bluuebunny/crossref_metadata_2025 huggingface dataset:
The mammalian SKI complex is a broad-spectrum antiviral drug target that upregulates cellular cholesterol to inhibit viral replication
Authors: Weston Stuart , Baracco Lauren , Taylor Louis , Scott Alison , Kumar Gaurav , Shapiro Paul , MacKerell Alexander D. , Frieman Matthew B.
Published: December 2024

There is a need for the development of broad-spectrum antiviral compounds that can act as first line therapeutic countermeasures to emerging viral infections. Host-directed approaches present a promising avenue of development and carry the benefit of mitigating risks of viral escape mutants. We have previously found the SKI (super killer) complex to be a broad-spectrum, host-target with our lead compound ("UMB18") showing activity against influenza, coronaviruses, and filoviruses. The SKI complex is a cytosolic RNA helicase and we previously found that targeting it with UMB18 inhibited viral RNA production but did not further define the mechanism. Here, transcriptomic analysis of UMB18 treated A549 cells revealed an upregulation of genes in the mevalonate pathway which drives cholesterol synthesis. Further investigation validated the genetic upregulation and confirmed an increase in total cellular cholesterol. This upregulation was dependent on the SKI complex, the sterol regulatory element binding proteins (SREBPs) and their regulator SCAP, the major regulators for cholesterol and fatty acid synthesis. Depletion of the SREBPs or SCAP with siRNA, or extraction of cholesterol with methyl β-cyclodextrin attenuated UMB18 antiviral activity, emphasizing the role of increased cholesterol synthesis in this mechanism of action. Our findings further define the antiviral mechanism of a developmental host-directed therapeutic approach with broad applicability against emerging viral pathogens.

Author Summary

The COVID-19 pandemic has underscored the urgent need for effective countermeasures to novel and emerging viral pathogens. Our research presented here builds upon our previously published data on an experimental novel antiviral compound termed UMB18. We have found this compound capable of inhibiting replication of influenza A virus, coronaviruses and the filoviruses Marburg and Ebola virus, but did not fully define a mechanism of action. In this work, we demonstrate that UMB18 exerts antiviral activity by modulating cellular cholesterol levels. By targeting the SKI complex, UMB18 triggers an increase in endogenous cellular cholesterol which disrupts the fine balance viruses rely on for efficient infection. We demonstrate that this mechanism inhibits replication of SARS-CoV-2, revealing a previously undescribed host-directed strategy for antiviral intervention. These findings highlight UMB18’s potential as a broad-spectrum antiviral agent and pave the way for further research into its mechanism and therapeutic applications, offering a promising avenue for development of antiviral countermeasures to current, novel and emerging pathogens.
Social patch foraging theory in an egalitarian group
Authors: Blum Moyse Lisa , El Hady Ahmed
Published: December 2024

Foraging is a widespread behavior, and being part of a group may bring several benefits compared to solitary foraging, such as collective pooling of information and reducing environmental uncertainty. Often theoretical models of collective behavior use coarse-grained representations, or are too complex for analytical treatment, and generally do not take into account the noisy decision making process implemented by individual agents. This calls for the development of a mechanistic, analytically tractable, and stochastic framework to study the underlying processes of social foraging, tying the microscopic to the macroscopic levels. Based on an evidence accumulation framework, we developed a model of patch-leaving decisions in a large egalitarian group. Across a variety of environmental statistics and information sharing mechanisms, we were able to analytically derive optimal agent strategies. The environmental statistics considered are either two non-depleting or several successive depleting patches. The social information sharing mechanisms are either through observation of others’ food rewards or through belief sharing, with continuous sharing, pulsatile observation of others’ departures or arrivals, or through counting the number of individuals in a patch. Throughout all these conditions, we quantified how cohesive a group is over time, how much time agents spend on average in a patch and what are their group equilibrium dynamics. We found that social coupling strongly modulates these features across a variety of environmental statistics. This general modeling framework is crucial to both designing social foraging experiments and generating hypotheses that can be tested. Moreover, this framework can be extended to groups exhibiting hierarchical relations.
Identification of anti-resorptive GPCRs by high-content imaging in human osteoclasts
Authors: Price Maria L. , Wyatt Rachael A. , Correia Joao , Areej Zakia , Hinds Maisie , Crastin Ana , Hardy Rowan S. , Frost Morten , Gorvin Caroline M.
Published: December 2024

