bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src Family Kinase Signaling and Oxidative Phosphorylation, Killing Acute Myeloid Leukemia Cells
Authors: Gamma Jay M. , Liu Qiang , Beauchamp Erwan , Iyer Aishwarya , Yap Megan C. , Zak Zoulika , Ekstrom Cassidy , Pain Rony , Kostiuk Morris A. , Mackey John R. , Brandwein Joseph , Wang Jean C.Y. , Berthiaume Luc G.
Published: January 2025

Abstract
Acute myeloid leukemia (AML) is a hematologic malignancy with limited treatment options and a high likelihood of recurrence after chemotherapy. We studied N-myristoylation, the myristate modification of proteins linked to survival signaling and metabolism, as a potential therapeutic target for AML. N-myristoylation is catalyzed by two N-myristoyltransferases (NMT), NMT1 and NMT2, with varying expressions in AML cell lines and patient samples. We identified NMT2 expression as a marker for survival of patients with AML, and low NMT2 expression was associated with poor outcomes. We used the first-in-class pan-NMT inhibitor, zelenirstat, to investigate the role of N-myristoylation in AML. Zelenirstat effectively inhibits myristoylation in AML cell lines and patient samples, leading to degradation of Src family kinases, induction of endoplasmic reticulum stress, apoptosis, and cell death. Zelenirstat was well tolerated in vivo and reduced the leukemic burden in an ectopic AML cell line and in multiple orthotopic AML patient-derived xenograft models. The leukemia stem cell–enriched fractions of the hierarchical OCI-AML22 model were highly sensitive to myristoylation inhibition. Zelenirstat also impairs mitochondrial complex I and oxidative phosphorylation, which are critical for leukemia stem cell survival. These findings suggest that targeting N-myristoylation with zelenirstat represents a novel therapeutic approach for AML, with promise in patients with currently poor outcomes.
Data from Advances and Challenges in RAS Signaling Targeted Therapy in Leukemia
Authors: Chen Yu , Yin Zhenghao , Westover Kenneth D. , Zhou Zhiwei , Shu Liping
Published: January 2025

Abstract
RAS mutations are prevalent in leukemia, including mutations at G12, G13, T58, Q61, K117, and A146. These mutations are often crucial for tumor initiation, maintenance, and recurrence. Although much is known about RAS function in the last 40 years, a substantial knowledge gap remains in understanding the mutation-specific biological activities of RAS in cancer and the approaches needed to target specific RAS mutants effectively. The recent approval of KRASG12C inhibitors, adagrasib and sotorasib, has validated KRAS as a direct therapeutic target and demonstrated the feasibility of selectively targeting specific RAS mutants. Nevertheless, KRASG12C remains the only RAS mutant successfully targeted with FDA-approved inhibitors for cancer treatment in patients, limiting its applicability for other oncogenic RAS mutants, such as G12D, in leukemia. Despite these challenges, new approaches have generated optimism about targeting specific RAS mutations in an allele-dependent manner for cancer therapy, supported by compelling biochemical and structural evidence, which inspires further exploration of RAS allele-specific vulnerabilities. This review will discuss the recent advances and challenges in the development of therapies targeting RAS signaling, highlight emerging therapeutic strategies, and emphasize the importance of allele-specific approaches for leukemia treatment.
Supplementary Table S3 from Loss of PI5P4Kα Slows the Progression of a Pten Mutant Basal Cell Model of Prostate Cancer
Authors: Triscott Joanna , Lehner Marika , Benjak Andrej , Reist Matthias , Emerling Brooke M. , Ng Charlotte K.Y. , de Brot Simone , Rubin Mark A.
Published: January 2025

Table S3. Crowley et al. markers for scRNA-Seq module scores
Supplementary Figure S8 from Loss of PI5P4Kα Slows the Progression of a Pten Mutant Basal Cell Model of Prostate Cancer
Authors: Triscott Joanna , Lehner Marika , Benjak Andrej , Reist Matthias , Emerling Brooke M. , Ng Charlotte K.Y. , de Brot Simone , Rubin Mark A.
Published: January 2025

Figure S8. Differentially abundant pathways and metabolites from targeting PIP4K2A.
Supplementary Figure S8 from N-Linked Fucosylated Glycans Are Biomarkers for Prostate Cancer with a Neuroendocrine and Metastatic Phenotype
Authors: Ippolito Joseph E. , Hartig Jordan P. , Bejar Kaitlyn , Nakhoul Hani , Sehn Jennifer K. , Weimholt Cody , Grimsley Grace , Nunez Elena , Trikalinos Nikolaos A. , Chatterjee Deyali , Kim Eric H. , Mehta Anand S. , Angel Peggi M. , Troyer Dean A. , Leach Robin J. , Corey Eva , Wu Jennifer D. , Drake Richard R.
Published: January 2025

Figure S8. Fucosylated glycan expression in tumors from prostatectomy specimens do not associate with PSA, grade, or stage.
Supplementary Figure S7 from Loss of PI5P4Kα Slows the Progression of a Pten Mutant Basal Cell Model of Prostate Cancer
Authors: Triscott Joanna , Lehner Marika , Benjak Andrej , Reist Matthias , Emerling Brooke M. , Ng Charlotte K.Y. , de Brot Simone , Rubin Mark A.
Published: January 2025

