bluuebunny/crossref_metadata_2025 huggingface dataset:
The prognostic value of HALP score and sPESI in predicting in-hospital mortality in patients with pulmonary thromboembolism
Authors: Yaman Mahmut , Orak Murat , Durgun Hasan Mansur , Tekin Veysi , Ülgüt Şilan Göger , Belek Sema , Günel Berçem Tugay , Üstündağ Mehmet , Güloğlu Cahfer , Gündüz Ercan
Published: September 2024

Background

Pulmonary thromboembolism (PTE), often arising from deep vein thrombosis, remains a high-mortality condition despite diagnostic advancements. Prognostic models like Pulmonary Embolism Severity Index (PESI) and sPESI identify low-risk groups effectively. The Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) score, reflecting nutritional status and systemic inflammation, shows prognostic value in cancers and cardiovascular diseases. This study examines the relationship between in-hospital mortality HALP score and simplified PESI (sPESI) in PTE patients.

Methods

This retrospective observational study included patients diagnosed with PTE in the emergency department of a tertiary medical faculty from 2018 to 2023. PTE diagnosis was confirmed via computed tomography pulmonary angiography. Data on transthoracic echocardiography, D-dimer levels, demographics, laboratory results, PESI, sPESI, and HALP scores, and in-hospital mortality were collected.

Results

In this study, clinical characteristics of 171 patients with PTE were analysed. The average age was 61.88 ± 19.94 years, and 53.2% were female. Mortality was observed in 19.3% of patients. PESI and sPESI scores were significant predictors of mortality, with area under the curve values of 0.938 and 0.879, respectively. PESI score > 175.50 indicated a significantly higher mortality risk (HR = 18.208; P < .001), while sPESI >2.50 was also a strong predictor (HR = 11.840; P < .001). No significant cut-off value for HALP in predicting mortality was identified.

Conclusions

Our study supports the reliability of sPESI and PESI scores in predicting in-hospital mortality in PTE patients. However, the prognostic value of the HALP score requires further investigation. Our findings highlight the need for developing risk stratification models.

Key message What is already known on this topic?  The PESI and sPESI scores are established prognostic models that effectively identify low-risk groups in patients with PTE. The HALP score, reflecting nutritional status and systemic inflammation, has shown prognostic value in cancer and cardiovascular diseases. What this study adds?  This study demonstrates that while PESI and sPESI scores are significant predictors of in-hospital mortality in PTE patients, the HALP score does not have a significant cut-off value for predicting mortality. How this study might affect research, practice, or policy?  The findings support the continued use of PESI and sPESI scores for risk stratification in clinical practice, potentially influencing guidelines and policies on managing PTE. Further research into the HALP score's role in other contexts may refine its prognostic utility.
Data availability and requirements relevant for the Ariel space mission and other exoplanet atmosphere applications
Authors: Chubb Katy L , Robert Séverine , Sousa-Silva Clara , Yurchenko Sergei N , Allard Nicole F , Boudon Vincent , Buldyreva Jeanna , Bultel Benjamin , Coustenis Athena , Foltynowicz Aleksandra , Gordon Iouli E , Hargreaves Robert J , Helling Christiane , Hill Christian , Hrodmarsson Helgi Rafn , Karman Tijs , Lecoq-Molinos Helena , Migliorini Alessandra , Rey Michaël , Richard Cyril , Sadiek Ibrahim , Schmidt Frédéric , Sokolov Andrei , Stefani Stefania , Tennyson Jonathan , Venot Olivia , Wright Sam O M , Arenales-Lope Rosa , Barstow Joanna K , Bocchieri Andrea , Carrasco Nathalie , Dubey Dwaipayan , Egorov Oleg , Muñoz Antonio García , Gharib-Nezhad Ehsan (Sam) , Gkouvelis Leonardos , Grübel Fabian , Irwin Patrick Gerard Joseph , Knížek Antonín , Lewis David A , Lodge Matt G , Ma Sushuang , Martins Zita , Molaverdikhani Karan , Morello Giuseppe , Nikitin Andrei , Panek Emilie , Rengel Miriam , Rinaldi Giovanna , Skinner Jack W , Tinetti Giovanna , van Kempen Tim A , Yang Jingxuan , Zingales Tiziano
Published: September 2024

The goal of this white paper is to provide a snapshot of the data availability and data needs primarily for the Ariel space mission, but also for related atmospheric studies of exoplanets and cool stars. It covers the following data-related topics: molecular and atomic line lists, line profiles, computed cross-sections and opacities, collision-induced absorption and other continuum data, optical properties of aerosols and surfaces, atmospheric chemistry, UV photodissociation and photoabsorption cross-sections, and standards in the description and format of such data. These data aspects are discussed by addressing the following questions for each topic, based on the experience of the ‘data-provider’ and ‘data-user’ communities: (1) what are the types and sources of currently available data, (2) what work is currently in progress, and (3) what are the current and anticipated data needs. We present a GitHub platform for Ariel-related data, with the goal to provide a go-to place for both data-users and data-providers, for the users to make requests for their data needs and for the data-providers to link to their available data. Our aim throughout the paper is to provide practical information on existing sources of data whether in data bases, theoretical, or literature sources.
Identification of Wheat Stripe Rust Inoculum Sources and Dispersal Routes Responsible for Initial Rust Establishment in Southern Henan of China
Authors: Wang Aolin , Cao Shiqin , Peng Hong , Jiang Ru , Zhang Meihui , Nie Xiao , Xu Fei , Huang Liang , Sun Zhenyu , Hu Xiaoping , Liu Wei , Fan Jieru , Zhou Yilin , Xu Xiangming
Published: September 2024

