bluuebunny/crossref_metadata_2025 huggingface dataset:
The microRNA-34 Family and Its Functional Role in Lung Cancer
Authors: Zhang Tinghua , Hu Youyuan , Yang Na , Yu Shaofu , Pu Xingxiang
Published: May 2024

Lung cancer is one of the most common malignant tumors in humans and the leading cause of cancer-related deaths worldwide. The microRNA-34 (miR-34) family is dysregulated in various human cancers and is an important family of tumor suppressor genes among microRNAs. The miR-34 family is downregulated in lung cancer. It inhibits cell proliferation, metastasis, and invasion, arrests the cell cycle, and induces apoptosis or senescence by negatively regulating many oncogenes. It is commonly used to detect and treat lung cancer. This study describes the regulatory role of the miR-34 family in lung cancer and the associated research advances in treatment.
The expected changes with different periods of home-based resistance exercise in patients with chronic kidney disease
Authors: Chen Shu-Hua , Hsu Ching-Ping , Chang Hsiao-Hua , Liu Tai-Ju , Sun Fang-Ju , Liang Yao-Jen
Published: May 2024

Background:

The comprehensive impact of prolonged home-based resistance training on individuals grappling with chronic kidney disease (CKD) have yet to be fully elucidated. This study aimed to explore the outcomes of varying exercise durations on physical performance, nutritional status, and kidney function within this specific population, encompassing patients undergoing dialysis and those affected by severe sarcopenia.

Methods:

This was a 1-year observational double cohort study following a 52-week longitudinal design, we enrolled 101 adult CKD outpatients. These participants were divided into two groups: the continuous group, comprising individuals who consistently exercised for over 6 months, and the interrupted group, which included those who did not sustain regular exercise for the same duration. The exercise regimen involved resistance exercises conducted at least 3 to 5 days per week, involving activities like lifting dumbbells and executing weighted wall squats. Physical activity assessments and biochemical blood tests were conducted at weeks 0, 4, 16, 28, 40, and 52 for all participants.

Results:

The continuous exercise group exhibited better handgrip strength and sit-to-stand movement compared to the interrupted group. Their estimated glomerular filtration rate stayed steady while the interrupted group was declined. Additionally, those who exercised consistently had better metabolism: higher carbon dioxide levels, increased albumin, better nutritional scores, and lower levels of blood urea nitrogen, creatinine, fasting blood glucose, and body weight. Subsequent adjustments for potential confounding factors continued to show improved physical performance and kidney function over time.

Conclusion:

Our findings indicate the advantageous impact of extended resistance exercise training on overall health of CKD patients, even those on dialysis or with severe sarcopenia. Dedication to this exercise routine could improve kidney function, metabolism, and physical abilities in these patients.
Radiographic Evidence of Bone Changes Around Intraosseous Transcutaneous Amputation Prosthesis: An 11-Year Retrospective Cohort Study
Authors: Ahmed Kirstin , Pendegrass Catherine , Aston William , Blunn Gordon
Published: May 2024

Introduction

Percutaneous Osseointegrated Implants (POIs) influence the load transfer path to the host bone. In turn, mechano-regulatory processes (strain adaptive bone remodeling) drive periprosthetic bone changes that influence implant stability and fixation outcome. These bone changes have not yet been reported for the Intraosseous Transcutaneous Amputation Prosthesis (ITAP) clinical trial.

Objectives

This study will first standardize the zoning and reporting of periprosthetic bone change in POI radiographs. Second, it will retrospectively measure periprosthetic bone change from radiographs of 12 participants with an ITAP up to 11 years. Finally, the results will be qualitatively compared with those from participants with different POI designs.

Materials and Methods

Twenty participants with unilateral transfemoral amputations received an ITAP in a 2-center UK clinical trial in either 2008/09 or 2013/14. Participant radiographs from one center were available (n = 12) over 11 years and have been collated and processed in a repeatable way. Transverse plane periprosthetic bone change measurements at 3 equidistant points along the implant stem were measured in AP and ML.

Results

Total median bone growth in AP was double that in ML (57.6 mm and 31.12 mm, respectively). Median lateral and posterior bone change (1.44 mm and 1.09 mm) was greater than median medial and anterior (0.83 mm and −0.005 mm) bone changes, respectively. The greatest change in radial bone growth was observed distally and the least proximally.

Conclusions

Bone changes were similar to other collared pressfit POIs in the literature. We demonstrate the influence of stem design and mechano-regulatory remodeling in stable fixation; however, additional influences on periprosthetic bone change were inferred from the results and further investigations are necessary.

Clinical Relevance

To identify ITAP design features and fixations that minimize endosteal resorption, thus promoting implant stability and contributing to clinical guidelines for rehabilitation and future design and fixation choices.
Radiomics-based machine learning approach for the prediction of grade and stage in upper urinary tract urothelial carcinoma: a step towards virtual biopsy
Authors: Alqahtani Abdulsalam , Bhattacharjee Sourav , Almopti Abdulrahman , Li Chunhui , Nabi Ghulam
Published: May 2024

Objectives:

Upper tract urothelial carcinoma (UTUC) is a rare, aggressive lesion, with early detection a key to its management. This study aimed to utilise computed tomographic urogram data to develop machine learning models for predicting tumour grading and staging in upper urothelial tract carcinoma patients and to compare these predictions with histopathological diagnosis used as reference standards.