Figure S7. Immunohistochemical staining of CK5-PipPten model.
Supplementary Figure S6 from Loss of PI5P4Kα Slows the Progression of a Pten Mutant Basal Cell Model of Prostate Cancer
Authors: Triscott Joanna , Lehner Marika , Benjak Andrej , Reist Matthias , Emerling Brooke M. , Ng Charlotte K.Y. , de Brot Simone , Rubin Mark A.
Published: January 2025

Figure S6. Prostate morphology resulting from genomic loss of Pip4k2b isoform.
Supplementary Figure S3 from N-Linked Fucosylated Glycans Are Biomarkers for Prostate Cancer with a Neuroendocrine and Metastatic Phenotype
Authors: Ippolito Joseph E. , Hartig Jordan P. , Bejar Kaitlyn , Nakhoul Hani , Sehn Jennifer K. , Weimholt Cody , Grimsley Grace , Nunez Elena , Trikalinos Nikolaos A. , Chatterjee Deyali , Kim Eric H. , Mehta Anand S. , Angel Peggi M. , Troyer Dean A. , Leach Robin J. , Corey Eva , Wu Jennifer D. , Drake Richard R.
Published: January 2025

Figure S3. Ley expression in small cell prostate cancer.
Supplementary Figure 5 from B-type Plexins Regulate Mitosis via RanGTPase
Authors: Mukhwana Nicholus , Garg Ritu , Azad Abul , Mitchell Alexandria R. , Williamson Magali
Published: January 2025

Localisation of PlexinB1 and Sema4D in dividing cells
Figure S5 from The Distinct Roles of NEIL1 and XPA in Limiting Aflatoxin B1–Induced Mutagenesis in Mice
Authors: Luzadder Michael M. , Minko Irina G. , Vartanian Vladimir L. , Davenport Marten , Fedorov Lev M. , McCullough Amanda K. , Lloyd R. Stephen
Published: January 2025

Heatmap of cosine similarity scores
Figure S4 from The Distinct Roles of NEIL1 and XPA in Limiting Aflatoxin B1–Induced Mutagenesis in Mice
Authors: Luzadder Michael M. , Minko Irina G. , Vartanian Vladimir L. , Davenport Marten , Fedorov Lev M. , McCullough Amanda K. , Lloyd R. Stephen
Published: January 2025

Mutation frequencies of multiple nucleotide variants, deletions and insertions
Figure S3 from Depletion of Adipose Stroma-Like Cancer-Associated Fibroblasts Potentiates Pancreatic Cancer Immunotherapy
Authors: Rupert Joseph , Daquinag Alexes , Yu Yongmei , Dai Yulin , Zhao Zhongming , Kolonin Mikhail G.
Published: January 2025

A, Fig. 4 schematic testing if D-CAN synergizes with immune checkpoint blockade (aPDL1) in male and female mice. B, Initial body weights in experimental mice. C, Tumor weight from an experiment in female mice investigating the effects of D-CAN / aPDL1 with non-immune IgG and IgG + D-CAN data combined with Fig. 4B and 4D data. *=p<0.05, **=p<0.001, ***=p<0.0001. D, Metastatic liver tumor colony assay from mice in C.
Figure 4 from Depletion of Adipose Stroma-Like Cancer-Associated Fibroblasts Potentiates Pancreatic Cancer Immunotherapy
Authors: Rupert Joseph , Daquinag Alexes , Yu Yongmei , Dai Yulin , Zhao Zhongming , Kolonin Mikhail G.
Published: January 2025

ASC-like CAF depletion synergizes with immune checkpoint blockade. Following orthotopic grafting of KPC-Luc cells, female (N = 3 per group) and male (N = 3 per group) mice received PBS, D-CAN, aPDL1, or the combination D-CAN + aPDL1. A, IVIS images of two representative mice at day 22 showing the location of pancreatic primary tumor graft (arrow) and extrapancreatic area of tumor invasion and metastases (punctate). B, KPC tumor size upon resection from females and males. C, Paraffin sections of representative tumors subjected to αSMA and endomucin immunofluorescence. Scale bar, 50 μm. D, Quantification of KPC cells in livers based on colony counts. Images: representative wells. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001, ANOVA. Max, maximum; Min, minimum.
Teaching counts! Open Educational Resources as an object of measurement for scientometric analysis
Authors: Kullmann Sylvia
Published: January 2025

At present, performance assessment in science focuses mainly on scientific publications. Teaching is not given the same attention in the reward and recognition system, even though it is an integral part of science. Open Educational Resources (OER) are open teaching and learning materials, the creation and publication of which can, under certain conditions, be considered equivalent to other scientific output. A scientometric analysis of OER is in principle possible. However, as an object of measurement, OER show a number of peculiarities. These include often missing comprehensible quality assessments procedures, the treatment of OER versions regarding a sufficient level of creation, and the consideration of different granularities. This work discusses the special OER features in detail and suggests an applicable definition for OER in scientometric contexts. OER can have many different forms. To simplify measurability, the categories Dedicated Learning Content and Learning Design Content are proposed for use in scientometric analysis of OER. A third category, OER Ecosystem, is suggested for capturing services such as consulting, providing funding, or operating OER infrastructures that create an OER-conducive environment. In addition, practical challenges are considered, such as the separate collection of attribution and citation data for OER.
A new species of the genus Eurycotis Stål (Blattodea, Blattidae) from the eastern region of Cuba
Authors: GUTIÉRREZ ESTEBAN
Published: January 2025

