Shi Xiaojin , Li Qunyi , Wang Tianxiao
Published: July 2024

The incomplete prediction of prognosis in esophageal squamous cell carcinoma (ESCC) patients is attributed to various therapeutic interventions and complex prognostic factors. Consequently, there is a pressing demand for enhanced predictive biomarkers that can facilitate clinical management and treatment decisions. This study recruited 491 ESCC patients who underwent surgical treatment at Huashan Hospital, Fudan University. We incorporated 14 blood metabolic indicators and identified independent prognostic indicators for overall survival through univariate and multivariate analyses. Subsequently, a metabolism score formula was established based on the biochemical markers. We constructed a nomogram and machine learning models utilizing the metabolism score and clinically significant prognostic features, followed by an evaluation of their predictive accuracy and performance. We identified alkaline phosphatase, free fatty acids, homocysteine, lactate dehydrogenase, and triglycerides as independent prognostic indicators for ESCC. Subsequently, based on these five indicators, we established a metabolism score that serves as an independent prognostic factor in ESCC patients. By utilizing this metabolism score in conjunction with clinical features, a nomogram can precisely predict the prognosis of ESCC patients, achieving an area under the curve (AUC) of 0.89. The random forest (RF) model showed superior predictive ability (AUC = 0.90, accuracy = 86%, Matthews correlation coefficient = 0.55). Finally, we used an RF model with optimal performance to establish an online predictive tool. The metabolism score developed in this study serves as an independent prognostic indicator for ESCC patients.
Using de novo transcriptomes to decipher the relationships in cutthroat trout subspecies (Oncorhynchus clarkii)
Authors: Kokkonen Andrea L. , Searle Peter C. , Shiozawa Dennis K. , Evans R. Paul
Published: July 2024

For almost 200 years, the taxonomy of cutthroat trout (Oncorhynchus clarkii), a salmonid native to Western North America, has been in flux as ichthyologists and fisheries biologists have tried to describe the diversity within these fishes. Starting in the 1950s, Robert Behnke reexamined the cutthroat trout and identified 14 subspecies based on morphological traits, Pleistocene events, and modern geographic ranges. His designations became instrumental in recognizing and preserving the remaining diversity of cutthroat trout. Over time, molecular techniques (i.e. karyotypes, allozymes, mitochondrial DNA, SNPs, and microsatellite arrays) have largely reinforced Behnke's phylogenies, but have also revealed that some relationships are consistently weakly supported. To further resolve these relationships, we generated de novo transcriptomes for nine cutthroat subspecies, as well as a Bear River Bonneville form and two Colorado River lineages (blue and green). We present phylogenies of these subspecies generated from multiple sets of orthologous genes extracted from our transcriptomes. We confirm many of the relationships identified in previous morphological and molecular studies, as well as discuss the importance of significant differences apparent in our phylogenies from these studies within a geological perspective. Specific findings include three distinct clades: (1) Bear River Bonneville form and Yellowstone cutthroat trout; (2) Bonneville cutthroat trout (n = 2); and (3) Greenback and Rio Grande cutthroat trout. We also identify potential gene transfer between Bonneville cutthroat trout and a population of Colorado River green lineage cutthroat trout. Using these findings, it appears that additional groups warrant species‐level consideration if other recent species elevations are retained.
The future of immunology: a Lofoten perspective
Authors: Borowicz Pawel , King Carolyn G , Dustin Michael L , Wherry E John , Koretzky Gary A , Spurkland Anne
Published: July 2024

This Future Challenges article summarizes views on future directions in immunological research presented at round‐table discussions at the 4th Immunology workshop in the Lofoten Islands in Norway, held in August 2023, and subsequent responses to surveys sent to meeting participants. It also summarizes some of the conversations around the responsibility of scientists to communicate with the non‐science community, and the approaches that we may use to meet this obligation.
Effects of a mattress cover with special airflow technology on the structure and function of the sacral and heel skin during loading: A two‐arm exploratory crossover trial
Authors: Kottner Jan , Amin Ruhul , Tomova‐Simitchieva Tsenka , Hillmann Kathrin , Blume‐Peytavi Ulrike
Published: July 2024