Methods:

Protocol-based computed tomographic urogram data from 106 patients were obtained and visualised in 3D. Digital segmentation of the tumours was conducted by extracting textural radiomics features. They were further classified using 11 predictive models. The predicted grades and stages were compared to the histopathology of radical nephroureterectomy specimens.

Results:

Classifier models worked well in mining the radiomics data and delivered satisfactory predictive machine learning models. The multilayer panel showed 84% sensitivity and 93% specificity while predicting UTUC grades. The Logistic Regression model showed a sensitivity of 83% and a specificity of 76% while staging. Similarly, other classifier algorithms [e.g. Support Vector classifier (SVC)] provided a highly accurate prediction while grading UTUC compared to clinical features alone or ureteroscopic biopsy histopathology.

Conclusion:

Data mining tools could handle medical imaging datasets from small (<2 cm) tumours for UTUC. The radiomics-based machine learning algorithms provide a potential tool to model tumour grading and staging with implications for clinical practice and the upgradation of current paradigms in cancer diagnostics.

Clinical Relevance:

Machine learning based on radiomics features can predict upper tract urothelial cancer grading and staging with significant improvement over ureteroscopic histopathology. The study showcased the prowess of such emerging tools in the set objectives with implications towards virtual biopsy.
A review: targeting UBR5 domains to mediate emerging roles and mechanisms – chance or necessity?
Authors: Wang Yizhu , Niu Kaiyi , Shi Yanlong , Zhou Feilong , Li Xinhao , Li Yunxin , Chen Tianyi , Zhang Yewei
Published: May 2024

Ubiquitinases are known to catalyze ubiquitin chains on target proteins to regulate various physiological functions like cell proliferation, autophagy, apoptosis, and cell cycle progression. As a member of E3 ligase, ubiquitin protein ligase E3 component n-recognin 5 (UBR5) belongs to the HECT E3 ligase and has been reported to be correlated with various pathophysiological processes. In this review, the authors give a comprehensive insight into the structure and function of UBR5. The authors discuss the specific domains of UBR5 and explore their biological functions separately. Furthermore, the authors describe the involvement of UBR5 in different pathophysiological conditions, including immune response, virus infection, DNA damage response, and protein quality control. Moreover, the authors provide a thorough summary of the important roles and regulatory mechanisms of UBR5 in cancers and other diseases. On the whole, investigating the domains and functions of UBR5, elucidating the underlying mechanisms of UBR5 with various substrates in detail may provide new theoretical basis for the treatment of diseases, including cancers, which could improve future studies to construct novel UBR5-targeted therapy strategies.
Effect of pretransplant dialysis modalities on pancreas-kidney transplant outcomes: a systematic review and meta-analysis
Authors: Li Yue , Tang Yangming , Fan Yu , Lin Tao , Song Turun
Published: May 2024

Background:

The impact of different pretransplant dialysis modalities on post-transplant outcomes for pancreas-kidney transplantation is currently unclear. This study aims to assess the association between pretransplant dialysis modalities [hemodialysis (HD) and peritoneal dialysis] and outcomes following pancreas-kidney transplantation.

Methods:

The authors searched PubMed, EMBASE, and the Cochrane Library for relevant studies published from inception until 1 December 2023. The authors included studies that examined the relationship between pretransplant dialysis modalities and clinical outcomes for pancreas-kidney transplantation. The primary outcomes considered were patient, pancreas and kidney graft survival, and intra-abdominal infection.

Results:

A total of 13 studies involving 1503 pancreas-kidney transplant recipients were included. Pretransplant HD was associated with improved pancreas graft survival (hazard ratio = 0.71, 95% confidence interval: 0.51–0.99, I²=12%) and a decreased risk of intra-abdominal infection [odds ratio (OR)=0.69, 95% CI: 0.51–0.93, I²=5%). However, no significant association was found between the dialysis modalities and patient or kidney graft survival. Furthermore, pretransplant HD was linked to a reduced risk of anastomotic leak (OR=0.32, 95% CI: 0.161–0.68, I²=0%) and graft thrombosis (OR=0.56, 95% CI: 0.33–0.96, I²=20%).

Conclusion:

Pretransplant HD is the preferred dialysis modality while awaiting pancreas-kidney transplantation, although well-designed prospective studies are needed to confirm these findings.
Research trends on acupuncture for neuropathic pain: A bibliometric analysis from 1979 to 2023
Authors: Li Tao , Yan Qilu , Huang Wei
Published: May 2024

Background:

Acupuncture has drawn increasing attention as a complementary and alternative therapy for neuropathic pain (NP). The present study aimed to summarize the current status and research trends on acupuncture for NP over the past several decades.

Methods:

The publications on acupuncture for NP in the database of Web of Science Core Collection from 1979 to 2023 were searched. VOSviewer (1.6.15) and CiteSpace software (5.5.R2) were applied to identify active authors, journals, countries and institutions, co-cited references and hot keywords.

