bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genomic landscape of 2,023 colorectal cancers
Authors: Cornish Alex J. , Gruber Andreas J. , Kinnersley Ben , Chubb Daniel , Frangou Anna , Caravagna Giulio , Noyvert Boris , Lakatos Eszter , Wood Henry M. , Thorn Steve , Culliford Richard , Arnedo-Pac Claudia , Househam Jacob , Cross William , Sud Amit , Law Philip , Leathlobhair Maire Ni , Hawari Aliah , Woolley Connor , Sherwood Kitty , Feeley Nathalie , Gül Güler , Fernandez-Tajes Juan , Zapata Luis , Alexandrov Ludmil B. , Murugaesu Nirupa , Sosinsky Alona , Mitchell Jonathan , Lopez-Bigas Nuria , Quirke Philip , Church David N. , Tomlinson Ian P. M. , Sottoriva Andrea , Graham Trevor A. , Wedge David C. , Houlston Richard S. 
Published: August 2024

AbstractColorectal carcinoma (CRC) is a common cause of mortality1, but a comprehensive description of its genomic landscape is lacking2–9. Here we perform whole-genome sequencing of 2,023 CRC samples from participants in the UK 100,000 Genomes Project, thereby providing a highly detailed somatic mutational landscape of this cancer. Integrated analyses identify more than 250 putative CRC driver genes, many not previously implicated in CRC or other cancers, including several recurrent changes outside the coding genome. We extend the molecular pathways involved in CRC development, define four new common subgroups of microsatellite-stable CRC based on genomic features and show that these groups have independent prognostic associations. We also characterize several rare molecular CRC subgroups, some with potential clinical relevance, including cancers with both microsatellite and chromosomal instability. We demonstrate a spectrum of mutational profiles across the colorectum, which reflect aetiological differences. These include the role of Escherichiacolipks+ colibactin in rectal cancers10 and the importance of the SBS93 signature11–13, which suggests that diet or smoking is a risk factor. Immune-escape driver mutations14 are near-ubiquitous in hypermutant tumours and occur in about half of microsatellite-stable CRCs, often in the form of HLA copy number changes. Many driver mutations are actionable, including those associated with rare subgroups (for example, BRCA1 and IDH1), highlighting the role of whole-genome sequencing in optimizing patient care.
Teosinte Pollen Drive guides maize diversification and domestication by RNAi
Authors: Berube Benjamin , Ernst Evan , Cahn Jonathan , Roche Benjamin , de Santis Alves Cristiane , Lynn Jason , Scheben Armin , Grimanelli Daniel , Siepel Adam , Ross-Ibarra Jeffrey , Kermicle Jerry , Martienssen Robert A. 
Published: August 2024

AbstractSelfish genetic elements contribute to hybrid incompatibility and bias or ‘drive’ their own transmission1,2. Chromosomal drive typically functions in asymmetric female meiosis, whereas gene drive is normally post-meiotic and typically found in males. Here, using single-molecule and single-pollen genome sequencing, we describe Teosinte Pollen Drive, an instance of gene drive in hybrids between maize (Zea mays ssp. mays) and teosinte mexicana (Z. mays ssp. mexicana) that depends on RNA interference (RNAi). 22-nucleotide small RNAs from a non-coding RNA hairpin in mexicana depend on Dicer-like 2 (Dcl2) and target Teosinte Drive Responder 1 (Tdr1), which encodes a lipase required for pollen viability. Dcl2, Tdr1 and the hairpin are in tight pseudolinkage on chromosome 5, but only when transmitted through the male. Introgression of mexicana into early cultivated maize is thought to have been critical to its geographical dispersal throughout the Americas3, and a tightly linked inversion in mexicana spans a major domestication sweep in modern maize4. A survey of maize traditional varieties and sympatric populations of teosinte mexicana reveals correlated patterns of admixture among unlinked genes required for RNAi on at least four chromosomes that are also subject to gene drive in pollen from synthetic hybrids. Teosinte Pollen Drive probably had a major role in maize domestication and diversification, and offers an explanation for the widespread abundance of ‘self’ small RNAs in the germ lines of plants and animals.
Titration of RAS alters senescent state and influences tumour initiation
Authors: Chan Adelyne S. L. , Zhu Haoran , Narita Masako , Cassidy Liam D. , Young Andrew R. J. , Bermejo-Rodriguez Camino , Janowska Aleksandra T. , Chen Hung-Chang , Gough Sarah , Oshimori Naoki , Zender Lars , Aitken Sarah J. , Hoare Matthew , Narita Masashi 
Published: August 2024