Prolonged mechanical loading of the skin and underlying soft tissue cause pressure ulceration. The use of special support surfaces are key interventions in pressure ulcer prevention. They modify the degree and duration of soft tissue deformation and have an impact on the skin microclimate. The objective of this randomized cross‐over trial was to compare skin responses and comfort after lying for 2.5 h supine on a support surface with and without a coverlet that was intended to assist with heat and moisture removal at the patient/surface interface. In addition, physiological saline solution was administered to simulate an incontinence episode on the mattress next to the participants' skin surface. In total, 12 volunteers (mean age 69 years) with diabetes mellitus participated. After loading, skin surface temperature, stratum corneum hydration and skin surface pH increased, whereas erythema and structural stiffness decreased at the sacral area. At the heel skin area, temperature, erythema, and stratum corneum hydration increased. These results indicate occlusion and soft tissue deformation which was aggravated by the saline solution. The differences in skin response showed only minor differences between the support surface with or without the coverlet.
The effects of a digital lifestyle intervention in patients with hypertension: Results of a pilot randomized controlled trial
Authors: Wildenauer Alina , Maurer Leonie Franziska , Rötzer Laurin , Eggert Torsten , Schöbel Christoph
Published: July 2024

In this pilot study, the authors investigated the preliminary effectiveness of the digital lifestyle intervention, actensio (mementor DE GmbH), in treating arterial hypertension. Adults with arterial hypertension were randomly assigned to an intervention group (actensio + standard care) or a control group (waiting list + standard care) in a 1:1 ratio. Primary and secondary endpoints were assessed at baseline (t0) and 3 months post‐randomization (t1). The primary endpoint was average systolic blood pressure, measured at home for 1 week. Secondary endpoints included patient engagement (measured using the “patient activation measure”; PAM‐13), average diastolic blood pressure, and heart rate. All endpoints were analyzed using ANCOVA models, following an intention‐to‐treat approach, while adjusting for baseline values. Missing data were estimated using multiple imputation models. A total ofN = 102 participants (f = 59, age = 52.94 ± 9.01) were randomized to either the intervention (IG;N = 52) or the control group (CG;N = 50), of whichN = 80 completed the blood pressure diary, andN = 81 the PAM‐13 at t1. Between‐group comparisons showed an average group difference in systolic blood pressure of −5.06 mm Hg (95% CI = −8.71 to −1.41,p = .013) between the intervention group (M = 137.37 ± 10.13) and the control group (M = 142.35 ± 11.23). Average group difference for patient engagement was 3.35 points with a trend towards statistical significance (95% CI = −018 to 6.89,p = .064), favoring the intervention group (MIG = 79.38 ± 9.44 vs. MCG = 75.45 ± 10.62). There were no group differences in diastolic blood pressure (−1.78 mm Hg; 95% CI = −4.50 to 0.95,p = .402) and heart rate (−0.684; 95% CI = −3.73 to 2.36,p = 0.683). The results of the present pilot study confirm the preliminary effectiveness of the digital lifestyle intervention, actensio, in reducing high blood pressure in patients with hypertension.
Health technologies for tackling client absenteeism in primary and secondary care services
Authors: Pires Liandra Brasil , Lima Igor Lucas Pinheiro , Alves Thais Oliveira Santos , de Menezes Araújo Danillo , Santos Jeffersson , da Silva Flávia Janólio Costacurta Pinto
Published: July 2024

Background

Tackling client absenteeism in primary and secondary care settings is crucial to ensure the continuity of care for individuals, families and communities, as well as preventing waste of resources within healthcare systems.

Methodology

This article is an integrative review to identify advancements in health technologies that address client absenteeism in primary and secondary care. The databases Medical Literature and Retrieval System Online (MEDLINE/PubMed®), Scientific Electronic Library Online and Virtual Health Library were consulted. The inclusion criteria were as follows: full papers, published between 2013 and 2023, in English, Portuguese or Spanish. The descriptors used were the following: patients, mobile applications, health services management, absenteeism and primary care, and secondary care. Eleven articles published from 2014 to 2021 were included.

