bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiscale topology classifies cells in subcellular spatial transcriptomics
Authors: Benjamin Katherine , Bhandari Aneesha , Kepple Jessica D. , Qi Rui , Shang Zhouchun , Xing Yanan , An Yanru , Zhang Nannan , Hou Yong , Crockford Tanya L. , McCallion Oliver , Issa Fadi , Hester Joanna , Tillmann Ulrike , Harrington Heather A. , Bull Katherine R. 
Published: June 2024

AbstractSpatial transcriptomics measures in situ gene expression at millions of locations within a tissue1, hitherto with some trade-off between transcriptome depth, spatial resolution and sample size2. Although integration of image-based segmentation has enabled impactful work in this context, it is limited by imaging quality and tissue heterogeneity. By contrast, recent array-based technologies offer the ability to measure the entire transcriptome at subcellular resolution across large samples3–6. Presently, there exist no approaches for cell type identification that directly leverage this information to annotate individual cells. Here we propose a multiscale approach to automatically classify cell types at this subcellular level, using both transcriptomic information and spatial context. We showcase this on both targeted and whole-transcriptome spatial platforms, improving cell classification and morphology for human kidney tissue and pinpointing individual sparsely distributed renal mouse immune cells without reliance on image data. By integrating these predictions into a topological pipeline based on multiparameter persistent homology7–9, we identify cell spatial relationships characteristic of a mouse model of lupus nephritis, which we validate experimentally by immunofluorescence. The proposed framework readily generalizes to new platforms, providing a comprehensive pipeline bridging different levels of biological organization from genes through to tissues.
Human SARS-CoV-2 challenge uncovers local and systemic response dynamics
Authors: Lindeboom Rik G. H. , Worlock Kaylee B. , Dratva Lisa M. , Yoshida Masahiro , Scobie David , Wagstaffe Helen R. , Richardson Laura , Wilbrey-Clark Anna , Barnes Josephine L. , Kretschmer Lorenz , Polanski Krzysztof , Allen-Hyttinen Jessica , Mehta Puja , Sumanaweera Dinithi , Boccacino Jacqueline M. , Sungnak Waradon , Elmentaite Rasa , Huang Ni , Mamanova Lira , Kapuge Rakesh , Bolt Liam , Prigmore Elena , Killingley Ben , Kalinova Mariya , Mayer Maria , Boyers Alison , Mann Alex , Swadling Leo , Woodall Maximillian N. J. , Ellis Samuel , Smith Claire M. , Teixeira Vitor H. , Janes Sam M. , Chambers Rachel C. , Haniffa Muzlifah , Catchpole Andrew , Heyderman Robert , Noursadeghi Mahdad , Chain Benny , Mayer Andreas , Meyer Kerstin B. , Chiu Christopher , Nikolić Marko Z. , Teichmann Sarah A. 
Published: June 2024

AbstractThe COVID-19 pandemic is an ongoing global health threat, yet our understanding of the dynamics of early cellular responses to this disease remains limited1. Here in our SARS-CoV-2 human challenge study, we used single-cell multi-omics profiling of nasopharyngeal swabs and blood to temporally resolve abortive, transient and sustained infections in seronegative individuals challenged with pre-Alpha SARS-CoV-2. Our analyses revealed rapid changes in cell-type proportions and dozens of highly dynamic cellular response states in epithelial and immune cells associated with specific time points and infection status. We observed that the interferon response in blood preceded the nasopharyngeal response. Moreover, nasopharyngeal immune infiltration occurred early in samples from individuals with only transient infection and later in samples from individuals with sustained infection. High expression of HLA-DQA2 before inoculation was associated with preventing sustained infection. Ciliated cells showed multiple immune responses and were most permissive for viral replication, whereas nasopharyngeal T cells and macrophages were infected non-productively. We resolved 54 T cell states, including acutely activated T cells that clonally expanded while carrying convergent SARS-CoV-2 motifs. Our new computational pipeline Cell2TCR identifies activated antigen-responding T cells based on a gene expression signature and clusters these into clonotype groups and motifs. Overall, our detailed time series data can serve as a Rosetta stone for epithelial and immune cell responses and reveals early dynamic responses associated with protection against infection.
Entrectinib in ROS1-positive advanced non-small cell lung cancer: the phase 2/3 BFAST trial
Authors: Peters Solange , Gadgeel Shirish M. , Mok Tony , Nadal Ernest , Kilickap Saadettin , Swalduz Aurélie , Cadranel Jacques , Sugawara Shunichi , Chiu Chao-Hua , Yu Chong-Jen , Moskovitz Mor , Tanaka Tomohiro , Nersesian Rhea , Shagan Sarah M. , Maclennan Margaret , Mathisen Michael , Bhagawati-Prasad Vijay , Diarra Cheick , Assaf Zoe June , Archer Venice , Dziadziuszko Rafal 
Published: June 2024