AbstractOncogenic RAS-induced senescence (OIS) is an autonomous tumour suppressor mechanism associated with premalignancy1,2. Achieving this phenotype typically requires a high level of oncogenic stress, yet the phenotype provoked by lower oncogenic dosage remains unclear. Here we develop oncogenic RAS dose-escalation models in vitro and in vivo, revealing a RAS dose-driven non-linear continuum of downstream phenotypes. In a hepatocyte OIS model in vivo, ectopic expression of NRAS(G12V) does not induce tumours, in part owing to OIS-driven immune clearance3. Single-cell RNA sequencing analyses reveal distinct hepatocyte clusters with typical OIS or progenitor-like features, corresponding to high and intermediate levels of NRAS(G12V), respectively. When titred down, NRAS(G12V)-expressing hepatocytes become immune resistant and develop tumours. Time-series monitoring at single-cell resolution identifies two distinct tumour types: early-onset aggressive undifferentiated and late-onset differentiated hepatocellular carcinoma. The molecular signature of each mouse tumour type is associated with different progenitor features and enriched in distinct human hepatocellular carcinoma subclasses. Our results define the oncogenic dosage-driven OIS spectrum, reconciling the senescence and tumour initiation phenotypes in early tumorigenesis.
Local delivery of cell surface-targeted immunocytokines programs systemic antitumor immunity
Authors: Santollani Luciano , Maiorino Laura , Zhang Yiming J. , Palmeri Joseph R. , Stinson Jordan A. , Duhamel Lauren R. , Qureshi Kashif , Suggs Jack R. , Porth Owen T. , Pinney William , Msari Riyam Al , Walsh Agnes A. , Wittrup K. Dane , Irvine Darrell J. 
Published: August 2024

AbstractSystemically administered cytokines are potent immunotherapeutics but can cause severe dose-limiting toxicities. To overcome this challenge, cytokines have been engineered for intratumoral retention after local delivery. However, despite inducing regression of treated lesions, tumor-localized cytokines often elicit only modest responses at distal untreated tumors. In the present study, we report a localized cytokine therapy that safely elicits systemic antitumor immunity by targeting the ubiquitous leukocyte receptor CD45. CD45-targeted immunocytokines have lower internalization rates relative to wild-type counterparts, leading to sustained downstream cis and trans signaling between lymphocytes. A single intratumoral dose of αCD45-interleukin (IL)-12 followed by a single dose of αCD45-IL-15 eradicated treated tumors and untreated distal lesions in multiple syngeneic mouse tumor models without toxicity. Mechanistically, CD45-targeted cytokines reprogrammed tumor-specific CD8+ T cells in the tumor-draining lymph nodes to have an antiviral transcriptional signature. CD45 anchoring represents a broad platform for protein retention by host immune cells for use in immunotherapy.
The DNA-PAINT palette: a comprehensive performance analysis of fluorescent dyes
Authors: Steen Philipp R. , Unterauer Eduard M. , Masullo Luciano A. , Kwon Jisoo , Perovic Ana , Jevdokimenko Kristina , Opazo Felipe , Fornasiero Eugenio F. , Jungmann Ralf 
Published: August 2024

AbstractDNA points accumulation for imaging in nanoscale topography (DNA-PAINT) is a super-resolution fluorescence microscopy technique that achieves single-molecule ‘blinking’ by transient DNA hybridization. Despite blinking kinetics being largely independent of fluorescent dye choice, the dye employed substantially affects measurement quality. Thus far, there has been no systematic overview of dye performance for DNA-PAINT. Here we defined four key parameters characterizing performance: brightness, signal-to-background ratio, DNA-PAINT docking site damage and off-target signal. We then analyzed 18 fluorescent dyes in three spectral regions and examined them both in DNA origami nanostructures, establishing a reference standard, and in a cellular environment, targeting the nuclear pore complex protein Nup96. Finally, having identified several well-performing dyes for each excitation wavelength, we conducted simultaneous three-color DNA-PAINT combined with Exchange-PAINT to image six protein targets in neurons at ~16 nm resolution in less than 2 h. We thus provide guidelines for DNA-PAINT dye selection and evaluation and an overview of performances of commonly used dyes.
Research on the evolutionary patterns and control of surrounding rock superimposed stress field local area loading in double-layer Island face main roadway
Authors: Chen Dongdong , Li Zijian , Zhang Zhifeng , He Fulian , Xie Fuxing , Pan Hao , Wang Zhiqiang 
Published: August 2024