Results

Most articles were identified in the MEDLINE/PUBMED database, employed a randomized controlled trial methodology (36.36%), and were published between 2019 and 2021 (90.0%) in English (63.7%). The applications had managerial, assistive and/or educational purposes. In addition to absenteeism control, these applications strived to promote client engagement with health services, increase health literacy and tackle structural barriers to care, such as language barriers.

Conclusion

Efforts are needed to ensure that providers receive training to educate clients on the applications. Moreover, community‐based participatory studies to ensure the feasibility of applications are warranted.
Staff and client preferences for the design and delivery of an outcomes monitoring system in a mental health service
Authors: Batterham Philip J. , Martin Melonie , Calear Alison L. , Cherbuin Nicolas , Romaniuk Madeline , Banfield Michelle , Butterworth Peter , Burvill Michael , Massang Daniel
Published: July 2024

Background

Outcome monitoring can support the delivery of quality service that meets the needs of clients, clinicians and services. However, few studies have examined client or staff perspectives on the design and implementation of outcomes monitoring within a service. Implementation of outcomes monitoring requires understanding the preferences and expectations of relevant stakeholders.

Objective

Informed by the Consolidated Framework for Implementation Research, this study aimed to investigate the preferences and priorities of relevant staff, clients and family members to inform the design and implementation of an effective outcomes monitoring system in the context of a mental health service for military veterans and their families.

Method

Twenty‐nine staff participated across five online focus groups, including clinical staff, peer workers, policy staff and supervisors. Ten clients participated in online or telephone semi‐structured interviews. Thematic analysis was used to develop themes from the data.

Results

Clients and staff agreed that outcomes monitoring should cover more than symptoms, particularly by incorporating functional outcomes. Assessing mental health over time was considered a valuable tool for supporting treatment processes and providing actionable information. Challenges identified by clients and staff included the need for efficient processes, ensuring measures are relevant and acceptable, and maintaining client privacy. The ability to personalise data collection and have a streamlined, responsive system were key attributes of a quality outcomes monitoring framework.

Conclusions

Findings suggest that an effective outcome monitoring framework should be client‐led, tailored to the individual's needs, and provide feedback on progress. Outcomes monitoring should also be efficient, accessible and allow for safe information sharing.
Investigation on the environmental causes of tomato fruit cracking and its propagation prediction in greenhouse
Authors: Liu Ying , Yang Jun , Li Zhiguo , Tchuenbou‐Magaia Fideline , Liu Yande
Published: July 2024

In this study, Provence tomato variety was chosen for investigating the environmental causes of tomato fruit cracking, cracks characteristics, and their propagation prediction in a greenhouse. Fruit bagging approach was used to alter the temperature and humidity and to create a microclimate around the fruit to induce fruit cracking for testing. Results showed that the fruit cracking rate increased when the environment temperature exceeded 30°C, and the difference between the highest and lowest temperature values in a day was greater than 20°C. The cracking rate was aggravated when the difference between the highest and lowest humidity values in a day was less than 20%. The proportions of top cracking, longitudinal cracking, ring cracking, radial cracking, and combined cracking were 5.4%, 16.1%, 28.3%, 26.8%, and 32.1%, respectively. The fruit shoulder was the most susceptible region to crack, followed by fruit belly and top regions, whereas longer cracks were observed in the fruit belly region indicating a higher propensity to crack propagation in that region. Finally, the measured data were used to validate an extended finite element method developed to effectively predict cracking susceptibility and propagation in tomato fruit with a relative error of 4.68%.
Investigating the effects of oil type, emulsifier type, and emulsion particle size on textured fibril soy protein emulsion‐filled gels and soybean protein isolate emulsion‐filled gels
Authors: Luo Bin , Chen Lin , Peng Jiaqi , Sun Jianxia
Published: July 2024