A new species, Eurycotis armasi sp. nov. from the eastern region of Cuba (West Indies) is described. A taxonomic diagnosis is provided to distinguish the new taxon from the closest previously known species of the genus, E. galeoides Rehn & Hebard, 1927, and E. ferrumequinum Rehn & Hebard, 1927. The 19 Cuban species of the genus are summarised in a table with the respective authors, the years of publication and the type localities. Knowledge about the diversity of Eurycotis in the Cuban Archipelago increases to 20 species. The distribution of species and the future increase in diversity of the genus on the island are discussed.
The Importance of Perturbation Rank in Ensemble Simulations
Authors: Wu Pin-Ying , Kawabata Takuya , Duc Le
Published: January 2025

Ensemble simulations involve perturbations of error sources in numerical models to represent uncertainties. The rank of the perturbation matrix is expected to be equal to the ensemble size; thus, each ensemble member may have an independent perturbation. However, ensembles without independent perturbations for each member have been commonly adopted, and their impacts remain unknown. This study explores how a lack of perturbation rank affects the quality of an ensemble and its estimates. Focusing on mesoscale weather forecasts, lateral boundary conditions (LBCs) were considered since they are a primary source of uncertainty in regional models. Two sets of 1000-member ensemble simulations of Typhoon Hagibis (2019) were performed with different ranks of LBC perturbations (LBPs). A lack of perturbation rank caused members to cluster based on the given LBC because the LBCs strongly constrained the simulated states. This clustering is a sign of poor orthogonality, that is, a deficiency in the effective ensemble size. Clustering also implies distortion in the ensemble error space. A resulting spurious probability distribution can occur even when the ensemble mean and spread are valid. From the perspective of physical space, spurious probability distributions are caused by the clustering of typhoon locations and synoptic-scale environmental conditions owing to the lack of an LBP rank. Additionally, using positive and negative perturbation pairs was one cause of the perturbation rank defect. Our findings highlight the importance of the perturbation rank, particularly for high-order estimates of probability distributions with large ensembles.

Significance Statement

Ensemble methods address uncertainty in weather forecasts by presenting possible scenarios through simulations with small differences or perturbations in numerical model components that affect forecasts. This study examines how a lack of independent perturbations in the model’s lateral boundary conditions affects the quality of a large ensemble with 1000 scenarios of typhoon forecasts. The results demonstrated that a lack of independent perturbations damaged the ensemble scenario variety. This damage led to spurious estimates of ensemble probability distributions. The findings suggest that a large ensemble requires independent perturbations corresponding to its size to adequately provide advanced probability estimates.
Hearing Impairment in Oral Submucous Fibrosis: A Systematic Review
Authors: Krithika Chandrasekaran , Deshpande Ashwini , Sridhar Chitathoor , Kondreddy Kameswari , Byatnal Amit
Published: January 2025

Background: With serious oral and systemic implications, oral submucous fibrosis (OSMF) is a crippling disorder that is common in some areas, especially among areca nut chewers. A thorough investigation of the relationship between OSMF and hearing impairment is necessary due to the growing evidence that, despite its well-established effects on dental health, there may be a connection. Aim: To investigate the association between OSMF and hearing impairment, particularly the mechanisms behind Eustachian tube dysfunction (ETD) and auditory dysfunction in OSMF patients. Methodology: This systematic review aimed to assess the association between hearing impairment and OSMF using the PICOS framework. A comprehensive search of 1137 articles published between 2015 and 2024 across various databases was conducted, resulting in 18 studies meeting the inclusion criteria. Data on population demographics, audiological assessments, and outcomes were extracted independently by 3 reviewers. The quality of the included studies was evaluated using the Cochrane Risk of Bias Tool and the Newcastle–Ottawa Scale. Risk of bias assessments was conducted to categorize studies as low, moderate, or high risk. Results: The review identified 18 studies examining the link between OSMF and hearing impairment, revealing a significant correlation between OSMF severity and hearing loss. Patient-reported hearing issues ranged from 27.69% to 76.7%. Conductive hearing loss was prevalent, particularly in advanced OSMF stages. Most studies employed pure tone audiometry and tympanometry, highlighting ETD as a common contributor. Quality assessments indicated that most studies had good methodological rigor, with several rated as very good, underscoring the need for comprehensive evaluations in understanding the audiological implications of OSMF. Conclusion: There is a substantial association between OSMF and hearing loss, particularly through ETD. Multidisciplinary management and early audiological screening are essential for improving outcomes in OSMF patients.
Longitudinal Changes in Medial Meniscal Extrusion After ACL Injury and Reconstruction and Its Relationship With Cartilage Degeneration Assessed Using MRI-Based T1ρ and T2 Analysis
Authors: Watanabe Shotaro , Joseph Gabby B. , Sato Dai , Lansdown Drew A. , Brandao Guimaraes Julio , Link Thomas M. , Ma Chunbong Benjamin
Published: January 2025

Background:

Anterior cruciate ligament (ACL) injury often leads to posttraumatic osteoarthritis (PTOA), despite ACL reconstruction (ACLR). Medial meniscal extrusion (MME) is implicated in PTOA progression but remains understudied after ACL injury and ACLR.

Hypothesis/Purpose:

It was hypothesized that MME would increase longitudinally after ACL injury and ACLR, with greater changes in the ipsilateral knee compared with the contralateral knee, leading to cartilage degeneration. The study aimed to assess MME 3 years after ACLR and its relationship with magnetic resonance imaging (MRI) T1ρ and T2 as cartilage degeneration markers.