AbstractDouble-layer island working face main roadway coal pillars are affected by complex mining stress superposition, when different coal pillar width combinations, the surrounding rock stress field will produce different degrees of regional loading increase effect; the study of the surrounding rock stress field regional superposition loading increase law is meaningful to explaining the failure mode of the roadway and determining the critical control area. This study combines numerical simulation with on-site monitoring and other methods and draws the following conclusions: The superimposed loading increase law (“decreasing” → “increasing”) of the abutment pressure and deviatoric stress in the lower coal seam of the double-layer island working face during the mining; the type of the principal stress deflection in the advance working face region; and by obtaining the three types of development morphology of the deviatoric stress peak zone of the roadway and its corresponding nine evolution modes (one type of circular tube → four types of inverse hyperbolic body → four types of hyperbolic body) in the double-layered island working face mining. Indicated the critical reinforcement area corresponding to the main roadway when at different combinations of coal pillar widths; determined the main track roadway protective coal pillars width for 40 m and the shape of the roadway peak deviatoric stress zone is the inverse class hyperbolic body mode; according to the evolution mode of the peak deviatoric stress zone, determined the synergistic failure control program for the asymmetric critical zone of the roadway surrounding rock which is a targeted scientific support method; after the feedback of on-site monitoring and, the support program is reasonable and effective.
Investigating the impact of fuel price shocks on bicycle sharing usage in Budapest
Authors: Berezvai Zombor , Basile Vincenzo , Kálecz-Simon András , Bakó Barna 
Published: August 2024

AbstractThe creation of sustainable urban communities is contingent upon the establishment of a sustainable, efficient, and fast transportation system. Bicycle sharing systems (BSS) are one of the most sustainable and inclusive ways of transportation in cities. An important question is how to increase BSS ridership and whether it can effectively replace cars in cities, hence contributing to achieving the 11th Sustainable Development Goal and creating sustainable urban communities. This paper aims to contribute to this stream of research by investigating the effect of fuel prices on BSS ridership. We exploit a natural experiment from Budapest, Hungary, where fuel prices were capped between November 15, 2021, and December 6, 2022. Once the price cap was suddenly eliminated, fuel prices increased by around one-third immediately leading to a very substantial and rarely observable one-time price increase. The difference-in-difference regression results indicate a 2–6% increase in BSS ridership after the elimination of the fuel price cap. The geographical pattern of the change shows that BSS usage mainly increased in the outer part of the city; however, some areas observed a decline. The regression results are also reinforced by survey findings. Understanding these dynamics is crucial for effective urban planning and transportation policymaking.
Five-year follow-up after a single US-guided high intensity focused ultrasound treatment of breast fibroadenoma
Authors: Boeer B. , Oberlechner E. , Rottscholl R. , Gruber I. , Guergan S. , Brucker S. , Hahn M. 
Published: August 2024

