bluuebunny/crossref_metadata_2025 huggingface dataset:
Fault Coupling on a Creeping Thrust Fault: Joint Inversion Using Geodetic Data and Repeating Earthquakes
Authors: Peng Wei , Radiguet Mathilde , Pathier Erwan , Chen Kate Huihsuan
Published: September 2023

Due to the lack of recognized creep on dip‐slip faults, the nature of fault creep and its role in the generation of large earthquakes is largely unexplored. The Chihshang fault in Taiwan serves as one of the best examples of a thrust creeping fault in the world, exhibiting a fast creep rate of 2–3 cm/year and the capability of producing magnitude six earthquakes. Land‐based geodetic measurements are less sensitive to fault slip with depth, especially for the deeper portion of the seaward dipping fault. Taking advantage of slip rates inferred from repeating earthquake sequences (RESs) at greater depths (up to 30 km), we present a method that embeds RES‐derived slip rates into the neighboring fault patch for geodetic data inversion. Using the geodetic and seismological data from 2007 to 2011, we achieve a higher resolution of inter‐seismic slip rate distribution below a depth of 10 km. The inferred low coupling ratio establishes an extensive creeping area that coincides with a location of abundant RES and earthquake swarms. The inferred high coupling ratio, on the other hand, delineates a locked area corresponding to the two co‐seismic slip zones of the 2003 Mw 6.8 Chengkung and 2022 Mw 6.7 Yuli earthquakes. The transition zone marking the gradual change from fully locked to shallow creeping areas appears to coincide with the post‐seismic slip area of the 2003 Chengkung event. Using the fault coupling model, the moment rate deficit measured in the two locked areas is capable of generating a Mw 6.8 event every 78 years to the south and a Mw 6.7 event every 28 years to the north. This moment rate deficit is decreased by 10% when the closely located Central Range fault is considered in a two‐fault model, leading to the slightly longer recurrence interval on the Chihshang fault. The two‐fault model potentially contributes to a better understanding of the regional inter‐seismic deformation, which is recommended to be adopted in the future studies of seismic hazard assessment.
Shear‐Wave Splitting Reveals Layered‐Anisotropy Beneath the European Alps in Response to Mediterranean Subduction
Authors: Link F. , Rümpker G.
Published: September 2023

The European Alps formed at the boundary between the Eurasian plate and Adriatic microplate within a complex system of collision and subduction. However, the large‐scale three‐dimensional mantle‐flow field related to the underlying geodynamic processes has not yet been resolved in detail. In this study, we present the first comprehensive analysis of layered anisotropy for the complete Alpine range from shear‐wave splitting measurements at 591 seismic stations of the AlpArray experiment. Our findings suggest a combination of asthenospheric and distinct lithospheric contributions to the splitting observations, which can be seen as a generalization of previously reported models of single‐layer anisotropy. The enhanced vertical resolution exposes the impact of successive Mediterranean tectonic episodes, such as the opening of the Provençal‐Ligurian and Tyrrhenian Basins alongside the Adriatic slab retreat, as well as the Pannonian Basin opening and the Aegean slab retreat, resulting in deformation of the lithosphere and flow in the asthenospheric mantle. The dominant role of the larger scale Mediterranean subduction systems on mantle dynamics becomes evident. The observations provide supporting evidence that the Eurasian slab has broken off at its boundaries and that the resulting gaps channel flow from the mantle beneath the Eurasian plate to the Adriatic and Aegean subduction systems. The results provide new constraints on geodynamic processes involved in forming the European Alps, as previous tectonic episodes are preserved in the anisotropic fabric of the lithosphere‐asthenosphere system. This raises new questions regarding their geochemical and geophysical conditions, and their larger‐scale impact on the formation of the Alpine orogeny.
The Sensitivity of Southern Ocean Air‐Sea Carbon Fluxes to Background Turbulent Diapycnal Mixing Variability
Authors: Ellison Elizabeth , Mashayek Ali , Mazloff Matthew
Published: September 2023