Osteoporosis diagnoses are increasing in the ageing population and although several treatments exist, these have several disadvantages, highlighting the need to identify new drug targets. G protein-coupled receptors (GPCRs) are transmembrane proteins whose surface expression and extracellular activation make them desirable drug targets. Our previous studies have identified 144 GPCR genes to be expressed in primary human osteoclasts, which could provide novel drug targets. The development of high-throughput assays to assess osteoclast activity would improve the efficiency at which we could assess the effect of GPCR activation on human bone cells and could be utilised for future compound screening. Here we assessed the utility of a high-content imaging (HCI) assay that measured cytoplasmic-to-nuclear translocation of the nuclear factor of activated T cells-1 (NFATc1), a transcription factor that is essential for osteoclast differentiation and resorptive activity. We first demonstrated that the HCI assay detected changes in NFATc1 nuclear translocation in human primary osteoclasts using GIPR as a positive control, then developed an automated analysis platform to assess NFATc1 in nuclei in an efficient and unbiased manner. We assessed six GPCRs simultaneously and identified four receptors (FFAR2, FFAR4, FPR1, GPR35) that reduced osteoclast activity. Bone resorption assays and measurements of TRAP activity verified that activation of these GPCRs reduced osteoclast activity, and that receptor-specific antagonists prevented these effects. These studies demonstrate that HCI of NFATc1 can accurately assess osteoclast activity in human cells, reducing observer bias and increasing efficiency of target detection for future osteoclast-targeted osteoporosis therapies.
TheDictyostelium discoideum – Mycobacterium marinuminfection model, a powerful high throughput screening platform for anti-infective compounds
Authors: Nitschke Jahn , Hanna Nabil , Soldati Thierry
Published: December 2024

Tuberculosis is among the world’s deadliest diseases, causing approximately 2 million deaths annually. The urgent need for new antitubercular drugs has been intensified by the rise of drug-resistant strains. Despite recent advancements, most hits identified through traditional target-based screening exhibit limited efficacyin vivo. Consequently, there is a growing demand for whole-cell-based approaches that directly utilize host-pathogen systems. TheDictyostelium discoideum–Mycobacterium marinumhost–pathogen system is a well-established and powerful alternative model system to study mycobacterial infections. In this article, the phenotypic host-pathogen protocol assay is presented here which relies on monitoringM. marinumduring its infection of the amoebaD. discoideum. This assay is characterized by its scalability for high-throughput screening, robustness, and ease of manipulation, making it an effective system for compound screening. This system provides not only bacterial load readout via a bioluminescentM. marinumstrain, but now also host survival and growth via a fluorescentD. discoideumstrain enabling further host characterization by quantifying growth inhibition and potential cytotoxicity. Finally, the system was benchmarked with selected antibiotics and anti-infectives and calculated IC50s and MICs where applicable, demonstrating its capability to differentiate between antibiotics and anti-infective compounds.

Importance

This methods paper introduces a robust, scalable, and high-throughput phenotypic host-pathogen assay based on the well-establishedDictyostelium discoideum–Mycobacterium marinumsystem. In contrast to conventional target-based drug screening approaches, which often struggle to translate effectivelyin vivo, this platform directly monitors pathogen-host interactions, providing comprehensive insights into bacterial load, host survival, and potential cytotoxicity. By employing bioluminescentM. marinumand fluorescentD. discoideumstrains, we validated the system using established antibiotics and anti-infective compounds, effectively distinguishing their effects through IC50 and MIC calculations.
Transition paths across the EMT landscape are dictated by network logic
Authors: Dey Anupam , MacLean Adam L.
Published: December 2024

During development and cancer metastasis, cells transition reversibly from epithelial to mesenchymal via intermediate cell states during epithelial-mesenchymal transition (EMT). EMT is controlled by gene regulatory networks (GRNs) and can be described by a three-node GRN that permits tristable EMT landscapes. In this GRN, multiple inputs regulate the transcription factor ZEB that induces EMT. It is unknown how to choose the network logic for such regulation. Here we explore the effects of network logic on a tristable EMT network. We discover that the choice of additive vs multiplicative logic affects EMT phenotypes, leading to opposing predictions regarding the factors controlling EMT transition paths. We show that strong inhibition of miR-200 destabilizes the epithelial state and initiates EMT for multiplicative (AND) but not additive (OR) logic, suggesting that AND logic is in better agreement with experimental measurements of the effects of miR-200 regulation on EMT. Using experimental single-cell data, stochastic simulations, and perturbation analysis, we demonstrate how our results can be used to design experiments to infer the network logic of an EMT GRN in live cells. Our results explain how the manipulation of molecular interactions can stabilize or destabilize EMT hybrid states, of relevance during cancer progression and metastasis. More generally, we highlight the importance of the choice of network logic in GRN models in the presence of biological noise and multistability.
Structural and functional interrelationship of histone H2A and its variants H2A.Z and H2A.W in Arabidopsis
Authors: Wang Youchao , Wu Jiabing , Yang Shuoming , Li Xiang , Wang Jiachen , Lv Qinghe , Zhu Xiaoyu , Lu Guoliang , Zhang Jinru , Shen Wen-Hui , Liu Bing , Lin Jinzhong , Dong Aiwu
Published: December 2024