Study Design:

Cohort study; Level of evidence, 2.

Methods:

MME and relative percentage of extrusion (RPE) were measured on 3 coronal slices of 3-dimensional fast spin-echo images and the mean values were used. T1ρ and T2 sequences were obtained and cartilage compositional measurements were performed using in-house developed software with MATLAB. Mixed models were used to assess the longitudinal changes and linear regression was used to assess the relationships between RPE and T1ρ and T2 values.

Results:

A total of 54 participants with unilateral ACL injuries underwent preoperative bilateral knee MRI. A total of 36 participants completed MR scans at 6 months and 3 years after ACLR. MME and RPE measurements demonstrated high reliability (ICC > 0.88 and > 0.91, respectively). The predicted values of MME and RPE from the mixed models showed that the ipsilateral side had significantly greater MME and RPE than the contralateral side at all 3 time points ( P = .023 for MME; P = .013 for RPE at baseline; and P < .001 at 6 months and P < .001 at 3 years for both MME and RPE). The rate of change of MME and RPE on the ipsilateral side was significantly greater than that on the contralateral side ( P < .001). Postoperative RPE was associated with T1ρ and T2 values in the posterior medial femoral condyle.

Conclusion:

MME and RPE obtained pre- and postoperatively after ACLR on the ipsilateral side were significantly greater than those on the contralateral side, and the longitudinal increases on the ipsilateral side were greater than those on the contralateral side. Postoperative RPE was significantly associated with cartilage degeneration in the posterior medial femoral condyle.
Peripheral creator labor: Navigating regional marginalization and resistance in social media entertainment
Authors: Salamon Errol
Published: January 2025

This article examines how social media creators in the United Kingdom navigate regional labor dynamics in small urban cities and towns and their perceptions of potential resistance strategies. Grounded in a creator workers’ inquiry and thematic analysis of in-depth interviews with creators ( N  = 53), it expands the notion of peripheral creator labor. It reveals how digital factors and historically entrenched regional disparities exacerbate the global platform precarity experienced by different types of peripheral creators and the relative privilege of peripheral English-language Western-based creators. The study introduces the concepts of regional monetization precarity and localized production space and networking precarity to capture the unique challenges creators face in small urban cities and their shared strategic resistance strategies to effect change, combining professional support and unionization. This study contributes to theoretical understandings of creator labor by challenging a binary notion of “center-periphery” relations and a homogeneous Western user experience in creator economies.
Corruption and the social legitimacy of the welfare state: A comparative cross-national analysis
Authors: Basna Kristyna , Gugushvili Dimitri
Published: January 2025

In addition to reducing the effectiveness of welfare policies, a high level of corruption is argued to undermine the social legitimacy of the welfare state. In the current article, we subject this hypothesis to an empirical test by analyzing data from two rounds of the International Social Survey Program. We find that people have a greater preference for an extensive welfare state in countries where corruption is more widespread. Similarly, at the micro level, perceived corruption is associated with more support for welfare policies, though people who have experienced corruption show less support than others for welfare. The extent of corruption in a country also moderates the effects of two primary determinants of welfare preferences – self-interest and political affiliation.
Addressing the Presence of Arsenical Bindings in the British Library’s Collections
Authors: Baldwin Amy , Garside Paul , Monjeau Nicole
Published: January 2025

This paper covers our ongoing work to address the presence of copper acetoarsenite in nineteenth-century book materials at the British Library. We focus upon the challenges of identifying arsenical materials within a collection of over 100 million items stored in multiple locations, and detail the health and safety procedures specific to these materials which we are developing for Library staff and for the public. Since beginning this work in early 2020 it has been apparent to us that the scale of British Library’s collections, storage infrastructures, and institutional procedures would pose unique challenges. Methods for identifying arsenical book materials adopted within smaller institutions are not feasible within an organization of the size and complexity of the British Library, and our challenge has been to design an accessible, streamlined system which enables identification, limitation of exposure, and safe handling when necessary. Developing methods of identification has gone hand in hand with developing bespoke health and safety practices, as any staff who handle collection items are potentially at risk of exposure. Communication with internal stakeholders has emphasized the importance of existing health and safety measures while working collaboratively to develop new bespoke solutions to protect staff and readers.
Central statistical monitoring in clinical trial management: A scoping review
Authors: Fronc Maciej , Jakubczyk Michał , Love Sharon B , Talbot Susan , Rolfe Timothy
Published: January 2025

Background:

Clinical trials handle a huge amount of data which can be used during the trial to improve the ongoing study conduct. It is suggested by regulators to implement the remote approach to evaluate clinical trials by analysing collected data. Central statistical monitoring helps to achieve that by employing quantitative methods, the results of which are a basis for decision-making on quality issues.

Methods:

This article presents a scoping review which is based on a systematic and iterative approach to identify and synthesise literature on central statistical monitoring methodology. In particular, we investigated the decision-making processes (with emphasis on quality issues) of central statistical monitoring methodology and its place in the clinical trial workflow. We reviewed papers published over the last 10 years in two databases (Scopus and Web of Science) with a focus on data mining algorithms of central statistical monitoring and its benefit to the quality of trials.

Results:

As a result, 24 scientific papers were selected for this review, and they consider central statistical monitoring at two levels. First, the perspective of the central statistical monitoring process and its location in the study conduct in terms of quality issues. Second, central statistical monitoring methods categorised into practices applied in the industry, and innovative methods in development. The established methods are discussed through the prism of categories of their usage. In turn, the innovations refer to either research on new methods or extensions to existing ones.

