bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal single-cell profiling of chemotherapy response in acute myeloid leukemia
Authors: Naldini Matteo Maria , Casirati Gabriele , Barcella Matteo , Rancoita Paola Maria Vittoria , Cosentino Andrea , Caserta Carolina , Pavesi Francesca , Zonari Erika , Desantis Giacomo , Gilioli Diego , Carrabba Matteo Giovanni , Vago Luca , Bernardi Massimo , Di Micco Raffaella , Di Serio Clelia , Merelli Ivan , Volpin Monica , Montini Eugenio , Ciceri Fabio , Gentner Bernhard
Published: March 2023

Acute myeloid leukemia may be characterized by a fraction of leukemia stem cells (LSCs) that sustain disease propagation eventually leading to relapse. Yet, the contribution of LSCs to early therapy resistance and AML regeneration remains controversial. We prospectively identify LSCs in AML patients and xenografts by single-cell RNA sequencing coupled with functional validation by a microRNA-126 reporter enriching for LSCs. Through nucleophosmin 1 (NPM1) mutation calling or chromosomal monosomy detection in single-cell transcriptomes, we discriminate LSCs from regenerating hematopoiesis, and assess their longitudinal response to chemotherapy. Chemotherapy induced a generalized inflammatory and senescence-associated response. Moreover, we observe heterogeneity within progenitor AML cells, some of which proliferate and differentiate with expression of oxidative-phosphorylation (OxPhos) signatures, while others are OxPhos (low) miR-126 (high) and display enforced stemness and quiescence features. miR-126 (high) LSCs are enriched at diagnosis in chemotherapy-refractory AML and at relapse, and their transcriptional signature robustly stratifies patients for survival in large AML cohorts.
Digital nanoreactors to control absolute stoichiometry and spatiotemporal behavior of DNA receptors within lipid bilayers
Authors: Maingi Vishal , Zhang Zhao , Thachuk Chris , Sarraf Namita , Chapman Edwin R. , Rothemund Paul W. K.
Published: March 2023

Interactions between membrane proteins are essential for cell survival but are often poorly understood. Even the biologically functional ratio of components within a multi-subunit membrane complex—the native stoichiometry—is difficult to establish. Here we demonstrate digital nanoreactors that can control interactions between lipid-bound molecular receptors along three key dimensions: stoichiometric, spatial, and temporal. Each nanoreactor is based on a DNA origami ring, which both templates the synthesis of a liposome and provides tethering sites for DNA-based receptors (modelling membrane proteins). Receptors are released into the liposomal membrane using strand displacement and a DNA logic gate measures receptor heterodimer formation. High-efficiency tethering of receptors enables the kinetics of receptors in 1:1 and 2:2 absolute stoichiometries to be observed by bulk fluorescence, which in principle is generalizable to any ratio. Similar single-molecule-in-bulk experiments using DNA-linked membrane proteins could determine native stoichiometry and the kinetics of membrane protein interactions for applications ranging from signalling research to drug discovery.
General approach to surface-accessible plasmonic Pickering emulsions for SERS sensing and interfacial catalysis
Authors: Zhang Yingrui , Ye Ziwei , Li Chunchun , Chen Qinglu , Aljuhani Wafaa , Huang Yiming , Xu Xin , Wu Chunfei , Bell Steven E. J. , Xu Yikai
Published: March 2023

