bluuebunny/crossref_metadata_2025_split huggingface dataset:
The modulation of pulmonary group 2 innate lymphoid cell function in asthma: from inflammatory mediators to environmental and metabolic factors
Authors: Thio Christina Li-Ping , Chang Ya-Jen 
Published: September 2023

AbstractA dysregulated type 2 immune response is one of the fundamental causes of allergic asthma. Although Th2 cells are undoubtedly central to the pathogenesis of allergic asthma, the discovery of group 2 innate lymphoid cells (ILC2s) has added another layer of complexity to the etiology of this chronic disease. Through their inherent innate type 2 responses, ILC2s not only contribute to the initiation of airway inflammation but also orchestrate the recruitment and activation of other members of innate and adaptive immunity, further amplifying the inflammatory response. Moreover, ILC2s exhibit substantial cytokine plasticity, as evidenced by their ability to produce type 1- or type 17-associated cytokines under appropriate conditions, underscoring their potential contribution to nonallergic, neutrophilic asthma. Thus, understanding the mechanisms of ILC2 functions is pertinent. In this review, we present an overview of the current knowledge on ILC2s in asthma and the regulatory factors that modulate lung ILC2 functions in various experimental mouse models of asthma and in humans.
CD1-mediated immune responses in mucosal tissues: molecular mechanisms underlying lipid antigen presentation system
Authors: Kim Seohyun , Cho Sumin , Kim Ji Hyung 
Published: September 2023

AbstractThe cluster of differentiation 1 (CD1) molecule differs from major histocompatibility complex class I and II because it presents glycolipid/lipid antigens. Moreover, the CD1-restricted T cells that recognize these self and foreign antigens participate in both innate and adaptive immune responses. CD1s are constitutively expressed by professional and nonprofessional antigen-presenting cells in mucosal tissues, namely, the skin, lung, and intestine. This suggests that CD1-reactive T cells are involved in the immune responses of these tissues. Indeed, evidence suggests that these cells play important roles in diverse diseases, such as inflammation, autoimmune disease, and infection. Recent studies elucidating the molecular mechanisms by which CD1 presents lipid antigens suggest that defects in these mechanisms could contribute to the activities of CD1-reactive T cells. Thus, improving our understanding of these mechanisms could lead to new and effective therapeutic approaches to CD1-associated diseases. In this review, we discuss the CD1-mediated antigen presentation system and its roles in mucosal tissue immunity.
Effects of obstructive sleep apnea on non-alcoholic fatty liver disease in patients with obesity: a systematic review
Authors: Hany Mohamed , Abouelnasr Anwar Ashraf , Abdelkhalek Mohamed Hesham , Ibrahim Mohamed , Aboelsoud Mostafa R. , Hozien Adel Ibrahim , Torensma Bart 
Published: September 2023

Abstract
Introduction
Obesity has been linked to non-alcoholic fatty liver disease (NAFLD), a widespread chronic liver ailment, as well as obstructive sleep apnea (OSA). The development of NAFLD is influenced by repeated intermittent hypoxia, a feature of OSA.

Methods
This systematic review (SR) investigated CENTRAL, PubMed, and EMBASE databases. The endpoint of this SR was to assess which OSA-related indicators could predict the presence of NAFLD and the effect of bariatric metabolic surgery (BMS) on improving OSA and NAFLD over time.

Results
Compared to previous SRs published in 2013, 14 new publications were added to our SR, alongside studies conducted prior to 2013. The SR ultimately included 28 studies (18 cross-sectional and 10 cohort trials). In the majority of studies, significant correlations were observed between OSA, OSA-related outcomes, and NAFLD. However, the apnea-hypopnea index (AHI) alone proved to be an inadequate predictor of NAFLD. Instead, respiratory and metabolic changes were found to alleviate oxidative stress induced by hypoxemia.
Six studies involved patients who underwent BMS, with one evaluating patients before and after BMS, revealing associations between increased OSA and NAFLD improvement following BMS. Six months after surgery, 100% of patients in the mild-to-moderate OSA group were free from fatty liver, and an 89% reduction was observed in the severe OSA group.