Multiple histone H2A variants are known in eukaryotes. However, the functional relationship between H2A and its variants in plants remains largely obscure. Using CRISPR/Cas9 editing, we generated a mutant lacking four H2A isoforms in Arabidopsis and analyzed the functional and structural relationship between H2A and its variants H2A.Z and H2A.W. RNA-sequencing and phenotype analyses revealed mild changes in gene transcription and plant development in the mutants lacking H2A, H2A.Z, or H2A.W compared with the wild-type plants. Chromatin immunoprecipitation sequencing analysis showed that H2A is able to substitute for both H2A.Z and H2A.W across the genome, including in euchromatin and heterochromatin regions. However, H2A.Z replaced both H2A and H2A.W primarily within the euchromatin regions. By using DNA and histones derived from Arabidopsis, we constructed nucleosomes containing H2A, H2A.Z, or H2A.W and resolved their cryogenic electron microscopy structures at near-atomic resolution. Collectively, the results reveal the structural similarity and functional redundancy of H2A and H2A variants in Arabidopsis.
Theory of higher education learning
Authors: Awaah Fred
Published: December 2024

Purpose

This study proposes the theory of higher education learning (THEL). The theory argues that certain concepts are difficult to understand, so learners and instructors should consider common factors that will enhance learners’ understanding of key concepts that are difficult to comprehend across various fields of study. The components of this theory have been tested in three different fields (public administration, entrepreneurship and chemistry) in separate studies in Ghana, Nigeria and Burundi within a five-year span to validate their applicability to higher education learning.

Design/methodology/approach

The design covers empirical, philosophical and theoretical discussions and comparative studies of other researchers and the authors’ work and thinking.

Findings

This theory proposes five variables (gender, age, opportunity, instructor knowledge and instructor confidence) that address students’ difficulty in understanding concepts in higher education learning. These factors are premised on six assumptions: (1) gender orientation must be either male or female; (2) age must be consistent with the parameter set; (3) there must be learners’ desire to study the same subject after school; (4) there must be an institution offering further studies on the same subject; (5) the instructor might have understood the subject in his/her official training, experience or practice and (6) the instructor must demonstrate certainty, accuracy, verifiability and reliability in the transfer of knowledge to the learners. Given these assumptions, the uniqueness of this theory lies in its application of the five variables to solve challenges uniquely related to studies in higher education.

Originality/value

This theory will incite debate and provide further insights into higher education learning models. The novelty lies in the five prepositions proven to enhance effective teaching and learning in higher education. Specifically, it introduces an extension to Piaget’s cognitive constructivist theory by proposing higher age brackets for students at the university level, opportunity (for future studies) to close the gap in Ausubul’s theory of advance organizers and endogenous factors to bridge the gap in Okebukola’s culturo-techno-contextual approach.
Determinants of higher education graduates’ employability: a scoping review
Authors: Monteiro Sílvia , Santos Sandra , Teixeira José Nuno , Torres Leonor , Palhares José
Published: December 2024

Purpose

Graduates’ employability has been recognised as a complex and multidimensional phenomenon in the theoretical literature. However, some critics have emerged around the lack of relation between structural, contextual and individual dimensions that have been acknowledged as relevant for the understanding of graduates’ employability. This study aims to map empirical research, grounded on a scoping and integrative review of the research published to date on the determinants of graduates’ employability and offer a wider perspective of the knowledge produced across different disciplinary fields, and theoretical and methodological approaches.

Design/methodology/approach

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol for Scoping Reviews, a systematic and extensive search of the literature was carried out and 74 studies focusing on the determinants of graduates’ employability were selected through inclusion and exclusion criteria. Then, data were extracted, analysed and interpreted with quantitative and qualitative techniques.

Findings

The results evidence that multiple factors mainly related to higher education attributes, educational arrangement, personal and interpersonal attributes, and socioeconomic conditions predict the odds of obtaining a job after graduation. This review also demonstrates some fragmentation of knowledge produced in this field and identifies a lack of an integrative approach, calling for more multidisciplinary research that might favour a more comprehensive knowledge of graduates’ employability.

Originality/value

By considering the different factors together, from individual and contextual levels, the present review offers an original and clearer overall picture of what is currently known and what is still unresearched about the determinants of graduates’ employability.
Two-phase analysis of blood in microchannel architecture on plasma separation ability with dimensional variance
Authors: Khaliq Amin , Lee Byungkwon , Kamran Muhammad Ahmad , Jeong Myung Yung
Published: December 2024

Purpose

This paper aims to study the effects of varying inlet channel angle in a novel microfluidic architecture blood plasma separation ability over range of hematocrit values (5–45%) at multiple flowrates.

Design/methodology/approach

CAD designs for both micro architectures were designed in SOILWORKS. In the second step, these designs were imported into ANSYS to perform where meshing, model selection, defining blood as two-phase material and boundary conditions are performed.

Findings

Separation efficiency values close to 100% with diluted blood and 65.2% with whole blood were observed. Straight channel inlet design has significantly better performance at high hematocrit levels, whereas at lower hematocrit levels, both designs had almost same outcome. Furthermore, lower flowrates have shown the highest separation efficiency for lower hematocrit levels, whereas at higher hematocrit percentages, higher flowrates have shown better separation effects for both designs. Furthermore, trends obtained for flow ratio and flowrates against separation efficiency are demonstrated.

Research limitations/implications

This study is based on blood modeled as two-phase flow, with the phases consisting of blood plasma as primary phase and red blood cells as secondary particulate phase.