Pickering emulsions represent an important class of functional materials with potential applications in sustainability and healthcare. Currently, the synthesis of Pickering emulsions relies heavily on the use of strongly adsorbing molecular modifiers to tune the surface chemistry of the nanoparticle constituents. This approach is inconvenient and potentially a dead-end for many applications since the adsorbed modifiers prevent interactions between the functional nanosurface and its surroundings. Here, we demonstrate a general modifier-free approach to construct Pickering emulsions by using a combination of stabilizer particles, which stabilize the emulsion droplet, and a second population of unmodified functional particles that sit alongside the stabilizers at the interface. Freeing Pickering emulsions from chemical modifiers unlocks their potential across a range of applications including plasmonic sensing and interfacial catalysis that have previously been challenging to achieve. More broadly, this strategy provides an approach to the development of surface-accessible nanomaterials with enhanced and/or additional properties from a wide range of nano-building blocks including organic nanocrystals, carbonaceous materials, metals and oxides.
Structure of the Newcastle Disease Virus L protein in complex with tetrameric phosphoprotein
Authors: Cong Jingyuan , Feng Xiaoying , Kang Huiling , Fu Wangjun , Wang Lei , Wang Chenlong , Li Xuemei , Chen Yutao , Rao Zihe
Published: March 2023

Newcastle disease virus (NDV) belongs to Paramyxoviridae, which contains lethal human and animal pathogens. NDV RNA genome is replicated and transcribed by a multifunctional 250 kDa RNA-dependent RNA polymerase (L protein). To date, high-resolution structure of NDV L protein complexed with P protein remains to be elucidated, limiting our understanding of the molecular mechanisms of Paramyxoviridae replication/transcription. Here, we used cryo-EM and enzymatic assays to investigate the structure-function relationship of L-P complex. We found that C-terminal of CD-MTase-CTD module of the atomic-resolution L-P complex conformationally rearranges, and the priming/intrusion loops are likely in RNA elongation conformations different from previous structures. The P protein adopts a unique tetrameric organization and interacts with L protein. Our findings indicate that NDV L-P complex represents elongation state distinct from previous structures. Our work greatly advances the understanding of Paramyxoviridae RNA synthesis, revealing how initiation/elongation alternates, providing clues for identifying therapeutic targets against Paramyxoviridae.
Land-use diversity predicts regional bird taxonomic and functional richness worldwide
Authors: Martínez-Núñez Carlos , Martínez-Prentice Ricardo , García-Navas Vicente
Published: March 2023

Unveiling the processes that shape biodiversity patterns is a cornerstone of ecology. Land-use diversity (i.e., the variety of land-use categories within an area) is often considered an important environmental factor that promotes species richness at landscape and regional scales by increasing beta-diversity. Still, the role of land-use diversity in structuring global taxonomic and functional richness is unknown. Here, we examine the hypothesis that regional species taxonomic and functional richness is explained by global patterns of land-use diversity by analyzing distribution and trait data for all extant birds. We found strong support for our hypothesis. Land-use diversity predicted bird taxonomic and functional richness in almost all biogeographic realms, even after accounting for the effect of net primary productivity (i.e., a proxy of resource availability and habitat heterogeneity). This link was particularly consistent with functional richness compared to taxonomic richness. In the Palearctic and Afrotropic realms, a saturation effect was evident, suggesting a non-linear relationship between land-use diversity and biodiversity. Our results reveal that land-use diversity is a key environmental factor associated with several facets of bird regional diversity, widening our understanding of key large-scale predictors of biodiversity patterns. These results can contribute to policies aimed at minimizing regional biodiversity loss.
Molecular fingerprints resolve affinities of Rhynie chert organic fossils
Authors: Loron C. C. , Rodriguez Dzul E. , Orr P. J. , Gromov A. V. , Fraser N. C. , McMahon S.
Published: March 2023