Conclusion
For the first time, BMS has been tested in treating both OSA and NAFLD pre and postoperative with positive results. Further research, ideally with histological and functional data, is needed to confirm these findings. The SR identified 14 distinct liver outcome tests; however, high heterogeneity and incomplete data precluded a meta-analysis. It is imperative to pay greater attention to the influence of OSA-related factors and uniformity in liver outcomes testing concerning NAFLD. To accomplish this, study designs should be enhanced by incorporating more comprehensive pre- and postoperative evaluations, extending follow-up periods, and employing a more consistent methodology for liver diagnosis in patients with obesity.
3D free-assembly modular microfluidics inspired by movable type printing
Authors: Huang Shaoqi , Wu Jiandong , Zheng Lulu , Long Yan , Chen Junyi , Li Jianlang , Dai Bo , Lin Francis , Zhuang Songlin , Zhang Dawei 
Published: September 2023

AbstractReconfigurable modular microfluidics presents an opportunity for flexibly constructing prototypes of advanced microfluidic systems. Nevertheless, the strategy of directly integrating modules cannot easily fulfill the requirements of common applications, e.g., the incorporation of materials with biochemical compatibility and optical transparency and the execution of small batch production of disposable chips for laboratory trials and initial tests. Here, we propose a manufacturing scheme inspired by the movable type printing technique to realize 3D free-assembly modular microfluidics. Double-layer 3D microfluidic structures can be produced by replicating the assembled molds. A library of modularized molds is presented for flow control, droplet generation and manipulation and cell trapping and coculture. In addition, a variety of modularized attachments, including valves, light sources and microscopic cameras, have been developed with the capability to be mounted onto chips on demand. Microfluidic systems, including those for concentration gradient generation, droplet-based microfluidics, cell trapping and drug screening, are demonstrated. This scheme enables rapid prototyping of microfluidic systems and construction of on-chip research platforms, with the intent of achieving high efficiency of proof-of-concept tests and small batch manufacturing.
Insights adjusting for non-adherence in randomized clinical trials: a reanalysis of an adjuvant trial of tamoxifen duration in early breast cancer
Authors: Giudici Fabiola , Pistilli Barbara , Vaz-Luis Ines , Karimi Maryam , Delaloge Suzette , Bachelot Thomas , Michiels Stefan , Bardet Aurelie 
Published: September 2023

Abstract
Background
Several randomized clinical trials provide evidence of the survival benefit of extended adjuvant tamoxifen in women with estrogen receptor (ER)-positive early breast cancer (BC). However, non-adherence may lead to underestimate treatment effects using intention to treat (ITT) methods. We reanalyzed a randomized trial using contemporary statistical methods adjusting for non-adherence.

Methods
The TAM01 study was a phase 3 trial including women with early BC, who had completed 2–3 years of adjuvant tamoxifen between 1986 and 1995. Participants were randomly assigned to continue tamoxifen up to 10 years or to discontinue the treatment at randomization. Invasive disease-free survival (iDFS) and overall survival (OS) were estimated using marginal structural models (MSM) and rank preserving structural failure time model (RPSFTM).

Results
Of 3830 patients enrolled, 2485 were randomized to extended tamoxifen, and 1345 to treatment discontinuation. The 10-year non-adherence rate in the extended group was 27.2%. Among women with ER-positive BC (n = 2402), extended tamoxifen was associated with a 45% and 21% relative improvement in iDFS by MSM and RPSFTM, respectively (Hazard Ratio (HR), 0.55; 95% Confidence Interval (CI), 0.48–0.64 and HR, 0.79; 95%CI, 0.67–0.95, respectively), a considerable greater benefit than in the ITT analysis (HR, 0.90; 95%CI, 0.81–0.99). The OS reanalysis revealed a substantial benefit of extended tamoxifen (MSM: HR, 0.70; 95%CI, 0.59–0.83; RPSFTM: HR, 0.85; 95%CI, 0.67–1.04), compared to the ITT analyses (HR, 0.94; 95%CI, 0.84–1.07).

Conclusion
This analysis emphasizes both the importance of adherence to hormonotherapy in hormone-receptor positive early BC and the usefulness of more complex statistical analyses.
Tumor suppressor p53 mediates interleukin-6 expression to enable cancer cell evasion of genotoxic stress
Authors: Phan Trinh T. T. , Truong Nam V. , Wu Wen-Guey , Su Yi-Chun , Hsu Tzu-Sheng , Lin Lih-Yuan 
Published: September 2023

