bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility, efficacy, and safety of animal-assisted activities with visiting dogs in inpatient pediatric oncology
Authors: Steff Katja , Grasemann Maximilian , Ostermann Kira , Goretzki Sarah Christina , Rath Peter-Michael , Reinhardt Dirk , Schündeln Michael M.
Published: August 2024

Background

Childhood cancer entails a heavy burden for patients and their families. Recent advances in overall survival rates have increasingly brought long-term quality of life into focus. Animal-assisted activities (AAAs) have long been hypothesized to alleviate the burden on pediatric patients and their peers in the hospital setting. However, their use in inpatient pediatric oncology has been a sensitive issue mainly due to the fear of infections, resulting in a lack of studies. This study presents data on the feasibility, safety, and efficacy of AAAs from a single German center.

Methods

Between 2018 and 2022, 60 patients (median age = 10.3 years) diagnosed with malignancy and undergoing treatment were visited by an intervention dog (total visits = 100). Patients were screened for infections as per hospital policy, with additional microbiological testing performed based on symptoms. The dog was screened for human pathogens and zoonoses. Microbial data and hospitalizations were analyzed from two months prior to the first visit until two months after the last visit. Acceptance of being in the hospital, both with and without planned animal-assisted interventions and pre- and post-intervention state stress, were measured using a validated visual analogue scale (0–10).

Results

Patients benefited from AAAs, showing increased acceptance of being in the hospital (median: 7.25 vs. 4.50, P < 0.001) and decreased median state stress ratings one hour after the visit compared to one hour before the visit (1.00 vs. 4.25, P < 0.001). The intervention did not result in an increased number of infections or unplanned hospitalizations, and no zoonoses were detected. All microbial screening tests of the dog were negative.

Conclusions

AAAs with visiting dogs in inpatient pediatric oncology are feasible and safe. Although they hold promise for enhancing patients’ well-being, further prospective studies are needed.
Is the use of multiple-choice items and a holistically-scored paragraph translation task fair? Examining a large-scale translation subtest
Authors: Yang Zhiqiang , Yu Chengyuan
Published: August 2024

This study investigated the test fairness of the translation section of a large-scale English test in China by examining its Differential Test Functioning (DTF) and Differential Item Functioning (DIF) across gender and major. Regarding DTF, the entire translation section exhibits partial strong measurement invariance across female and male test takers, while exhibiting full measurement invariance across test takers in (1) arts & humanities and social sciences (A&HSS) and (2) science, technology, engineering or mathematics (STEM) majors. No major-based DIF was detected in this study. Objective test items tend to favor male test takers, while direct translation test task was more favorable to females. Combining the DIF and DTF results, there may be a cancelation effect in our case. However, the effect size of DIF is either negligible or slight to moderate, indicating minimal impact on the overall fairness of the translation test task. This study further discusses the necessity of exploring the source of DIF and the importance of combining DIF and DTF for test fairness research.
KCl acts as a flux to assist the growth of sub-millimeter-scale metallic 2D non-layered molybdenum dioxide
Authors: Deng Li-Ying , Zhang Qing , Li Wang-Yang , Ye Xiao-Yuan , Zhao Yi-Fan , Chen Shen-Zhong , Wang Yu-Lan , Wang Xing-Hui , Chen Hui-Peng , Yu Zhi-Yang , Yan Qun , Cheng Shu-Ying , Guo Tai-Liang , Hu Wen-Ping , Ding Feng , Sun Jie
Published: August 2024

Two-dimensional (2D) metal oxides (2DMOs), such as MoO2, have made impressive strides in recent years, and their applicability in a number of fields such as electronic devices, optoelectronic devices and lasers has been demonstrated. However, 2DMOs present challenges in their synthesis using conventional methods due to their non-van der Waals nature. We report that KCl acts as a flux to prepare large-area 2DMOs with sub-millimeter scale. We systematically investigate the effects of temperature, homogeneous time and cooling rate on the products in the flux method, demonstrating that in this reaction a saturated homogenous solution is obtained upon the melting of the salt and precursor. Afterward, the cooling rate was adjusted to regulate the thickness of the target crystals, leading to the precipitation of 2D non-layered material from the supersaturated solution; by applying this method, the highly crystalline non-layered 2D MoO2 flakes with so far the largest lateral size of up to sub-millimeter scale (~ 464 μm) were yielded. Electrical studies have revealed that the 2D MoO2 features metallic properties, with an excellent sheet resistance as low as 99 Ω·square−1 at room temperature, and exhibits a property of charge density wave in the measurement of resistivity as a function of temperature.