The affinities of extinct organisms are often difficult to resolve using morphological data alone. Chemical analysis of carbonaceous specimens can complement traditional approaches, but the search for taxon-specific signals in ancient, thermally altered organic matter is challenging and controversial, partly because suitable positive controls are lacking. Here, we show that non-destructive Fourier Transform Infrared Spectroscopy (FTIR) resolves in-situ molecular fingerprints in the famous 407 Ma Rhynie chert fossil assemblage of Aberdeenshire, Scotland, an important early terrestrial Lagerstätte. Remarkably, unsupervised clustering methods (principal components analysis and K-mean) separate the fossil spectra naturally into eukaryotes and prokaryotes (cyanobacteria). Additional multivariate statistics and machine-learning approaches also differentiate prokaryotes from eukaryotes, and discriminate eukaryotic tissue types, despite the overwhelming influence of silica. We find that these methods can clarify the affinities of morphologically ambiguous taxa; in the Rhynie chert for example, we show that the problematic “nematophytes” have a plant-like composition. Overall, we demonstrate that the famously exquisite preservation of cells, tissues and organisms in the Rhynie chert accompanies similarly impressive preservation of molecular information. These results provide a compelling positive control that validates the use of infrared spectroscopy to investigate the affinity of organic fossils in chert.
Trio-pharmacophore DNA-encoded chemical library for simultaneous selection of fragments and linkers
Authors: Cui Meiying , Nguyen Dzung , Gaillez Michelle Patino , Heiden Stephan , Lin Weilin , Thompson Michael , Reddavide Francesco V. , Chen Qinchang , Zhang Yixin
Published: March 2023

The split-and-pool method has been widely used to synthesize chemical libraries of a large size for early drug discovery, albeit without the possibility of meaningful quality control. In contrast, a self-assembled DNA-encoded chemical library (DEL) allows us to construct an m x n-member library by mixing an m-member and an n-member pre-purified sub-library. Herein, we report a trio-pharmacophore DEL (T-DEL) of m x l x n members through assembling three pre-purified and validated sub-libraries. The middle sub-library is synthesized using DNA-templated synthesis with different reaction mechanisms and designed as a linkage connecting the fragments displayed on the flanking two sub-libraries. Despite assembling three fragments, the resulting compounds do not exceed the up-to-date standard of molecular weight regarding drug-likeness. We demonstrate the utility of T-DEL in linker optimization for known binding fragments against trypsin and carbonic anhydrase II and by de novo selections against matrix metalloprotease-2 and −9.
Assessing coupling interactions in a safe and just operating space for regional sustainability
Authors: Han Dongni , Yu Deyong , Qiu Jiangxiao
Published: March 2023

Human activities affect the Earth System with an unprecedented magnitude, causing undesirable irreversible degradation. The United Nation’s Sustainable Development Goals (SDGs) provide an integrated global action plan for sustainable development. However, it remains a great challenge to develop actionable strategies to achieve regional sustainability within social-environmental constraints. Here we proposed a framework, integrating safe and just operating space (SJOS) with SDGs, to assess regional sustainability and interactions between environmental performance and human well-being across scales. Despite China has not fully achieved sustainable development from 2000 to 2018, most provinces have shown significant improvements. Our analyses further delineated four development patterns (i.e., coupled and developed, coupled and underdeveloped, uncoupled and underdeveloped, and coupled and underdeveloped), and developed targeted strategies and pathways for each pattern to transition towards sustainability. Our operationalizable framework is broadly applicable to other regions or nations to actualize sustainable development.
Laser-induced topological spin switching in a 2D van der Waals magnet
Authors: Khela Maya , Da̧browski Maciej , Khan Safe , Keatley Paul S. , Verzhbitskiy Ivan , Eda Goki , Hicken Robert J. , Kurebayashi Hidekazu , Santos Elton J. G.
Published: March 2023

Two-dimensional (2D) van der Waals (vdW) magnets represent one of the most promising horizons for energy-efficient spintronic applications because their broad range of electronic, magnetic and topological properties. However, little is known about the interplay between light and spin properties in vdW layers. Here we show that ultrafast laser excitation can not only generate different type of spin textures in CrGeTe3 vdW magnets but also induce a reversible transformation between them in a topological toggle switch mechanism. Our atomistic spin dynamics simulations and wide-field Kerr microscopy measurements show that different textures can be generated via high-intense laser pulses within the picosecond regime. The phase transformation between the different topological spin textures is obtained as additional laser pulses are applied to the system where the polarisation and final state of the spins can be controlled by external magnetic fields. Our results indicate laser-driven spin textures on 2D magnets as a pathway towards reconfigurable topological architectures at the atomistic level.
Clinical outcome and biomarker assessments of a multi-centre phase II trial assessing niraparib with or without dostarlimab in recurrent endometrial carcinoma
Authors: Madariaga Ainhoa , Garg Swati , Tchrakian Nairi , Dhani Neesha C. , Jimenez Waldo , Welch Stephen , MacKay Helen , Ethier Josee-Lyne , Gilbert Lucy , Li Xuan , Rodriguez Angela , Chan Lucy , Bowering Valerie , Clarke Blaise , Zhang Tong , King Ian , Downs Gregory , Stockley Tracy , Wang Lisa , Udagani Smitha , Oza Amit M. , Lheureux Stephanie
Published: March 2023