AbstractAlthough comprehensive biomarker testing is recommended for all patients with advanced/metastatic non-small cell lung cancer (NSCLC) before initiation of first-line treatment, tissue availability can limit testing. Genomic testing in liquid biopsies can be utilized to overcome the inherent limitations of tissue sampling and identify the most appropriate biomarker-informed treatment option for patients. The Blood First Assay Screening Trial is a global, open-label, multicohort trial that evaluates the efficacy and safety of multiple therapies in patients with advanced/metastatic NSCLC and targetable alterations identified by liquid biopsy. We present data from Cohort D (ROS1-positive). Patients ≥18 years of age with stage IIIB/IV, ROS1-positive NSCLC detected by liquid biopsies received entrectinib 600 mg daily. At data cutoff (November 2021), 55 patients were enrolled and 54 had measurable disease. Cohort D met its primary endpoint: the confirmed objective response rate (ORR) by investigator was 81.5%, which was consistent with the ORR from the integrated analysis of entrectinib (investigator-assessed ORR, 73.4%; data cutoff May 2019, ≥12 months of follow-up). The safety profile of entrectinib was consistent with previous reports. These results demonstrate consistency with those from the integrated analysis of entrectinib in patients with ROS1-positive NSCLC identified by tissue-based testing, and support the clinical value of liquid biopsies to inform clinical decision-making. The integration of liquid biopsies into clinical practice provides patients with a less invasive diagnostic method than tissue-based testing and has faster turnaround times that may expedite the reaching of clinical decisions in the advanced/metastatic NSCLC setting. ClinicalTrials.gov registration: NCT03178552.
Stability assessment of selected chrysanthemum (Dendranthema grandiflora Tzvelev) hybrids over the years through AMMI and GGE biplot in the mid hills of North-Western Himalayas
Authors: Kamal Shilpa , Rana Amit , Devi Rajni , Kumar Ravi , Yadav Niketa , Chaudhari Aniket Anant , Yadav Shimran , Singh Sanatsujat , Bhargava Bhavya , Singh Satbeer , Chauhan Ramesh , Kumar Ashok 
Published: June 2024

AbstractDendranthema grandiflora is an important cut flower with high economic importance in the floriculture industry. Identification of stable and high yielding genotypes of Dendranthema grandiflora, hence becomes paramount for ensuring its year-round production. In this context, the genotype by environment interaction effects on 22 chrysanthemum hybrids across six test environments were investigated. The experiment was conducted using Randomized Complete Block Design with three replications for 6 years and data on various agro-morphological and yield-contributing traits were evaluated. Our analysis revealed significant mean sum of squares due to environmental, genotypic and genotype by environment interaction variations for all examined traits. A 2D GGE biplot constructed using first two principal components computed as 59.2% and 23.3% of the differences in genotype by environment interaction for flower yield per plant. The GGE biplot identified two top-performing genotypes, G2 and G5, while the AMMI model highlighted genotypes G17, G15, G6, G5, and G2 as the best performers. Genotype G17 ranked highest for multiple traits, while G2 displayed high mean flower yield as well as stability across all environments. According to AEC line, genotypes G2 and G5 exhibited exceptional stability, whereas genotypes G4, G18 and G19 demonstrated lower stability but maintained high average flower yields. Hence, our findings provide valuable insights into chrysanthemum hybrids that were not only best performing but also hold promise to meet the growers demand of the cut flower industry and can be recommended for large scale commercial cultivation.
High-proportions of tailwater discharge alter microbial community composition and assembly in receiving sediments
Authors: Zhou Yaqian , Cheng Li , Lian Ying , Feng Jiaying , Zhou Mengling , Jing Dan , Yin Weiwen , Wang Heli , Liu Lei 
Published: June 2024