Results:

A total of 642 publications were finally included, and the quantitative trend of annual publications on acupuncture for NP have shown overall upward from 1979 to 2023. Peoples R China was the most productive and influential country, while Kyung Hee University from South Korea was both the first in publications and citations. Fang JQ ranked the first productive author and Han JS was the first 1 among the co-cited authors. The first productive journal was Evidence-based Complementary and Alternative Medicine, while the first co-cited journal was Pain. The high-frequency keywords were divided into 9 clusters, and the frontier topic focused on “Chronic pain”.

Conclusion:

This present study visually showed the research status and trends of acupuncture for NP from 1979 to 2023 on the basis of bibliometric analysis, which may in some way help researcher discovery and explore some new research directions and ideas in the future.
Evaluating the Quality of Postpartum Hemorrhage Nursing Care Plans Generated by Artificial Intelligence Models
Authors: Karacan Emine
Published: May 2024

Background:

With the rapidly advancing technological landscape of health care, evaluating the potential use of artificial intelligence (AI) models to prepare nursing care plans is of great importance.

Purpose:

The purpose of this study was to evaluate the quality of nursing care plans created by AI for the management of postpartum hemorrhage (PPH).

Methods:

This cross-sectional exploratory study involved creating a scenario for an imaginary patient with PPH. Information was put into 3 AI platforms (GPT-4, LaMDA, Med-PaLM) on consecutive days without prior conversation. Care plans were evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scale.

Results:

Med-PaLM exhibited superior quality in developing the care plan compared with LaMDA (Z = 4.354; P = .000) and GPT-4 (Z = 3.126; P = .029).

Conclusions:

Our findings suggest that despite the strong performance of Med-PaLM, AI, in its current state, is unsuitable for use with real patients.
An Exploration of Nurses’ Attitudes and Beliefs on Reporting Medication Errors
Authors: Schuermann Andrea A. , Arkin Laura , Loerzel Victoria
Published: May 2024

Background:

Medication errors in health care are prevalent. Nurses play an important role in reporting; however errors remain underreported in incident reporting systems. Understanding the perspective of nurses will inform strategies to improve reporting and build systems to reduce errors.

Purpose:

The purpose of this study was to explore nurses’ perceptions and attitudes of medication error reporting practices.

Methods:

This qualitative study used direct content analysis to analyze interview sessions with 21 total nurses.

Results:

Participant’s description of medication error reporting practices fell into 2 themes. Internal factors described circumstances within nurses themselves that affect reporting. External factors described outside influences from processes or places.

Conclusions:

Medication error reporting is a multidimensional phenomenon with internal and external factors impacting nurses’ attitudes and willingness to report errors. Nurses need support from leadership to understand that reporting medication errors can improve practice and impact patient outcomes.
Plasmacytoma and Amyloid Lymphadenopathy, FDG, and Fluorocholine
Authors: Kaya Gursan , Akin Serkan , Tuncel Murat , Kiratli Pinar
Published: May 2024

A 56-year-old man with thoracal mass suspected of solitary plasmacytoma was referred for 18F-FDG PET-CT scan. His PET-CT revealed FDG-avid rib mass and cervical lesion at level 2. He also underwent 18F-fluorocholine (FCH) PET-CT to evaluate possible metastatic spread of the disease. FCH PET-CT showed increased uptake at the rib mass, while the cervical lesion was not FCH-avid. Biopsies confirmed rib lesion was a solitary plasmacytoma; however, the cervical lesion was an amyloid deposited lymph node. This case showed FCH PET-CT is a valuable companion of FDG scan for the evaluation of plasma cell dyscrasias with a better specificity.
Radiomics Analysis of Pericoronary Adipose Tissue From Baseline Coronary Computed Tomography Angiography Enables Prediction of Coronary Plaque Progression
Authors: Chen Rui , Li Xiaohu , Jia Han , Feng Changjing , Dong Siting , Liu Wangyan , Lin Shushen , Zhu Xiaomei , Xu Yi , Zhu Yinsu
Published: May 2024

Purpose:

The relationship between plaque progression and pericoronary adipose tissue (PCAT) radiomics has not been comprehensively evaluated. We aim to predict plaque progression with PCAT radiomics features and evaluate their incremental value over quantitative plaque characteristics.

Patients and Methods:

Between January 2009 and December 2020, 500 patients with suspected or known coronary artery disease who underwent serial coronary computed tomography angiography (CCTA) ≥2 years apart were retrospectively analyzed and randomly stratified into a training and testing data set with a ratio of 7:3. Plaque progression was defined with annual change in plaque burden exceeding the median value in the entire cohort. Quantitative plaque characteristics and PCAT radiomics features were extracted from baseline CCTA. Then we built 3 models including quantitative plaque characteristics (model 1), PCAT radiomics features (model 2), and the combined model (model 3) to compare the prediction performance evaluated by area under the curve.

Results:

The quantitative plaque characteristics of the training set showed the values of noncalcified plaque volume (NCPV), fibrous plaque volume, lesion length, and PCAT attenuation were larger in the plaque progression group than in the nonprogression group (P < 0.05 for all). In multivariable logistic analysis, NCPV and PCAT attenuation were independent predictors of coronary plaque progression. PCAT radiomics exhibited significantly superior prediction over quantitative plaque characteristics both in the training (area under the curve: 0.814 vs 0.615, P < 0.001) and testing (0.736 vs 0.594, P = 0.007) data sets.

