bluuebunny/crossref_metadata_2025 huggingface dataset:
AMEND 2.0: module identification and multi-omic data integration with multiplex-heterogeneous graphs
Authors: Boyd Samuel S. , Slawson Chad , Thompson Jeffrey A.
Published: February 2025

Background

Multi-omic studies provide comprehensive insight into biological systems by evaluating cellular changes between normal and pathological conditions at multiple levels of measurement. Biological networks, which represent interactions or associations between biomolecules, have been highly effective in facilitating omic analysis. However, current network-based methods lack generalizability to accommodate multiple data types across a range of diverse experiments.

Results

We present AMEND 2.0, an updated active module identification method which can analyze multiplex and/or heterogeneous networks integrated with multi-omic data in a highly generalizable framework, in contrast to existing methods, which are mostly appropriate for at most two specific omic types. It is powered by Random Walk with Restart for multiplex-heterogeneous networks, with additional capabilities including degree bias adjustment and biased random walk for multi-objective module identification. AMEND was applied to two real-world multi-omic datasets: renal cell carcinoma data from The cancer genome atlas and an O-GlcNAc Transferase knockout study. Additional analyses investigate the performance of various subroutines of AMEND on tasks of node ranking and degree bias adjustment.

Conclusions

While the analysis of multi-omic datasets in a network context is poised to provide deeper understanding of health and disease, new methods are required to fully take advantage of this increasingly complex data. The current study combines several network analysis techniques into a single versatile method for analyzing biological networks with multi-omic data that can be applied in many diverse scenarios. Software is freely available in the R programming language at https://github.com/samboyd0/AMEND.
Fine-tuning GBS data with comparison of reference and mock genome approaches for advancing genomic selection in less studied farmed species
Authors: Fischer Daniel , Tapio Miika , Bitz Oliver , Iso-Touru Terhi , Kause Antti , Tapio Ilma
Published: February 2025

Background

Diversifying animal cultivation demands efficient genotyping for enabling genomic selection, but non-model species lack efficient genotyping solutions. The aim of this study was to optimize a genotyping-by-sequencing (GBS) double-digest RAD-sequencing (ddRAD) pipeline. Bovine data was used to automate the bioinformatic analysis. The application of the optimization was demonstrated on non-model European whitefish data.

Results

DdRAD data generation was designed for a reliable estimation of relatedness and is scalable to up to 384 samples. The GBS sequencing yielded approximately one million reads for each of the around 100 assessed samples. Optimizing various strategies to create a de-novo reference genome for variant calling (mock reference) showed that using three samples outperformed other building strategies with single or very large number of samples. Adjustments to most pipeline tuning parameters had limited impact on high-quality data, except for the identity criterion for merging mock reference genome clusters. For each species, over 15k GBS variants based on the mock reference were obtained and showed comparable results with the ones called using an existing reference genome. Repeatability analysis showed high concordance over replicates, particularly in bovine while in European whitefish data repeatability did not exceed earlier observations.

Conclusions

The proposed cost-effective ddRAD strategy, coupled with an efficient bioinformatics workflow, enables broad adoption of ddRAD GBS across diverse farmed species. While beneficial, a reference genome is not obligatory. The integration of Snakemake streamlines the pipeline usage on computer clusters and supports customization. This user-friendly solution facilitates genotyping for both model and non-model species.
A sarcopenia prediction model based on the calf maximum muscle circumference measured by ultrasound
Authors: Wei An , Zou Yan , Tang Zhen-Hua , Guo Feng , Zhou Yan
Published: February 2025

Background

The correlation between calf circumference（CC）and sarcopenia has been demonstrated, but the correlation between calf maximum muscle circumference (CMMC) measured by ultrasound and sarcopenia has not been reported. We aims to construct a predictive model for sarcopenia based on CMMC in hospitalized older patients.

Methods

This was a retrospective controlled study of patients > 60 years of age hospitalized in the geriatric department of Hunan Provincial People’s Hospital. The patients were thoroughly evaluated by questionnaires, laboratory, and ultrasound examinations, including measuring muscle thickness and calf muscle maximum circumference using ultrasound. Patients were categorized into sarcopenia and non-sarcopenia groups according to the consensus for diagnosis of sarcopenia recommended by the Asian Working Group on Sarcopenia 2019 (AWGS2). Independent predictors of sarcopenia were identified by univariate and multivariate logistic regression analyses, and a predictive model was developed and simplified. The prediction performance of the models was assessed using sensitivity, specificity, and area under the curve (AUC) and compared with independent predictors.

Results

We found that patient age, albumin level (ALB), brachioradialis muscle thickness (BRMT), gastrocnemius lateral head muscle thickness (Glh MT), and calf maximum muscle circumference (CMMC) were independent predictors of sarcopenia in hospitalized older patients. The prediction model was established and simplified to Logistic P = -4.5 + 1.4 × age + 1.3 × ALB + 1.6 × BR MT + 3.7 × CMMC + 1.8 × Glh MT, and the best cut-off value of the model was 0.485. The sensitivity, specificity, and AUC of the model were 0.884 (0.807–0.962), 0.837 (0.762–0.911), and 0.927 (0.890–0.963), respectively. The kappa coefficient between this model and the diagnostic criteria recommended by AWGS2 was 0.709.