AbstractThe tailwater from wastewater treatment plants serves as an important water resource in arid regions, alleviating the conflict between supply and demand. However, the effects of different tailwater discharge proportions on microbial community dynamics remain unclear. In this study, we investigated the effects of different tailwater discharge proportions on the water quality and microbial community characteristics of sediments in receiving water bodies under controlled conditions (WF-1, WF-2, WF-3, WF-4, and WF-5, containing 0% tailwater + 100% natural water, 25% tailwater + 75% natural water, 50% tailwater + 50% natural water, 75% tailwater + 25% natural water, and 100% tailwater + 0% natural water, respectively). Microbial co-occurrence networks and structural equation model were used to unveil the relationship between microbial communities and their shaping factors. Results showed that distinct microbial community compositions were found in the sediments with low- (< 50%) and high- (> 50%) proportions of tailwater. Specifically, WCHB1-41 and g_4-29–1, which are involved in organic degradation-related functions, were the key genera in the high-proportion cluster. A total of 21 taxa were more abundant in the low-proportion (< 50%) cluster than that in high-proportion (> 50%). Moreover, higher modularity was observed in the low-proportion. Total phosphorus directly affected while ammonia nitrogen indirectly affected the microbial community structure. Our findings support the distinct heterogeneity of microbial communities driven by tailwater discharge in receiving water bodies, and further confirmed that high-proportion tailwater depletes sensitive microbial communities, which may be avoided through scientific management.
The brain of fetuses with congenital diaphragmatic hernia shows signs of hypoxic injury with loss of progenitor cells, neurons, and oligodendrocytes
Authors: Biouss George , Antounians Lina , Aguet Julien , Kopcalic Katarina , Fakhari Nikan , Baranger Jerome , Mertens Luc , Villemain Olivier , Zani Augusto 
Published: June 2024

AbstractCongenital diaphragmatic hernia (CDH) is a birth defect characterized by incomplete closure of the diaphragm, herniation of abdominal organs into the chest, and compression of the lungs and the heart. Besides complications related to pulmonary hypoplasia, 1 in 4 survivors develop neurodevelopmental impairment, whose etiology remains unclear. Using a fetal rat model of CDH, we demonstrated that the compression exerted by herniated organs on the mediastinal structures results in decreased brain perfusion on ultrafast ultrasound, cerebral hypoxia with compensatory angiogenesis, mature neuron and oligodendrocyte loss, and activated microglia. In CDH fetuses, apoptosis was prominent in the subventricular and subgranular zones, areas that are key for neurogenesis. We validated these findings in the autopsy samples of four human fetuses with CDH compared to age- and sex-matched controls. This study reveals the molecular mechanisms and cellular changes that occur in the brain of fetuses with CDH and creates opportunities for therapeutic targets.
High capacity clinical SARS-CoV-2 molecular testing using combinatorial pooling
Authors: Zismanov Shosh , Shalem Bar , Margolin-Miller Yulia , Rosin-Grunewald Dalia , Adar Roy , Keren-Naus Ayelet , Amichay Doron , Ben-Dor Anat , Shemer-Avni Yonat , Porgador Angel , Shental Noam , Hertz Tomer 
Published: June 2024

Abstract
Background
The SARS-CoV-2 pandemic led to unprecedented testing demands, causing major testing delays globally. One strategy used for increasing testing capacity was pooled-testing, using a two-stage technique first introduced during WWII. However, such traditional pooled testing was used in practice only when positivity rates were below 2%.

Methods
Here we report the development, validation and clinical application of P-BEST - a single-stage pooled-testing strategy that was approved for clinical use in Israel.

Results
P-BEST is clinically validated using 3636 side-by-side tests and is able to correctly detect all positive samples and accurately estimate their Ct value. Following regulatory approval by the Israeli Ministry of Health, P-BEST was used in 2021 to clinically test 837,138 samples using 270,095 PCR tests - a 3.1fold reduction in the number of tests. This period includes the Alpha and Delta waves, when positivity rates exceeded 10%, rendering traditional pooling non-practical. We also describe a tablet-based solution that allows performing manual single-stage pooling in settings where liquid dispensing robots are not available.

Conclusions
Our data provides a proof-of-concept for large-scale clinical implementation of single-stage pooled-testing for continuous surveillance of multiple pathogens with reduced test costs, and as an important tool for increasing testing efficiency during pandemic outbreaks.
Increased [18F]FDG uptake of radiation-induced giant cells: a single-cell study in lung cancer models
Authors: Das Neeladrisingha , Nguyen Hieu T. M. , Lu Wan-Jin , Natarajan Arutselvan , Khan Syamantak , Pratx Guillem 
Published: June 2024