AbstractThe aim of this study was to evaluate the long-term efficacy of a single ultrasound-guided high-intensity focused ultrasound (US-HIFU) treatment in patients with breast fibroadenoma (FA) in terms of volume and pain reduction as well as palpation findings. From december 2013 until november 2014 27 women with a symptomatic FA were treated in one HIFU-session. Follow-up visits were performed after 7 days, 6 months and 1, 2, 3 and 5 years with clinical examination and ultrasound. One year after the procedure, a core needle biopsy of the residual lesion was offered. There was a significant volume reduction 6 months after HIFU from 1083.10 to 347.13 mm3 (p < 0.0001) with a mean volume reduction ratio (VRR) of 61.63%. Thereafter the FAs showed a further, but no longer significant decrease in size. One patient with an initial incomplete ablation and histologically confirmed persistent vital cells after 1 year showed a strong regrowth after 3 years. Excluding this patient from analysis, the mean VRR at months 12, 24, 36, and 60 was 86.44%, 94.44%, 94.90%, and 97.85%, respectively. Before HIFU, 59.26% of the patients had pain (22.33/100 VAS) which decreased to 6.56/100 after 12 months and remained reduced over the 5 year follow up period. A decrease in palpability from 85.19 to 7.69% was observed within 24 months. A single HIFU intervention let to a substantial reduction in size, pain, and palpability with its most potential effect during the first 12 months. Subsequently, the observed effect remained stable over a 5 year follow up period. Incomplete initial treatment was associated with the risk of regrowth.
No observable non-thermal effect of microwave radiation on the growth of microtubules
Authors: Hammarin Greger , Norder Per , Harimoorthy Rajiv , Chen Guo , Berntsen Peter , Widlund Per O. , Stoij Christer , Rodilla Helena , Swenson Jan , Brändén Gisela , Neutze Richard 
Published: August 2024

AbstractDespite widespread public interest in the health impact of exposure to microwave radiation, studies of the influence of microwave radiation on biological samples are often inconclusive or contradictory. Here we examine the influence of microwave radiation of frequencies 3.5 GHz, 20 GHz and 29 GHz on the growth of microtubules, which are biological nanotubes that perform diverse functions in eukaryotic cells. Since microtubules are highly polar and can extend several micrometres in length, they are predicted to be sensitive to non-ionizing radiation. Moreover, it has been speculated that tubulin dimers within microtubules might rapidly toggle between different conformations, potentially participating in computational or other cooperative processes. Our data show that exposure to microwave radiation yields a microtubule growth curve that is distorted relative to control studies utilizing a homogeneous temperature jump. However, this apparent effect of non-ionizing radiation is reproduced by control experiments using an infrared laser or hot air to heat the sample and thereby mimic the thermal history of samples exposed to microwaves. As such, no non-thermal effects of microwave radiation on microtubule growth can be assigned. Our results highlight the need for appropriate control experiments in biophysical studies that may impact on the sphere of public interest.
Manipulation of artificial and living small objects by light driven diffusioosmotic flow
Authors: Muraveva Valeriia , Lomadze Nino , Gordievskaya Yulia D. , Ortner Philipp , Beta Carsten , Santer Svetlana 
Published: August 2024

AbstractHere we report on light-triggered generation of local flow utilizing a bio-compatible non-ionic photo-active surfactant. The mechanism is based on diffusioosmotic phenomenon, where the gradient of relative concentration with respect to different chemical species near a surface leads to an osmotic pressure gradient driving liquid flow along the surface. The application of a photo-responsive surfactant allows for easy and reversible changes in concentration gradient by positioning a light source at the desired place. Along with the so-inscribed concentration gradient one can change reversible the direction and strength of the flow even in a closed system. The phenomenology of light-driven diffusioosmotic flow (LDDO) can be used in a rather flexible way: colloids can be gathered or dispersed and bio-compatibility extends the range of colloid types also to living microorganisms such as soil bacterium Pseudomonas putida. We show that DO flow can be considered a versatile method to set hydrodynamic conditions along the sample for investigating the motility of living cells. Further advantages of employing LDDO are the flexibility of flow generation in a reversible way and with spatiotemporal control, without the need to either change the channel geometry by loading a different device, or the periphery of pumps and connectors.
Investigation of screening questions to identify insomnia in cancer patients
Authors: Pfeifer K. , Ates G. , Pogorzelski M. , Zaun G. , Rötger A. , Schuler M. , Schöbel C. , Tewes M. 
Published: August 2024