Conclusion

We constructed a sarcopenia prediction model with five variables: age, ALB level, BR MT, Glh MT, and CMMC. The model could quickly predict sarcopenia in older hospitalized patients.
Case report of glomerular histiocytosis associated with non-crystalline IgG-kappa paraproteinemia
Authors: Kishore Aditya , McRae Susanna A. , Telio David , Beaulieu Monica C.
Published: February 2025

Background

Monoclonal gammopathy of renal significance (MGRS) represents a range of disease processes arising from monoclonal proteins depositing in the kidney. These deposits vary and can be broadly grouped as containing a substructure or being non-organised. Their clinical phenotype can include proteinuria, haematuria, kidney injury and tubulopathies resulting in electrolyte changes.

Case presentation

Crystal storing histiocytosis (CSH) is a rare form of MGRS that typically deposits in the interstitium but rarely in the glomerulus to cause progressive kidney disease. We report a case of a male with known monoclonal protein and progressive proteinuria, whose biopsy showed glomerular histiocytosis with non-crystallizing IgG kappa inclusions.

Conclusion

This case reviews an unusual case of a glomerular histiocytosis with non-crystallizing IgG kappa inclusions.
Prevalence of mental disorders and work ability among unemployed individuals in Germany: a register-based analysis of socio-medical assessments by the Federal Employment Agency between 2016 and 2021
Authors: Roser Patrik , Manz Kirsi , Scherbaum Norbert , Lotz-Metz Gabriele , Franke Andreas G.
Published: February 2025

Background

The interactions between unemployment and mental health are complex. However, broad and current epidemiological data about the mental health status of unemployed individuals in Germany are scarce. This study aimed to evaluate the prevalence rates of mental disorders and work ability among all unemployed people who underwent socio-medical assessment by the Federal Employment Agency (FEA).

Methods

Socio-medical assessments between 2016 and 2021 were taken from the FEA database and analyzed regarding sociodemographic characteristics, mental disorders and work ability. Standard descriptive statistics were used to analyze the data.

Results

A total of 4,249,028 unemployed individuals were assessed. Of these, 2,213,048 persons (52.1%) had at least one psychiatric diagnosis (mean age 40.6 ± 13.5 years, 51.7% female). Mood disorders (53.9%), neurotic, stress-related and somatoform disorders (43.9%), as well as substance use disorders (15.3%) showed the highest prevalence rates among mental disorders and accounted for about 80% of all psychiatric diagnoses. About 40% of them were evaluated to be able to work full time.

Conclusions

Psychiatric morbidity among unemployed people is high. However, a significant proportion of them was assessed to be able to return to the labor market. Therefore, close collaborations between unemployment agencies and mental health care institutions as well as specific re-integration programs including supported job placement and vocational training, long-term job coaching as well as integrated mental health care are required in order to improve mental health status, prevent further chronification, avoid labor market exit, and increase employment rate.
Patients’ preferences on atopic dermatitis skincare and social media use: a qualitative study
Authors: Mazilu Roxana , Ziehfreund Stefanie , Traidl Stephan , Zink Alexander
Published: February 2025

Background

Atopic dermatitis (AD) is a chronic inflammatory disease with a complex pathophysiology, necessitating strict therapeutic management. Over-the-counter products play a crucial role in AD treatment. The emergence of social media (SM) as a vast information source for skincare and healthy lifestyle has transformed its role from mere entertainment. This study aimed to explore the attitudes of AD patients towards SM as an information source for their AD products, understand their purchase behavior, and identify unmet needs.

Methods

Qualitative semi-structured interviews were conducted with AD patients recruited from a university hospital in Southern Germany and social media networks. The interviews took place between November 2022 and January 2023. The recorded interviews were transcribed verbatim and analyzed using Mayring’s qualitative content analysis.

Results

A total of ten patients (3 men, 7 women) aged 23–42 years were interviewed. Participants reported new perspectives in four categories: opportunities and advantages of SM as information source for AD products, risks and disadvantages, important aspects for patients’ choice of AD products, and extent and purpose of SM use in selecting AD skincare.