Discussion:

Our review suggests directions for further research into central statistical monitoring methodology – including increased application of multivariate analysis and using advanced distance metrics – and guidance on how central statistical monitoring operates in response to regulators’ requirements.
Innovative payloads for ADCs in cancer treatment: moving beyond the selective delivery of chemotherapy
Authors: Izzo Davide , Ascione Liliana , Guidi Lorenzo , Marsicano Renato Maria , Koukoutzeli Chrysanthi , Trapani Dario , Curigliano Giuseppe
Published: January 2025

Antibody–drug conjugates (ADCs) have emerged as a transformative approach in cancer therapy by enhancing tumor targeting and minimizing systemic toxicity compared to traditional chemotherapy. Initially developed with chemotherapy agents as payloads, ADCs have now incorporated alternative payloads, such as immune-stimulating agents, natural toxins, and radionuclides, to improve therapeutic efficacy and specificity. A significant advancement in ADC technology is the integration of Proteolysis Targeting Chimeras (PROTACs), which enable the precise degradation of cellular targets involved in tumorigenesis. This strategy enhances the specificity and precision of cancer therapies, addressing key mechanisms in cancer cell survival. Moreover, incorporating radioactive isotopes into ADCs is an emerging strategy aimed at further improving therapeutic outcomes. By delivering localized radiation, this approach offers the potential to enhance the efficacy of treatment and expand the therapeutic arsenal. Despite these innovations, challenges remain, including dysregulated immune activation, severe adverse effects, and intrinsic immunogenicity of some agents. These emerging issues highlight the ongoing need for optimization in ADC therapy. This review summarizes the latest developments in ADC technology, focusing on novel payloads, PROTAC integration, and the potential for combining ADCs with other therapeutic modalities to refine cancer treatment and improve patient outcomes.
Age-stratified analysis of adverse event signals for clarithromycin: a disproportionality analysis using the FDA Adverse Event Reporting System
Authors: Mai Haiyan , Zhang Zhenpo , Liang Yankun , Zheng Jingping , Su Ling
Published: January 2025

Background:

Clarithromycin is a widely used antibiotic, but its safety profile, particularly in different age groups, remains inadequately explored.

Objectives:

This study aims to characterize and illustrate the features of clarithromycin-related adverse events (AEs) across different age groups using the FDA Adverse Event Reporting System (FAERS) database, providing a reference for the clinical detection, prevention, and management of AEs in various age groups.

Design:

A disproportionality analysis was performed using data from the FAERS database. The study included all AE reports related to clarithromycin, stratified by age groups.

Methods:

Disproportionality analysis was conducted using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multiple gamma Poisson shrinkers. Statistical analyses included descriptive statistics and Chi-square tests.

Results:

A total of 7319 reports of clarithromycin AEs were retrieved from the FAERS database. Vomiting, diarrhea, drug interactions, and drug interactions were reported most frequently in the age groups 0–17, 18–44, 45–64, and ⩾65 years, respectively. Abnormal product taste, taste disorder, and medication errors related to drug interactions specified in the package insert were the strongest signals in the age groups 0–17, 18–44, 45–64, and ⩾65 years, respectively. A total of 41 Preferred Terms signals were not explicitly included in the clarithromycin package insert and were mainly associated with psychiatric disorders, skin and subcutaneous tissue disorders, and gastrointestinal disorders, among others. Specific signals for age differences were identified, with 18 signals being age-specific, including 3 in children and 15 in elderly individuals.

Conclusion:

The safety profile of clarithromycin varies across age groups. In children, it is mainly associated with vomiting, hypersensitivity, and dyspnea, while in adults, psychiatric AEs are more common. In the elderly, clarithromycin should be used cautiously, with attention to drug interactions.
The Role of Digital Therapy in Promoting Post-Secondary Student Mental Health
Authors: Austin Sydney , Bandealy Ahad , Cawley Elizabeth
Published: January 2025

Post-secondary mental health has reached crisis levels. Students attending post-secondary institutions such as universities, colleges, and trade schools are facing higher rates of negative mental health symptoms than before the pandemic, and have a higher prevalence of mental illnesses than found in the general population. Barriers to accessing mental health support prove to be a major obstacle for students—many of whom do not seek professional help when they need it. This mental health crisis is particularly poignant within marginalized student populations who face higher rates of mental illness as well as intersecting barriers to accessing support. Examples include cultural norms, chronic stress related to ongoing discrimination, and language barriers. Digital therapy presents a novel method of delivering mental health support and increasing accessibility to students in need. Mental health issues among post-secondary students, the barriers to care that they are facing, and specific digital mental health platforms to increase accessibility are outlined in this article.
Rapid quantitative PCR on tongue swabs for pulmonary tuberculosis in adults: a prospective multicentre study
Authors: Wang Yilin , Cui Junwei , Li Yuanyuan , Wang Miao , Han Wenge , Liu Aimei , Wang Furong , Liu Rongmei , Kang Shuhui , Zhang Jianping , Zhu Sihong , Lai Zhonghai , Guan Wenlong , Zou Shaomu , Yin Xiangyu , Qing JianZhi , Mu Guilan , Guan Liying , Li Liang , Pang Yu
Published: January 2025

Background

Tuberculosis (TB) remains a major cause of infectious disease mortality globally, with significant underdiagnosis perpetuating transmission. Tongue swab analysis has emerged as a promising non-invasive method for pulmonary TB diagnosis. This study evaluates the diagnostic accuracy of the TB-EASY quantitative PCR (qPCR) assay using tongue swab specimens.