Wheat stripe rust (yellow rust), caused by Puccinia striiformis f. sp. tritici (Pst), is an important airborne disease worldwide. Pst inoculum strength in southern Henan in winter or early spring is important for spring epidemics in the main autumn-sown wheat-growing regions of China. However, there is limited knowledge about the source and time of initial infection on winter wheat in southern Henan. The first occurrence of wheat stripe rust in southern Henan was recorded annually from 2011 to 2022, from which we used the backward trajectory approach to infer the likely source of Pst inoculum responsible for the initial disease occurrence. The results suggested that the Pst inoculum responsible for initial rust established in the winter in southern Henan originated from the Gansu Pst oversummering area in China, whereas it originated from the adjacent winter Pst sporulation regions in southern Shaanxi and northwestern Hubei if Pst symptoms were first observed in early spring in southern Henan. Another possible Pst source is southern Hubei where Pst can also sporulate in the winter. Thus, early Pst development in winter in the main wheat production region in China (Henan) is likely to be caused by Pst inoculum spread from the oversummering inocula or Pst epidemics in autumn seedlings in Gansu.
Development and Application of a qPCR-Based Method Coupled with Spore Trapping to Monitor Airborne Pathogens of Wheat Causing Stripe Rust, Powdery Mildew, and Fusarium Head Blight
Authors: Wang Aolin , Shang Zhaoyue , Jiang Ru , Zhang Meihui , Wang Jifeng , Li Hongfu , Zhang Bin , Tang Huarong , Xu Fei , Hu Xiaoping , Liu Wei , Fan Jieru , Zhou Yilin , West Jonathan S.
Published: September 2024

Common wheat (Triticum aestivum L.) production in China is challenged by stripe (yellow) rust, powdery mildew, and Fusarium head blight. Airborne inoculum of these pathogens is the causative driver of disease epidemics. Thus, monitoring of airborne inoculum on such fungal diseases is expected to provide some reliable estimations of disease development, especially by targeting multiple diseases simultaneously. This paper reports the development of a new practical qPCR-based method coupled with spore trapping to quantify simultaneously airborne inoculum of Puccinia striiformis f. sp. tritici (Pst), Blumeria graminis f. sp. tritici (Bgt), as well as Fusarium graminearum (Fg) and F. asiaticum and discusses its potential use in disease-risk warnings. The technique can detect DNA of Pst and Bgt at quantities as low as 0.2 pg, and 2 pg for Fg (i.e., representing 0.65 urediniospores, 1.18 conidia, and 10 macroconidia, respectively), and neither T. aestivum DNA nor DNA of other common wheat pathogens were amplified. Linear relationships were produced between the number of spores on tapes determined by qPCR and conventional microscopy, with a small variation (R2 value 0.97 to 0.99 depending on pathogen species). The daily concentrations of spores of the three pathogens were monitored using a Burkard 7-day recording spore trap, and the airborne spores were collected from a field near Langfang City, Hebei Province, China. The patterns of spore concentration dynamics in the air determined by triplex qPCR were close to those counted by conventional microscopy in a duplicated subsample. The developed assay can be an alternative to conventional microscopy to process large samples. This will improve monitoring power by providing timely risk warning information to growers regarding the timing of fungicide applications.
Surface engineering enhances the therapeutic potential of systemically delivered extracellular vesicles following acute myocardial infarction
Authors: Mentkowski Kyle I. , Tarvirdizadeh Touba , Manzanero Cody A. , Eagler Lisa A. , Lang Jennifer K.
Published: September 2024

The objective of the study was to assess the therapeutic efficacy of targeting remote zone cardiomyocytes with cardiosphere‐derived cell (CDC) extracellular vesicles (EVs) delivered via intramyocardial and intravenous routes following acute myocardial infarction (MI). Cardiomyocyte (CM) cell death plays a significant role in left ventricular (LV) remodeling and cardiac dysfunction following MI. While EVs secreted by CDCs have shown efficacy in promoting cardiac repair in preclinical models of MI, their translational potential is limited by their biodistribution and requirement for intramyocardial delivery. We hypothesized that engineering the surface of EVs to target cardiomyocytes would enhance their therapeutic efficacy following systemic delivery in a model of acute MI. CDC‐derived EVs were engineered to express a CM‐specific binding peptide (CMP) on their surface and characterized for size, morphology, and protein expression. Mice with acute MI underwent both intramyocardial and intravenous delivery of EVs, CMP‐EVs and placebo in a double‐blind study. LVEF was assessed by echo at 2‐ and 28‐days post‐MI and tissue samples processed for assessment of EV biodistribution and histological endpoints. CMP‐EVs demonstrated superior cardiac targeting and retention when compared with unmodified EVs 24 h post‐MI. Mice treated with IV delivered CMP‐EVs demonstrated a significant improvement in LVEF and a significant reduction in remote zone cardiomyocyte apoptosis when compared with IV delivered non‐targeted EVs at 28‐day post‐MI. Systemic administration of CMP‐EVs improved cardiac function and reduced remote zone cardiomyocyte apoptosis compared with IV‐administered unmodified EVs, demonstrating a strategy to optimize therapeutic EV delivery post‐MI.
Risk of Autism After Prenatal Topiramate, Valproate, or Lamotrigine Exposure
Authors: Hernández-Diaz Sonia , Straub Loreen , Bateman Brian T. , Zhu Yanmin , Mogun Helen , Wisner Katherine L. , Gray Kathryn J. , Lester Barry , McDougle Christopher J. , DiCesare Elyse , Pennell Page B. , Huybrechts Krista F.
Published: September 2024