Conclusions

Patients exhibit diverse patterns of SM use when selecting daily products and critically evaluate the online content, demonstrating a greater trust in healthcare professionals or familial connections. Electronic word-of-mouth, disease severity and prior product experiences emerge as prevalent factors influencing patients’ product selection. Furthermore, female patients express interest in complementary and alternative therapies as part of an integrative therapeutical approach. Understanding patients’ needs and preferences regarding AD skincare can inform physicians in recommending more personalized therapies. Additionally, educational interventions on SM, addressing patients’ questions and concerns with evidence-based information, hold the potential for beneficial outcomes.
Association of ambient temperatures with suicide attempts and violence with the future projections under climate change scenarios: a nationwide time-stratified case-crossover study in South Korea
Authors: Park Jiwoo , Oh Jieun , Lee Whanhee , Kim Yeonsu , Park Jeong Ho , Kim Ho , Hwang Seungsik
Published: February 2025

Background

Both climate change and intentional injuries (suicide attempts and violence) are recognized as crucial factors that affect human health. Previous studies revealed the association between ambient temperatures and deaths due to intentional injuries but mostly about the consequences of severe events. Our study aimed to examine suicide attempts and violence incidence including mild and moderate cases with future projections, using each injury’s burden about climate change scenarios.

Methods

We collected nationally representative cases of suicide attempts (8,512 cases) and violence (9,742 cases) from the Korea National Hospital Discharge In-depth Injury Survey from 2005 to 2019. We performed a two-stage analysis with a time-stratified case-crossover design to evaluate the associations of outdoor temperatures with suicide attempts and violence using historical data (2005–2019). Based on the estimated associations in the historical period, we projected the excess suicide attempts and violence attributable to ambient temperatures in the future (2020–2099) using the three shared socioeconomic pathway (SSP) scenarios.

Results

We found positive associations between outdoor temperatures with suicide attempts and violence individually, and the association with violence was more linear. The excess suicide attempts attributable to temperatures in the historical period were around 11%, and it was expected to increase in all SSP scenarios (up to 14.35%). For violence, the excess risk of violence attributable to temperatures in the historical period was around 3.5%, and it was also estimated to increase in the future (up to 7.92%).

Conclusions

The nationwide study about South Korea shows that there are associations between an increase in outdoor temperatures and increased risks of suicide attempts and violence, and each excess injury related to temperature is projected to grow under the SSP scenarios. Our findings might provide informative evidence for relevant action plans against climate change and intentional injuries.
A ribodepletion and tagging protocol to multiplex samples for RNA-seq based virus detection: application to the cassava virome
Authors: Otron Daniel H. , Pita Justin S. , Hoareau Murielle , Tiendrébéogo Fidèle , Lett Jean-Michel , Lefeuvre Pierre
Published: February 2025

Background

Cassava (Manihot esculenta, Crantz), is a staple food and the main source of calories for many populations in Africa, but the plant is beset by several damaging viruses. So far, eight families of virus infecting cassava have been identified; the Geminiviridae (ssDNA viruses responsible for cassava mosaic disease, CMD) and Potyviridae (ssRNA + viruses responsible for cassava brown streak disease, CBSD) families being the most damaging to cassava in Africa. In several cassava-growing regions, the co-existence of species and strains from these two families results in a complex epidemiological situation making it difficult to correctly identify the viruses in circulation and delaying the implementation of disease management schemes. Nevertheless, the development of next generation sequencing (NGS) methods has revolutionized plant virus detection and identification. One NGS method that has been successfully used in virus detection and identification is ribodepleted RNA sequencing. Unfortunately, the relatively high cost makes it difficult to upscale this method to large epidemiological surveys and limits its adoption as a diagnostic tool.

Results

Here, we develop a high-throughput sequencing protocol, named Ribo-M-Seq, that combines plant rRNA ribodepletion, cDNA synthesis, tagging with a 96 multiplexing scheme and Illumina sequencing. We evaluated the protocol on a series of cassava samples with a known assemblage of viruses. After confirming that the protocol was suitable for ribodepletion, we demonstrated it was possible to detect RNA and DNA viruses via identification of near full-size genomes. Additional phylogenetic analyses confirmed the presence of begomoviruses and ipomoviruses responsible for CMD and CBSD, respectively. We also detected a recently described ampelovirus (Manihot esculenta-associated virus) that was not detected in previous analyses.

Conclusions

The use of the Ribo-M-Seq protocol will pave the way for large-scale sample analyses of collections with potentially complex viromes, such as those collected in the West African cassava integrated pest management program.
Supported biopsychosocial self-management for back-related leg pain: a randomized feasibility study integrating a whole person perspective
Authors: Leininger Brent , Evans Roni , Greco Carol M. , Hanson Linda , Schulz Craig , Schneider Michael , Connett John , Keefe Francis , Glick Ronald M. , Bronfort Gert
Published: February 2025

Background

There is limited high-quality research examining conservative treatments for back-related leg pain (BRLP). This feasibility study was done in preparation for a full-scale trial comparing a whole-person supported self-management intervention to medical care for chronic BRLP.

Methods

Participants were randomized to 12 weeks of individualized supported self-management delivered by physical therapists and chiropractors or medical care consisting of guideline-based pharmacologic care. Supported self-management was based on a behavioral model that used a whole person approach to enhance participants capabilities, opportunities, and motivations to engage in self-care. It combined BRLP education with psychosocial strategies (e.g., relaxed breathing, progressive muscle relaxation, guided imagery, communication skills) and physical modalities such as exercise and spinal manipulation therapy. Providers were trained to address participants’ individualized needs and use behavior change and motivational communication techniques to develop a therapeutic alliance to facilitate self-management. Feasibility was assessed using pre-specified targets for recruitment and enrollment, intervention delivery, and data collection over the six-month study period. In addition, areas for potential refinement and optimization of processes and protocols for the full-scale trial were assessed.