Methods

In this prospective multicentre study, conducted across seven designated TB hospitals in China, 729 participants were included in the analysis. Tongue swabs were tested using the new TB-EASY assay from Hugobiotech, while sputum samples were analysed by Xpert MTB/RIF (Xpert), smear and culture tests. Diagnostic performance was compared to a composite microbiological reference standard (MRS).

Results

The TB-EASY assay demonstrated high diagnostic accuracy, with sensitivity and specificity of 89.6% and 96.2% compared to sputum Xpert, and 87.4% and 98.0% compared to the MRS. Sensitivity varied by bacterial load, ranging from 100% in high-load cases to 70.4% in very-low-load cases. The assay demonstrated robust performance in diverse epidemiological settings.

Conclusions

The TB-EASY qPCR assay using tongue swabs offers a reliable, non-invasive diagnostic alternative for pulmonary TB, especially where sputum collection is challenging. Its potential for wider use in high TB burden settings warrants further validation in community-based studies. Limitations include potential overestimation of sensitivity due to the selection of symptomatic patients and the use of sputum Xpert rather than Xpert Ultra. Additionally, the performance in non-sputum-producing patients remains untested, and the cost-effectiveness should be further evaluated to assess the feasibility of its implementation.
Traumatic head injuries in children: demographics, injury patterns, and outcomes in Saudi Arabia
Authors: Albargi Hussin , Alharbi Rayan Jafnan , Almuwallad Ateeq , Harthi Naif , Khormi Yahya , Kanthimathinathan Hari Krishnan , Chowdhury Sharfuddin
Published: January 2025

Background

Traumatic head injuries (THIs) are among the leading cause of mortality and intensive care unit (ICU) admission in children worldwide. Most of the published literature concerning THIs arises predominantly from North America and Europe. However, only limited data about the incidence, characteristics and impact on children in Saudi Arabia exists.

Methods

We conducted a retrospective analysis of THIs in children (≤ 18 years of age) using data from the Saudi TraumA Registry (STAR) from August 2017 to December 2022. Data included patient demographic characteristics, the mechanism, type and severity of injury. We used multivariable logistic regression to assess the association between outcomes and clinical factors.

Results

We identified 466 children with THI. Most children were over six years of age (69.5%) and male (76.6%). Motor vehicle crashes (MVCs) were the most common cause of THIs (51.9%), with falls being more common in infants (69.8%). Over half of the children required ICU admission. Children with higher injury severity score, heart rate at presentation to the ED, hospital stay duration, respiratory assistance and need for surgery were more likely to require ICU admission. The overall mortality rate was 7.7%, with schoolchildren (age: 6–12 years) having the highest mortality rate (10.8%). Higher rates of ICU admission were associated with increases in the injury severity score (ISS), hospital stay duration, respiratory assistance and the need for surgery.

Conclusions

Children in the 6–12 year age-group had the highest mortality rate, reflecting high injury severities associated with increased ICU admissions. These findings highlight the importance of targeting preventive measures for MVCs in older children and improving trauma care for severe cases.

Clinical trial number

Not applicable.
Cross-cultural adaptation and validation of the Chinese version of the modified Fresno test for physical therapists
Authors: Chen Li-Yang , Lue Yi-Jing , Wu Po-Hsun , Kuo Yi-Liang
Published: January 2025

Background

The modified Fresno test was developed to assess knowledge and skills related to evidence-based practice among physical therapists and students, however no Chinese version is available. Therefore, the aim of this study was to cross-culturally adapt the English version of the modified Fresno test into Chinese and to evaluate its validity and reliability.

Methods

This was a cross-sectional validation study. During Phase 1 cross-cultural adaptation, forward translation, synthesis, back-translation, expert review, and prefinal test were carried out. Content validity was analyzed. During Phase 2 validation, two groups representing different levels of evidence-based practice competence completed the tests twice, two weeks apart. Known-group validity, internal consistency, and test-retest reliability were analyzed.

Results

Phase 1: According to the expert review, the Chinese version of the modified Fresno test demonstrated good content validity (item-level content validity index = 0.93 to 1.0; scale-level content validity index = 0.99). Phase 2: The expert group scored (115.3 ± 36.2) significantly higher than the novice group did (79.7 ± 25.8) for the entire test (p = 0.01), suggesting good known-group validity. However, the superior performance of the expert group over the novice group was not consistently found across all the questions on the test. In addition, the internal consistency was good (Cronbach’s α = 0.96) and the test-retest reliability (ICC2,1 = 0.89, 95% CI = 0.81 to 0.94) was good to excellent.

Conclusions

The Chinese version of the modified Fresno test is a valid and reliable tool for objectively assessing evidence-based practice knowledge and skills in Chinese-speaking physical therapists and students.
Specifically blocking αvβ8-mediated TGF-β signaling to reverse immunosuppression by modulating macrophage polarization
Authors: Guo Cuicui , Sun Hui , Du Yulei , Dai Xiaodong , Pang Yu , Han Zhen , Xiong Xinhui , Li Shaowei , Zhang Junhua , Zheng Qingbing , Gui Xun
Published: January 2025

Background

Targeting the TGF-β pathway in tumor therapy has proven challenging due to the highly context-dependent functions of TGF-β. Integrin αvβ8, a pivotal activator of TGF-β, has been implicated in TGF-β signaling within tumors, as demonstrated by the significant anti-tumor effects of anti-αvβ8 antibodies. Nevertheless, the expression profile of αvβ8 remains a subject of debate, and the precise mechanisms underlying the anti-tumor effects of anti-αvβ8 antibodies are not yet fully elucidated.