Practical implications

Implications of this study are far reaching for point-of-care health-care systems. A practical system of this numerical study can provide a microchannel device which take very small amount of blood sample to separate it into constituents which can be coupled with detection module to detect a particular disease for which it is designed for. This microsystem can be very beneficial for remote areas where a large hospital facility is far away.

Originality/value

This study has carried out a detailed analysis on the ability of a novel microchannel architecture to separate blood plasma from other blood constituents. Inlet channel angle variation effects are observed over a range of hematocrit percentages. These trends are further investigated for three different flowrates to assess the microchannel design behavior.
Simulation and theoretical studies on the influence of removable panel deformation on the seal characteristics of ceramic wafer seal
Authors: Wang Qiliang , Shao Xulong , Wang Dagang , Wei Shijun , Kang Jinyuan , Wang Jun
Published: December 2024

Purpose

The purpose of this study is to investigate the influence of geometric parameters of removable panels on the sealing characteristics of ceramic wafer seal structure subjected to high-temperature gas flow.

Design/methodology/approach

Based on the laminar flow Reynolds equation, the theoretical and numerical calculation models were constructed to investigate the influence of external convex deformation of removable panel on leakage rate. The theoretical formula for leakage rate after deformation of the removable panel was derived, and the flow field and leakage characteristics of ceramic wafer seal under different operating parameters were studied.

Findings

The leakage rate exhibits consistent trends between theoretical calculation, numerical simulation and experimental value, with a maximum discrepancy of 8.9%. This validates the accuracy of both the theoretical model and numerical simulation. As the deformation angle of the removable panel increases, the sealing gap gradually widens, resulting in a compromised sealing effect. Moreover, the leakage rate in the central region of the sealing area is lower compared to that at both ends.

Originality/value

The leakage of the ceramic wafer seal structure under the removable panel with different deformation angles can be monitored based on Reynolds equation. The pseudo-transient numerical calculation method can be used to determine the leakage value of the micro-state ceramic wafer seal structure. These research findings provide a theoretical foundation and numerical investigation approach for studying ceramic wafer seal structures.
A CAM-UNet for pose determination of supercapacitor cell module assembly based on monocular vision
Authors: Wu Zhichao , Shu Weijing , Song Limei , Zhu Xinjun , Yang Yangang
Published: December 2024

Purpose

This paper aims to solve the problems of low stacking efficiency and long production time in the supercapacitor module assembly process, a stacking system based on monocular vision is proposed, including bracket visual positioning, grasping and stacking, and it is applied in actual production.

Design/methodology/approach

To enhance the robustness of the workpiece location method and improve the location accuracy, the improved U-Net network and image processing algorithms are used to segment the collected images. In addition, for the extracted feature points, the objective function that can be globally optimized is obtained by parameterizing the rotation matrix to construct a polynomial equation system and, finally, the equation system is solved to obtain the final pose estimation, which could improve the accuracy of workpiece location.

Findings

The result indicates that the proposed method is successfully performed on the manipulator. Besides, this method can well solve the problem of object reflection on the conveyor belt. The Intersection over Union of the image segmentation of the object is 0.9948, and the Pixel Accuracy is 0.9973, which has a high segmentation accuracy for the image. The error range between the method proposed in this paper and the pose estimation is within 2 mm, and the qualified rate of supercapacitor module stacking products is over 99.8%.

Originality/value

This paper proposes a method of accurately extracting feature points by integrating an improved U-Net network and image processing and uses the workpiece positioning algorithm of the optimal solution PnP problem algorithm. The calculation results show that the algorithm improves the positioning accuracy of the workpiece, realizes the assembly of stacked supercapacitor modules and is applied in industrial production.
Expert consensus on serratus anterior plane block education and credentialing: A modified‐Delphi study
Authors: Partyka Christopher , Gaetani Daniel , Delaney Anthony , Curtis Kate
Published: December 2024

Objective

The serratus anterior plane block (SAPB) is a regional anaesthesia technique with increasing use as an analgesic adjunct in patients with rib fractures. The present study aimed to generate consensus of the requirements of education, training and credentialing for the use of a ‘single shot’ SAPB in the management of rib fractures.

Methods

A modified Delphi process was designed using online questionnaires. Expert panellists from Australian and Aotearoa New Zealand were invited from the fields of Emergency Medicine and Anaesthesia and were asked to rate the importance of different components of SAPB education, training and credentialling on a 9‐point Likert scale. Consensus was achieved if ≥70% of experts provided a score of seven or greater on this scale for any given statement.

Results

Thirty specialists (60% FACEM, 40% FANZCA) representing New Zealand plus all states and territories of Australia formed the expert panel. Participant response rates were 100% (first round), 83% (second round) and 63% (final round). At the end of three survey rounds, 59 consensus statements were formed (27 for education, 5 for training and 17 for credentialing).