(Abstracted from N Engl J Med 2024;390:1069–1079)

Individuals with epilepsy usually are recommended to continue their treatment during pregnancy, though many antiseizure medications are known teratogens. Valproate in particular has been associated with fetal anomalies and decreased neurocognitive function in prenatally exposure children.
Statistical Power and Performance of Strategies to Analyze Composites of Survival and Duration of Ventilation in Clinical Trials
Authors: Chen Ziming , Harhay Michael O. , Fan Eddy , Granholm Anders , McAuley Daniel F. , Urner Martin , Yarnell Christopher J. , Goligher Ewan C. , Heath Anna
Published: September 2024

BACKGROUND:

Patients with acute hypoxemic respiratory failure are at high risk of death and prolonged time on the ventilator. Interventions often aim to reduce both mortality and time on the ventilator. Many methods have been proposed for analyzing these endpoints as a single composite outcome (days alive and free of ventilation), but it is unclear which analytical method provides the best performance. Thus, we aimed to determine the analysis method with the highest statistical power for use in clinical trials.

METHODS:

Using statistical simulation, we compared multiple methods for analyzing days alive and free of ventilation: the t, Wilcoxon rank-sum, and Kryger Jensen and Lange tests, as well as the proportional odds, hurdle-Poisson, and competing risk models. We compared 14 scenarios relating to: 1) varying baseline distributions of mortality and duration of ventilation, which were based on data from a registry of patients with acute hypoxemic respiratory failure and 2) the varying effects of treatment on mortality and duration of ventilation.

RESULTS AND CONCLUSIONS:

All methods have good control of type 1 error rates (i.e., avoid false positive findings). When data are simulated using a proportional odds model, the t test and ordinal models have the highest relative power (92% and 90%, respectively), followed by competing risk models. When the data are simulated using survival models, the competing risk models have the highest power (100% and 92%), followed by the t test and a ten-category ordinal model. All models struggled to detect the effect of the intervention when the treatment only affected one of mortality and duration of ventilation. Overall, the best performing analytical strategy depends on the respective effects of treatment on survival and duration of ventilation and the underlying distribution of the outcomes. The evaluated models each provide a different interpretation for the treatment effect, which must be considered alongside the statistical power when selecting analysis models.
Vitamin D in the critically ill – update 2024
Authors: Geiger Christina , McNally James Dayre , Christopher Kenneth B. , Amrein Karin
Published: September 2024

Purpose of review

This review aims to summarize the latest publications on vitamin D focused on critically ill patients.

Recent findings

Vitamin D deficiency is common in critically ill patients (children and adults) and associated with a higher risk for mortality and morbidity as well as sepsis, acute respiratory failure, acute renal failure and prolonged ICU stay. As it is an inexpensive substance with a wide safety margin, acute treatment in form of a loading dose in addition to ongoing maintenance therapy is an interesting option in the ICU. The potential benefit of acute native (biologically inactive) vitamin D treatment has not fully been answered but even a small survival benefit demonstrable in very large analyses could be relevant to critical care. To date, less than 5000 patients cumulative have been enrolled in randomized controlled trials concerning vitamin D, with substantial heterogeneity in trial design regarding population (with or without deficiency, coronavirus disease 2019, different age groups, underlying illnesses), metabolite, dosing, outcome, and more.

More research is needed, but vitamin D supplementation represents a simple intervention with an excellent safety profile. As adequate vitamin D is essential to the health of multiple organ systems, rapid normalization of deficiency states could translate to benefits across the wide range of diagnoses and organ dysfunctions experienced in the ICU setting. As a minimum, we recommend administering the standard daily dose of vitamin D3 in the critically ill patient.
Coronary Computed Tomography Angiography Using an Optimal Acquisition Time Window Based on Heart Rate Determined During Breath-Holding Following Free Breathing
Authors: Liu Zi-yan , Ma Ze-peng , Gao Kai , Ding Wei , Zhao Yong-xia
Published: September 2024

Objectives

To compare the image quality and radiation dose in coronary computed tomography angiography (CCTA) based on different acquisition time windows corresponding to the heart rate of breath-holding after free breathing.

Methods

Two hundred patients who underwent CCTA with a basal heart rate between 70 and 85 beats/min were divided into groups A and B, with 100 patients in each group. Patients in groups A and B were scanned with the acquisition time window corresponding to the heart rate determined during a breath hold obtained after free breathing and the basal heart rate during free breathing, respectively. Computed tomography (CT) attenuation values of the coronary artery, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were calculated. The subjective image scores of the groups were assessed blindly by 2 experienced physicians using a 4-point system, and score consistency was compared using the κ test. The volume CT dose index and dose-length product were recorded for each patient, and the effective dose (ED) was calculated. The Kruskal-Wallis H test was performed to evaluate differences in age, heart rate, and body mass index. A χ
2 test was used to evaluate sex differences. An independent-sample t test was employed to compare objective and subjective data such as dose-length product, volume CT dose index, ED, SNR, CNR, and averaged subjective assessment scores. Statistical significance was set at P < 0.05.