Results

We met or exceeded nearly all feasibility targets. Forty-two participants were enrolled over a six-month period in 2022 and very few individuals declined participation due to preferences for one treatment. All but one participant received treatment and 95% of participants attended the minimum number of visits (self-management = 6, medical care = 2). At 12 weeks, 95% of participants in the self-management group reported engaging in self-management practices learned in the program and 77% of medical care participants reported taking medications as prescribed. Satisfaction with the self-management intervention was high with 85% of participants reporting satisfaction with the program overall. Self-management intervention providers delivered all required activities at 72% of visits. Providers also noted some challenges navigating the shared decision-making process and deciding what self-management tools to prioritize. Over the six-month study period, completion rates were 91% for monthly surveys and 86% for weekly surveys.

Conclusion

We were able to demonstrate that a full-scale randomized trial comparing a whole-person supported self-management intervention to medical care for chronic BRLP is feasible and identified important areas for optimization.
The role of natural products targeting macrophage polarization in sepsis-induced lung injury
Authors: Li Yake , Ai Sinan , Li Yuan , Ye Wangyu , Li Rui , Xu Xiaolong , Liu Qingquan
Published: February 2025

Sepsis-induced acute lung injury (SALI) is characterized by a dysregulated inflammatory and immune response. As a key component of the innate immune system, macrophages play a vital role in SALI, in which a macrophage phenotype imbalance caused by an increase in M1 macrophages or a decrease in M2 macrophages is common. Despite significant advances in SALI research, effective drug therapies are still lacking. Therefore, the development of new treatments for SALI is urgently needed. An increasing number of studies suggest that natural products (NPs) can alleviate SALI by modulating macrophage polarization through various targets and pathways. This review examines the regulatory mechanisms of macrophage polarization and their involvement in the progression of SALI. It highlights how NPs mitigate macrophage imbalances to alleviate SALI, focusing on key signaling pathways such as PI3K/AKT, TLR4/NF-κB, JAK/STAT, IRF, HIF, NRF2, HMGB1, TREM2, PKM2, and exosome-mediated signaling. NPs influencing macrophage polarization are classified into five groups: terpenoids, polyphenols, alkaloids, flavonoids, and others. This work provides valuable insights into the therapeutic potential of NPs in targeting macrophage polarization to treat SALI.

Graphical Abstract
Protocol paper: randomized controlled trial of the smart online-to-offline model development for chronic diseases management through digital health in real world setting
Authors: Shin Jae Eun , Choi Juho , Lee Heejung , Lee Suk-Won , Oh Juhwan
Published: February 2025

Background

Chronic diseases such as diabetes and hypertension pose significant health and economic challenges globally, and South Korea is no exception. Innovative digital health services have the potential to revolutionize chronic disease management by providing patients with real-time, personalized care and empowering them to take an active role in their health. There is a critical need to evaluate the effectiveness of such services. This protocol describes a randomized controlled trial that evaluates the effectiveness of an online-to-offline (O2O) digital healthcare service for patients with chronic diseases, specifically diabetes and hypertension, in Pyeongchang-gun.

Methods

This study presents a comprehensive protocol for the assessment of an online-to-offline (O2O) digital health service model aimed at managing chronic diseases. The study consists of two main groups of participants: those with diabetes and those with hypertension. Participants are randomized into treatment and control arms for each group. The intervention includes personalized digital healthcare support, continuous data monitoring, and online education, with primary care provided by healthcare professionals. To evaluate the primary and secondary outcomes—such as HbA1c, systolic blood pressure, and cholesterol levels—the study applies a range of statistical methods. These include intention-to-treat (ITT) analysis to account for all randomized participants, regression models to estimate the treatment effect, and adjustments for baseline covariates to improve precision. Subgroup analyses will explore variations in treatment effects based on factors such as intervention intensity, comorbidity, and healthcare provider.

Discussion

This protocol outlines a novel approach to evaluating the O2O digital health service model for chronic disease management. It offers insights into the nuanced effects of the intervention, highlighting the potential for tailoring future interventions for maximum benefit. By assessing its real-world effectiveness, this study can inform healthcare policies, expand the application scope of O2O service models, and identify additional chronic diseases that can benefit from digital health services. This research bridges the gap between theory and practice, contributing to evidence-based healthcare decision-making and improving patient outcomes in the era of digital health.