The Southern Ocean (SO) connects major ocean basins and hosts large air‐sea carbon fluxes due to the resurfacing of deep nutrient and carbon‐rich waters. While wind‐induced turbulent mixing in the SO mixed layer is significant for air‐sea fluxes, the importance of the orders‐of‐magnitude weaker background mixing below is less well understood. The direct impact of altering background mixing on tracers, as opposed to the response due to a longer‐term change in large‐scale ocean circulation, is also poorly studied. Topographically induced upward propagating lee waves, wind‐induced downward propagating waves generated at the base of the mixed layer, shoaling of southward propagating internal tides, and turbulence under sea ice are among the processes known to induce upper ocean background turbulence but typically are not represented in models. Here, we show that abruptly altering the background mixing in the SO over a range of values typically used in climate models ( m2 s−1– m2 s−1) can lead to a ∼70% change in annual SO air‐sea CO2 fluxes in the first year of perturbations, and around a ∼40% change in annual SO air‐sea CO2 fluxes over the 6‐year duration of the experiment, with even greater changes on a seasonal timescale. This is primarily through altering the temperature and the dissolved inorganic carbon and alkalinity distribution in the surface water. Given the high spatiotemporal variability of processes that induce small‐scale background mixing, this work demonstrates the importance of their representation in climate models for accurate simulation of global biogeochemical cycles.
Reconfigurable Antennas and Their Practical Applications—A Review
Authors: Subbaraj Sangeetha , Thomas Shweta B.
Published: September 2023

This paper presents the review on the design of various reconfigurable antennas and their applications in the current scenario. There are more challenges involved in the design of these antennas. This paper also describes the various methods used for reconfiguring the frequency bands. The single parameter reconfiguration and hybrid reconfiguration examples are analyzed with their performances. The parameters such as gain, efficiency, and size of the existing antenna is compared. The various switches deployed in the antenna for achieving the reconfiguration are presented in this paper. The switches such as pin diodes, varactor diodes, MEMS, and mechanical switching are also elaborated with their corresponding merits and demerits. The diodes are switched on and off to activate and deactivate the structure of the antenna. Similarly, mechanical actuators are used for mechanical switching mechanism. The polarization reconfiguration mechanism between linear and circular; pattern reconfiguration mechanism between directional and omnidirectional are reviewed with various examples. In addition to that, several designs of reconfigurable filtering antennas, MIMO antennas are also reviewed in detail.
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

A 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

The 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

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

Reconfigurable 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

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

The 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

Gene 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

Fibrous 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

The 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

What 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

Embolization (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

The 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

Magnetism 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

Anthracycline-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.
Viral genetic clustering and transmission dynamics of the 2022 mpox outbreak in Portugal
Authors: Borges Vítor , Duque Mariana Perez , Martins João Vieira , Vasconcelos Paula , Ferreira Rita , Sobral Daniel , Pelerito Ana , de Carvalho Isabel Lopes , Núncio Maria Sofia , Borrego Maria José , Roemer Cornelius , Neher Richard A. , O’Driscoll Megan , Rocha Raquel , Lopo Sílvia , Neves Raquel , Palminha Paula , Coelho Luís , Nunes Alexandra , Isidro Joana , Pinto Miguel , Santos João Dourado , Mixão Verónica , Santos Daniela , Duarte Silvia , Vieira Luís , Martins Fátima , Machado Jorge , Veríssimo Vítor Cabral , Grau Berta , Peralta-Santos André , Neves José , Caldeira Margarida , Pestana Mafalda , Fernandes Cândida , Caria João , Pinto Raquel , Póvoas Diana , Maltez Fernando , Sá Ana Isabel , Salvador Mafalda Brito , Teófilo Eugénio , Rocha Miguel , Moneti Virginia , Duque Luis Miguel , e Silva Francisco Ferreira , Baptista Teresa , Vasconcelos Joana , Casanova Sara , Mansinho Kamal , Alves João Vaz , Alves João , Silva António , Alpalhão Miguel , Brazão Cláudia , Sousa Diogo , Filipe Paulo , Pacheco Patrícia , Peruzzu Francesca , de Jesus Rita Patrocínio , Ferreira Luís , Mendez Josefina , Jordão Sofia , Duarte Frederico , Gonçalves Maria João , Pena Eduarda , Silva Claúdio Nunes , Guimarães André Rodrigues , Tavares Margarida , Freitas Graça , Cordeiro Rita , Gomes João Paulo
Published: September 2023

Pathogen genome sequencing during epidemics enhances our ability to identify and understand suspected clusters and investigate their relationships. Here, we combine genomic and epidemiological data of the 2022 mpox outbreak to better understand early viral spread, diversification and transmission dynamics. By sequencing 52% of the confirmed cases in Portugal, we identified the mpox virus sublineages with the highest impact on case numbers and fitted them into a global context, finding evidence that several international sublineages probably emerged or spread early in Portugal. We estimated a 62% infection reporting rate and that 1.3% of the population of men who have sex with men in Portugal were infected. We infer the critical role played by sexual networks and superspreader gatherings, such as sauna attendance, in the dissemination of mpox virus. Overall, our findings highlight genomic epidemiology as a tool for the real-time monitoring and control of mpox epidemics, and can guide future vaccine policy in a highly susceptible population.
Investigation of optimizing indocyanine green solution for in vivo lymphatic research using near-infrared fluorescence indocyanine green lymphangiography
Authors: Cheon Hwayeong , Kim Sang Ah , Kim Bumchul , Jeon Jae Yong
Published: September 2023