The effects of oil type, emulsifier type, and emulsion particle size on the texture, gel strength, and rheological properties of SPI emulsion‐filled gel (SPI‐FG) and TFSP emulsion‐filled gel (TFSP‐FG) were investigated. Using soybean protein isolate or sodium caseinate as emulsifiers, emulsions with cocoa butter replacer (CBR), palm oil (PO), virgin coconut oil (VCO), and canola oil (CO) as oil phases were prepared. These emulsions were filled into SPI and TFSP gel substrates to prepare emulsion‐filled gels. Results that the hardness and gel strength of both gels increased with increasing emulsion content when CBR was used as the emulsion oil phase. However, when the other three liquid oils were used as the oil phase, the hardness and gel strength of TFSP‐FG decreased with the increasing of emulsion content, but those of SPI‐FG increased when SPI was used as emulsifier. Additionally, the hardness and gel strength of both TFSP‐FG and SPI‐FG increased with the decreasing of mean particle size of emulsions. Rheological measurements were consistent with textural measurements and found that compared with SC, TFSP‐FG, and SPI‐FG showed higher G′ values when SPI was used as emulsifier. Confocal laser scanning microscopy (CLSM) observation showed that the distribution and stability of emulsion droplets in TFSP‐FG and SPI‐FG were influenced by the oil type, emulsifier type and emulsion particle size. SPI‐stabilized emulsion behaved as active fillers in SPI‐FG reinforcing the gel matrix; however, the gel matrix of TFSP‐FG still had many void pores when SPI‐stabilized emulsion was involved. In conclusion, compared to SPI‐FG, the emulsion filler effect that could reinforce gel networks became weaker in TFSP‐FG.
Does racial impact statement reform reduce Black–White disparities in imprisonment: Mixed methods evidence from Minnesota
Authors: Gottlieb Aaron , Harper Toyan , Jung Hye‐Min
Published: July 2024

Increasingly scholars have argued that, if the United States is to reduce Black–White disparities in incarceration, it is necessary to move away from race‐neutral efforts and ensure that policies consider race. Despite this perspective, criminal legal policies have almost exclusively been race‐neutral, with one general exception at the state level: racial impact statement reform. Although racial impact statement reform exists now in 10 states, no scholarship has empirically examined the implications of this approach for racial disparities in imprisonment. Using a mixed methods approach, we begin to fill this gap by examining the implications of Minnesota's racial impact statement reform on Black–White imprisonment rate disparities. Our quasi‐experimental results do not suggest that Minnesota's reform reduced Black–White disparities in imprisonment. Our legislative analysis suggests that the null effects we observed were likely due to the fact that racial impact statements are responses to legislation that has already been proposed, and that the legislation proposed in Minnesota was not sufficient to significantly address Black–White imprisonment disparities, regardless of the extent to which these statements impacted the votes of legislators.
Mineralogy of the Martian mantle inferred from bulk chemical compositions
Authors: Yang Shuying , Humayun Munir , Righter Kevin
Published: July 2024

Understanding the mineralogy of the Martian mantle is essential for constructing geochemical and geophysical models of Mars. This study employs the pMELTS program to determine the mineralogy at the solidus from 11 published bulk silicate Mars (BSM) compositions, within a pressure range of 2–5 GPa. The pMELTS results align with experimental data and calculations from another thermodynamic program (Perple_X/stx11). Mineral modes from compositional models based on Martian meteorite geochemistry show relatively consistent abundances modes (olivine: 48–56 wt%, orthopyroxene: 20–25 wt%, clinopyroxene: 15–17 wt%, garnet: 6–9 wt%). In contrast, mineral modes from compositional models that are not based on Martian meteorite geochemistry exhibit a wider range of olivine and garnet abundances. Additionally, we constrained the mineral modes of the Martian mantle using trace element partitioning and partial melting models. Our calculations indicate that melts derived from mantle sources with a hypothesized garnet content of 5–10 wt% closely match the analyzed compositions of shergottites, validating the garnet mode (6–9 wt%) constrained in our pMELTS calculations. Extracting low‐degree (<4 wt%) melts from a BSM to form depleted Martian mantle (DMM) does not significantly alter the mineralogical modes of solid residues, but it does lead to substantial trace elemental depletion in the DMM. Therefore, enriched, intermediate, and depleted shergottite sources are likely characterized by similar mineral modes yet differ in incompatible element abundances.