AbstractThe tumor suppressor p53 primarily functions as a mediator of DNA damage-induced cell death, thereby contributing to the efficacy of genotoxic anticancer therapeutics. Here, we show, on the contrary, that cancer cells can employ genotoxic stress-induced p53 to acquire treatment resistance through the production of the pleiotropic cytokine interleukin (IL)-6. Mechanistically, DNA damage, either repairable or irreparable, activates p53 and stimulates Caspase-2-mediated cleavage of its negative regulator mouse double minute 2 (MDM2) creating a positive feedback loop that leads to elevated p53 protein accumulation. p53 transcriptionally controls the major adenosine triphosphate (ATP) release channel pannexin 1 (Panx1), which directs IL-6 induction via a mechanism dependent on the extracellular ATP-activated purinergic P2 receptors as well as their downstream intracellular calcium (iCa2+)/PI3K/Akt/NF-ĸB signaling pathway. Thus, p53 silencing impairs Panx1 and IL-6 expression and renders cancer cells sensitive to genotoxic stress. Moreover, we confirm that IL-6 hampers the effectiveness of genotoxic anticancer agents by mitigating DNA damage, driving the expression of anti-apoptotic Bcl-2 family genes, and maintaining the migratory and invasive properties of cancer cells. Analysis of patient survival and relevant factors in lung cancer and pan-cancer cohorts supports the prognostic and clinical values of Panx1 and IL-6. Notably, IL-6 secreted by cancer cells during genotoxic treatments promotes the polarization of monocytic THP-1-derived macrophages into an alternative (M2-like) phenotype that exhibits impaired anti-survival activities but enhanced pro-metastatic effects on cancer cells as compared to nonpolarized macrophages. Our study reveals the precise mechanism for genotoxic-induced IL-6 and suggests that targeting p53-mediated IL-6 may improve the responsiveness of cancer cells to genotoxic anticancer therapy.
A pilot study to determine the optimal dose of scAAVIL-1ra in a large animal model of post-traumatic osteoarthritis
Authors: Thampi P. , Seabaugh K. A. , Pezzanite L. M. , Chu C. R. , Phillips J. N. , Grieger J. C. , McIlwraith C. W. , Samulski R. J. , Goodrich L. R. 
Published: September 2023

AbstractGene therapy approaches using adeno-associated viral vectors have been successfully tested in the equine post-traumatic osteoarthritis (PTOA) model. Owing to differences in the levels of transgene expression and adverse tissue reactions observed in published studies, we sought to identify a safe therapeutic dose of scAAVIL-1ra in an inflamed and injured joint that would result in improved functional outcomes without any adverse events. scAAVIL-1ra was delivered intra-articularly over a 100-fold range, and horses were evaluated throughout and at the end of the 10-week study. A dose-related increase in IL-1ra levels with a decrease in PGE2 levels was observed, with the peak IL-1ra concentration being observed 7 days post-treatment in all groups. Perivascular infiltration with mononuclear cells was observed within the synovial membrane of the joint treated with the highest viral dose of 5 × 1012 vg, but this was absent in the lower-dosed joints. The second-highest dose of scAAVeqIL-1ra 5 × 1011 vg demonstrated elevated IL-1ra levels without any cellular response in the synovium. Taken together, the data suggest that the 10-fold lower dose of 5 × 1011vg scAAVIL-1ra would be a safe therapeutic dose in an equine model of PTOA.
Building block aspect ratio controls assembly, architecture, and mechanics of synthetic and natural protein networks
Authors: Hughes Matt D. G. , Cussons Sophie , Hanson Benjamin S. , Cook Kalila R. , Feller Tímea , Mahmoudi Najet , Baker Daniel L. , Ariëns Robert , Head David A. , Brockwell David J. , Dougan Lorna 
Published: September 2023

AbstractFibrous networks constructed from high aspect ratio protein building blocks are ubiquitous in nature. Despite this ubiquity, the functional advantage of such building blocks over globular proteins is not understood. To answer this question, we engineered hydrogel network building blocks with varying numbers of protein L domains to control the aspect ratio. The mechanical and structural properties of photochemically crosslinked protein L networks were then characterised using shear rheology and small angle neutron scattering. We show that aspect ratio is a crucial property that defines network architecture and mechanics, by shifting the formation from translationally diffusion dominated to rotationally diffusion dominated. Additionally, we demonstrate that a similar transition is observed in the model living system: fibrin blood clot networks. The functional advantages of this transition are increased mechanical strength and the rapid assembly of homogenous networks above a critical protein concentration, crucial for in vivo biological processes such as blood clotting. In addition, manipulating aspect ratio also provides a parameter in the design of future bio-mimetic and bio-inspired materials.
Phylotranscriptomics unveil a Paleoproterozoic-Mesoproterozoic origin and deep relationships of the Viridiplantae
Authors: Yang Zhiping , Ma Xiaoya , Wang Qiuping , Tian Xiaolin , Sun Jingyan , Zhang Zhenhua , Xiao Shuhai , De Clerck Olivier , Leliaert Frederik , Zhong Bojian 
Published: September 2023