Conclusions

This series of expert statements provides consensus on the education, training and credentialling of the SAPB for the management of rib fractures. These serve as the minimum standard by which this procedure should be taught while providing clinicians with a syllabus for the development of training programmes.
Humble Leadership and Employee Feedback Seeking: The Role of Affective Trust in the Leader and Perceived Human Resource Management Strength
Authors: Jia Jianfeng , Zheng Yuyan , Jiao Yuxin
Published: December 2024

Despite the burgeoning literature on leadership and employees' feedback‐seeking behaviors, research linking contemporary leadership styles and feedback seeking is still limited. Our study examines the role of humble leadership on employees' feedback‐seeking behaviors. Based on three‐wave data from 172 leader‐follower dyadic pairs, our results show that humble leadership has a positive effect on feedback‐seeking behaviors via employees' affective trust in the leader when the mediating effects of psychological safety and cognitive trust were controlled. Furthermore, the overall mediation effect of affective trust is strengthened by higher levels of employees' perceived human resource management strength. Theoretical and practical implications are discussed.
Characteristic volatile compounds of white tea with different storage times using E‐nose, HS–GC–IMS, and HS–SPME–GC–MS
Authors: Huang Haoran , Chen Xinyu , Wang Ying , Cheng Ye , Liu Zhijian , Hu Yunchao , Wu Xianzhi , Wu Caie , Xiong Zhixin
Published: December 2024

This paper studied the influence of storage duration on the flavor profile of white tea in detail, with samples produced between 2020 and 2023. Sensory evaluation was performed by quantitative descriptive analysis (QDA), followed by an in‐depth aroma components analysis employing an electronic nose (E‐nose), headspace gas chromatography–ion mobility spectrometry (HS–GC–IMS), and headspace solid–phase microextraction–gas chromatography–mass spectrometry (HS–SPME–GC–MS). The QDA findings revealed a gradual transition in the flavor profile of white tea during storage, shifting from sweet, fruity, and floral to more herbal and stale characteristics. E‐nose could well distinguish white tea with different storage times. A total of 55 and 53 volatile compounds were identified by HS–GC–IMS and HS–SPME–GC–MS, respectively. The orthogonal partial least squares‐discriminant analysis models, based on HS–GC–IMS (R2Y = 0.998, Q2 = 0.987) and HS–SPME–GC–MS (R2Y = 0.984, Q2 = 0.993), successfully distinguished white tea samples stored for different storage times. Furthermore, 14 and 8 key compounds were screened based on the double variable criterion of one‐way analysis of variance (p < 0.05) and variable importance in projection (VIP) >1.2, and their content changes were also compared. It is the gradual decrease of important aroma components such as 2‐hexenal, 2‐methyl‐2‐hepten‐6‐one, linalool, and geraniol, which are positively correlated with sweet, fruity, and floral aromas, and the gradual increase of hexanoic acid, thiophene, propanoic acid, dimethyl disulfide, and borneyl acetate, which are positively correlated with herbal and stale flavor, that leads to the changes in flavor and aroma of white tea during storage. The results of the study provided a reference for elucidating the aroma characteristics of white tea at different storage times as well as a theoretical basis for the quality control of white tea.
Bone Erosions and Systemic Bone Loss on HR‐pQCT in Men With Tophaceous Gout
Authors: Rocha Gabriela F. , Santos Jeane B. , Sales Lucas P. , Franco André S. , Caparbo Valéria F. , Takayama Liliam , Domiciano Diogo S. , Fuller Ricardo , Figueiredo Camille P.
Published: December 2024

Aims

Gout, a prevalent inflammatory arthropathy, predominantly affects males and arises from persistent hyperuricemia, resulting in monosodium urate crystal deposition. Hyperuricemia is associated with comorbidities, exacerbating patient morbidity. Conflicting literature exists regarding uric acid's impact on bone mineral density (BMD), with potential proinflammatory effects in gout patients. Localized bone destruction (erosions) is a hallmark of gout, necessitating early detection due to its predictive role in musculoskeletal disability.

Methods

This cross‐sectional study included 26 tophaceous gout patients. Clinical and densitometric parameters were assessed, and high‐resolution peripheral quantitative computed tomography (HR‐pQCT) was used for bone microarchitecture evaluation, as well as bone erosions in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. A healthy control group of 52 age and BMI‐matched individuals was included.

Results

Despite normal areal bone mineral density (BMD), tophaceous gout patients exhibited impaired HR‐pQCT parameters, including lower cortical volumetric BMD (Ct.vBMD) and higher cortical porosity at the distal radius. Similar trends were observed at the tibia. Bone erosions were prevalent (96%), with distribution across MCP and PIP joints. Patients with ≥ 4 erosions displayed increased tophi prevalence and longer uricosuric use. Erosions correlated with compromised microarchitecture, emphasizing their association with disease activity.