AbstractThe high prevalence of insomnia in cancer patients leads to a significant reduction in the quality of life of those affected. A detailed record of symptoms therefore plays an essential role for further course of treatment. Which screening instruments enable identification of cancer patients with insomnia is the subject of this single-arm nonrandomized study. During the data collection period, cancer patients meeting the following criteria: self-reported tiredness and/or trouble falling or staying asleep or sleeping too much in an electronic patient-reported outcome measurement were enrolled. For further analysis, focus was placed on the Patient Health Questionnaire Depression Scale (PHQ-8), the Minimal Documentation System (MIDOS2) and the Insomnia Severity Index (ISI). Frequency, correlation, and variance analyses were conducted to identify likely predictors of insomnia. Our findings indicate a closer correlation between the screening question pertaining to sleep disorders and the ISI, compared to the question on tiredness and the ISI. The initial recording of sleep-related parameters plays an essential role for cancer patients in order to identify and treat modifiable factors as promptly as possible. For an initial assessment, we recommend asking about trouble falling or staying asleep or sleeping too much.
Neuromodulation with transcranial direct current stimulation contributes to motor function recovery via microglia in spinal cord injury
Authors: Oishi Ryotaro , Takeda Ikuko , Ode Yukihito , Okada Yuya , Kato Daisuke , Nakashima Hiroaki , Imagama Shiro , Wake Hiroaki 
Published: August 2024

AbstractSpinal cord injury (SCI) is damage or trauma to the spinal cord, which often results in loss of function, sensation, or mobility below the injury site. Transcranial direct current stimulation (tDCS) is a non-invasive and affordable brain stimulation technique used to modulate neuronal circuits, which changes the morphology and activity of microglia in the cerebral cortex. However, whether similar morphological changes can be observed in the spinal cord remains unclear. Therefore, we evaluated neuronal population activity in layer 5 (L5) of M1 following SCI and investigated whether changes in the activities of L5 neurons affect microglia-axon interactions using C57BL/6J mice. We discovered that L5 of the primary motor cortex (corticospinal neurons) exhibited reduced synchronized activity after SCI that correlates with microglial morphology, which was recovered using tDCS. This indicates that tDCS promotes changes in the morphological properties and recovery of microglia after SCI. Combining immunotherapy with tDCS may be effective in treating SCI.
ICDXML: enhancing ICD coding with probabilistic label trees and dynamic semantic representations
Authors: Wang Zeqiang , Wang Yuqi , Zhang Haiyang , Wang Wei , Qi Jun , Chen Jianjun , Sastry Nishanth , Johnson Jon , De Suparna 
Published: August 2024

AbstractAccurately assigning standardized diagnosis and procedure codes from clinical text is crucial for healthcare applications. However, this remains challenging due to the complexity of medical language. This paper proposes a novel model that incorporates extreme multi-label classification tasks to enhance International Classification of Diseases (ICD) coding. The model utilizes deformable convolutional neural networks to fuse representations from hidden layer outputs of pre-trained language models and external medical knowledge embeddings fused using a multimodal approach to provide rich semantic encodings for each code. A probabilistic label tree is constructed based on the hierarchical structure existing in ICD labels to incorporate ontological relationships between ICD codes and enable structured output prediction. Experiments on medical code prediction on the MIMIC-III database demonstrate competitive performance, highlighting the benefits of this technique for robust clinical code assignment.
An in vitro evaluation of the effect of antimicrobial treatment on bovine mammary microbiota
Authors: Winther Anja R. , Perrin Aurelie , Nordraak Anne O. O. , Kjos Morten , Porcellato Davide 
Published: August 2024

AbstractAntimicrobial-resistant bacteria have been an increasing problem in human medicine and animal husbandry since the introduction of antimicrobials on the market in the 1940s. Over the last decades, efforts to reduce antimicrobial usage in animal husbandry have been shown to limit the development of resistant bacteria. Despite this, antimicrobial-resistant bacteria are still commonly detected and isolated worldwide. In this study, we investigated the presence of antimicrobial-resistant bacteria in bovine milk samples using a multiple approach based on culturing and amplicon sequencing. We first enriched milk samples obtained aseptically from bovine udders in the presence of two antimicrobials commonly used to treat mastitis and then described the resistant microbiota by amplicon sequencing and isolate characterization. Our results show that several commensal species and mastitis pathogens harbor antimicrobial resistance and dominate the enriched microbiota in milk in presence of antimicrobial agents. The use of the two different antimicrobials selected for different bacterial taxa and affected the overall microbial composition. These results provide new information on how different antimicrobials can shape the microbiota which is able to survive and reestablish in the udder and point to the fact that antimicrobial resistance is widely spread also in commensal species.