Results

No statistically significant differences occurred in sex, age, or body mass index between patients in group A and group B (all P > 0.05). No significant differences occurred in the mean CT values, mean SNR values, mean CNR values, or mean subjective scores of CCTA images between the patients in groups A and B (P > 0.05). The ED values of the patients in group A were 52.93% lower than those in group B (P < 0.001).

Conclusion

The radiation dose in CCTA examinations can be significantly reduced while maintaining image quality by narrowing the acquisition time window for breath-holding after free breathing.
Breaking Barriers and Navigating the Future of Emergency Care
Authors: Davis Wesley D.
Published: September 2024

Over the past two decades, the emergency nurse practitioner (ENP) role has significantly enhanced emergency care in the United States. With the increasing complexity of emergency care, ENPs have expanded into nontraditional settings, necessitating regulatory updates to maintain patient safety. The Consensus Model for Advanced Practice Registered Nurse Regulation has influenced ENP practice, yet consistent regulatory recognition is still needed due to the marked evolution in ENP practice. Despite collaborative efforts to prepare the ENP workforce and ensure competency through standardized education, certification, and licensure, recent unethical publications and skewed statistics have threatened the specialty’s progress. Addressing these challenges is crucial for advancing the ENP role and ensuring high-quality emergency care delivery.
Executive Leadership and Entrepreneurship of Emergency Nurse Practitioners
Authors: Davis Wesley D.
Published: September 2024

For more than five decades, emergency nurse practitioners have developed partnerships and led improvements in emergency care delivery. Through these endeavors the quality of patient care has been amplified and access to emergency care has been augmented. Nurse practitioners providing emergency care possess fundamental leadership qualities necessary for leading teams in delivery of exceptional care. Though advanced practice nurse entrepreneurship is relatively new, engagement of emergency nurse practitioners in business ventures continues to evolve and expand. This article showcases the work of five emergency nurse practitioners whose leadership and entrepreneurship have elevated emergency care bringing recognition to the aptitude and versatility of the emergency nurse practitioner specialty.
Molecular Signature Associated With Acute Rejection in Vascularized Composite Allotransplantation
Authors: Cassidy Michael F. , Doudican Nicole A. , Frazzette Nicholas , Rabbani Piul S. , Carucci John A. , Gelb Bruce E. , Rodriguez Eduardo D. , Lu Catherine P. , Ceradini Daniel J.
Published: September 2024

Background.

A deeper understanding of acute rejection in vascularized composite allotransplantation is paramount for expanding its utility and longevity. There remains a need to develop more precise and accurate tools for diagnosis and prognosis of these allografts, as well as alternatives to traditional immunosuppressive regimens.

Methods.

Twenty-seven skin biopsies collected from 3 vascularized composite allotransplantation recipients, consisting of face and hand transplants, were evaluated by histology, immunohistochemistry staining, and gene expression profiling.

Results.

Biopsies with clinical signs and symptoms of rejection, irrespective of histopathological grading, were significantly enriched for genes contributing to the adaptive immune response, innate immune response, and lymphocyte activation. Inflammation episodes exhibited significant fold change correlations between the face and hands, as well as across patients. Immune checkpoint genes were upregulated during periods of inflammation that necessitated treatment. A gene signature consisting of CCL5, CD8A, KLRK1, and IFNγ significantly predicted inflammation specific to vascularized composite allografts that required therapeutic intervention.

Conclusions.

The mechanism of vascularized composite allograft-specific inflammation and rejection appears to be conserved across different patients and skin on different anatomical sites. A concise gene signature can be utilized to ascertain graft status along with a continuous scale, providing valuable diagnostic and prognostic information to supplement current gold standards of graft evaluation.
Interpenetrating networks of fibrillar and amorphous collagen promote cell spreading and hydrogel stability
Authors: Brunel Lucia G. , Long Chris M. , Christakopoulos Fotis , Cai Betty , Johansson Patrik K. , Singhal Diya , Enejder Annika , Myung David , Heilshorn Sarah C.
Published: September 2024

Hydrogels composed of collagen, the most abundant protein in the human body, are widely used as scaffolds for tissue engineering due to their ability to support cellular activity. However, collagen hydrogels with encapsulated cells often experience bulk contraction due to cell-generated forces, and conventional strategies to mitigate this undesired deformation often compromise either the fibrillar microstructure or cytocompatibility of the collagen. To support the spreading of encapsulated cells while preserving the structural integrity of the gels, we present an interpenetrating network (IPN) of two distinct collagen networks with different crosslinking mechanisms and microstructures. First, a physically self-assembled collagen network preserves the fibrillar microstructure and enables the spreading of encapsulated human corneal mesenchymal stromal cells. Second, an amorphous collagen network covalently crosslinked with bioorthogonal chemistry fills the voids between fibrils and stabilizes the gel against cell-induced contraction. This collagen IPN balances the biofunctionality of natural collagen with the stability of covalently crosslinked, engineered polymers. Taken together, these data represent a new avenue for maintaining both the fiber-induced spreading of cells and the structural integrity of collagen hydrogels by leveraging an IPN of fibrillar and amorphous collagen networks.