Conclusions:

NCPV and PCAT attenuation were independent predictors of coronary plaque progression. PCAT radiomics derived from baseline CCTA achieved significantly better prediction than quantitative plaque characteristics.
Comparison of two audit and feedback approaches: descriptive analysis of personal and contextual dynamics
Authors: Pagano Maria , Cappadona Irene , Corallo Francesco , Cardile Davide , Ielo Augusto , D’Aleo Giangaetano , Cola Maria Cristina De , Bramanti Placido , Ciurleo Rosella
Published: May 2024

Introduction:

Audit and feedback (A&F) is a systematic intervention that can be used to improve the quality of health care. The EASY-NET Network Project proposes an innovative A&F model.

Aim:

This study aimed to describe the newly proposed A&F model. An analysis was conducted, examining the participants’ attitudes and their individual and interpersonal mechanisms to understand how they influence the work context and vice versa.

Methods:

Two A&F models were compared, involving emergency and rehabilitation health workers, who were divided into two groups. The classic A&F model was compared with a new model, using a desk audit followed by interactive feedback. Communication training was provided to the audit team by psychologists before commencement of the project. The experimental group underwent psychological screening using two standardized tools (COPE-NVI and ProQoL) to evaluate personal and relational dynamics using the context-mechanism-outcome (CMO) paradigm.

Results:

The exchange of ideas among health professionals is more effective when using face-to-face feedback than written feedback. The COPE-NVI and ProQoL questionnaires highlighted the difficulties experienced by health care professionals in implementing effective coping strategies to deal with stressful events.

Conclusions:

Identifying signs of stress in health care workers is essential for improvement strategies to be implemented and for establishing new, optimal conditions. Remote feedback makes it possible to overcome logistical barriers and, in the future, this method can be used for inter-organizational collaboration.

Spanish abstract:

http://links.lww.com/IJEBH/A203
Rapid Assessment of Biomarkers on Single Extracellular Vesicles Using ‘Catch and Display’ on Ultrathin Nanoporous Silicon Nitride Membranes
Authors: Walker Samuel N. , Lucas Kilean , Dewey Marley J. , Badylak Stephen , Hussey George , Flax Jonathan , McGrath James L.
Published: May 2024

Extracellular vesicles (EVs) are particles secreted by all cells that carry bioactive cargo and facilitate intercellular communication with roles in normal physiology and disease pathogenesis. EVs have tremendous diagnostic and therapeutic potential and accordingly, the EV field has grown exponentially in recent years. Bulk assays lack the sensitivity to detect rare EV subsets relevant to disease, and while single EV analysis techniques remedy this, they are undermined by complicated detection schemes often coupled with prohibitive instrumentation. To address these issues, we propose a microfluidic technique for EV characterization called ‘catch anddisplay forliquidbiopsy (CAD-LB)’. CAD-LB rapidly captures fluorescently labeled EVs in the similarly-sized pores of an ultrathin silicon nitride membrane. Minimally processed sample is introducedviapipette injection into a simple microfluidic device which is directly imaged using fluorescence microscopy for a rapid assessment of EV number and biomarker colocalization. In this work, nanoparticles were first used to define the accuracy and dynamic range for counting and colocalization by CAD-LB. Following this, the same assessments were made for purified EVs and for unpurified EVs in plasma. Biomarker detection was validated using CD9 in which Western blot analysis confirmed that CAD-LB faithfully recapitulated differing expression levels among samples. We further verified that CAD-LB captured the known increase in EV-associated ICAM-1 following the cytokine stimulation of endothelial cells. Finally, to demonstrate CAD-LB’s clinical potential, we show that EV biomarkers indicative of immunotherapy responsiveness are successfully detected in the plasma of bladder cancer patients undergoing immune checkpoint blockade.
Optimal control of combination immunotherapy for a virtual murine cohort in a glioblastoma-immune dynamics model
Authors: Anderson Hannah G. , Takacs Gregory P. , Harrison Jeffrey K. , Rong Libin , Stepien Tracy L.
Published: May 2024

The immune checkpoint inhibitor anti-PD-1, commonly used in cancer immunotherapy, has not been successful as a monotherapy for the highly aggressive brain cancer glioblastoma. However, when used in conjunction with a CC-chemokine receptor-2 (CCR2) antagonist, anti-PD-1 has shown efficacy in preclinical studies. In this paper, we aim to optimize treatment regimens for this combination immunotherapy using optimal control theory. We extend a treatment-free glioblastoma-immune dynamics ODE model to include interventions with anti-PD-1 and the CCR2 antagonist. An optimized regimen increases the survival of an average mouse from 32 days post-tumor implantation without treatment to 111 days with treatment. We scale this approach to a virtual murine cohort to evaluate mortality and quality of life concerns during treatment, and predict survival, tumor recurrence, or death after treatment. A parameter identifiability analysis identifies five parameters suitable for personalizing treatment within the virtual cohort. Sampling from these five practically identifiable parameters for the virtual murine cohort reveals that personalized, optimized regimens enhance survival: 84% of the virtual mice survive to day 100, compared to 60% survival in a previously studied experimental regimen. Subjects with high tumor growth rates and low T cell kill rates are identified as more likely to die during and after treatment due to their compromised immune systems and more aggressive tumors. Notably, the MDSC death rate emerges as a long-term predictor of either disease-free survival or death.

