bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying core MRI sequences for reliable automatic brain metastasis segmentation
Authors: Buchner Josef A , Peeken Jan C , Etzel Lucas , Ezhov Ivan , Mayinger Michael , Christ Sebastian M , Brunner Thomas B , Wittig Andrea , Menze Björn , Zimmer Claus , Meyer Bernhard , Guckenberger Matthias , Andratschke Nicolaus , El Shafie Rami A , Debus Jürgen , Rogers Susanne , Riesterer Oliver , Schulze Katrin , Feldmann Horst J , Blanck Oliver , Zamboglou Constantinos , Ferentinos Konstantinos , Bilger Angelika , Grosu Anca L , Wolff Robert , Kirschke Jan S , Eitz Kerstin A , Combs Stephanie E , Bernhardt Denise , Rückert Daniel , Piraud Marie , Wiestler Benedikt , Kofler Florian 
Published: May 2023

AbstractBackgroundMany automatic approaches to brain tumor segmentation employ multiple magnetic resonance imaging (MRI) sequences. The goal of this project was to compare different combinations of input sequences to determine which MRI sequences are needed for effective automated brain metastasis (BM) segmentation.MethodsWe analyzed preoperative imaging (T1-weighted sequence ± contrast-enhancement (T1/T1-CE), T2-weighted sequence (T2), and T2 fluid-attenuated inversion recovery (T2-FLAIR) sequence) from 339 patients with BMs from six centers. A baseline 3D U-Net with all four sequences and six U-Nets with plausible sequence combinations (T1-CE, T1, T2-FLAIR, T1-CE+T2-FLAIR, T1-CE+T1+T2-FLAIR, T1-CE+T1) were trained on 239 patients from two centers and subsequently tested on an external cohort of 100 patients from five centers.ResultsThe model based on T1-CE alone achieved the best segmentation performance for BM segmentation with a median Dice similarity coefficient (DSC) of 0.96. Models trained without T1-CE performed worse (T1-only: DSC = 0.70 and T2-FLAIR-only: DSC = 0.73). For edema segmentation, models that included both T1-CE and T2-FLAIR performed best (DSC = 0.93), while the remaining four models without simultaneous inclusion of these both sequences reached a median DSC of 0.81-0.89.ConclusionsA T1-CE-only protocol suffices for the segmentation of BMs. The combination of T1-CE and T2-FLAIR is important for edema segmentation. Missing either T1-CE or T2-FLAIR decreases performance. These findings may improve imaging routines by omitting unnecessary sequences, thus allowing for faster procedures in daily clinical practice while enabling optimal neural network-based target definitions.
Single-cell dissection of the immune response after acute myocardial infarction
Authors: van Blokland Irene V. , Oelen Roy , Groot Hilde E. , Benjamins Jan Walter , Pekayvaz Kami , Losert Corinna , Knottenberg Viktoria , Heinig Matthias , Nicolai Leo , Stark Konstantin , van der Harst Pim , Franke Lude H. , van der Wijst Monique G. P. 
Published: May 2023

AbstractThe role of the immune system during and in response to acute myocardial infarction (MI) is poorly characterized but is an important driver of recurrent cardiovascular events. Anti-inflammatory drugs have shown promising effects on lowering this recurrency risk, but broadly impair the immune system and may induce severe side effects. To overcome these challenges a more detailed understanding of the immune response to myocardial infarction is needed.For this, we compared peripheral blood mononuclear cell (PBMC) single-cell RNA-sequencing expression and plasma protein profiles over time (hospital admission, 24h and 6-8 weeks after STEMI) in 38 patients and in comparison to 38 controls (95,995 diseased and 33,878 control PBMCs). Compared to controls, we observed a relative increase in classical monocytes and a decrease in CD56dimnatural killer cells in STEMI patients at admission, and these differences persisted until 24h after STEMI. The monocytes also showed the largest gene expression changes in each of the conditions, which was associated with changes in toll-like receptor, IFN and IL-1 signaling activity. Finally, a targeted protein cardiovascular biomarker panel revealed 33/92 plasma proteins to be changed after STEMI. Interestingly, three of these proteins were found to be affected by coronary artery disease-associated genetic risk variation, disease status and time after STEMI. Indicating the importance of taking all these aspects into consideration when defining potential future therapies.Altogether, our analyses have revealed the immunological pathways that are disturbed upon MI, and in which cell type and during which stage of the disease this occurs. Additionally, we also provide insights in which patients are expected to benefit most from anti-inflammatory treatments, by identifying the genetic variants and disease stage at which these variants affect the outcome of these (drug-targeted) pathways. These findings advance our knowledge of the immune response after MI and provide further guidance for future therapeutic studies.
Disruptions of Hierarchical Cortical Organisation in Early Psychosis and Schizophrenia
Authors: Holmes Alexander , Levi Priscila T. , Chen Yu-Chi , Chopra Sidhant , Aquino Kevin M. , Pang James C. , Fornito Alex 
Published: May 2023