AbstractPositron emission tomography (PET), a cornerstone in cancer diagnosis and treatment monitoring, relies on the enhanced uptake of fluorodeoxyglucose ([18F]FDG) by cancer cells to highlight tumors and other malignancies. While instrumental in the clinical setting, the accuracy of [18F]FDG-PET is susceptible to metabolic changes introduced by radiation therapy. Specifically, radiation induces the formation of giant cells, whose metabolic characteristics and [18F]FDG uptake patterns are not fully understood. Through a novel single-cell gamma counting methodology, we characterized the [18F]FDG uptake of giant A549 and H1299 lung cancer cells that were induced by radiation, and found it to be considerably higher than that of their non-giant counterparts. This observation was further validated in tumor-bearing mice, which similarly demonstrated increased [18F]FDG uptake in radiation-induced giant cells. These findings underscore the metabolic implications of radiation-induced giant cells, as their enhanced [18F]FDG uptake could potentially obfuscate the interpretation of [18F]FDG-PET scans in patients who have recently undergone radiation therapy.
Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma
Authors: Sementsov Mark , Ott Leonie , Kött Julian , Sartori Alexander , Lusque Amelie , Degenhardt Sarah , Segier Bertille , Heidrich Isabel , Volkmer Beate , Greinert Rüdiger , Mohr Peter , Simon Ronald , Stadler Julia-Christina , Irwin Darryl , Koch Claudia , Andreas Antje , Deitert Benjamin , Thewes Verena , Trumpp Andreas , Schneeweiss Andreas , Belloum Yassine , Peine Sven , Wikman Harriett , Riethdorf Sabine , Schneider Stefan W , Gebhardt Christoffer , Pantel Klaus , Keller Laura 
Published: June 2024

AbstractCirculating tumor DNA (ctDNA) is the cornerstone of liquid biopsy diagnostics, revealing clinically relevant genomic aberrations from blood of cancer patients. Genomic analysis of single circulating tumor cells (CTCs) could provide additional insights into intra-patient heterogeneity, but it requires whole-genome amplification (WGA) of DNA, which might introduce bias. Here, we describe a novel approach based on mass spectrometry for mutation detection from individual CTCs not requiring WGA and complex bioinformatics pipelines. After establishment of our protocol on tumor cell line-derived single cells, it was validated on CTCs of 33 metastatic melanoma patients and the mutations were compared to those obtained from tumor tissue and ctDNA. Although concordance with tumor tissue was superior for ctDNA over CTC analysis, a larger number of mutations were found within CTCs compared to ctDNA (p = 0.039), including mutations in melanoma driver genes, or those associated with resistance to therapy or metastasis. Thus, our results demonstrate proof-of-principle data that CTC analysis can provide clinically relevant genomic information that is not redundant to tumor tissue or ctDNA analysis.
Flux dependence of redshift distribution and clustering of LOFAR radio sources
Authors: Bhardwaj Nitesh , Schwarz Dominik J. , Hale Catherine L. , Duncan Kenneth J. , Camera Stefano , Heneka Caroline S. , Nakoneczny Szymon J. , Röttgering Huub J. A. , Siewert Thilo M. , Tiwari Prabhakar , Zheng Jinglan , Miley George , Tasse Cyril 
Published: June 2024

Context. We study the flux density dependence of the redshift distribution of low-frequency radio sources observed in the LOFAR Two-metre Sky Survey (LoTSS) deep fields and apply it to estimate the clustering length of the large-scale structure of the Universe, examining flux density limited samples (1 mJy, 2 mJy, 4 mJy and 8 mJy) of LoTSS wide field radio sources.
Methods. We utilise and combine the posterior probability distributions of photometric redshift determinations for LoTSS deep field observations from three different fields (Boötes, Lockman hole and ELAIS-N1, together about 26 square degrees of sky), which are available for between 91% to 96% of all sources above the studied flux density thresholds and observed in the area covered by multi-frequency data. We estimate uncertainties by a bootstrap method. We apply the inferred redshift distribution on the LoTSS wide area radio sources from the HETDEX field (LoTSS-DR1; about 424 square degrees) and make use of the Limber approximation and a power-law model of three dimensional clustering to measure the clustering length, r0, for various models of the evolution of clustering.
Results. We find that the redshift distributions from all three LoTSS deep fields agree within expected uncertainties. We show that the radio source population probed by LoTSS at flux densities above 1 mJy has a median redshift of at least 0.9. At 2 mJy, we measure the clustering length of LoTSS radio sources to be r0 = (10.1 ± 2.6) h−1 Mpc in the context of the comoving clustering model.
Conclusions. Our findings are in agreement with measurements at higher flux density thresholds at the same frequency and with measurements at higher frequencies in the context of the comoving clustering model. Based on the inferred flux density limited redshift distribution of LoTSS deep field radio sources, the full wide area LoTSS will eventually cover an effective (source weighted) comoving volume of about 10 h−3 Gpc3.
TOI-837 b: Characterisation, formation, and evolutionary history of an infant warm Saturn-mass planet
Authors: Damasso M. , Polychroni D. , Locci D. , Turrini D. , Maggio A. , Cubillos P. E. , Baratella M. , Biazzo K. , Benatti S. , Mantovan G. , Nardiello D. , Desidera S. , Bonomo A. S. , Pinamonti M. , Malavolta L. , Marzari F. , Sozzetti A. , Spinelli R. 
Published: June 2024