Highlights

A mathematical model of glioma-immune dynamics integrates combination immunotherapy.

An optimized regimen extends survival in an average virtual mouse by 79 days.

Quality of life and survival outcomes were evaluated for a virtual murine cohort.

A high death rate of myeloid-derived suppressor cells predicts long-term survival.
Beyond a diagnostic tool: Validating standardized Mahalanobis distance as a species distribution model for invasive alien species in North America
Authors: Stinziano JR , Charron A , Damus M
Published: May 2024

Species distribution models (SDMs) are useful tools for predicting where new invasive species can establish within a country, supporting both preparatory and response activities. National Plant Protection Organizations use SDMs to inform risk assessment and surveillance activities for emerging plant pests. However, SDMs face multiple and difficult statistical challenges, including multi-collinearity of input variables, correlation structures in climate variables that vary through time and space, limited species observation data, and they often lack formal tests of model performance.

We have implemented a previously-reported extrapolation-detection tool as an SDM, rather than a diagnostic tool of SDMs. This method characterizes the observed multivariate climate envelope by using Mahalanobis distance to take advantage of the correlation between climate variables, and identifies areas where the climatic conditions are outside the range of the observed climate envelope. Model outputs include climate suitability maps, and most-important covariate analyses to identify the environmental drivers of the results while assisting in variable reduction. We performed a formal test to assess the ability of the SDM to identify areas invaded by invasive plant pests in North America.

Using a list of 23 species from the Canadian Food Inspection Agency’s regulated plant pest list, we demonstrate that this method achieves a high level of accuracy (> 85%) for determining climate suitability for North American plant pest invasions, especially when combined with most-important covariate-guided variable reduction. This suggests that the model is suitable for identifying areas of North America that are susceptible to future invasions. We show that many of the errors occur at the edge of climate suitable areas, where we would expect greater uncertainty in model predictions due to potential over-constraining and geospatial averaging. We present additional analyses to support recommendations on the use and limitations of this SDM in a regulatory context.
Dataset of emerging contaminants in surface water, bottom water, porewater, and sediment: Urban and aquaculture impacts in the central and southern coast of Chile
Authors: Inostroza Pedro A. , Soriano Yolanda , Carmona Eric , Krauss Martin , Brack Werner , Backhaus Thomas , Quiñones Renato A.
Published: May 2024

Synthetic organic chemicals, including pesticides, pharmaceuticals, and industrial compounds, pose a growing threat to marine ecosystems as they enter through a variety of pathways, including direct discharges of wastewater (untreated or treated) from industrial, agricultural, and urban sources. Additionally, runoff from residential and agricultural land, as well as inland waterways, transport these chemicals to coastal zones. Despite their potential impact, data on the co-occurrence of these contaminants in the marine environment remains limited. Such information is critical for assessing coastal chemical status, establishing environmental quality benchmarks, and conducting comprehensive environmental risk assessments. In this study, we describe a multifaceted monitoring campaign targeting pesticides, pharmaceuticals, and industrial chemicals along the central-south coast and in northern Patagonia, Chile. Surface water, bottom water, porewater, and adjacent sediment samples were collected for analysis. Our results show the detection of up to 83 chemicals in surface water, 71 in bottom water, 101 in porewater, and 244 in sediments. To enhance data utility, we provide valuable information on the mode of action and molecular targets of the identified chemicals. This comprehensive dataset contributes to defining pollution fingerprints in coastal areas of the Global South, including remote regions in Patagonia. It serves as a critical resource for future research, policymaking, and the advancement of environmental protection in these regions.
Fusarium Protein Toolkit: AI-powered tools to combat fungal threats to agriculture
Authors: Kim Hye-Seon , Haley Olivia C. , Portwood John L. , Harding Stephen , Proctor Robert H. , Woodhouse Margaret R. , Sen Taner Z. , Andorf Carson M.
Published: May 2024

Background

The fungal genusFusariumposes significant threats to food security and safety worldwide because it consists of numerous species that cause destructive diseases in crops, as well as mycotoxin contamination. The adverse effects of climate change are exacerbating some existing threats and causing new problems. These challenges highlight the need for innovative solutions, including the development of advanced tools to identify targets to control crop diseases and mycotoxin contamination incited byFusarium.

Description

In response to these challenges, we developed the Fusarium Protein Toolkit (FPT,https://fusarium.maizegdb.org/), a web-based tool that allows users to interrogate the structural and variant landscape within theFusariumpan-genome. FPT offers a comprehensive approach to understanding and mitigating the detrimental effects ofFusariumon agriculture. The tool displays both AlphaFold and ESMFold-generated protein structure models from sixFusariumspecies. The structures are accessible through a user-friendly web portal and facilitate comparative analysis, functional annotation inference, and identification of related protein structures. Using a protein language model, FPT predicts the impact of over 270 million coding variants in two of the most agriculturally important species,Fusarium graminearum, which causes Fusarium head blight and trichothecene mycotoxin contamination of cereals, andF. verticillioides, which causes ear rot and fumonisin mycotoxin contamination of maize. To facilitate the assessment of naturally occurring genetic variation, FPT provides variant effect scores for proteins in aFusariumpan-genome constructed from 22 diverse species. The scores indicate potential functional consequences of amino acid substitutions and are displayed as intuitive heatmaps using the PanEffect framework.