This multi-centre, non-randomized, open-label, phase II trial (NCT03016338), assessed niraparib monotherapy (cohort 1, C1), or niraparib and dostarlimab (cohort 2, C2) in patients with recurrent serous or endometrioid endometrial carcinoma. The primary endpoint was clinical benefit rate (CBR), with ≥5/22 overall considered of interest. Secondary outcomes were safety, objective response rate (ORR), duration of response, progression free survival and overall survival. Translational research was an exploratory outcome. Potential biomarkers were evaluated in archival tissue by immunohistochemistry and next generation sequencing panel. In C1, 25 patients were enrolled, and CBR was 20% (95% CI: 9–39) with median clinical benefit duration of 5.3 months. The ORR was 4% (95% CI: 0–20). In C2, 22 patients were enrolled, and the CBR was 31.8% (95% CI: 16–53) with median clinical benefit duration of 6.8 months. The ORR was 14% (95% CI: 3–35). No new safety signals were detected. No significant association was detected between clinical benefit and IHC markers (PTEN, p53, MMR, PD-L1), or molecular profiling (PTEN, TP53, homologous recombination repair genes). In conclusion, niraparib monotherapy did not meet the efficacy threshold. Niraparib in combination with dostarlimab showed modest activity.
Inhibition of lysyl oxidases synergizes with 5-azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies
Authors: Xu Qingyu , Streuer Alexander , Jann Johann-Christoph , Altrock Eva , Schmitt Nanni , Flach Johanna , Sens-Albert Carla , Rapp Felicitas , Wolf Julia , Nowak Verena , Weimer Nadine , Obländer Julia , Palme Iris , Kuzina Mariia , Jawhar Ahmed , Darwich Ali , Weis Cleo-Aron , Marx Alexander , Wuchter Patrick , Costina Victor , Jäger Evelyn , Sperk Elena , Neumaier Michael , Fabarius Alice , Metzgeroth Georgia , Nolte Florian , Steiner Laurenz , Levkin Pavel A. , Jawhar Mohamad , Hofmann Wolf-Karsten , Riabov Vladimir , Nowak Daniel
Published: March 2023

Limited response rates and frequent relapses during standard of care with hypomethylating agents in myelodysplastic neoplasms (MN) require urgent improvement of this treatment indication. Here, by combining 5-azacytidine (5-AZA) with the pan-lysyl oxidase inhibitor PXS-5505, we demonstrate superior restoration of erythroid differentiation in hematopoietic stem and progenitor cells (HSPCs) of MN patients in 20/31 cases (65%) versus 9/31 cases (29%) treated with 5-AZA alone. This effect requires direct contact of HSPCs with bone marrow stroma components and is dependent on integrin signaling. We further confirm these results in vivo using a bone marrow niche-dependent MN xenograft model in female NSG mice, in which we additionally demonstrate an enforced reduction of dominant clones as well as significant attenuation of disease expansion and normalization of spleen sizes. Overall, these results lay out a strong pre-clinical rationale for efficacy of combination treatment of 5-AZA with PXS-5505 especially for anemic MN.
Optimizing transcranial magnetic stimulation for spaceflight applications
Authors: Romanella S. M. , Mencarelli L. , Seyedmadani K. , Jillings S. , Tomilovskaya E. , Rukavishnikov I. , Sprugnoli G. , Rossi S. , Wuyts F. L. , Santarnecchi E.
Published: March 2023