Graphical abstract

TOC (Table of Content)
Biopolymer and Gypsum Added Na Bentonite for a More Effective Clay Liner
Authors: Garoushi Ali Hossien Basheer , Uygar Eris
Published: August 2024

Bentonite soil is frequently utilized as a compacted clay liner, which is a critical component of municipal waste landfill systems. This study aims to investigate the feasibility of treating sodium bentonite (NAB) with natural biopolymers to obtain an effective clay liner. The NAB was treated with three biopolymers: sodium alginate (SA), agar gum (A), and xanthan gum (X), at different replacement percentages (2%, 4%, 6%, and 8%). Additionally, an investigation was conducted to determine the extent to which replacing 50% of these additives with gypsum (G) would improve the biopolymer treatments. Fourier-transform infrared spectroscopy (FTIR), pH, one-dimensional swelling, and unconfined compressive strength (UCS) were carried out in this study. The FTIR results indicated the presence of intermolecular hydrogen bonding when NAB was treated with biopolymers and gypsum, which is crucial for enhancing the UCS. Furthermore, the thermal treatment of biopolymers significantly contributes to improving the UCS. Among the various biopolymers tested, agar gum demonstrated the most significant improvement, specifically, replacing 8% of the NAB with agar gum resulted in a 55% increase in UCS. Volume change behavior was most influenced by replacement of NAB with gypsum by 8%, which reduced the vertical swelling to 21% as opposed to 79% for the untreated NAB. The use of SA conversely resulted in an increased vertical swelling of 91%.
Extremity fractures, attempted suicide, blood transfusion and thromboembolic events are independent risk factors for a prolonged hospital stay in severely injured elderly
Authors: Störmann Philipp , Hörauf Jason A. , Sturm Ramona , Zankena Lara , Zumsteg Jonin Serafin , Lefering Rolf , Marzi Ingo , Pape Hans-Christoph , Jensen Kai Oliver ,   TraumaRegister DGU
Published: August 2024

Methods

Due to demographic change, the number of polytraumatized geriatric patients (> 64 years) is expected to further increase in the coming years. In addition to the particularities of the accident and the associated injury patterns, prolonged inpatient stays are regularly observed in this group. The aim of the evaluation is to identify further factors that cause prolonged inpatient stays.

A study of the data from the TraumaRegister DGU® from 2016–2020 was performed. Inclusion criteria were an age of over 64 years, intensive care treatment in the GAS-region, and an Injury Severity Score (ISS) of at least 16 points. All patients who were above the 80th percentile for the average length of stay or average intensive care stay of the study population were defined as so-called long-stay patients. This resulted in a prolonged inpatient stay of > 25 days and an intensive care stay of > 13 days. Among other, the influence of the cause of the accident, injury patterns according to body regions, the occurrence of complications, and the influence of numerous clinical parameters were examined.

Results

A total of 23,026 patients with a mean age of 76.6 years and a mean ISS of 24 points were included. Mean ICU length of stay was 11 ± 12.9 days (regular length of stay: 3.9 ± 3.1d vs. prolonged length of stay: 12.8 ± 5.7d) and mean inpatient stay was 22.5 ± 18.9 days (regular length of stay: 20.7 ± 15d vs. 35.7 ± 22.3d). A total of n = 6,447 patients met the criteria for a prolonged length of stay. Among these, patients had one more diagnosis on average (4.6 vs. 5.8 diagnoses) and had a higher ISS (21.8 ± 6 pts. vs. 26.9 ± 9.5 pts.)

Independent risk factors for prolonged length of stay were intubation duration greater than 6 days (30-fold increased risk), occurrence of sepsis (4x), attempted suicide (3x), presence of extremity injury (2.3x), occurrence of a thromboembolic event (2.7x), and administration of red blood cell concentrates in the resuscitation room (1.9x).