Conclusion

FPT fills a knowledge gap by providing previously unavailable tools to assess structural and missense variation in proteins produced byFusarium, the most agriculturally important group of mycotoxin-producing plant pathogens. FPT will deepen our understanding of pathogenic mechanisms inFusarium, and aid the identification of genetic targets that can be used to develop control strategies that reduce crop diseases and mycotoxin contamination. Such targets are vital to solving the agricultural problems incited byFusarium, particularly evolving threats affected by climate change. By providing a novel approach to interrogateFusarium-induced crop diseases, FPT is a crucial step toward safeguarding food security and safety worldwide.
Structural insights into human propionyl-CoA carboxylase (PCC) and 3-methylcrotonyl-CoA carboxylase (MCC)
Authors: Zhou Fayang , Zhang Yuanyuan , Zhu Yuyao , Zhou Qiang , Shi Yigong , Hu Qi
Published: May 2024

Propionyl-CoA carboxylase (PCC) and 3-methylcrotonyl-CoA carboxylase (MCC) are biotin-dependent carboxylases (BDCs) that catalyze the metabolism of odd-chain fatty acids, cholesterol, and specific amino acids. For human PCC and MCC, only a low-resolution (15 Å) three-dimensional structure of human PCC has been reported. Here, we report high-resolution (2.29-3.38 Å) cryo-EM structures of human PCC and MCC holoenzymes in their apo and acetyl-CoA and propionyl-CoA-bound states. Propionyl-CoA and acetyl-CoA bind to PCC with almost identical binding modes, indicating that the acyl-CoA specificity of PCC is largely attributed to minor differences in interactions mediated by the acyl groups. In MCC, biotin is relocated from an exo-site to an endo-site upon acetyl-CoA binding, suggesting coordination between biotin binding and acyl-CoA binding. Our work provides insights into the substrate specificity and catalytic process of BDCs.
PlasEval: a framework for comparing and evaluating plasmid detection tools
Authors: Mane Aniket , Sanderson Haley , White Aaron P. , Zaheer Rahat , Beiko Robert G. , Chauve Cedric
Published: May 2024

Plasmids play a major role in the transfer of antimicrobial resistance (AMR) genes among bacteria via horizontal gene transfer. The identification of plasmids in short-read assemblies is a challenging problem and a very active research area.Plasmid binningaims at detecting, in a draft genome assembly, groups (bins) of contigs likely to originate from the same plasmid. Several methods for plasmid binning have been developed recently, such as PlasBin-flow, HyAsP, gplas, MOB-suite, and plasmidSPAdes. This motivates the problem of evaluating the performances of plasmid binning methods, either against a given ground truth or between them.

We describe PlasEval, a novel method aimed at comparing the results of plasmid binning tools. PlasEval computes a dissimilarity measure between two sets of plasmid bins, that can originate either from two plasmid binning tools, or from a plasmid binning tool and a ground truth set of plasmid bins. The PlasEval dissimilarity accounts for the contig content of plasmid bins, the length of contigs and is repeat-aware. Moreover, the dissimilarity score computed by PlasEval is broken down into several parts, that allows to understand qualitative differences between the compared sets of plasmid bins. We illustrate the use of PlasEval by benchmarking four recently developed plasmid binning tools – PlasBin-flow, HyAsP, gplas, and MOB-recon – on a data set of 54E. colibacterial genomes.

PlasEval is freely available athttps://github.com/acme92/PlasEval
Cross-site harmonization of diffusion MRI data without matched training subjects
Authors: De Luca Alberto , Swartenbroekx Tine , Seelaar Harro , van Swieten John C , Cetin Karayumak Suheyla , Rathi Yogesh , Pasternak Ofer , Jiskoot Lize C , Leemans Alexander
Published: May 2024

Purpose: Diffusion MRI (dMRI) data typically suffer of significant cross-site variability, which prevents naively performing pooled analyses. To attenuate cross-site variability, harmonization methods such as the rotational invariant spherical harmonics (RISH) have been introduced to harmonize the dMRI data at the signal level. A common requirement of the RISH method, is the availability of healthy individuals who are matched at the group level, which may not always be readily available, particularly retrospectively. In this work, we propose a framework to harmonize dMRI without matched training groups. Methods: Our framework learns harmonization features while controlling for potential covariates using a voxel-based generalized linear model (RISH-GLM). RISH-GLM allows to simultaneously harmonize data from any number of sites while also accounting for covariates of interest, thus not requiring matched training subjects. Additionally, RISH-GLM can harmonize data from multiple sites in a single step, whereas RISH is performed for each site independently. Results: We considered data of training subjects from retrospective cohorts acquired with 3 different scanners and performed 3 harmonization experiments of increasing complexity. First, we demonstrate that RISH-GLM is equivalent to conventional RISH when trained with data of matched training subjects. Secondly, we demonstrate that RISH-GLM can effectively learn harmonization with two groups of highly unmatched subjects. Thirdly, we evaluate the ability of RISH-GLM to simultaneously harmonize data from 3 different sites. Discussion: RISH-GLM can learn cross-site harmonization both from matched and unmatched groups of training subjects, and can effectively be used to harmonize data of multiple sites in one single step.
Tipping point inα-synuclein–membrane interactions: stable protein-covered vesicles or amyloid aggregation
Authors: Makasewicz Katarzyna , Carlström Göran , Stenström Olof , Bernfur Katja , Fridolf Simon , Akke Mikael , Linse Sara , Sparr Emma
Published: May 2024