Trial registration

This study is registered at ClinicalTrials.gov of the US National Library of Medicine. The registration number is NCT06150508, and the registered date is 2023–11-29
Molecular prevalence and associated risk factors of Entamoeba spp. in donkeys in Shanxi Province, North China
Authors: Zhang Ze-Dong , Xiao Han-Dan , Wang Dong-Yang , Su Nan , Liu Xun-Zhi , Wang Zi-Rui , Xie Shi-Chen , Zhu Xing-Quan , Zhang Shuo , Gao Wen-Wei
Published: February 2025

Background

The intestinal protozoa Entamoeba spp. can infect humans and various animals, including donkeys, causing diarrhea and malabsorption and presenting significant risks to animal husbandry and public health. Most Entamoeba species are not pathogenic except for Entamoeba histolytica. China has among the highest rates of donkey farming worldwide. Donkey (Equus asinus) farming is increasingly important in China because of their draft and medicinal value; however, epidemiological data on Entamoeba spp. in donkeys remains limited globally. This study aimed to investigate the prevalence of Entamoeba in donkeys in Shanxi Province, North China, and assess associated risk factors using a molecular approach.

Methods

Fecal samples of 815 donkeys from three representative geographical locations in Shanxi Province were collected to investigate the presence of Entamoeba spp. A portion of the small-subunit rRNA gene (SSU rRNA) was amplified and sequenced to determine the prevalence and species/genotypes of Entamoeba spp. Statistical analysis of possible risk factors was performed using Statistical Product and Service Solutions (SPSS) 26.0 software. The phylogenetic relationship of Entamoeba spp. was reconstructed using the neighbor-joining (NJ) method in Molecular Evolutionary Genetics Analysis (Mega) 7.0 software.

Results

The overall prevalence of Entamoeba spp. in donkeys in Shanxi Province was 7.12% (58/815). Two species (Entamoeba sp. RL9 and Entamoeba equi) were identified by sequence analysis; of these, Entamoeba sp. RL9 was the most prevalent species in donkeys in this study. Statistical analysis revealed that the donkeys' sex, region, age, and altitude are the risk factors associated with Entamoeba spp. prevalence (P < 0.05). Phylogenetic analysis indicated that the sequences of Entamoeba sp. RL9 and E. equi isolated from donkeys in this study were clustered with previously reported animal-derived Entamoeba sp. RL9 and E. equi sequences, respectively.

Conclusions

This study reports the occurrence and prevalence of Entamoeba spp. in donkeys worldwide for the first time to our knowledge. This not only expands the geographical distribution but also broadens the host range of Entamoeba spp., addressing the knowledge gap regarding the prevalence of Entamoeba spp. in donkeys, providing baseline data for carrying out prevention and control of Entamoeba spp. in donkeys in China.

Graphical Abstract
Barlow Twins deep neural network for advanced 1D drug–target interaction prediction
Authors: Schuh Maximilian G. , Boldini Davide , Bohne Annkathrin I. , Sieber Stephan A.
Published: February 2025

Accurate prediction of drug–target interactions is critical for advancing drug discovery. By reducing time and cost, machine learning and deep learning can accelerate this laborious discovery process. In a novel approach, BarlowDTI, we utilise the powerful Barlow Twins architecture for feature-extraction while considering the structure of the target protein. Our method achieves state-of-the-art predictive performance against multiple established benchmarks using only one-dimensional input. The use of our hybrid approach of deep learning and gradient boosting machine as the underlying predictor ensures fast and efficient predictions without the need for substantial computational resources. We also propose the use of an influence method to investigate how the model reaches its decision based on individual training samples. By comparing co-crystal structures, we find that BarlowDTI effectively exploits catalytically active and stabilising residues, highlighting the model’s ability to generalise from one-dimensional input data. In addition, we further benchmark new baselines against existing methods. Together, these innovations improve the efficiency and effectiveness of drug–target interactions predictions, providing robust tools for accelerating drug development and deepening the understanding of molecular interactions. Therefore, we provide an easy-to-use web interface that can be freely accessed at https://www.bio.nat.tum.de/oc2/barlowdti.

Scientific contribution

Our computationally efficient and effective hybrid approach, combining the deep learning model Barlow Twins and gradient boosting machines, outperforms state-of-the-art methods across multiple splits and benchmarks using only one-dimensional input. Furthermore, we advance the field by proposing an influence method that elucidates model decision-making, thereby providing deeper insights into molecular interactions and improving the interpretability of drug-target interactions predictions.

Graphical Abstract
Epsin3 promotes non-small cell lung cancer progression via modulating EGFR stability
Authors: Su Huiling , Shen Jie , Gao Chenzi , Zhao Yue , Deng Wanyu , Qin Bo , Zhang Xin , Lai Juan , Wang Qian , Dou Jie , Guo Min
Published: February 2025

Background

The abnormal expression and overactivation of the epidermal growth factor receptor (EGFR), a typical cancer marker for non-small cell lung cancer (NSCLC), are closely related to the tumorigenesis and progression of NSCLC. However, the endocytosis mechanism of EGFR in lung cancer is not yet known. Epsin3 (EPN3), a member of the endocytic adaptor protein family, is essential for the endocytosis of multiple receptors. In this study, we aimed to investigate the role of EPN3 in modulating EGFR function, its effects on NSCLC progression, and its potential involvement in tyrosine kinase inhibitor (TKI) resistance, which remains a significant hurdle in NSCLC treatment.