Statement of significance

Collagen hydrogels are widely used as scaffolds for tissue engineering due to their support of cellular activity. However, collagen hydrogels often undergo undesired changes in size and shape due to cell-generated forces, and conventional strategies to mitigate this deformation typically compromise either the fibrillar microstructure or cytocompatibility of the collagen. In this study, we introduce an innovative interpenetrating network (IPN) that combines physically self-assembled, fibrillar collagen—ideal for promoting cell adhesion and spreading—with covalently crosslinked, amorphous collagen—ideal for enhancing bulk hydrogel stability. Our IPN design maintains the native fibrillar structure of collagen while significantly improving resistance against cell-induced contraction, providing a promising solution to enhance the performance and reliability of collagen hydrogels for tissue engineering applications.

Graphical abstract
Global Genotype by Environment Prediction Competition Reveals That Diverse Modeling Strategies Can Deliver Satisfactory Maize Yield Estimates
Authors: Washburn Jacob D. , Varela José Ignacio , Xavier Alencar , Chen Qiuyue , Ertl David , Gage Joseph L. , Holland James B. , Lima Dayane Cristina , Romay Maria Cinta , Lopez-Cruz Marco , de los Campos Gustavo , Barber Wesley , Zimmer Cristiano , Trucillo Silva Ignacio , Rocha Fabiani , Rincent Renaud , Ali Baber , Hu Haixiao , Runcie Daniel E , Gusev Kirill , Slabodkin Andrei , Bax Phillip , Aubert Julie , Gangloff Hugo , Mary-Huard Tristan , Vanrenterghem Theodore , Quesada-Traver Carles , Yates Steven , Ariza-Suárez Daniel , Ulrich Argeo , Wyler Michele , Kick Daniel R. , Bellis Emily S. , Causey Jason L. , Soriano Chavez Emilio , Wang Yixing , Piyush Ved , Fernando Gayara D. , Hu Robert K , Kumar Rachit , Timon Annan J. , Venkatesh Rasika , Segura Abá Kenia , Chen Huan , Ranaweera Thilanka , Shiu Shin-Han , Wang Peiran , Gordon Max J. , Amos B K. , Busato Sebastiano , Perondi Daniel , Gogna Abhishek , Psaroudakis Dennis , Chen C. P. James , Al-Mamun Hawlader A. , Danilevicz Monica F. , Upadhyaya Shriprabha R. , Edwards David , de Leon Natalia
Published: September 2024

Predicting phenotypes from a combination of genetic and environmental factors is a grand challenge of modern biology. Slight improvements in this area have the potential to save lives, improve food and fuel security, permit better care of the planet, and create other positive outcomes. In 2022 and 2023 the first open-to-the-public Genomes to Fields (G2F) initiative Genotype by Environment (GxE) prediction competition was held using a large dataset including genomic variation, phenotype and weather measurements and field management notes, gathered by the project over nine years. The competition attracted registrants from around the world with representation from academic, government, industry, and non-profit institutions as well as unaffiliated. These participants came from diverse disciplines include plant science, animal science, breeding, statistics, computational biology and others. Some participants had no formal genetics or plant-related training, and some were just beginning their graduate education. The teams applied varied methods and strategies, providing a wealth of modeling knowledge based on a common dataset. The winner’s strategy involved two models combining machine learning and traditional breeding tools: one model emphasized environment using features extracted by Random Forest, Ridge Regression and Least-squares, and one focused on genetics. Other high-performing teams’ methods included quantitative genetics, classical machine learning/deep learning, mechanistic models, and model ensembles. The dataset factors used, such as genetics; weather; and management data, were also diverse, demonstrating that no single model or strategy is far superior to all others within the context of this competition.
A Comparative Study of Radiomic and Connectomic Approaches to Classification of IDH1 Status and 1p/19q Co-deletion in Lower Grade Gliomas
Authors: Paradkar Rohit V. , Alterman Ron L.
Published: September 2024

Purpose

Grade III and IV brain tumors are labeled “high grade”, or malignant. Lower grade tumors (grade II and III) can progress to high grade and must be closely monitored. In lower grade gliomas, the presence of a specific IDH1 gene mutation and the 1p/19q chromosomal co-deletion confer favorable prognosis and alternative treatment strategy. Presently, these markers are evaluated using surgically obtained tissue specimens. In this study, we evaluate noninvasive approaches to classification of these genetic markers. We hypothesized that connectomic and radiomic approaches to classification would perform similarly. We also tested combined classification, incorporating radiomics and connectomics.

Methods

Binary classifiers used radiomic and connectomic features from MRI to classify IDH1 and 1p/19q co-deletion status. Radiomic features were calculated to characterize tumor gray-level, texture, and shape. Voxel-based morphometry was performed to create gray-matter structural connectomes. Nodal efficiencies of brain regions, number of nodes and connections were computed. Binary classifiers predicted IDH1 and 1p/19q co-deletion status. Statistical analysis quantified differences in model performance.

Results

Connectomic and radiomic features had insignificant difference in classification of IDH1 status. Radiomic and connectomic classification of 1p/19q co-deletion status had no significant accuracy difference, however, radiomics had significantly higher AUC score. The combined approach had no significant difference to radiomics and connectomics except for a significantly higher AUC score than connectomics in 1p/19q co-deletion classification.