α-synuclein is a neuronal protein implicated in neurotransmitter release. Its function is thought to critically depend on the dynamic equilibrium between free and membrane-bound protein.α-synuclein amyloid formation implicated in Parkinson’s Disease was also shown to be modulated by lipid membranes. However, it remains elusive whetherα-synuclein-related pathology is due to loss-of-function or gain-of-toxic-function. To help address this question, we studied the coupling of the equilibrium between free and membrane-boundα-synuclein and membrane-induced amyloid formation – phenomena that are usually treated separately. We present a description of the system on a wide range of length scales and timescales for lipid-to-protein ratio conditions where amyloid formation is either accelerated or inhibited by lipid membranes. We find a clear difference between the dynamics and heterogeneity of the protein-covered membrane interface in the two sets of conditions. In aggregation-accelerating conditions, the membrane interface is dynamic and heterogeneous with rapid exchange between free and membrane-bound protein, and disordered protein segments of varying lengths exposed to solution. All these characteristics of the membrane interface are likely to decrease the free energy barrier for amyloid formation. Conversely, the membrane interface is homogeneous and less dynamic in conditions where amyloid formation is inhibited. Importantly, any factors affecting the equilibrium between free and membrane-boundα-synuclein may trigger a change from non-aggregating to aggregating conditions. Altogether, our results highlight a strong coupling of the dynamic equilibrium between the free and membrane-boundα-synuclein and membrane-modulated amyloid formation and thus of the physiological function ofα-synuclein and its aberrant aggregation.
miR214regulates sex determination throughgsdfin zebrafish
Authors: Wittkopp N. , de Jesus Domingues A.M. , Ketting R.F.
Published: May 2024

Sex determination is a variable and complex mechanism, yet it can be found all over the plant and animal kingdoms. It creates two morphological different outcomes from one and the same species. Our work demonstrates the involvement of the non-coding RNAdnm3os, and its embedded microRNAmiR214in this process for the teleostDanio rerio. First, we find thatmiR214acts throughgsdfto drive female development. Second, additional alleles ofdnm3osrevealed that this lncRNA can also promote male development through yet unknown mechanisms. Finally, we describe that the sex-determining activities ofdnm3osdisplay a maternal effect, suggesting that imbalances in this gene-regulatory system can be compensated in a stable manner. Although we cannot fully explain the complexity of the mechanisms we have started to reveal, our work once again highlights the complexity and flexibility of sex determination and identifies miRNA and other non-coding RNA mediated activities in this crucial process.
The prevalentNR2E3c.932G>A mutation induces aberrant splicing that can be rescued using splice-shifting antisense oligonucleotides
Authors: Sztainberg Yehezkel , David Teitelbaum Maya , Buchumenski Ilana , Porath Hagit , Sharon Dror , Banin Eyal , Karni Rotem , Levanon Erez Y. , Feiglin Ariel
Published: May 2024

Mutations inNR2E3have been implicated in several progressive retinal disease phenotypes such as enhanced S-cone syndrome, Goldmann-Favre syndrome and retinitis pigmentosa. One of the most frequent mutations in NR2E3 is c.932G>A (p.R311Q), where pathogenicity is thought to stem from the resulting amino acid substitution. However, multiple studies that evaluated the effect of this substitution on the protein, did not elucidate the molecular basis underlying the pathogenicity.

Primed by bioinformatic analyses, we hypothesized and experimentally validated that theNR2E3c.932G>A mutation leads to aberrant splicing which results in a short, non-functional protein isoform. Using cell models expressing WT and mutant constructs of the fullNR2E3sequence (including exonic and intronic regions), we observed that the mutated transcript exhibits a high level (75%) of aberrant splicing through gain of a novel splice acceptor site within exon 6. This mis-splicing results in the in-frame loss of 186 base pairs that code for a portion of the protein ligand binding domain. We further designed and evaluated splice-shifting antisense oligonucleotides (ASOs), that circumvented the aberrant splicing. The best performing ASO successfully restored 70% of the total NR2E3 full-length isoform levels and demonstrated rescue of nuclear localization and rhodopsin transcriptional activation.