Despite the tireless efforts of many researchers in lymphatic research, indocyanine green (ICG) solution conditions suitable for lymphatic circulation tests have not been perfectly established yet. We aimed to investigate the optimal in vivo conditions of ICG solution to avoid photobleaching and quenching effects, which may affect the accuracy of lymphatic circulation evaluation. After ICG fluorescence intensity (or ICG intensity) was assessed under different in vitro conditions, the image quality of brachial lymph nodes (LNs) and collecting lymphatic vessels (LVs) in eight rats was investigated. The in vitro results showed that ICG intensity depends on concentration and time in various solvents; however, the brightest intensity was observed at a concentration of 8–30 μg/mL in all solvents. ICG concentration in the albumin (bovine serum albumin; BSA) solution and rat’s plasma showed more than two times higher fluorescence intensity than in distilled water (DW) in the same range. However, saline reduced the intensity by almost half compared to DW. In the in vivo experiment, we obtained relatively high-quality images of the LNs and LVs using ICG in the BSA solution. Even at low concentrations, the result in the BSA solution was comparable to those obtained from high-concentration solutions commonly used in conventional circulation tests. This study provides valuable information about the conditions for optimal ICG intensity in near infrared fluorescence indocyanine green (NIRF-ICG) lymphangiography, which may be useful not only for the diagnosis of lymphatic circulation diseases such as lymphedema but also for preclinical research for the lymphatic system.
Sex and menstrual cycle influence human spatial navigation strategies and performance
Authors: Brown Alana , Burles Ford , Iaria Giuseppe , Einstein Gillian , Moscovitch Morris
Published: September 2023

Which facets of human spatial navigation do sex and menstrual cycle influence? To answer this question, a cross-sectional online study of reproductive age women and men was conducted in which participants were asked to demonstrate and self-report their spatial navigation skills and strategies. Participants self-reported their sex and current menstrual phase [early follicular (EF), late follicular/periovulatory (PO), and mid/late luteal (ML)], and completed a series of questionnaires and tasks measuring self-reported navigation strategy use, topographical memory, cognitive map formation, face recognition, and path integration. We found that sex influenced self-reported use of cognitive map- and scene-based strategies, face recognition, and path integration. Menstrual phase moderated the influence of sex: compared to men, women had better face recognition and worse path integration, but only during the PO phase; PO women were also better at path integration in the presence of a landmark compared to EF + ML women and men. These findings provide evidence that human spatial navigation varies with the menstrual cycle and suggest that sensitivity of the entorhinal cortex and longitudinal axis of the hippocampus to differential hormonal effects may account for this variation.
Comparison of Gastric Alimetry® body surface gastric mapping versus electrogastrography spectral analysis
Authors: Schamberg Gabriel , Calder Stefan , Varghese Chris , Xu William , Wang William Jiaen , Ho Vincent , Daker Charlotte , Andrews Christopher N. , O’Grady Greg , Gharibans Armen A.
Published: September 2023

Electrogastrography (EGG) non-invasively evaluates gastric motility but is viewed as lacking clinical utility. Gastric Alimetry® is a new diagnostic test that combines high-resolution body surface gastric mapping (BSGM) with validated symptom profiling, with the goal of overcoming EGG’s limitations. This study directly compared EGG and BSGM to define performance differences in spectral analysis. Comparisons between Gastric Alimetry BSGM and EGG were conducted by protocolized retrospective evaluation of 178 subjects [110 controls; 68 nausea and vomiting (NVS) and/or type 1 diabetes (T1D)]. Comparisons followed standard methodologies for each test (pre-processing, post-processing, analysis), with statistical evaluations for group-level differences, symptom correlations, and patient-level classifications. BSGM showed substantially tighter frequency ranges vs EGG in controls. Both tests detected rhythm instability in NVS, but EGG showed opposite frequency effects in T1D. BSGM showed an 8× increase in the number of significant correlations with symptoms. BSGM accuracy for patient-level classification was 0.78 for patients vs controls and 0.96 as compared to blinded consensus panel; EGG accuracy was 0.54 and 0.43. EGG detected group-level differences in patients, but lacked symptom correlations and showed poor accuracy for patient-level classification, explaining EGG’s limited clinical utility. BSGM demonstrated substantial performance improvements across all domains.
Fibulin-3 is necessary to prevent cardiac rupture following myocardial infarction
Authors: Murtha Lucy A. , Hardy Sean A. , Mabotuwana Nishani S. , Bigland Mark J. , Bailey Taleah , Raguram Kalyan , Liu Saifei , Ngo Doan T. , Sverdlov Aaron L. , Tomin Tamara , Birner-Gruenberger Ruth , Hume Robert D. , Iismaa Siiri E. , Humphreys David T. , Patrick Ralph , Chong James J. H. , Lee Randall J. , Harvey Richard P. , Graham Robert M. , Rainer Peter P. , Boyle Andrew J.
Published: September 2023