Conclusion

Altogether, the study shows that radiomics, connectomics, and a combination of the two are viable classification approaches for these markers. Future studies could incorporate these methods to improve diagnostic performance.
Carboxy-terminal blockade of sortilin binding enhances progranulin gene therapy, a potential treatment for frontotemporal dementia
Authors: Kashyap Shreya N. , Fox Stephanie N. , Wilson Katherine I. , Murchison Charles F. , Ambaw Yohannes A. , Walther Tobias C. , Farese Robert V. , Arrant Andrew E. , Roberson Erik D.
Published: September 2024

Frontotemporal dementia is commonly caused by loss-of-function mutations in the progranulin gene. Potential therapies for this disorder have entered clinical trials, including progranulin gene therapy and drugs that reduce progranulin interactions with sortilin. Both approaches ameliorate functional and pathological abnormalities in mouse models of progranulin insufficiency. Here we investigated whether modifying the progranulin carboxy terminus to block sortilin interactions would improve the efficacy of progranulin gene therapy. We compared the effects of treating progranulin-deficient mice with gene therapy vectors expressing progranulin with intact sortilin interactions, progranulin with the carboxy terminus blocked to reduce sortilin interactions, or GFP control. We found that expressing carboxy-terminally blocked progranulin generated higher levels of progranulin both at the injection site and in more distant regions. Carboxy-terminally blocked progranulin was also more effective at ameliorating microgliosis, microglial lipofuscinosis, and lipid abnormalities including ganglioside accumulation and loss of bis(monoacylglycero)phosphate lipids. Finally, only carboxy-terminally blocked progranulin reduced plasma neurofilament light chain, a biomarker of neurodegeneration, in progranulin-deficient mice. These results demonstrate that modifying the progranulin cargo to block sortilin interactions may be important for increasing the effectiveness of progranulin gene therapy.

One-sentence Summary

The effectiveness of progranulin gene therapy in models of FTD is improved by blocking the protein’s carboxy terminus, which prevents sortilin binding
GWA-X: An Extensible GPU Accelerated Package for Permutation Testing in Genome-Wide Association Studies
Authors: Agung Mulya , Tenesa Albert
Published: September 2024

Genome-wide association studies (GWAS) aim to identify genetic variants that are associated with a trait or disease. The scale of genomic datasets has increased to millions of genetic variants and hundreds of thousands of individuals, opening the possibilities for GWAS discoveries. However, large-scale GWAS analyses are prone to high false positive rates because of the multiple testing problem. Permutation testing is the gold standard for maintaining false positive rates, yet it is impractical for large-scale GWAS because it demands vast computational resources. This paper presents GWA-X, a software package that can exploit GPU potential to accelerate permutation testing in GWAS. Unlike previous methods, GWA-X employs a novel whole-genome regression method and a permutation testing strategy to batch the computations of many genetic markers. It achieved a two-order magnitude speed-up compared with the existing CPU-based and GPU-based permutation methods. In addition, it provides an extensible package for GWAS permutation testing on GPUs.
Automated speech artefact removal from MEG data utilizing facial gestures and mutual information
Authors: Tuomaala Sara , Autti Salla , Cotroneo Silvia Federica , Lioumis Pantelis , Renvall Hanna , Liljeström Mia
Published: September 2024

The ability to speak is one of the most crucial human skills, motivating neuroscientific studies of speech production and speech-related neural dynamics. Increased knowledge in this area, allows e.g., for development of rehabilitation protocols for language-related disorders. While our understanding of speech-related neural processes has greatly enhanced owing to non-invasive neuroimaging techniques, the interpretations have been limited by speech artefacts caused by the activation of facial muscles that mask important languagerelated information. Despite earlier approaches applying independent component analysis (ICA), the artefact removal process continues to be time-consuming, poorly replicable and affected by inconsistencies between different observers, typically requiring manual selection of artefactual components. The artefact component selection criteria have been variable, leading to non-standardized speech artefact removal processes. To address these issues, we propose here a pipeline for automated speech artefact removal from MEG data. We developed an ICA-based speech artefact removal routine by utilizing EMG data measured from facial muscles during a facial gesture task for isolating the speech-induced artefacts. Additionally, we used mutual information (MI) as a similarity measure between the EMG signals and the ICA-decomposed MEG to provide a feasible way to identify the artefactual components. Our approach efficiently and in an automated manner removed speech artefacts from MEG data. The method can be feasibly applied to improve the understanding of speech-related cortical dynamics, while transparently evaluating the removed and preserved MEG activation.
TRPC3 suppression ameliorates synaptic dysfunctions and memory deficits in Alzheimer’s disease
Authors: Wang Jiaxing , Chen Ling , Wang Zhengjun , Zhang Sicheng , Ding Dongyi , Lin Geng , Zhang Hua , Boda Vijay K. , Kong Dehui , Ortyl Tyler C. , Wang Xusheng , Lu Lu , Zhou Fu-Ming , Bezprozvanny Ilya , Du Jianyang , Wu Zhongzhi , Li Wei , Liao Francesca-Fang
Published: September 2024