Conclusions

The present analysis identified numerous independent risk factors for significantly prolonged hospitalization of the geriatric polytraumatized patient, which should be given increased attention during treatment. In particular, the need for a smooth transition to psychiatric follow-up treatment or patient-adapted rehabilitative care for geriatric patients with prolonged immobility after extremity injuries is emphasized by these results.
An overview of potential excavation compensation method for tunnelling in deep rock engineering
Authors: Hu Jie , He Manchao , Tao Zhigang , Cheng Tai , Xiao Yingming , Li Hongru , Li Limin
Published: August 2024

The complicated geological environment of deep rocks poses new challenges to tunnel and mining engineering. Some thorny disasters such as large deformation of soft rock and rockburst are becoming more and more prominent. However, the classic tunnelling methods represented by the mine tunnelling method and the new Austrian tunnelling method are generally unsatisfactory in addressing these issues due to the limited self-stability of surrounding rock mass. Therefore, the excavation compensation method (ECM) with the core of active stress compensation has been proposed and applied in practical engineering construction to solve the above problems. After extensive engineering practice, the theoretical foundation, key technologies, and construction system of ECM have been established and improved. This article provides a comprehensive overview of this novel tunnelling method. In addition, its controlling effects on surrounding rock are demonstrated by two typical engineering examples. It could provide some new ideas and references for the development of future tunnelling technology.
Opinion dynamics models describing the emergence of polarization phenomena
Authors: Bertotti Maria Letizia , Menale Marco
Published: August 2024

Some novel models of opinion dynamics are here formulated in terms of ordinary and of stochastic differential equations. The focus is on the possible emergence of polarization phenomena. Alongside attitudes and mechanisms related to individual-individual interactions, issues such as the influence of persuaders, acting perhaps on different time-scales, and uncertainty are taken into account. The existence of stationary solutions corresponding to polarized opinion distributions, together with their stability or instability properties, is established in correspondence to different parameter values.
Applications of Population Sampling to Insurance Ratemaking and Reserving
Authors: Calcetero Vanegas Sebastián , Lin X. Sheldon
Published: August 2024

This paper explores the underutilized application of population sampling in the realm of actuarial science, a field where these statistical methodologies have been traditionally overlooked. Focusing on two distinct applications within insurance ratemaking and reserving, we unveil innovative approaches to address challenges in actuarial contexts and provide valuable insights into advancing methodologies in the field. The first application introduces population sampling as a solution to the computational complexities inherent in credibility premium calculation, particularly under Bayesian regression models. By combining population sampling with surrogate modeling, we present a method to manage computation challenges effectively. The second application delves into incurred but not reported reserves, challenging the conventional Chain–Ladder method and individual reserving models by incorporating population sampling. Proposing a reserve estimator based on inverse probability weighting techniques, we demonstrate a statistically robust, distribution-free method for IBNR reserving, emphasizing the integration of granular policyholder information
Within-Person Dynamics of Job Boredom and Counterproductive Work Behavior: A Latent Change Score Modeling Approach
Authors: Kim JeongJin , Kaplan Seth A. , Aitken John A. , Ponce Lida P.
Published: August 2024

Job boredom is one of the most common negative affective states experienced in the workplace, yet also among the least well-understood. One stream of research suggests that employees frequently react to job boredom by engaging in counterproductive work behaviors (CWB). However, recent studies show the converse—that engaging in CWB relates to job boredom. As studies on the job boredom-CWB relationship primarily have been cross-sectional and at the between-person level of analysis, the directionality between these constructs remains in question. Therefore, research examining the within-person dynamics of job boredom and CWB within a short timeframe is needed. In the current study, we explore whether job boredom influences subsequent changes in CWB and vice versa. We examined these relationships using latent change score (LCS) modeling with 10-day experience sampling data (N = 120 individuals providing 1,161 observations). Findings supported a reciprocal relationship. Employees’ level of job boredom on a given day was associated with a subsequent increase in CWB on the next day, and the level of CWB on a given day was associated with a subsequent increase in job boredom on the next day. We discuss the implications of our findings, study limitations, and future research directions.
DialogueNeRF: towards realistic avatar face-to-face conversation video generation
Authors: Yan Yichao , Zhou Zanwei , Wang Zi , Gao Jingnan , Yang Xiaokang
Published: August 2024

Conversation is an essential component of virtual avatar activities in the metaverse. With the development of natural language processing, significant breakthroughs have been made in text and voice conversation generation. However, face-to-face conversations account for the vast majority of daily conversations, while most existing methods focused on single-person talking head generation. In this work, we take a step further and consider generating realistic face-to-face conversation videos. Conversation generation is more challenging than single-person talking head generation, because it requires not only the generation of photo-realistic individual talking heads, but also the listener’s response to the speaker. In this paper, we propose a novel unified framework based on the neural radiance field (NeRF) to address these challenges. Specifically, we model both the speaker and the listener with a NeRF framework under different conditions to control individual expressions. The speaker is driven by the audio signal, while the response of the listener depends on both visual and acoustic information. In this way, face-to-face conversation videos are generated between human avatars, with all the interlocutors modeled within the same network. Moreover, to facilitate future research on this task, we also collected a new human conversation dataset containing 34 video clips. Quantitative and qualitative experiments evaluate our method in different aspects, e.g., image quality, pose sequence trend, and natural rendering of the scene in the generated videos. Experimental results demonstrate that the avatars in the resulting videos are able to carry on a realistic conversation, and maintain individual styles.
Perceptions of a Global Democratic Deficit: An International Survey Experiment
Authors: Ghassim Farsan
Published: August 2024