Methods

We utilized single-cell RNA sequencing to assess αvβ8 expression across various human tumors. An anti-αvβ8 antibody was developed and characterized for its binding and blocking properties in vitro. Cryo-EM single-particle analysis was employed to study the detailed interaction between αvβ8 and the antibody Fab fragment. The anti-tumor efficacy of the antibody was evaluated in syngeneic mouse models with varying levels of αvβ8 expression, both as a monotherapy and in combination with PD-1 antibodies. Human PBMCs were isolated to investigate αvβ8 expression in myeloid cells, and macrophages were exposed to the antibody to study its impact on macrophage polarization. Pharmacokinetic studies of the αvβ8 antibody were conducted in cynomolgus monkeys.

Results

Integrin αvβ8 is notably expressed in certain tumor types and tumor-infiltrating macrophages. The specific αvβ8 antibody 130H2 demonstrated high affinity, specificity, and blocking potency in vitro. Cryo-EM analysis further revealed that 130H2 interacts exclusively with the β8 subunit, without binding to the αv subunit. In vivo studies showed that this antibody significantly inhibited tumor growth and alleviated immunosuppression by promoting immune cell infiltration. Furthermore, combining the antibody with PD-1 inhibition produced a synergistic anti-tumor effect. In human PBMCs, monocytes exhibited high αvβ8 expression, and the antibody directly modulated macrophage polarization. Tumors with elevated αvβ8 expression were particularly responsive to 130H2 treatment. Additionally, favorable pharmacokinetic properties were observed in cynomolgus monkeys.

Conclusions

In summary, integrin αvβ8 is highly expressed in certain tumors and tumor-infiltrating macrophages. Targeting αvβ8 with a blocking antibody significantly inhibits tumor growth by modulating macrophage polarization and enhancing immune cell infiltration. Combining αvβ8 targeting with PD-1 treatment markedly increases the sensitivity of immune-excluded tumors. These results support further clinical evaluation of αvβ8 antibodies.

Graphical abstract
The effect of fintech M&As on short-term stock return in the context of macroeconomic environment
Authors: Ochirova Elena , Miriakov Mikhail
Published: January 2025

Mergers and acquisitions (M&A) with financial technology (fintech) companies can be an effective way for firms to obtain new technologies and capabilities. However, the market reaction to fintech M&A announcements has received limited attention in the empirical academic literature. This study assesses the impact of fintech M&As on stock returns and examines whether macroeconomic variables influence the abnormal return of fintech M&As. Using event study analysis, we found that fintech M&A announcements generate a significant positive short-term abnormal return. Furthermore, we demonstrated that macroeconomic parameters, including Gross domestic product (GDP) growth, inflation rate, the share of services in GDP, and aggregate export growth, positively affect abnormal returns. In contrast, private investment, consumer spending, and an economy’s size negatively influence fintech M&As’ abnormal returns.
Unlocking the diversification benefits of DeFi for ASEAN stock market portfolios: a quantile study
Authors: Ali Shoaib , Manel Youssef
Published: January 2025

This study examines the return connectedness between decentralized finance (DeFi)’s and the Association of Southeast Asian Nations (ASEAN) stock markets using the quantile vector autoregressive framework, which allows us to investigate the connectedness at conditional quantiles. Our sample includes four major DeFi’s and six ASEAN stock markets, spanning from March 2018 to December 2022. The static results indicate a moderate level of return transmission between the system at mean and median quantile. This propagation increases substantially under extreme market conditions, establishing an asymmetric transmission across quantiles. Despite being a relatively new asset class, DeFi dominates the equity market and acts as the primary shock transmitter to the system in most instances. The dynamic analysis reveals that total system connectedness fluctuates over time and quantiles. The total system connectedness peaked during the COVID-19 and the Russia–Ukraine conflict period, indicating the impact of global events on system transmission. The optimal weight and hedge ratio estimated using the DCC-GARCH model indicate that DeFi is beneficial for portfolio construction and risk management. The rising trend in dynamic optimal weight and hedge ratio during the COVID-19 pandemic demonstrates that investors should decrease their investments in DeFi and increase hedging costs. Therefore, portfolio managers and investors should readjust their portfolio allocation in a timely manner according to different market states to build additional effective hedging and diversification strategies to avoid large losses and to reduce portfolio risk exposure.
A novel recycling technology for chrome shavings: efficient separation of chromium and collagen fibers based on swelling inhibition in alkali-acid processing
Authors: Chen Honghong , Li Minghui , Chattha Sadaqat Ali , Zhang Xu , Peng Biyu , Zhang Chunxiao
Published: January 2025