Context. The detection and characterisation of planets younger than ~100 Myr offer the opportunity to get snapshots of systems immediately after their formation, where the main evolutionary processes that sculpt mature planetary systems are still ongoing. Known infant exoplanets are currently scarce, and dedicated surveys are required to increase their number.
Aims. We aim to determine the fundamental properties of the ~35 Myr old star TOI-837 and its close-in Saturn-sized planet, and to investigate the system’s formation and evolutionary history.
Methods. We analysed TESS photometry and HARPS spectroscopic data, measured stellar and planetary parameters, and characterised the stellar activity. We performed population synthesis simulations to track the formation history of TOI-837 b, and to reconstruct its possible internal structure. We investigated the planetary atmospheric evolution through photo-evaporation, and quantified the prospects for atmospheric characterisation with JWST.
Results. TOI-837 b has similar radius, mass, and bulk density to those of Saturn (rb=9.71−0.60+0.93 R⊕, mb=116−18+17 M⊕, and ρb=0.68−0.18+0.20 g cm−3) and is on a primordial circular orbit. Population synthesis and early migration simulations suggest that the planet could have originally formed between 2 and 4 au, and have either a large and massive core, or a smaller Saturn-like core, depending on the opacity of the protoplanetary gas and on the growth rate of the core. We find that photo-evaporation produced negligible effects even at early ages (3–10 Myr). Transmission spectroscopy with JWST is very promising, and is expected to provide constraints on atmospheric metallicity and the abundances of H2O, CO2, and CH4 molecules, and to probe the presence of refractory elements.
Conclusions. TOI-837 offers valuable prospects for follow-up observations, which are needed for a thorough characterisation. JWST will help to better constrain the formation and evolution history of the system, and to clarify whether or not TOI-837 b is a Saturn-analogue.
Uveitis bei juveniler idiopathischer Arthritis
Authors: Heiligenhaus Arnd , Baquet-Walscheid Karoline , Tappeiner Christoph 
Published: June 2024

ZUSAMMENFASSUNGDarstellung der aktualisierten deutschsprachigen interdisziplinären Leitlinie zur Diagnostik und Therapie der juvenilen idiopathischen Arthritis (JIA)-assoziierten Uveitis. Nach JIA-Erstdiagnose sollten zeitnah regelmäßige augenärztliche Kontrollen erfolgen mit dem Ziel, die Uveitis vor Manifestation irreversibler Folgeschäden zu diagnostizieren. Zur antientzündlichen Therapie finden aktuell Kortikosteroide, konventionell synthetische (cs), biologische (b) und andere Disease-Modifying Antirheumatic Drugs (DMARD) Verwendung. Eine enge Kooperation durch einen mit der JIA-assoziierten Uveitis und ihrer Behandlung erfahrenen Augenarzt und einen Kinder- und Jugendrheumatologen sollte gewährleistet werden. Frühzeitige Diagnose und aktuelle leitliniengerechte Therapie können die Langzeitprognose der JIA-assoziierten Uveitis wesentlich verbessern. Ausgewählte Kasuistiken illustrieren das therapeutische Management bei therapierefraktärem Krankheitsverlauf.
Kommunikation
Authors: Kerlen-Petri Katharina 
Published: June 2024

Ein wichtiger Teil der HebammenarbeitEin wichtiger Teil der Hebammenarbeit
„Man kann nicht nicht kommunizieren“ – dieser Satz des Philosophen und Psychotherapeuten Paul Watzlawick
ist Ihnen sicher schon begegnet. Er leuchtet ein und doch fällt es uns schwer – im Beruflichen wie
im Privaten – uns so auszudrücken, dass wir verstanden werden. Die vielen Aspekte der Kommunikation
machen sich oft in Missverständnissen bemerkbar.
Dabei ist das Miteinandersprechen erlernbar – aber nehmen wir uns die Zeit dafür?