Despite the high prevalence of heart failure in the western world, there are few effective treatments. Fibulin-3 is a protein involved in extracellular matrix (ECM) structural integrity, however its role in the heart is unknown. We have demonstrated, using single cell RNA-seq, that fibulin-3 was highly expressed in quiescent murine cardiac fibroblasts, with expression highest prior to injury and late post-infarct (from ~ day-28 to week-8). In humans, fibulin-3 was upregulated in left ventricular tissue and plasma of heart failure patients. Fibulin-3 knockout (Efemp1−/−) and wildtype mice were subjected to experimental myocardial infarction. Fibulin-3 deletion resulted in significantly higher rate of cardiac rupture days 3–6 post-infarct, indicating a weak and poorly formed scar, with severe ventricular remodelling in surviving mice at day-28 post-infarct. Fibulin-3 knockout mice demonstrated less collagen deposition at day-3 post-infarct, with abnormal collagen fibre-alignment. RNA-seq on day-3 infarct tissue revealed upregulation of ECM degradation and inflammatory genes, but downregulation of ECM assembly/structure/organisation genes in fibulin-3 knockout mice. GSEA pathway analysis showed enrichment of inflammatory pathways and a depletion of ECM organisation pathways. Fibulin-3 originates from cardiac fibroblasts, is upregulated in human heart failure, and is necessary for correct ECM organisation/structural integrity of fibrotic tissue to prevent cardiac rupture post-infarct.
Optimal energy management applying load elasticity integrating renewable resources
Authors: Ragab Mohamed Mustafa , Ibrahim Rania A. , Desouki Hussein , Swief Rania
Published: September 2023

Urban growth aimed at developing smart cities confronts several obstacles, such as difficulties and costs in constructing stations and meeting consumer demands. These are possible to overcome by integrating Renewable Energy Resources (RESs) with the help of demand side management (DSM) for managing generation and loading profiles to minimize electricity bills while accounting for reduction in carbon emissions and the peak to average ratio (PAR) of the load. This study aims to achieve a multi-objective goal of optimizing energy management in smart cities which is accomplished by optimally allocating RESs combined with DSM for creating a flexible load profile under RESs and load uncertainty. A comprehensive study is applied to IEEE 69-bus with different scenarios using Sea-Horse Optimization (SHO) for optimal citing and sizing of the RESs while serving the objectives of minimizing total power losses and reducing PAR. SHO performance is evaluated and compared to other techniques such as Genetic Algorithm (GA), Grey Wolf Optimization (GWO), Whale Optimization (WO), and Zebra Optimization (ZO) algorithms. The results show that combining elastic load shifting with optimal sizing and allocation using SHO achieves a global optimum solution for the highest power loss reduction while using a significantly smaller sized RESs than the counterpart.
Global proteomic identifies multiple cancer-related signaling pathways altered by a gut pathobiont associated with colorectal cancer
Authors: Pasquereau-Kotula Ewa , Nigro Giulia , Dingli Florent , Loew Damarys , Poullet Patrick , Xu Yi , Kopetz Scott , Davis Jennifer , Peduto Lucie , Robbe-Masselot Catherine , Sansonetti Philippe , Trieu-Cuot Patrick , Dramsi Shaynoor
Published: September 2023

In this work, we investigated the oncogenic role of Streptococcus gallolyticus subsp. gallolyticus (SGG), a gut bacterium associated with colorectal cancer (CRC). We showed that SGG UCN34 accelerates colon tumor development in a chemically induced CRC murine model. Full proteome and phosphoproteome analysis of murine colons chronically colonized by SGG UCN34 revealed that 164 proteins and 725 phosphorylation sites were differentially regulated. Ingenuity Pathway Analysis (IPA) indicates a pro-tumoral shift specifically induced by SGG UCN34, as ~ 90% of proteins and phosphoproteins identified were associated with digestive cancer. Comprehensive analysis of the altered phosphoproteins using ROMA software revealed up-regulation of several cancer hallmark pathways such as MAPK, mTOR and integrin/ILK/actin, affecting epithelial and stromal colonic cells. Importantly, an independent analysis of protein arrays of human colon tumors colonized with SGG showed up-regulation of PI3K/Akt/mTOR and MAPK pathways, providing clinical relevance to our findings. To test SGG’s capacity to induce pre-cancerous transformation of the murine colonic epithelium, we grew ex vivo organoids which revealed unusual structures with compact morphology. Taken together, our results demonstrate the oncogenic role of SGG UCN34 in a murine model of CRC associated with activation of multiple cancer-related signaling pathways.
An analytical method informed by clinical imaging data for estimating outlet boundary conditions in computational fluid dynamics analysis of carotid artery blood flow
Authors: Kizhisseri Muhsin , Gharaie Saleh , Schluter Jorg
Published: September 2023