Transient receptor potential canonical (TRPC) channels are widely expressed in the brain; however, their precise roles in neurodegeneration, such as Alzheimer’s disease (AD) remain elusive. Bioinformatic analysis of the published single-cell RNA-seq data collected from AD patient cohorts indicates that theTrpc3gene is uniquely upregulated in excitatory neurons. TRPC3 expression is also upregulated in post-mortem AD brains, and in both acute and chronic mouse models of AD. Functional screening of TRPC3 antagonists resulted in a lead inhibitor JW-65, which completely rescued Aβ-induced neurotoxicity, impaired synaptic plasticity (e.g., LTP), and learning memory in acute and chronic experimental AD models. In cultured rat hippocampal neurons, we found that treatment with soluble β-amyloid oligomers (AβOs) induces rapid and sustained upregulation of the TRPC3 expression selectively in excitatory neurons. This aberrantly upregulated TRPC3 contributes to AβOs-induced Ca2+overload through the calcium entry and store-release mechanisms. The neuroprotective action of JW-65 is primarily mediated via restoring AβOs-impaired Ca2+/calmodulin-mediated signaling pathways, including calmodulin kinases CaMKII/IV and calcineurin (CaN). The synaptic protective mechanism via TRPC3 inhibition was further supported by hippocampal RNA-seq data from the symptomatic 5xFAD mice after chronic treatment with JW-65. Overall, these findings not only validate TRPC3 as a novel therapeutic target for treating synaptic dysfunction of AD but most importantly, disclose a distinct role of upregulated TRPC3 in AD pathogenesis in mediating Ca2+dyshomeostasis.
AusAMF: database of arbuscular mycorrhizal fungal communities in Australia
Authors: Frew Adam , Powell Jeff , Heuck Meike Katharina , Albornoz Felipe , Birnbaum Christina , Dearnaley John , Egidi Eleonora , Finn Luke , Kath Jarrod , Koorem Kadri , Oja Jane , Opik Maarja , Vahter Tanel , Vasar Martti , Watts-Williams Stephanie , Zheng Yuxiong , Aguilar-Trigueros Carlos A
Published: September 2024

Motivation: Arbuscular mycorrhizal (AM) fungi are integral to plant nutrient acquisition, carbon cycling, and ecosystem resilience, yet our knowledge of their biogeography is severely limited, especially in the Southern Hemisphere. Australia, despite its landmass and unique ecological characteristics, has been vastly undersampled, leaving a significant gap in our understanding of AM fungal diversity and distribution. The AusAMF database was created to address this deficiency, the first release comprises AM fungal community data from 610 sampling locations across mainland Australia and Tasmania, collected between 2011 and 2023. Using standardised sampling, DNA extraction, sequencing methods and platforms, this database provides a robust resource for exploring spatial patterns in AM fungal diversity, community composition, and the ecological drivers shaping AM fungal biogeography. The AusAMF database will continue to be updated and maintain standardised approaches to facilitate future research into plant-mycorrhizal interactions, nutrient cycling, and to understand the broader role of AM fungi in ecosystem processes. The data here will provide the foundation for more informed management and conservation efforts in Australia while providing valuable data for global scale analyses. Main types of variables contained: Georeferenced occurrence and abundance of high throughput amplicon sequences of arbuscular mycorrhizal (AM) fungi. Spatial location and grain Australia. Decimal degrees between 0.000001 to 0.1 resolution Time period and grain: 2011 to 2023. Month and year of sampling. Major taxa and level of measurement: Arbuscular mycorrhizal fungi identified to family, genus, and virtual taxon (VT). Geographic occurrence and amplicon sequence abundance. Software format: Interact with data via online application. Dataset available as .csv files and raw sequencing data as .fastq files.
Evaluating Best Practices for Isolating Pyrophilous Bacteria and Fungi from Burned Soil
Authors: Enright Dylan J. , Quaal Ryan , Verabeehu Aishwarya , Nguyen Anna , Maddox Jenna , Glassman Sydney I.
Published: September 2024

A live microbial culture is invaluable to assess traits and functions via ‘omics and biophysical assays. However, it is not always logistically feasible to culture immediately from freshly obtained soil, and selecting the proper media for culturing is not trivial. While building a culture collection of pyrophilous microbes obtained from burnt soil, we tested the best 1) method of storing soil to retain culturable viability and 2) media to garner the most microbial diversity. We tested four methods of soil storage (dried, stored at 4°C, stored at -80°C alone or in glycerol) and compared to fresh soil obtained 6 months after a severe California chapparal shrubland wildfire. For bacteria, soil frozen at -80°C with glycerol preserved the greatest diversity (25 species, 13 genera) compared to fresh soil (26 species, 13 genera). For fungi, soil stored at -80°C alone preserved the greatest diversity (10 species, 3 genera) compared to fresh soil (13 species, 7 genera). We also tested 3 media types: rich media (Lysogeny Broth (LB) for bacteria; Malt Yeast Agar (MYA) for fungi), oligotrophic media (Reasoner’s 2 Agar (R2A) and media made from pyrogenic organic matter (PyOM). For bacteria, culturing on LB and R2A garnered the greatest diversity (LB = 26 species, 13 genera, R2A = 27 species, 15 genera). For fungi a combination of R2A and PyOM captured the greatest diversity (R2A = 15 species, 8 genera, PyOM = 12 species, 6 genera). For both bacteria and fungi, some species of interest were only captured using the PyOM media. Using a combination of these methods from 2018-2022, we cultured >500 isolates (286 bacteria; 258 fungi) from burned soils of 7 Southern California wildfires.
Glial scar formation by reactive astrocytes derived from oligodendrocyte progenitor cells after closed-head injury
Authors: Matsuda Hinata , Tsuji Erika , Riberu Agnes Antonetta Orchidia , Okano Hideyuki , Morita Mitsuhiro
Published: September 2024