Results

Our findings revealed that the expression of EPN3 is significantly up-regulated in NSCLC patients. Elevated EPN3 expression was proportional to shorter overall survival in patients with NSCLC. Functional analyses revealed that EPN3 directly interacts with EGFR, enhancing its recycling to the plasma membrane and preventing its degradation via the lysosomal pathway. This stabilization of EGFR led to sustained downstream signalling, promoting NSCLC cell proliferation and migration. Notably, mutations in the EGFR tyrosine kinase domain, which typically confer resistance to TKIs, did not alter the regulatory effect of EPN3.

Conclusions

EPN3 enhances EGFR signalling by promoting its recycling and stability, contributing to NSCLC progression and TKI resistance. Targeting EPN3 could offer a novel therapeutic strategy to overcome drug resistance in EGFR-driven NSCLC.
Intra-specific variation in mortality of even-aged Cryptomeria japonica (L. f.) D. Don. forests can be explained using relationships among long-term stand characteristics
Authors: Fukumoto Keiko , Nishizono Tomohiro , Kitahara Fumiaki
Published: February 2025

Context

Understanding tree mortality is critical for sustainable forest management. Long-term tree mortality may differ depending on the stand development process and can be influenced by forest management regimes. Logistic regression is widely used to explain tree mortality based on site productivity, age, size, and competition. However, the explanatory variables are interrelated. Thus, we attempted to explain long-term Japanese cedar tree mortality by considering interrelated variables.

Aims

The aim of this study was to elucidate the direct and indirect effects of site productivity, age, individual size, and competition on the long-term mortality of Japanese cedars.

Methods

Data were collected from 5130 even-aged Japanese cedar trees over approximately 50 years. We compared each variable between dead and living trees. We then constructed a mortality model using a conventional logistic approach and selected the best model for the stepwise methods. Finally, we applied a piecewise structural equation model (SEM) to identify these variables’ direct and indirect effects. We compared the conventional logistic model and piecewise SEM models and discussed the advantage of applying the SEM models.

Results

Annual mortality was approximately 4% in the most fertile stands, increasing gradually with decreasing site fertility. Dead tree size and competition status differed according to age and site productivity. Competition, individual size, and stand density were selected for the best logistic model (area under the curve (AUC) = 0.74, Brier score = 0.042), whereas age and site productivity were not (p > 0.05). The piecewise SEM results showed that age and site productivity indirectly affected tree mortality through individual size and stand density (Fisher’s C = 4.569, p = 0.102).

Conclusion

Long-term Japanese cedar tree mortality can be explained by individual size and competition as direct influencing factors and age and site productivity as indirect influencing factors. This indicated that hidden factors cannot be explained using the conventional logistic approach. Further studies are required to explore the potential factors contributing to tree mortality thoroughly.
Advancing numerical solutions for a system of singularly perturbed delay differential equations at linear rate
Authors: Joy Dany , S Dinesh Kumar , Rihan Fathalla A
Published: February 2025

This work introduces a numerical technique designed to efficiently solve a specific type of differential equations known as a weakly coupled system of singularly perturbed delay differential equations. The innovation of this approach stems from its unique integration of three key elements: the Numerov method, known for its accuracy in solving second-order ODEs; a fitting factor, which improves handling of the singular perturbation parameter essential for accurately modeling SPDDEs; and the Taylor series expansion, which approximates first-order derivative terms, facilitating the application of the Numerov method to the system. Numerical experiments are conducted with varying perturbation parameters and mesh sizes to validate the method’s effectiveness. The results, expressed in terms of maximum absolute errors and the rate of convergence, demonstrate that the proposed approach achieves first-order uniform convergence.
The role of IELTS teacher’s metapathy in IELTS candidates’ overall band score, language learning orientation, and active/passive motivation
Authors: Ghaemi Hamed , Kirkpatrick Robert
Published: February 2025

This study examines the impact of teacher metapathy, or teachers’ capacity to comprehend and sympathize with students’ emotional and cognitive requirements, on the academic outcomes of IELTS applicants, such as total band scores, motivation, and language learning orientation. Ten IELTS teachers from five language training centers and 100 IELTS candidates participated in the mixed methods design. Standardized surveys and official IELTS scores were used to collect quantitative data, and semi-structured interviews were used to acquire qualitative data. The associations between teacher metapathy, student motivation (passive vs. active), learning orientation (integrative vs. instrumental), and band scores were examined using logistic regression, Pearson correlation, chi-square tests, and structural equation modeling (SEM). Thematic analysis was used to explore participants’ perceptions of metapathy in the classroom. Results revealed a significant positive correlation between teacher metapathy and students’ overall IELTS band scores. High levels of teacher metapathy were associated with increased active motivation and integrative learning orientation among students. Additionally, the frequency of teacher-student interaction was found to mediate the relationship between teacher metapathy and students’ motivation levels. Qualitative findings reinforced these results, highlighting the importance of emotional and instructional support in promoting student engagement and success.
Physiochemical performance of electrospun PLA-lignin and PVA-lignin
Authors: Odili C C. , Gbenebour O. P. , Olanrewaju O A , Badaru T O , Adeosun S. O.
Published: February 2025