AbstractBackgroundThe cerebral cortex is organised hierarchically along an axis that spans unimodal sensorimotor to transmodal association areas. This hierarchy is often characterised using low-dimensional embeddings, termed gradients, of inter-regional functional coupling estimates measured with resting-state functional magnetic resonance imaging (fMRI). Such analyses may offer insights into the pathophysiology of schizophrenia, which is frequently linked to dysfunctional interactions between association and sensorimotor areas.MethodsTo examine disruptions of hierarchical cortical function across distinct stages of psychosis, we applied diffusion map embedding to two independent fMRI datasets: one comprised 114 patients with early psychosis and 48 controls, and the other comprising 50 patients with established schizophrenia and 121 controls. We then analysed the primary sensory-fugal and secondary visual-to-sensorimotor gradients of each participant in both datasets.ResultsThere were no significant differences in regional gradient scores between patients with early psychosis and controls. Patients with established schizophrenia showed significant differences in the secondary, but not primary, gradient relative to controls. Gradient differences in schizophrenia were characterised by lower within-network dispersion in the Dorsal Attention (pFDR<.001), Visual (pFDR=.003), Frontoparietal (pFDR=.018), and Limbic (pFDR=.020) networks and lower between-network dispersion between the Visual network and other networks (pFDR<.001).ConclusionsThese findings indicate that differences in cortical hierarchical function occur along the secondary visual-to-sensorimotor axis rather than the primary sensory-fugal axis, as previously thought. The absence of differences in early psychosis suggests that visual-sensorimotor abnormalities may emerge as the illness progresses.
Becoming a resilient scientist series: An intervention program
Authors: Han H. Anna , Klenke Ulrike , McNulty Laurie Chaikind , Scheiner Annie , Milgram Sharon L. 
Published: May 2023

AbstractCompared to the general population, science trainees experience challenges and heightened stressors that often lead to adverse mental health outcomes. With COVID-19, the stressors of social distancing, isolation, truncated lab time, and uncertainty about the future have all likely exacerbated these issues. Now, more than ever, practical and effective interventions are vitally needed to address the core causes of stress among science trainees and increase their resilience. This paper introduces a new resilience program targeted to biomedical trainees and scientists – Becoming a Resilient Scientist Series (BRS), a multi-part workshop complemented by facilitated group discussions all aimed at bolstering resilience, particularly in the context of academic and research environments. To assess the program’s efficacy, participants completed resilience measures and related assessments before and after completing the series. The results demonstrate that BRS significantly enhances trainee resilience (primary outcome) and reduces perceived stress, anxiety, and work-related presenteeism, as well as increased adaptability, self-awareness, and self-efficacy (secondary outcomes). Furthermore, program participants reported a high level of satisfaction, a strong willingness to recommend the program to others, and perceived positive changes in their resilience skills. To the best of our knowledge, this is the first resilience program designed explicitly for biomedical trainees and scientists, tailored to their unique professional culture and work environment.
Did knowledge, attitudes, and practices matter during the second wave of COVID-19 pandemic in Bangladesh? Results from a web-based cross-sectional study
Authors: Khan Md. Robin , Hossain Md. Jamal , Islam Md. Ariful , Zaman Shadid Uz , Islam Mohammad Touhidul , Haque Md. Anamul , Islam Md. Rabiul , Ripa Farhana Alam , Islam Md. Monirul , Ahmmed Foyez 
Published: May 2023