The diversity of reactive astrocytes is key to understanding complicated pathological processes in the brain. The accumulation of reactive astrocytes expressing the neural stem/precursor cell marker Nestin is common after brain injury, but the pathological implications of this reactive astrocyte subpopulation remain elusive. This study initially aimed to determine the origin and fate of these reactive astrocytes expressing Nestin by characterizing cells labeled with green fluorescent protein (GFP) after closed-head injury, using aNestinpromoter region widely utilized to study neural stem/precursor cells. Unexpectedly, oligodendrocyte progenitor cells (OPCs), rather than astrocytes, were robustly and selectively labeled with GFP. A fraction of these cells showed a subsequent upregulation of astrocyte markers and were incorporated into glial scars. These glial scars are aggregates of reactive astrocytes that form between lesion cores and the perilesional recovering region. Deletion of theStat3gene, which is essential for astrocyte activation, using aNestinpromoter reduced glial scars, further confirming that OPCs are involved in glial scar formation. Reactive astrocytes labeled with aglial fibrillary acidic proteinpromoter differed in morphology and distribution from astrocytes derived from OPCs. This confirms that astrocytes and OPCs produce distinct reactive astrocyte subpopulations. Some GFP-labeled OPCs lacking astrocyte markers were found to distribute in perilesional recovering regions. The reduced expression of Nestin and OPC markers in these non-astrocytic descendants of OPCs, coupled with a significant fraction of these cells remaining olig2-positive, suggests that OPCs give rise to both reactive astrocytes and oligodendrocytes. These findings suggest that OPCs are activated by a novel process after brain injury.
A Potential Method for Identifying Milk Adulteration and Pb(II) Contamination Scenarios Using Principal Component Analysis From Smartphone Photographs
Authors: Chandra Alicia Catelyn , Lianto Cheralyn Clarecia , Sulimro Felicia Liem , Santoso Gabriella Anna , Wang Michelle Aiko , Miah Lie , Prabowo Norbertus Krisnu
Published: September 2024

Heavy metal contaminants and adulteration in cow milk products are major issues affecting milk safety and quality, posing health risks to consumers of all ages. These contaminants are sometimes difficult to detect with the naked eye and can potentially pass sensory tests, particularly in white cow milk. This research explores the detection of lead(II) poisoning in milk post-production and the adulteration of different milk samples using an alternative approach through chemometric techniques based on RGB and Grey Area image analysis. A controlled photography environment was used. We analyzed over 105 samples of control, adulterated, and lead(II)-added milk in this study using image processing software. Each photograph was analyzed to provide triplicate Regions of Interest (ROI), resulting in a total of 315 statistical datasets. We found that Principal Component Analysis (PCA) effectively clustered control white milk and Pb(II)-contaminated milk. Clusters of different adulterants were recognized simply by feeding RGB and Grey Area data into PCA. However, some clusters, such as mixed chocolate milk and white milk with lead(II) contamination, were not well distinguished. In this early-stage method, a comparison study with infrared spectra will be required in future research. This alternative method shows potential promise for deployment in limited settings for real-world food quality surveillance and regulation.
FEATURE-SPECIFIC ANTICIPATORY PROCESSING FADES DURING HUMAN SLEEP
Authors: Topalidis Pavlos I. , Reisinger Lisa , Shubert Juliane , Ameen Mohamed S. , Weisz Nathan , Schabus Manuel
Published: September 2024

Imagine you are listening to a familiar song on the radio. As the melody and rhythm unfold, you can often anticipate the next note or beat, even before it plays. This ability demonstrates the brain’s capacity to extract statistical regularities from sensory input and to generate predictions about future sensory events. It is considered automatic, requiring no conscious effort or attentional resources (1–4). But to what extent does this predictive ability operate when our attention is greatly reduced, such as during sleep? Experimental findings from animal and human studies reveal a complex picture of how the brain engages in predictive processing during sleep (5–13). Although evidence suggests that the brain differentially reacts to unexpected stimuli and rhythmic music (5,7,13), there is a notable disruption in feedback processing, which is essential for generating accurate predictions of upcoming stimuli (10). Here, for the first time, we examine the brain’s ability during sleep to predict or pre-activate low-level features of expected stimuli before presentation. We use sequences of predictable or unpredictable/random tones in a passive-listening paradigm while recording simultaneous electroencephalography (EEG) and magnetoencephalography (MEG) during wakefulness and sleep. We found that during wakefulness, N1 sleep and N2 sleep, subtle changes in tone frequencies elicit unique/distinct neural activations. However, these activations are less distinct and less sustained during sleep than during wakefulness. Critically, replicating previous work in wakefulness (4), we find evidence that neural activations specific to the anticipated tone occur before its presentation. Extending previous findings, we show that such predictive neural patterns fade as individuals fall into sleep.

In Brief

The extent to which predictive processing takes place in sleep is yet to be determined. Using a passive-listening EEG/MEG paradigm, Topalidis et al. show that auditory representations in sleep are brief and unstable, easily overwritten by subsequent inputs, which possibly hinders the tracking and extraction of sensory associations.

Highlights

Participants passively listened to random and predictable sequences of tones during both wakefulness and sleep, without being made aware of the underlying pattern.

The brain reta

ins the ability to process basic low-level features during sleep.

While these feature-specific responses are preserved during sleep, they are less distinct and sustained than in wakefulness.

Unlike in wakefulness, during sleep, the brain does not predict or anticipate upcoming sounds, despite continuing to process basic auditory information.