While scholars consider the global democratic deficit a key issue, we know little about citizens’ perceptions in this regard. To what extent and why do citizens perceive global democratic deficiencies? I conceptualize deficiencies absolutely and relatively—theorizing countries, knowledge, and framing as explanatory factors. Between 2018 and 2021, I conducted survey experiments on around 42,000 respondents in 17 highly diverse countries. Contrary to many scholarly assessments, I find that most people do not perceive major global democratic deficiencies, in the sense that global governance is generally not perceived as highly undemocratic in absolute terms and more democratic than developing democracies. However, the results vary by the object and aspect of inquiry: World politics (versus international organizations) and input (versus output) are perceived as less democratic. Plus, neither gains in relevant knowledge nor common framings affect public perceptions, which are thus quite robust. These findings add novel evidence to debates about global governance.
Strongly Negative Low‐Field Variation of Magnetic Susceptibility: Rock Magnetic Character of the Basement‐Cover Interface of Northeastern Oklahoma
Authors: Hamilton Matt , Jackson Mike , Chadima Martin , Egli Ramon , Elmore R. Douglas
Published: August 2024

Some rock and soil samples exhibit significant loss of magnetic susceptibility (χ) with increasing applied field amplitude even at relatively low (10–100s of A/m) fields, a behavior which remains unexplained. Exceptionally strong negative field‐dependence of susceptibility (χHD) is present in sandstones and altered intermediate‐felsic igneous rocks in several cores from the northeastern Oklahoma subsurface. These same rocks also show elevated frequency‐dependence of susceptibility (χFD), with reasonable correlation of χHD to χFD, and frequency‐dependent χHD. Results from multiple characterization methods indicate that strongly negative χHD in these rocks is linked to a yet‐unidentified phase which begins the approach to magnetic saturation in low fields (<1 mT/800 A/m), shows elevated χFD to low temperatures, is unstable at high temperatures, possesses significant anisotropy of magnetic susceptibility, and becomes paramagnetic above ∼83°C. Clear associations with fluid alteration features indicate that this material may be highly relevant to rock alteration, diagenetic, and environmental studies.
A Probabilistic Approach to Characterizing Drought Using Satellite Gravimetry
Authors: Saemian Peyman , Tourian Mohammad J. , Elmi Omid , Sneeuw Nico , AghaKouchak Amir
Published: August 2024

In the recent past, the Gravity Recovery and Climate Experiment (GRACE) satellite mission and its successor GRACE Follow‐On (GRACE‐FO), have become invaluable tools for characterizing drought through measurements of Total Water Storage Anomaly (TWSA). However, the existing approaches have often overlooked the uncertainties in TWSA that stem from GRACE orbit configuration, background models, and intrinsic data errors. Here we introduce a fresh view on this problem which incorporates the uncertainties in the data: the Probabilistic Storage‐based Drought Index (PSDI). Our method leverages Monte Carlo simulations to yield realistic realizations for the stochastic process of the TWSA time series. These realizations depict a range of plausible drought scenarios that later on are used to characterize drought. This approach provides probability for each drought category instead of selecting a single final category at each epoch. We have compared PSDI with the deterministic approach (Storage‐based Drought Index, SDI) over major global basins. Our results show that the deterministic approach often leans toward an overestimation of storage‐based drought severity. Furthermore, we scrutinize the performance of PSDI across diverse hydrologic events, spanning continents from the United States to Europe, the Middle East, Southern Africa, South America, and Australia. In each case, PSDI emerges as a reliable indicator for characterizing drought conditions, providing a more comprehensive perspective than conventional deterministic indices. In contrast to the common deterministic view, our probabilistic approach provides a more realistic characterization of the TWS drought, making it more suited for adaptive strategies and realistic risk management.
A New View of Shear Wavespeed and the Lithosphere‐Asthenosphere Boundary in the Southwestern United States
Authors: Golos E. M. , Brunsvik B. , Eilon Z. , Fischer K. M. , Byrnes J. , Gaherty J.
Published: August 2024