AbstractThe Viridiplantae comprise two main clades, the Chlorophyta (including a diverse array of marine and freshwater green algae) and the Streptophyta (consisting of the freshwater charophytes and the land plants). Lineages sister to core Chlorophyta, informally refer to as prasinophytes, form a grade of mainly planktonic green algae. Recently, one of these lineages, Prasinodermophyta, which is previously grouped with prasinophytes, has been identified as the sister lineage to both Chlorophyta and Streptophyta. Resolving the deep relationships among green plants is crucial for understanding the historical impact of green algal diversity on marine ecology and geochemistry, but has been proven difficult given the ancient timing of the diversification events. Through extensive taxon and gene sampling, we conduct large-scale phylogenomic analyses to resolve deep relationships and reveal the Prasinodermophyta as the lineage sister to Chlorophyta, raising questions about the necessity of classifying the Prasinodermophyta as a distinct phylum. We unveil that incomplete lineage sorting is the main cause of discordance regarding the placement of Prasinodermophyta. Molecular dating analyses suggest that crown-group green plants and crown-group Prasinodermophyta date back to the Paleoproterozoic-Mesoproterozoic. Our study establishes a plausible link between oxygen levels in the Paleoproterozoic-Mesoproterozoic and the origin of Viridiplantae.
The spatial and temporal structure of neural activity across the fly brain
Authors: Schaffer Evan S. , Mishra Neeli , Whiteway Matthew R. , Li Wenze , Vancura Michelle B. , Freedman Jason , Patel Kripa B. , Voleti Venkatakaushik , Paninski Liam , Hillman Elizabeth M. C. , Abbott L. F. , Axel Richard 
Published: September 2023

AbstractWhat are the spatial and temporal scales of brainwide neuronal activity? We used swept, confocally-aligned planar excitation (SCAPE) microscopy to image all cells in a large volume of the brain of adult Drosophila with high spatiotemporal resolution while flies engaged in a variety of spontaneous behaviors. This revealed neural representations of behavior on multiple spatial and temporal scales. The activity of most neurons correlated (or anticorrelated) with running and flailing over timescales that ranged from seconds to a minute. Grooming elicited a weaker global response. Significant residual activity not directly correlated with behavior was high dimensional and reflected the activity of small clusters of spatially organized neurons that may correspond to genetically defined cell types. These clusters participate in the global dynamics, indicating that neural activity reflects a combination of local and broadly distributed components. This suggests that microcircuits with highly specified functions are provided with knowledge of the larger context in which they operate.
Janus particle-engineered structural lipiodol droplets for arterial embolization
Authors: Tao Sijian , Lin Bingquan , Zhou Houwang , Sha Suinan , Hao Xiangrong , Wang Xuejiao , Chen Jianping , Zhang Yangning , Pan Jiahao , Xu Jiabin , Zeng Junling , Wang Ying , He Xiaofeng , Huang Jiahao , Zhao Wei , Fan Jun-Bing 
Published: September 2023

AbstractEmbolization (utilizing embolic materials to block blood vessels) has been considered one of the most promising strategies for clinical disease treatments. However, the existing embolic materials have poor embolization effectiveness, posing a great challenge to highly efficient embolization. In this study, we construct Janus particle-engineered structural lipiodol droplets by programming the self-assembly of Janus particles at the lipiodol-water interface. As a result, we achieve highly efficient renal embolization in rabbits. The obtained structural lipiodol droplets exhibit excellent mechanical stability and viscoelasticity, enabling them to closely pack together to efficiently embolize the feeding artery. They also feature good viscoelastic deformation capacities and can travel distally to embolize finer vasculatures down to 40 μm. After 14 days post-embolization, the Janus particle-engineered structural lipiodol droplets achieve efficient embolization without evidence of recanalization or non-target embolization, exhibiting embolization effectiveness superior to the clinical lipiodol-based emulsion. Our strategy provides an alternative approach to large-scale fabricate embolic materials for highly efficient embolization and exhibits good potential for clinical applications.
Endogenous fluctuations in cortical state selectively enhance different modes of sensory processing in human temporal lobe
Authors: Parajuli Arun , Gutnisky Diego , Tandon Nitin , Dragoi Valentin 
Published: September 2023