Conclusion

Despite normal BMD, tophaceous gout patients manifest systemic bone loss, with bone microarchitectural deterioration and localized bone erosions, underscoring the need for detailed clinical approaches to prevent musculoskeletal disabilities, including fragility fractures, in this population.
Estimating industry conduct using promotion data
Authors: Michel Christian , Paz y Miño Jose Manuel , Weiergraeber Stefan
Published: December 2024

We estimate the evolution of competition in the ready‐to‐eat cereal industry. To separately identify detailed patterns of industry conduct from unobserved marginal cost shocks, we construct novel instruments that interact data on rival firms' promotions with measures of products' relative isolation in the characteristics space. We find strong evidence for partial price coordination among cereal manufacturers in the beginning of our sample. After a merger in 1993 conduct becomes more competitive and on average consistent with multiproduct Nash pricing. The last part of our sample is characterized by even more aggressive pricing, implying median wholesale margins of less than 5%.
Skeletal muscle mitochondrial fragmentation predicts age‐associated decline in physical capacity
Authors: Goulding Richie P. , Charlton Braeden T. , Breedveld Ellen A. , van der Laan Matthijs , Strating Anne R. , Noort Wendy , Kolodyazhna Aryna , Appelman Brent , van Vugt Michèle , Grootemaat Anita E. , van der Wel Nicole N. , de Koning Jos J. , Bloemers Frank W. , Wüst Rob C. I.
Published: December 2024

Ageing substantially impairs skeletal muscle metabolic and physical function. Skeletal muscle mitochondrial health is also impaired with ageing, but the role of skeletal muscle mitochondrial fragmentation in age‐related functional decline remains imprecisely characterized. Here, using a cross‐sectional study design, we performed a detailed comparison of skeletal muscle mitochondrial characteristics in relation to in vivo markers of exercise capacity between young and middle‐aged individuals. Despite similar overall oxidative phosphorylation capacity (young: 99 ± 17 vs. middle‐aged: 99 ± 27 pmol O2.s−1.mg−1, p = 0.95) and intermyofibrillar mitochondrial density (young: 5.86 ± 0.57 vs. middle‐aged: 5.68 ± 1.48%, p = 0.25), older participants displayed a more fragmented intermyofibrillar mitochondrial network (young: 1.15 ± 0.17 vs. middle‐aged: 1.55 ± 0.15 A.U., p < 0.0001), a lower mitochondrial cristae density (young: 23.40 ± 7.12 vs. middle‐aged: 13.55 ± 4.10%, p = 0.002) and a reduced subsarcolemmal mitochondrial density (young: 22.39 ± 6.50 vs. middle‐aged: 13.92 ± 4.95%, p = 0.005). Linear regression analysis showed that 87% of the variance associated with maximal oxygen uptake could be explained by skeletal muscle mitochondrial fragmentation and cristae density alone, whereas subsarcolemmal mitochondrial density was positively associated with the capacity for oxygen extraction during exercise. Intramuscular lipid accumulation was positively associated with mitochondrial fragmentation and negatively associated with cristae density. Collectively, our work highlights the critical role of skeletal muscle mitochondria in age‐associated declines in physical function.
Comparative analysis of gut microbiota in hormone‐sensitive and castration‐resistant prostate cancer in Japanese men
Authors: Fujimoto Saizo , Hatano Koji , Banno Eri , Motooka Daisuke , De Velasco Marco Antonio , Kura Yurie , Toyoda Shingo , Hashimoto Mamoru , Adomi Shogo , Minami Takafumi , Yoshimura Kazuhiro , Oka Toshiki , Hata Junya , Matsushita Makoto , Takao Tetsuya , Takada Shingo , Tsujimura Akira , Kojima Yasuyuki , Obara Wataru , Nakamura Shota , Uemura Hirotsugu , Nonomura Norio , Fujita Kazutoshi
Published: December 2024

Gut microbiota plays a crucial role in the development and progression of prostate cancer, with previous studies indicating that certain bacterial taxa are more abundant in castration‐resistant prostate cancer (CRPC) compared to hormone‐sensitive prostate cancer (HSPC). Notably, the composition of gut microbiota can vary significantly by geographic region, and Japanese individuals have a distinct microbial profile. However, research exploring these differences within Japanese populations remains limited. This study investigated the gut microbiota differences between Japanese men with HSPC and CRPC and further validated these findings using a transgenic mouse model. Rectal swab samples were collected from 140 Japanese men diagnosed with HSPC (n = 84) or CRPC (n = 56) between September 2020 and July 2022. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Additionally, Pten‐KO mice, which model the progression from HSPC to CRPC, underwent similar microbiota analysis. Results revealed significant differences in gut microbiota composition between HSPC and CRPC patients. Specifically, the CRPC group showed a higher abundance of Firmicutes, including Gemella and Lactobacillus, compared to the HSPC group. These differences were mirrored in the mouse model, where CRPC mice also showed an increase in these bacteria. This study identifies distinct microbial differences between HSPC and CRPC in Japanese men, suggesting that Gemella and Lactobacillus may be associated with the progression to castration resistance in prostate cancer. These findings suggest that gut microbiota differences may be associated with prostate cancer progression. Further research is needed to explore the potential of targeting the microbiota as a therapeutic strategy.
Nonpharmacological Interventions Aimed at Promoting the Mental Health of Children and Adolescents During the COVID‐19 Pandemic: A Systematic Review
Authors: Quiroga Carolina Villanova , Caobelli Anna Clara Sarmento Leite , Rodrigues Gabriela Veiga Alano , Viola Thiago Wendt
Published: December 2024

Background

Interventions to promote mental health in paediatrics need to be effective, especially in crisis contexts. This systematic review proposes to compile and analyse the findings of nonpharmacological interventions conducted in samples of children and adolescents during the COVID‐19 pandemic, focusing on mental health.