Dechroming techniques with a low degree of collagen hydrolysis and a high degree of dechroming are more suitable for the resource utilization of chrome shavings. However, achieving efficient simultaneous separation of chromium and collagen fibers is challenging because swollen collagen fibers absorb a large amount of chromium-containing water and are prone to hydrolysis after dechroming. This study investigated the correlation between the swelling inhibition of collagen fibers and the extent of dechroming and optimized the process parameters. The results demonstrated that the incorporation of neutral salt significantly increased the rate of dechroming and reduced the degree of collagen hydrolysis. The optimized alkali-acid-washing process was as follows: soaking in a Na2SO4 solution (4%, w/w), dechroming with a NaOH solution at pH 13.5, rapidly adjusting the pH of reactants to 1.0 with an H2SO4 solution, pressure filtration, washing the filtered residue with 5% Na2SO4 solution (w/w) at pH 1.0, followed by pressure filtration. After two cycles of the alkali-acid-washing process, the filtered residue was washed with an oxalic acid-Na2SO4 solution (5%, w/w) and pressure-filtered again. The chromium content of recovered collagen was reduced to 34.0 mg/kg. The degree of collagen hydrolysis was confined to 9% with the fiber morphology completely retained. The wastewater chromium content was reduced to 0.4 mg/L after the simple precipitation, meeting the direct discharge requirement. The recycled chrome was utilized as chrome-tanning agent. These results suggested that the established method could be a promising resource reutilization route for the sustainable development of the leather industry.

Graphical abstract
Advances in the molecular mechanism of grapevine resistance to fungal diseases
Authors: Li Zhi , Wu Ronghui , Guo Fangying , Wang Yuejin , Nick Peter , Wang Xiping
Published: January 2025

Grapevine is an important economic fruit tree worldwide, but grape production has been plagued by a vast number of fungal diseases, which affect tree vigor and the quality and yield of berries. To seek remedies for such issues, researchers have always been committed to conventional and biotechnological breeding. In recent years, increasing progress has been made in elucidating the molecular mechanisms of grape–pathogenic fungi interactions and resistance regulation. Here, we summarize the current knowledge on the molecular basis of grapevine resistance to fungal diseases, including fungal effector-mediated susceptibility and resistance, resistant regulatory networks in grapevine, innovative approaches of genetic transformation, and strategies to improve grape resistance. Understanding the molecular basis is important for exploring and accurately regulating grape resistance to fungal diseases.
Geophysics Bright Spots
Authors: Behura Jyoti
Published: January 2025

Geophysics Bright Spots reviews a number of interesting research articles from recent issues of the journal Geophysics.
Appetite-related Gut Hormone Responses to Feeding Across the Life Course
Authors: Holliday Adrian , Horner Katy , Johnson Kelsie O , Dagbasi Aygul , Crabtree Daniel R
Published: January 2025

Appetite-related hormones are secreted from the gut, signaling the presence of nutrients. Such signaling allows for cross-talk between the gut and the appetite-control regions of the brain, influencing appetite and food intake. As nutritional requirements change throughout the life course, it is perhaps unsurprising that appetite and eating behavior are not constant. Changes in appetite-related gut hormones may underpin these alterations in appetite and eating.

In this article, we review evidence of how the release of appetite-related gut hormones changes throughout the life course and how this impacts appetite and eating behaviour. We focus on hormones for which there is the strongest evidence of impact on appetite, food intake, and body weight: the anorexigenic glucagon like peptide-1, peptide tyrosine tyrosine, and cholecystokinin, and the orexigenic ghrelin. We consider hormone concentrations, particularly in response to feeding, from the very early days of life, through childhood and adolescence, where responses may reflect energy requirements to support growth and development. We discuss the period of adulthood and midlife, with a particular focus on sex differences and the effect of menstruation, pregnancy, and menopause, as well as the potential influence of appetite-related gut hormones on body composition and weight status. We then discuss recent advancements in our understanding of how unfavorable changes in appetite-related gut hormone responses to feeding in later life may contribute to undernutrition and a detrimental aging trajectory. Finally, we briefly highlight priorities for future research.
A comparative view of human and mouse telencephalon inhibitory neuron development
Authors: Chung Changuk , Girgiss Joseph , Gleeson Joseph G.
Published: January 2025

Human GABAergic inhibitory neurons (INs) in the telencephalon play crucial roles in modulating neural circuits, generating cortical oscillations, and maintaining the balance between excitation and inhibition. The major IN subtypes are based on their gene expression profiles, morphological diversity and circuit-specific functions. Although previous foundational work has established that INs originate in the ganglionic eminence regions in mice, recent studies have questioned origins in humans and non-human primates. We review the origins of INs in mice and compare with recent findings from primary human prenatal brain tissue culture experiments and lineage analysis from somatic variants in neurotypical human cadavers and human brain organoids. Together, these studies suggest potential primate- or human-specific processes that may have been overlooked in mouse models and could have implications for brain disorders.
The Ethics of War and Peace in Russian Philosophy and the Ethical Consequences of Modern Legal Precedents on Warfare and Armed Forces
Authors: Minchenko Tatiana
Published: January 2025

The first part of the study is devoted to a comparative analysis of the concepts of the Ethics of War and Peace in Russian philosophy and its influence on the world practice of nonviolence. The second part of the study is devoted to analyzing the impact of changes in legislation and law enforcement practice on the moral state of society concerning the Armed Forces and military operations after the collapse of the USSR. In conclusion, a summary of the research is given. The relevance of the ideas of Russian thinkers about the need for a clear definition of the concepts with which we describe reality, the relevance of non-violent conflict resolution, the priority of preserving and developing human-oriented culture, law and morality for the formation of a healthy society with the conditions of the Noosphere are drawn.