The Southwestern United States experiences active deformation, seismicity, and magmatism, remarkable in an intraplate setting. The Basin and Range and Colorado Plateau (CP) are inferred to differ in lithospheric thickness, but modeling geophysical properties of the lithosphere, in particular the depth of the Lithosphere‐Asthenosphere Boundary (LAB), across the entirety of the region, has proved challenging. Here, we introduce a new model of 1‐D depth profiles in shear wavespeed, determined through a probabilistic joint inversion of information from Sp receiver functions and Rayleigh wave phase velocity. From these profiles we quantify the locations and Vs contrast of wavespeed gradients that represent boundaries such as the Moho, the LAB, and intralithospheric discontinuities. We infer a lithosphere that is thinner and lower in Vs in the Basin and Range. In the CP and farther north, the LAB is more gradual, deeper, and intermittently observed. We also observe Mid‐Lithospheric Discontinuities (MLDs) near the boundaries between the CP, Wyoming Craton, and Northern Basin and Range, as well as within the Craton. When both an MLD and LAB are observed, the Vs gradient associated with the LAB is narrower than expected. Finally, we image Positive Velocity Gradients beneath areas of thinner lithosphere, which are consistent with recent global observations that have been attributed to the base of a partially molten zone below the lithosphere. Overall, the picture of the lithosphere‐asthenosphere system that emerges is one of considerable structural complexity with a strong dependency on tectonic regime and geological history.
Capillary effect-based selective sealing strategy for increasing piezoelectric MEMS speaker performance
Authors: Wang Yan , Lv Tunan , Zhang Junning , Yu Hongbin
Published: August 2024

To address the serious acoustic performance deterioration induced by air leakage in the low-frequency range and the asynchronous vibration in electroacoustic transduction structures near the resonant frequency, a novel sealing strategy is proposed that targets one of the most widely reported piezoelectric MEMS speaker designs. This design consists of multiple cantilever beams, in which the air gaps between cantilevers are automatically and selectively filled with liquid polydimethylsiloxane (PDMS) via the capillary effect, followed by curing. In the proof-of-concept demonstration, the sound pressure level (SPL) within the frequency range lower than 100 Hz markedly increased after sealing in an experiment using an IEC ear simulator. Specifically, the SPL is increased by 4.9 dB at 20 Hz for a 40 Vpp driving voltage. Moreover, the deteriorated SPL response near the resonant frequencies of the cantilever beams (18 kHz–19 kHz) caused by their asynchronous vibration induced by the fabrication process nonuniformity also significantly improved, which successfully increased the SPL to approximately 17.5 dB. Moreover, sealed devices feature nearly the same SPL response as the initial counterpart in the frequency band from 100 Hz to 16 kHz and a total harmonic distortion (THD) of 0.728% at 1 kHz for a 40 Vpp driving voltage. Compared with existing sealing methods, the current approach offers easy operation, low damage risk, excellent repeatability/reliability and excellent robustness advantages and provides a promising technical solution for MEMS acoustic devices.
Serum levels of B-cell activating factor are associated with a reduced risk of chronic lymphocytic leukemia
Authors: Frost Eleanor , Hofmann Jonathan N. , Huang Wen-Yi , Frazer-Abel Ashley A. , Deane Kevin D. , Berndt Sonja I.
Published: August 2024

Impact

Immune dysregulation is thought to contribute to chronic lymphocytic leukemia (CLL) risk, but biological mechanisms are unclear. We discovered that increased serum levels of B-cell activating factor (BAFF), an important regulator of B-cell maturation, were associated with a decreased risk of CLL, even >10 years after blood draw. Our findings suggest that BAFF could be a useful biomarker to assess risk among individuals at high risk, such as those with monoclonal b-cell lymphocytosis.
Systematic multi-trait AAV capsid engineering for efficient gene delivery
Authors: Eid Fatma-Elzahraa , Chen Albert T. , Chan Ken Y. , Huang Qin , Zheng Qingxia , Tobey Isabelle G. , Pacouret Simon , Brauer Pamela P. , Keyes Casey , Powell Megan , Johnston Jencilin , Zhao Binhui , Lage Kasper , Tarantal Alice F. , Chan Yujia A. , Deverman Benjamin E.
Published: August 2024