Methods

The research was carried out in PsycINFO, PubMed and Web of Science databases for empirical studies, including interventions in which measures of outcome variables were collected at least twice (pre and post). The studies' samples were children and adolescents up to 19 years old, and interventions were developed throughout the COVID‐19 pandemic. After eligibility analyses, 16 studies were included in this review.

Results

Studies used different theoretical approaches, focusing on the promotion, prevention and treatment of mental health in specific contexts. Some were delivered online, in‐person or in hybrid formats. Particularly, depression, the most frequently assessed outcome, demonstrated more favourable results within the interventions than other evaluated outcomes. However, due to the considerable risk of bias, the qualitative analysis of the results of many included studies should be performed with caution.

Conclusions

Most of the interventions necessitate further validation, highlighting the ongoing need for research in this area. However, the emergence of interventions during crises, such as the COVID‐19 pandemic, provides an opportunity to expand evidence‐based mental health practices, paving the way for their application in other crisis situations. Given that mental health prevention and promotion practices can be integrated into the roles of all healthcare providers, possessing insight into the most suitable evidence‐based interventions can elevate the quality of care delivered.
Services Addressing Mental Health Needs of Youth in Physical Rehabilitation: Perspectives of Clinicians, Youth and Family Members
Authors: Tremblay Stephanie M. , Lal Shalini , Ferro Mark A. , Anaby Dana
Published: December 2024

Background

Knowledge about services addressing mental health provided in a rehabilitation setting to youth with physical disabilities is limited. This study aimed to better understand the needs, supports, challenges and potential solutions to optimize rehabilitation services for co‐occurring physical and mental health needs, from the perspectives of youth, family members and clinicians.

Methods

A qualitative descriptive approach using 22 individual interviews with youth, parents and clinicians from five rehabilitation centres in a large Canadian city was employed. Inductive thematic analysis was conducted.

Results

Three themes were identified across the three stakeholder groups: (1) available clinical resources for mental health (access to mental health professionals, impact of organizational structures and mandates and continuity of services during transition to adult care); (2) clinician workforce capacity (mental health knowledge, skills and professional development, and therapeutic rapport between clinician and youth); and (3) links and partnerships with key players (improved pathways to access mental health services across programmes and organizations, and family involvement and advocacy).

Conclusion

This study provides insights to barriers for mental health care (such as limited mental health knowledge, tools and professional development and access to specialists within the team, restrictive organizational mandates and disruption of services during the transition to adult care), illustrating important aspects to address. Clinicians can be better equipped to address mental health in rehabilitation settings via training opportunities and peer and organizational support in addition to establishing links with external partners. Organizations can also ensure adequate staffing and create pathways within and beyond their institutions to deliver well‐coordinated mental health services in a more accessible way.
Diet Quality Scores and Central Precocious Puberty Risk in Chinese Girls: A Case–Control Study
Authors: Qin Yujie , Deng Hongyang , Lu Mengnan , Liu Lujie , Li Meng , Zhou Jing , Xiao Yanfeng
Published: December 2024

Objective

Diet is an important factor influencing central precocious puberty (CPP). This study aimed to investigate the relationship among diet quality, pro‐inflammatory diets, and CPP in Chinese girls.

Design, Patients and Measurements

This case–control study enroled 112 Chinese girls with CPP and 131 healthy controls. Children's dietary intake was assessed using a validated food frequency questionnaire, anthropometric and sociodemographic data were collected and serum interleukin‐6 levels were measured. We calculated the Children's Dietary Inflammatory Index (C‐DII), Chinese Children's Dietary Index (CCDI), Dietary Approaches to Stop Hypertension (DASH) score, and the adjusted Dietary Approaches to Stop Hypertension (aDASH) score. The association between diet and the risk of CPP was analysed using logistic regression models.

Results

After adjustment, higher C‐DII scores were associated with an increased risk of CPP (P for trend = 0.034), and aDASH scores were significantly negatively associated with the risk of CPP (P for trend = 0.048). Serum IL‐6 levels were significantly higher in the case group than in the control group and were positively correlated with the risk of CPP (P for trend = 0.006).