AbstractGlobally, health promotion measures have been undertaken in preventing the emergence and spread of coronavirus disease 2019 (COVID-19). However, whether these measures influence public awareness and behaviors is unclear and evidence is limited in particular in low-and-middle income country. We conducted an online survey among internet users in Bangladesh to understand the status and attributes of their knowledge, attitudes and practices towards COVID-19 during second wave of the pandemic when COVID educational information was more accessible to the public. Survey data were analyzed using descriptive statistics, Chi-square tests, and multivariate logistic regression analysis. Of 964 respondents, 40.2%, 51.5%, and 64.3% had good knowledge, confident attitudes, and proper practices towards COVID-19, respectively. The multivariate regression analysis found that the knowledge and practice scores were associated (p<0.05) with gender, age, and occupation. Females had better knowledge and practices compared to males (p<0.05). There were major gaps in awareness, attitudes, and practices among internet users in particular males and elders that needs to be addressed to control the further spread of COVID-19 infections before at least COVID-19 vaccine become accessible at population level in Bangladesh.
GATA3 ZnF2-defective mutant condensation underlies type I IFN-activating in breast cancer
Authors: Chen Yatao , Wan Yajie , Pei Xiaoying , Wang Tan , Ma Zhifang , Chen Liming 
Published: May 2023

AbstractZinc finger (ZnF) transcription factors (TFs) consist of ZnF-containing DNA-binding domains (DBDs) and intrinsically disordered region (IDR)-containing activation domains (ADs). Recent studies have suggested that liquid-liquid phase separation (LLPS) is the fundamental mechanism underlying human health and disease, with ZnF TFs activating gene expression through the LLPS capacity of their IDR-containing ADs. However, little is known about how the well-folded DBD of ZnF TFs is involved in their LLPS mechanism. GATA3 is one of the most frequently mutated genes in breast cancer, and its encoded protein GATA3, which contains two ZnFs (ZnF1 and ZnF2) in its DBD, is a master regulator of immunity. Here, we show that GATA3 undergoes LLPS in cells and in vitro, and its DBD plays an important regulatory role. Mechanistically, ZnF2 in the DBD contains two arginine amino acids (R329 and R330) that provide critical charges to regulate GATA3 LLPS and DNA binding by generating multivalent electrostatic interactions. Functionally, we demonstrated that ZnF2-regulated GATA3 LLPS is the mechanism underlying the multifaceted function of GATA3 in breast cancer development and immune regulation, where aberrant GATA3 LLPS caused by artificial or breast cancer-associated ZnF2-defective mutations by reducing Suv39H1 protein stability showed significantly reduced potential in promoting breast cancer development and exhibited remarkably enhanced capacities for activating type I interferon signaling. Since ZnF is a common feature in the DBDs of ZnF TFs, by describing GATA3 as a proof-of-principle, our data suggest that ZnF-regulated LLPS may be a general mechanism underlying the multifaceted function of ZnF TFs in human health and disease.
Single cell transcriptomics of the human parasiteSchistosoma mansonifirst intra-molluscan stage reveals tentative tegumental and stem cell regulators
Authors: Soria Carmen L. Diaz , Attenborough Teresa , Lu Zhigang , Graham Jennie , Hall Christopher , Thompson Sam , Andrews Toby G. R. , Rawlinson Kate A. , Berriman Matthew , Rinaldi Gabriel 
Published: May 2023