Broadening gene therapy applications requires manufacturable vectors that efficiently transduce target cells in humans and preclinical models. Conventional selections of adeno-associated virus (AAV) capsid libraries are inefficient at searching the vast sequence space for the small fraction of vectors possessing multiple traits essential for clinical translation. Here, we present Fit4Function, a generalizable machine learning (ML) approach for systematically engineering multi-trait AAV capsids. By leveraging a capsid library that uniformly samples the manufacturable sequence space, reproducible screening data are generated to train accurate sequence-to-function models. Combining six models, we designed a multi-trait (liver-targeted, manufacturable) capsid library and validated 88% of library variants on all six predetermined criteria. Furthermore, the models, trained only on mouse in vivo and human in vitro Fit4Function data, accurately predicted AAV capsid variant biodistribution in macaque. Top candidates exhibited production yields comparable to AAV9, efficient murine liver transduction, up to 1000-fold greater human hepatocyte transduction, and increased enrichment relative to AAV9 in a screen for liver transduction in macaques. The Fit4Function strategy ultimately makes it possible to predict cross-species traits of peptide-modified AAV capsids and is a critical step toward assembling an ML atlas that predicts AAV capsid performance across dozens of traits.
Exome-wide association study identifies KDELR3 mutations in extreme myopia
Authors: Yuan Jian , Zhuang You-Yuan , Liu Xiaoyu , Zhang Yue , Li Kai , Chen Zhen Ji , Li Dandan , Chen He , Liang Jiacheng , Yao Yinghao , Yu Xiangyi , Zhuo Ran , Zhao Fei , Zhou Xiangtian ,   Myopia Associated Genetics and Intervention Consortium, Xu Liangde , Qu Jia , Lyu Fan , Yang Jian , Wang Hong , Yuan Jian , Ma Yunlong , Xue Zhengbo , Liu Hui , Dai Wei , Zhang Riyan , Yu Xiaoguang , Qu Jia , Su Jianzhong
Published: August 2024

Extreme myopia (EM), defined as a spherical equivalent (SE) ≤ −10.00 diopters (D), is one of the leading causes of sight impairment. Known EM-associated variants only explain limited risk and are inadequate for clinical decision-making. To discover risk genes, we performed a whole-exome sequencing (WES) on 449 EM individuals and 9606 controls. We find a significant excess of rare protein-truncating variants (PTVs) in EM cases, enriched in the retrograde vesicle-mediated transport pathway. Employing single-cell RNA-sequencing (scRNA-seq) and a single-cell polygenic burden score (scPBS), we pinpointed PI16 + /SFRP4+ fibroblasts as the most relevant cell type. We observed that KDELR3 is highly expressed in scleral fibroblast and involved in scleral extracellular matrix (ECM) organization. The zebrafish model revealed that kdelr3 downregulation leads to elongated ocular axial length and increased lens diameter. Together, our study provides insight into the genetics of EM in humans and highlights KDELR3’s role in EM pathogenesis.
ILC2-derived LIF licences progress from tissue to systemic immunity
Authors: Gogoi Mayuri , Clark Paula A. , Ferreira Ana C. F. , Rodriguez Rodriguez Noe , Heycock Morgan , Ko Michelle , Murphy Jane E. , Chen Victor , Luan Shi-Lu , Jolin Helen E. , McKenzie Andrew N. J.
Published: August 2024

Migration and homing of immune cells are critical for immune surveillance. Trafficking is mediated by combinations of adhesion and chemokine receptors that guide immune cells, in response to chemokine signals, to specific locations within tissues and the lymphatic system to support tissue-localized immune reactions and systemic immunity1,2. Here we show that disruption of leukaemia inhibitory factor (LIF) production from group 2 innate lymphoid cells (ILC2s) prevents immune cells leaving the lungs to migrate to the lymph nodes (LNs). In the absence of LIF, viral infection leads to plasmacytoid dendritic cells (pDCs) becoming retained in the lungs where they improve tissue-localized, antiviral immunity, whereas chronic pulmonary allergen challenge leads to marked immune cell accumulation and the formation of tertiary lymphoid structures in the lung. In both cases immune cells fail to migrate to the lymphatics, leading to highly compromised LN reactions. Mechanistically, ILC2-derived LIF induces the production of the chemokine CCL21 from lymphatic endothelial cells lining the pulmonary lymphatic vessels, thus licensing the homing of CCR7+ immune cells (including dendritic cells) to LNs. Consequently, ILC2-derived LIF dictates the egress of immune cells from the lungs to regulate tissue-localized versus systemic immunity and the balance between allergen and viral responsiveness in the lungs.
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

Colorectal 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

Selfish 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

Oncogenic 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

Systemically 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

DNA 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

Double-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

The 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

The 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

Despite 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

Here 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.