This study demonstrates the importance of understanding splicing consequences of pathogenic mutations, allowing the design and development of ASO-based therapies. Our findings set the stage for the potential treatment ofNR2E3-related retinal degeneration caused by the c.932G>A mutation using splice-shifting ASOs.
Super homotypic targeting by exosome surface engineering
Authors: Wang Huai-Song , Ding Tianben , Liu Yuhong , Zhou Yuqi , Zhao Yaqi , Hayashi Mika , Hu Xin-Yuan , Yang Zi-Wei , Ishii Natsumi Tiffany , Matsumura Hiroki , Umirbaeva Anel , Guo Hongwei , Su Jing-Lian , Yan Yin-Yu , Gao Fu-Han , Li Jia-Jing , Nitta Nao , Nishikawa Masako , Yatomi Yutaka , Ding Ya , Sonoshita Masahiro , Di Carlo Dino , Suetsugu Shiro , Goda Keisuke
Published: May 2024

Homotypic targeting is the inherent ability of cells for preferential interaction with cells of similar or identical types, a phenomenon commonly seen in cell adhesion, tissue formation, and immune responses. Unfortunately, its full potential remains largely untapped. Here we introduce an approach to drastically boost the homotypic targeting capabilities of cells via exosomes (nanoscale extracellular vesicles secreted by cells). By engineering exosome surfaces with lanthanides, we amplify specific cell-exosome interactions by more than 25-fold, significantly accelerating the selective capture of exosomes by cells of the same lineage. This substantial enhancement in cellular homophilicity opens up an entirely new class of applications, two of which we showcase here with unprecedented performance: using cells to detect specific exosomes and using exosomes to detect specific cells. The concept of “super homotypic targeting” offers enormous potential to transform cancer diagnostics, immunotherapy, targeted drug delivery, tissue engineering, and vaccine development.
Leaflet specific phospholipid imaging using genetically encoded proximity sensors
Authors: Moore William M. , Brea Roberto J. , Knittel Caroline , Wrightsman Ellen , Hui Brandon , Lou Jinchao , Ancajas Christelle F. , Best Michael D. , Devaraj Neal K. , Budin Itay
Published: May 2024

The lipid composition of cells varies widely across organelles and between individual membrane leaflets. Transport proteins acting within and between membranes are thought to generate this heterogeneity, but measuring their functions has been hampered by limited tools for imaging lipid composition at relevant spatial resolutions. Here we present fluorogen-activating coincidence sensing (FACES), a chemogenetic tool capable of quantitatively imaging subcellular lipid pools and reporting their transbilayer orientation in living cells. FACES combines bioorthogonal chemistry with genetically encoded fluorogen-activating proteins (FAPs) for reversible proximity sensing of conjugated molecules. We first apply this approach to identify roles for lipid transfer proteins (LTP) that traffic phosphatidylcholine pools between the ER and mitochondria. We then show that transmembrane domain-containing FAPs can be used to reveal the membrane asymmetry of multiple lipid classes that is generated at the trans-Golgi network (TGN). Using FACES, we show how the asymmetry of a phosphatidylserine analogue at the TGN is supported by the activity of both cytosolic LTPs and transmembrane flippases. Lastly, we demonstrate that FACES is a generalizable tool for subcellular detection of other molecule classes by measuring changes in mitochondrialN-acetylhexosamine levels. These results introduce the application of fluorogenic tags for spatially-defined molecular imaging.
Longitudinal Study to Better Understand Neuropathic Back Pain as a Means of Improving Patient Selection for 10 kHz Spinal Cord Stimulation
Authors: Mandloi Shreya , Tran Christian V , Thalheimer Sara , Jaffe Samantha , Braitman Leonard , Hines Kevin , Sharan Ashwini , Wu Chengyuan
Published: May 2024

Objective

To create a questionnaire that can identify patients who will respond well to high-frequency spinal cord stimulation.

Materials and Methods

Thirty-three patients who received permanent implantation of a high-frequency spinal cord stimulator were followed for up to one year. Preoperative patient data in the form of a packet containing pain metrics, the Douleur Neuropathique 4 (DN4) questionnaire, and a questionnaire thought to contain clinically useful questions were collected. Visual analog scale (VAS), Oswestry Disability Index (ODI), and subjective overall percent pain reduction were collected at time points of 6 weeks, 3 months, 6 months, and 12 months.

Results

Patients who revealed that they could walk before a long period of time before their pain worsened, whose pain was consistent throughout the day, whose pain wakes them up from sleep and whose pain is worse when leaning side to side had a significant increase in ODI following SCS. Additionally, patients who reported only being able to sit or lie down for less than thirty minutes before having to move experienced significantly decreased ODI.

Conclusions

While literature has shown that patients with neuropathic pain respond to SCS, identifying which patients clinically would have an optimal response remains a challenge. Future studies on a greater number of patients are needed to further develop a questionnaire to better identify clinical signs consistent with low back pain that will respond to spinal cord stimulation.

Statements and Declarations

Sources of Financial Support

Financial support for this project was provided by Nevro

Conflict of Interests

Dr. Ashwini Sharan reports personal fees from Neuspera, personal fees from Medtronic, grants and personal fees from Dixi, personal fees and other from Cerebral Therapeutics, outside the submitted work. Dr. Chengyuan Wu reports grants from Nevro, during the conduct of the study; personal fees from Nevro, personal fees from Abbott, personal fees from Medtronic, personal fees from Boston Scientific, personal fees from MicroSystems Engineering, outside the submitted work.