AbstractThe degree of synchronized fluctuations in neocortical network activity can vary widely during alertness. One influential idea that has emerged over the past few decades is that perceptual decisions are more accurate when the state of population activity is desynchronized. This suggests that optimal task performance may occur during a particular cortical state – the desynchronized state. Here we show that, contrary to this view, cortical state can both facilitate and suppress perceptual performance in a task-dependent manner. We performed electrical recordings from surface-implanted grid electrodes in the temporal lobe while human subjects completed two perceptual tasks. We found that when local population activity is in a synchronized state, network and perceptual performance are enhanced in a detection task and impaired in a discrimination task, but these modulatory effects are reversed when population activity is desynchronized. These findings indicate that the brain has adapted to take advantage of endogenous fluctuations in the state of neural populations in temporal cortex to selectively enhance different modes of sensory processing during perception in a state-dependent manner.
Large anomalous Hall, Nernst effect and topological phases in the 3d-4d/5d-based oxide double perovskites
Authors: Samanta Kartik , Noky Jonathan , Robredo Iñigo , Kuebler Juergen , Vergniory Maia G. , Felser Claudia 
Published: September 2023

AbstractMagnetism and spin-orbit coupling are two fundamental and interconnected properties of oxide materials, that can give rise to various topological transport phenomena, including anomalous Hall and anomalous Nernst effects. These transport responses can be significantly enhanced by designing an electronic structure with a large Berry curvature. In this context, rocksalt-ordered double perovskites (DP), denoted as A2BB’O6, with two distinct transition metal sites are very powerful platforms for exploration and research. In this work, we present a comprehensive study based on the intrinsic anomalous transport in cubic and tetragonal stable DP compounds with 3d-4d/5d elements. Our findings reveal that certain DP compounds show a large anomalous Hall effect, displaying topological band crossings in the proximity of the Fermi energy.
Subsequent female breast cancer risk associated with anthracycline chemotherapy for childhood cancer
Authors: Wang Yuehan , Ronckers Cécile M. , van Leeuwen Flora E. , Moskowitz Chaya S. , Leisenring Wendy , Armstrong Gregory T. , de Vathaire Florent , Hudson Melissa M. , Kuehni Claudia E. , Arnold Michael A. , Demoor-Goldschmidt Charlotte , Green Daniel M. , Henderson Tara O. , Howell Rebecca M. , Ehrhardt Matthew J. , Neglia Joseph P. , Oeffinger Kevin C. , van der Pal Helena J. H. , Robison Leslie L. , Schaapveld Michael , Turcotte Lucie M. , Waespe Nicolas , Kremer Leontien C. M. , Teepen Jop C. ,   The International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer, van Leeuwen Flora E. , de Vathaire Florent , van der Pal Helena J. H. , Haddy Nadia , Diallo Ibrahima , Baker K. Scott , Berrington de González Amy , Conces Miriam R. , Constine Louis S. , Hawkins Mike , Loonen Jacqueline J. , Louwerens Marloes , Janssens Geert O. , Mellemkjaer Lene , Reulen Raoul , Winther Jeanette F. 
Published: September 2023

AbstractAnthracycline-based chemotherapy is associated with increased subsequent breast cancer (SBC) risk in female childhood cancer survivors, but the current evidence is insufficient to support early breast cancer screening recommendations for survivors treated with anthracyclines. In this study, we pooled individual patient data of 17,903 survivors from six well-established studies, of whom 782 (4.4%) developed a SBC, and analyzed dose-dependent effects of individual anthracycline agents on developing SBC and interactions with chest radiotherapy. A dose-dependent increased SBC risk was seen for doxorubicin (hazard ratio (HR) per 100 mg m−2: 1.24, 95% confidence interval (CI): 1.18–1.31), with more than twofold increased risk for survivors treated with ≥200 mg m−2 cumulative doxorubicin dose versus no doxorubicin (HR: 2.50 for 200–299 mg m−2, HR: 2.33 for 300–399 mg m−2 and HR: 2.78 for ≥400 mg m−2). For daunorubicin, the associations were not statistically significant. Epirubicin was associated with increased SBC risk (yes/no, HR: 3.25, 95% CI: 1.59–6.63). For patients treated with or without chest irradiation, HRs per 100 mg m−2 of doxorubicin were 1.11 (95% CI: 1.02–1.21) and 1.26 (95% CI: 1.17–1.36), respectively. Our findings support that early initiation of SBC surveillance may be reasonable for survivors who received ≥200 mg m−2 cumulative doxorubicin dose and should be considered in SBC surveillance guidelines for survivors and future treatment protocols.