Conclusions

High‐quality dietary patterns and an anti‐inflammatory diet may contribute to the prevention of CPP in Chinese girls.
The State of the Art in User‐Adaptive Visualizations
Authors: Yanez Fernando , Conati Cristina , Ottley Alvitta , Nobre Carolina
Published: December 2024

Research shows that user traits can modulate the use of visualization systems and have a measurable influence on users' accuracy, speed, and attention when performing visual analysis. This highlights the importance of user‐adaptive visualization that can modify themselves to the characteristics and preferences of the user. However, there are very few such visualization systems, as creating them requires broad knowledge from various sub‐domains of the visualization community. A user‐adaptive system must consider which user traits they adapt to, their adaptation logic and the types of interventions they support. In this STAR, we survey a broad space of existing literature and consolidate them to structure the process of creating user‐adaptive visualizations into five components: Capture Ⓐ Input from the user and any relevant peripheral information. Perform computational Ⓑ User Modelling with this input to construct a Ⓒ User Representation. Employ Ⓓ Adaptation Assignment logic to identify when and how to introduce Ⓔ Interventions. Our novel taxonomy provides a road map for work in this area, describing the rich space of current approaches and highlighting open areas for future work.
The Distribution and Therapeutic Effectiveness of Clinical Unilateral Ménière's Disease Phenotypes
Authors: Chen Yongjia , Cai Xinzhang , Zhang Yulu , He Chufeng , Wu Xuewen , Jiang Lu , Chen Hongsheng , Liu Jing , Pang Bo , Zhang Shuai , Chen Anhai , Jiang Mengzhu , Huang Huping , Bai Yijiang , Nie Zequn , Mei Lingyun
Published: December 2024

Objectives

The first purpose of this study was to ascertain the distribution of unilateral Ménière's disease (MD) clinical subgroups in China and compare with the population reported in Europe and the United States. The second purpose was to investigate the effectiveness in different clinical phenotypes.

Methods

Participants were categorised into one of five subtypes using a previously reported classification scheme based on cluster analysis. The distribution and clinical characteristics were analysed and compared with the two cohorts reported in Europe and the United States. Participants were followed up to observe the therapeutic effectiveness over a 2‐year period.

Results

A total of 245 patients diagnosed with UMD were enrolled in the study, with 84 of these participants providing complete and detailed follow‐up data. All of the unilateral MD patients were accurately classified: 58.0% were classic MD, 25.7% were delayed MD, 1.2% was familial MD, 12.7% were sporadic MD with migraine and 2.4% were autoimmune MD. Our findings revealed a significant difference in the distribution between this cohort and the European cohort. Follow‐up assessments revealed worse vertigo control rate in the patients with migraine compared to the classical MD (50.0% vs. 82.6%, p = 0.034).

Conclusion

The distribution of unilateral MD subtypes in this Chinese population differs from that in the European population, and the therapeutic effectiveness varies across subtypes in this cohort. Our study highlights the importance of the clinical heterogeneity in unilateral MD, and further studies are needed to identify the optimal interventions for specific subgroups.
Population pharmacokinetic analysis identifies an absorption process model for mycophenolic acid in patients with renal transplant
Authors: Suzuki Yuki , Matsunaga Noriko , Aoyama Takahiko , Ogami Chika , Hasegawa Chihiro , Iida Satofumi , To Hideto , Kitahara Takashi , Tsuji Yasuhiro
Published: December 2024

The pharmacokinetics (PKs) of mycophenolic acid (MPA) exhibit considerable complexity and large variability. We developed a population pharmacokinetic (popPK) model to predict the complex PK of MPA by examining an absorption model. Forty‐two patients who had undergone renal transplantation were included in this study. popPK analysis, incorporating several absorption models, was performed using the nonlinear mixed‐effects modeling program NONMEM. The MPA area under the concentration‐time curve at 0–12 h (AUC0–12) was simulated using the final model to calculate the recommended dose. The PK of MPA was adequately described using a two‐compartment model incorporating sequential zero‐ and first‐order absorption with lag time. Total body weight, renal function (RF), and posttransplantation day (PTD) were included as covariates affecting MPA PK. The final model estimates were 7.56, 11.6 L/h, 104.0 L, 17.3 L/h, 169.0 L, 0.0453, 0.283, and 1.95 h for apparent nonrenal clearance, apparent renal clearance, apparent central volume of distribution, apparent intercompartmental clearance, apparent peripheral volume of distribution, absorption half‐life, lag time, and duration of zero‐order absorption, respectively. Simulation results showed that a dose regimen of 500–1000 mg twice daily is recommended during the early posttransplantation period. However, dose reduction could be required with increased PTD and decreased RF. The complex PK of MPA was explained using an absorption model. The developed popPK model can provide useful information regarding individual dosing regimens based on PTD and RF.
Caring for the environment: Plastic waste management and environmental concerns in Colombian coffee‐growing communities
Authors: Arboleda Muñoz Germán Antonio , Palacios Lily Marcela , Portela Guarín Hugo , Villada Castillo Héctor Samuel
Published: December 2024

A study was conducted with coffee growers from the municipalities of Caldono (Cauca) and Pitalito (Huila) in Colombia. Workshops, participant observation and farm visits were used to identify elements to understand (a) practices to the care of the environment, (b) the perception of the use of plastic materials, and (c) perspective toward biodegradable packages in their practices. Among the main results are an awareness for the care of the water resource and the care of the trees as its main contributions to the protection of its environment. In both communities, the problem is perceived due to the management of plastic waste and its influence on environmental deterioration due to poor management. They also recognize that the development of biodegradable bags can contribute to caring for their environment and make their economic activity more sustainable.