Stroke occur mainly due to arterial thrombosis and rupture of cerebral blood vessels. Previous studies showed that blood flow-induced wall shear stress is an essential bio marker for estimating atherogenesis. It is a common practice to use computational fluid dynamics (CFD) simulations to calculate wall shear stress and to quantify blood flow. Reliability of predicted CFD results greatly depends on the accuracy of applied boundary conditions. Previously, the boundary conditions were estimated by varying values so that they matched the clinical data. It is applicable upon the availability of clinical data. Meanwhile, in most cases all that can be accessed are arterial geometry and inflow rate. Consequently, there is a need to devise a tool to estimate boundary values such as resistance and compliance of arteries. This study proposes an analytical framework to estimate the boundary conditions for a carotid artery based on the geometries of the downstream arteries available from clinical images.
Erythropoietin mitigated thioacetamide-induced renal injury via JAK2/STAT5 and AMPK pathway
Authors: Elbaset Marawan A. , Mohamed Bassim M. S. A. , Gad Shaimaa A. , Afifi Sherif M. , Esatbeyoglu Tuba , Abdelrahman Sahar S. , Fayed Hany M.
Published: September 2023

The kidney flushes out toxic substances and metabolic waste products, and homeostasis is maintained owing to the kidney efforts. Unfortunately, kidney disease is one of the illnesses with a poor prognosis and a high death rate. The current investigation was set out to assess erythropoietin (EPO) potential therapeutic benefits against thioacetamide (TAA)-induced kidney injury in rats. EPO treatment improved kidney functions, ameliorated serum urea, creatinine, and malondialdehyde, increased renal levels of reduced glutathione, and slowed the rise of JAK2, STAT5, AMPK, and their phosphorylated forms induced by TAA. EPO treatment also greatly suppressed JAK2, Phosphatidylinositol 3-kinases, and The Protein Kinase R-like ER Kinase gene expressions and mitigated the histopathological alterations brought on by TAA toxicity. EPO antioxidant and anti-inflammatory properties protected TAA-damaged kidneys. EPO regulates AMPK, JAK2/STAT5, and pro-inflammatory mediator synthesis.
Material to system-level benchmarking of CMOS-integrated RRAM with ultra-fast switching for low power on-chip learning
Authors: Abedin Minhaz , Gong Nanbo , Beckmann Karsten , Liehr Maximilian , Saraf Iqbal , Van der Straten Oscar , Ando Takashi , Cady Nathaniel
Published: September 2023

Analog hardware-based training provides a promising solution to developing state-of-the-art power-hungry artificial intelligence models. Non-volatile memory hardware such as resistive random access memory (RRAM) has the potential to provide a low power alternative. The training accuracy of analog hardware depends on RRAM switching properties including the number of discrete conductance states and conductance variability. Furthermore, the overall power consumption of the system inversely correlates with the RRAM devices conductance. To study material dependence of these properties, TaOx and HfOx RRAM devices in one-transistor one-RRAM configuration (1T1R) were fabricated using a custom 65 nm CMOS fabrication process. Analog switching performance was studied with a range of initial forming compliance current (200–500 µA) and analog switching tests with ultra-short pulse width (300 ps) was carried out. We report that by utilizing low current during electroforming and high compliance current during analog switching, a large number of RRAM conductance states can be achieved while maintaining low conductance state. While both TaOx and HfOx could be switched to more than 20 distinct states, TaOx devices exhibited 10× lower conductance, which reduces total power consumption for array-level operations. Furthermore, we adopted an analog, fully in-memory training algorithm for system-level training accuracy benchmarking and showed that implementing TaOx 1T1R cells could yield an accuracy of up to 96.4% compared to 97% for the floating-point arithmetic baseline, while implementing HfOx devices would yield a maximum accuracy of 90.5%. Our experimental work and benchmarking approach paves the path for future materials engineering in analog-AI hardware for a low-power environment training.