AbstractBackgroundSchistosomiasis is a major Neglected Tropical Disease, caused by the infection with blood flukes in the genusSchistosoma. To complete the life cycle, the parasite undergoes asexual and sexual reproduction within an intermediate snail host and a definitive mammalian host, respectively. The intra-molluscan phase provides a critical amplification step that ensures a successful transmission. However, the cellular and molecular mechanisms underlying the development of the intra-molluscan stages remain poorly understood.MethodsS. mansonimother sporocysts were dissociated into single cell suspensions, and live cells enriched and sequenced using the single cell 10X Genomics Chromium platform. We defined somatic and stem/germinal cell clusters, identified cell type-enriched Gene Ontology (GO) terms, and predicted transcription factor binding sites for key marker genes.ResultsSix cell clusters comprising stem/germinal, two tegument, muscle, neuron, and parenchyma were identified and validated by Fluorescencein situHybridisation (FISH). GO term analysis predicted key biological processes for each of the clusters. Using the Self-Assembling Manifold (SAM) algorithm, three sub-clusters were identified within the stem/germinal cell population. Furthermore, transcription factor binding sites and putative transcription factors were predicted for stem/germinal and tegument clusters.ConclusionsWe report a spatially validated single cell transcriptomic analysis of the first intra-molluscan stage ofS. mansoni.Key cell regulators were identified, paving the way for future analyses to unveil their role during the parasite development and interaction with its intermediate host.
Molecular Mechanisms Underlying Medium-Chain Free Fatty Acid-regulated Activity of the Phospholipase PlaF fromPseudomonas aeruginosa
Authors: Gentile Rocco , Modric Matea , Thiele Björn , Jaeger Karl-Erich , Kovacic Filip , Schott-Verdugo Stephan , Gohlke Holger 
Published: May 2023

ABSTRACTPlaF is a membrane-bound phospholipase A1fromP. aeruginosathat is involved in remodeling membrane glycerophospholipids (GPLs) and modulation of virulence-associated signaling and metabolic pathways. Previously, we identified the role of medium-chain free fatty acids (FFA) in inhibiting PlaF activity and promoting homodimerization, yet the underlying molecular mechanism remained elusive. Here, we used unbiased and biased molecular dynamics simulations and free energy computations to assess how PlaF interacts with FFAs localized in the water milieu surrounding the bilayer or within the bilayer, and how these interactions regulate PlaF activity. Medium-chain FFAs localized in the upper bilayer leaflet can stabilize inactive dimeric PlaF, likely through interactions with charged surface residues as experimentally validated. Potential of mean force (PMF) computations indicate that membrane-bound FFAs may facilitate the activation of monomeric PlaF by lowering the activation barrier of changing into a tilted, active configuration. We estimated that the coupled equilibria of PlaF monomerization-dimerization and tilting at the physiological concentration of PlaF lead to the majority of PlaF forming inactive dimers when in a cell membrane loaded with decanoic acid (C10). This is in agreement with a suggestedin vivoproduct feedback loop and GC-MS profiling results indicating that PlaF catalyzes the release of C10 fromP. aeruginosamembranes. Additionally, we found that C10 in the water milieu can access the catalytic site of active monomeric PlaF, contributing to the competitive component of C10-mediated PlaF inhibition. Our study provides mechanistic insights into how medium-chain FFA may regulate the activity of PlaF, a potential bacterial drug target.
Specification of distinct cell types in a sensory-adhesive organ for metamorphosis in theCionalarva
Authors: Johnson Christopher J. , Razy-Krajka Florian , Zeng Fan , Piekarz Katarzyna M. , Biliya Shweta , Rothbächer Ute , Stolfi Alberto 
Published: May 2023

AbstractThe papillae of tunicate larvae contribute sensory, adhesive, and metamorphosis-regulating functions that are crucial for the biphasic lifestyle of these marine, non-vertebrate chordates. We have identified additional molecular markers for at least five distinct cell types in the papillae of the model tunicateCiona,allowing us to further study the development of these organs. Using tissue-specific CRISPR/Cas9-mediated mutagenesis and other molecular perturbations, we reveal the roles of key transcription factors and signaling pathways that are important for patterning the papilla territory into a highly organized array of different cell types and shapes. We further test the contributions of different transcription factors and cell types to the production of the adhesive glue that allows for larval attachment during settlement, and to the processes of tail retraction and body rotation during metamorphosis. With this study, we continue working towards connecting gene regulation to cellular functions that control the developmental transition between the motile larva and sessile adult ofCiona.
Enzyme stability-activity trade-off : new insights from protein stability weaknesses and evolutionary conservation
Authors: Hou Qingzhen , Rooman Marianne , Pucci Fabrizio 
Published: May 2023