Polylactic acid (PLA) and polyvinyl alcohol (PVA) are promising biocompatible and biodegradable materials for biomedical uses, yet they have limitations. Similarly, lignin is a precursor for carbon fiber but requires plasticizers to be spun into fibers. This hampers their use in areas like carbon fiber production and tissue engineering, thus the reason for this study. Lignin was extracted from the plantain stem, and a lignin blend with PLA and PVA was made and electrospun into fibers. Thereafter, the physiochemical properties of the composite fibers were analyzed. The XRD spectra revealed increased crystallinity in PLA/Lignin fiber. When 0.75 wt.% of lignin was added to PVA, a new peak and peak shift were formed in the composite fiber, indicating strong interaction. The crystallinity of PVA/lignin decreased from 71.5 to 60.1% when 0.25 wt. % of lignin was added. DSC showed miscibility of polymers and improved melting temperatures from 155 to 228 °C, for PLA/lignin (0.5wt.%) fiber, but a reduction in melting temperatures of PVA, with higher lignin content (149–143 °C). FTIR showed notable functional groups, typical of PLA, PVA, and lignin, such as the OH group between 3800 and 3459 cm−1. The minor peak shift in PLA/lignin showed that the level of molecular interaction is less than that of PVA/lignin. PLA/lignin displayed better fiber morphology compared to PVA/lignin, where fibers became sheet-like with higher lignin content. The addition of lignin improved the tensile strength of PVA (0.7 to 2.7 MPa). Conversely, PLA/lignin’s tensile strength decreased, due to reduced load transfer efficiency. Overall, PVA/lignin and PLA/lignin composites exhibit potential as reinforcement materials for biopolymers and carbon fiber precursors, with PVA showing more promise for carbon fiber production due to robust polymer-lignin interaction.
Chiari malformation with concurrent papilledema: a patient-level meta-analysis of case reports and case series
Authors: Pando Alejandro , Valdivia Daniel J. , Brenner Daniel A. , Alvi Mohammed Ali , Sun Hai , Liu James K. , Goldstein Ira
Published: February 2025

Background

Chiari I malformation, characterized by the displacement of cerebellar tonsils, and Chiari 1.5, involving cerebellar tonsils and brainstem displacement, share symptoms with Idiopathic Intracranial Hypertension, including headache, paresthesia, vision issues, shoulder/arm pain, diplopia, numbness, and motor weakness. Historically, papilledema marked IIH, but there are reports of papilledema in patients with Chiari I/1.5, leading to uncertainty about the most effective treatment strategies. We aim to address this gap by summarizing all reported cases of Chiari I/1.5 with papilledema.

Methods

Three primary electronic databases (PubMed, EMBASE, and SCOPUS) were screened to identify case reports and case series of patients with Chiari malformation presenting with papilledema. All variables such as year and region of study, age, sex, symptoms, diagnostic information, treatment details, and follow-up duration, were recorded and analyzed. Study quality for each study included was assessed according to four scales: selection, ascertainment, causality, and reporting.

Results

27 patients from 21 studies were included. Symptoms included headache (76.4%), decreased visual acuity (70.8%), and visual field loss (29.2%). 44.4% had lumbar punctures, and 40.7% received medical management. Of those managed medically, 41.7% fully recovered. Notably, none of 21 patients who underwent surgical decompression without improvement had prior lumbar puncture (0% vs. 64.3%, n = 9; p = 0.003) or medical management (0% vs. 57.1%, n = 8; p = 0.011) compared to those with symptom improvement.

Conclusion

Chiari malformation with papilledema exhibits varied symptoms. Medical management should be considered initially, offering standalone effectiveness and potential improvement for subsequent decompression if medication alone does not lead to recovery.
Correlation between serum neurofilament light chain and short-term outcomes in patients with hypertensive intracerebral hemorrhage
Authors: Zhou Jun , Zhao Yulin , Zhang Lichuang , Dong Yanrui , Li Zehu , Wang Yansong , Wang Xiangdong
Published: February 2025

Objective

To explore the correlation between changes in serum neurofilament light chain protein and clinical prognosis in patients with hypertensive intracerebral hemorrhage, combined with other clinical indicators. This article provides evidence for clinicians to effectively evaluate the prognosis of patients with hypertensive intracerebral hemorrhage and formulate diagnosis and treatment plans.

Methods

We selected 202 patients with hypertensive intracerebral hemorrhage admitted to different hospital from 2021 to 2022, and the clinical data of the patients were collected immediately after admission. Blood samples of the patients were collected, centrifuged, and the upper serum layer was collected and stored in the freezer at -80℃. During the same period, the sera of 30 age-matched healthy subjects were collected as the control group. The serum values of light chain protein of the experimental group and control group were measured by enzyme-linked immunosorbent assay. The Glasgow Outcome Scale of enrolled patients at 30 days of onset was recorded, and the collected data were statistically analyzed.

Results

After statistical treatment, systolic blood pressure, admission Glasgow coma scale score, hematoma volume, and serum light chain protein values on day 3 and day 7 were statistically significant between the groups with good prognosis and those with poor prognosis (all P < .001).

Conclusion

The serum light chain protein level of patients with hypertensive intracerebral hemorrhage was significantly higher than that of healthy people. The prognosis of the experimental group was correlated with the change trend of serum light chain protein.
Shared prognostic information in amyotrophic lateral sclerosis – systematic assessment of the patients’ perception of neurofilament light chain and the ALS functional rating scale
Authors: Möhwald Lukas Maximilian , Maier André , Grehl Torsten , Weyen Ute , Weydt Patrick , Günther René , Lingor Paul , Göricke Bettina , Petri Susanne , Grosskreutz Julian , Boentert Matthias , Cordts Isabell , Weishaupt Jochen H. , Dorst Johannes , Münch Christoph , Meyer Thomas , Baum Petra
Published: February 2025

Background

In amyotrophic lateral sclerosis (ALS), neurofilament light chain (NfL) was introduced as a prognostic biomarker. More recently, NfL values can be shared on the patient’s ALS app. Also, the ALS functional rating scale (ALSFRS-R) is an established patient-reported assessment of disease progression. The scale can be obtained during clinic visits or remotely. However, few systematic data are available on the patients’ perception of prognostic information about NfL and ALSFRS-R and the remote sharing of these data.

Methods

In a multicenter study, 149 ALS patients were assessed for their perception of shared information about NfL and ALSFRS-R using an investigator-designed survey and established questionnaires. The recommendation of NfL and ALSFRS-R to fellow patients was assessed using the Net Promoter Score (NPS). Burden by shared information was investigated in two distinct settings: (1) clinic information when receiving results on NfL and/or ALSFRS-R during clinic visits and (2) remote information about NfL values and self-rating of the ALSFRS-R via the ALS app. General anxiety was measured by the Fear of Progression Questionnaire – Short Form (FoP-Q-SF).

Results

Information about NfL and ALSFRS-R, respectively (n = 149), were regarded as relevant for patients themselves (75.2% and 77.2%) and for research (98% and 96%). The NPS showed a high recommendation rate for NfL (+ 21) and ALSFRS-R (+ 26). Only a minority of patients perceived shared information about NfL as burdensome, with a lower burden in the clinic setting (n = 1, 4.2%) than in the remote setting (n = 8, 12%; p = 0.015). Remote digital assessment of the ALSFRS-R was well received, with a reported burden in 9.8% (n = 9) of the participants. The FoP-Q-SF revealed fear of progression in 40% of the respondents (n = 60).

Conclusions

This study underscored the relevance of information about NfL and ALSFRS-R from the patient’s perspective. Furthermore, patients proved to appreciate the relevance of this data for ALS research. Sharing information about NfL or ALSFRS-R was rarely perceived as burdensome even in a remote setting using the ALS app. These findings pave the way for further development of the patient-centered approach to sharing prognostic information in ALS.
New anchovy burgers: a sustainable and nutritious alternative to red meat in fast food
Authors: Russo Giovanni Luca , Langellotti Antonio L. , Di Monaco Rossella , Buonocunto Gabriele , Colonna Francesca , Velleca Nunzio , Di Paola Anna Ilaria , Avella Lucia , Cavella Silvana , Masi Paolo
Published: February 2025

This study presents an innovative anchovy burger formulation optimized using response surface methodology and Ideal Profile method. The objective is to create a nutritious, appealing, and environmentally friendly alternative to traditional red meat burgers. The research utilized a two-tiered experimental approach: an initial screening using Plackett-Burman Design to evaluate the impact of various ingredients on cooking yield, texture, and moisture retention, followed by an optimization phase employing a Central Composite Design. Key findings revealed that oat fiber and potato flakes significantly enhance the burger’s cooking yield and sensory characteristics. The optimized formulation, comprising 4% oat fibers and 4% potato flakes, exhibited superior texture and consumer preference. Nutritional analysis demonstrates that the optimized anchovy burger outperforms conventional beef and popular fast food chain burgers in terms of protein content and dietary fibers, while also being a rich source of long-chain polyunsaturated fatty acids. This research contributes to the fast-food industry by offering a product that meets sensory and nutritional requirements while also promoting sustainability. The findings lay a foundation for future studies to further explore the interplay of sensory attributes and consumer preferences, potentially guiding the development of innovative and sustainable fast-food products.

Graphical Abstract