AbstractA general limitation of the use of enzymes in biotechnological processes under sometimes non-physiological conditions is the complex interplay between two key quantities, enzyme activity and stability, where the increase of one is often associated with the decrease of the other. A precise stability-activity trade-off is necessary for the enzymes to be fully functional, but its weight in different protein regions and its dependence on environmental conditions is not yet elucidated. To advance this issue, we used the formalism that we have recently developed to effectively identify stability strength and weakness regions in protein structures, and applied it to a large set of globular enzymes with known experimental structure and catalytic sites. Our analysis showed a striking oscillatory pattern of free energy compensation centered on the catalytic region. Indeed, catalytic residues are usually non-optimal with respect to stability, but residues in the first shell around the catalytic site are, on the average, stability strengths and thus compensate for this lack of stability; residues in the second shell are weaker again, and so on. This trend is consistent across all enzyme families. It is accompanied by a similar, but less pronounced, pattern of residue conservation across evolution. In addition, we analyzed cold- and heat-adapted enzymes separately and highlighted different patterns of stability strengths and weaknesses, which provide insight into the longstanding problem of catalytic rate enhancement in cold environments. The successful comparison of our stability and conservation results with experimental fitness data, obtained by deep mutagenesis scanning, led us to propose criteria for improving catalytic activity while maintaining enzyme stability, a key goal in enzyme design.
Structural Insights into the Iron Nitrogenase Complex
Authors: Schmidt Frederik V. , Schulz Luca , Zarzycki Jan , Oehlmann Niels N. , Prinz Simone , Erb Tobias J. , Rebelein Johannes G. 
Published: May 2023

AbstractNitrogenases are best known for catalysing the reduction of dinitrogen to ammonia at a complex metallic cofactor. Recently, nitrogenases were shown to reduce carbon dioxide (CO2) and carbon monoxide to hydrocarbons, offering a pathway to recycle carbon waste into hydrocarbon products. Among the nitrogenase family the iron nitrogenase is the isozyme with the highest wildtype activity for the reduction of CO2, but the molecular architecture facilitating these activities remained unknown. Here, we report a 2.35-Å cryogenic electron microscopy structure of the Fe nitrogenase complex fromRhodobacter capsulatus,revealing an [Fe8S9C-(R)-homocitrate]-cluster in the active site. The enzyme complex suggests that the AnfG-subunit is involved in cluster stabilisation, substrate channelling and confers specificity between nitrogenase reductase and catalytic components. Moreover, the structure highlights a different interface between the two catalytic halves of the iron and the molybdenum nitrogenase, potentially influencing the intra-subunit ‘communication’ and thus the nitrogenase mechanism.
Development of tools to detect and identify strains belonging to thePseudomonas syringaespecies complex responsible for vein clearing of zucchini
Authors: Lacault Caroline , Briand Martial , Jacques Marie-Agnès , Darrasse Armelle 
Published: May 2023

AbstractVein clearing of zucchini (VCZ) is a seed-borne bacterial disease that affects young plants ofCucurbita peposubsp.pepo. VCZ agents are distributed into four phylogenetic clusters within the clades 2a and 2ba of the phylogroup 2 ofPseudomonas syringaespecies complex. Strains belonging to clades 2b and 2d are sometimes isolated from zucchini seeds but have not been associated with VCZ epidemics. Development of tools able to identify VCZ agents is important to better control the disease. Primers were designed to implement a seven-gene MLSA scheme on a collection of strains isolated from zucchini seeds. A clear predominance of strains with a host range on cucurbits limited to the genusCucurbita(cluster 2ba-A) and the presence of VCZ strains in a fifth cluster (2ba-C) were evidenced. PCR tests were designed to characterize VCZ clusters and a multiplex qPCR test was proposed to distinguish strains having narrow cucurbit host range, associated to the presence ofavrRpt2andsylC,from broad host range strains associated to the presence ofhopZ5andsylC. Additional qPCR tests targeting clade 2b and 2d were also designed to gain insights onP. syringaestrains that could be isolated from cucurbits. Specificity of these tools was evaluatedin silicoon the whole NCBI database andin vitroon a strain collection, showing a 100% inclusivity, except for the test dedicated to clade-2b strains, and an exclusivity ranging from to 96.7% to 100%. These different tools are intended to serve phylogenetic studies, epidemiological monitoring and seed testing.