As space agencies aim to reach and build installations on Mars, the crews will face longer exposure to extreme environments that may compromise their health and performance. Transcranial magnetic stimulation (TMS) is a painless non-invasive brain stimulation technique that could support space exploration in multiple ways. However, changes in brain morphology previously observed after long-term space missions may impact the efficacy of this intervention. We investigated how to optimize TMS for spaceflight-associated brain changes. Magnetic resonance imaging T1-weighted scans were collected from 15 Roscosmos cosmonauts and 14 non-flyer participants before, after 6 months on the International Space Station, and at a 7-month follow-up. Using biophysical modeling, we show that TMS generates different modeled responses in specific brain regions after spaceflight in cosmonauts compared to the control group. Differences are related to spaceflight-induced structural brain changes, such as those impacting cerebrospinal fluid volume and distribution. We suggest solutions to individualize TMS to enhance its efficacy and precision for potential applications in long-duration space missions.
External to internal cranial perfusion shifts during simulated weightlessness: Results from a randomized cross-over trial
Authors: Boschert Alessa L. , Gauger Peter , Bach Anja , Gerlach Darius , Johannes Bernd , Jordan Jens , Li Zhili , Elmenhorst David , Bauer Andreas , Marshall-Goebel Karina , Tank Jens , Zange Jochen , Rittweger Jörn
Published: March 2023

The exact pathophysiology of the spaceflight-associated neuro-ocular syndrome (SANS) has so far not been completely elucidated. In this study we assessed the effect of acute head-down tilt position on the mean flow of the intra- and extracranial vessels. Our results suggest a shift from the external to the internal system that might play an important role in the pathomechanism of SANS.
Integrated assessment of the impact of land use changes on groundwater recharge and groundwater level in the Drava floodplain, Hungary
Authors: Salem Ali , Abduljaleel Yasir , Dezső József , Lóczy Dénes
Published: March 2023

Land-use/land-cover (LULC) change is considered a key human factor influencing groundwater recharge in floodplains. Without accurate estimations, the impact of LULC change on water balance components may be either significantly understated or exaggerated. This paper assesses the impacts of LULC changes from 1990 to 2018 on water balance components and groundwater levels of the Drava floodplain, Hungary, where human interference has led to a critical environmental situation. In this study, a spatially-distributed water balance model (WetSpass-M), and a groundwater flow model (MODFLOW-NWT) were integrated to assess the impacts of LULC changes. The moderate expansion of built-up areas increased surface runoff, while the afforestation of arable land and meadows and the overgrowth of bare mudflats with willow shrubs increased evapotranspiration. As a consequence, total annual groundwater recharge decreased by 5.3 × 107 m3 in the floodplain with an average of 335 mm year−1 and 317 mm year−1 in 2012 and 2018, respectively. Moreover, an average groundwater level decline by 0.1 m is observed in the same period. Declined groundwater recharge, increased runoff, and evapotranspiration exerted a negative effect on water resources in the Drava basin. The approach tested in this paper allows temporal and spatial estimation of hydrological components under the changes of LULC, providing quantitative information for decision-makers and stakeholders to implement efficient and sustainable management of water resources in the Drava floodplain. The provided integrated model is also applicable to regionally.
AI co-pilot: content-based image retrieval for the reading of rare diseases in chest CT
Authors: Haubold Johannes , Zeng Ke , Farhand Sepehr , Stalke Sarah , Steinberg Hannah , Bos Denise , Meetschen Mathias , Kureishi Anisa , Zensen Sebastian , Goeser Tim , Maier Sandra , Forsting Michael , Nensa Felix
Published: March 2023

The aim of the study was to evaluate the impact of the newly developed Similar patient search (SPS) Web Service, which supports reading complex lung diseases in computed tomography (CT), on the diagnostic accuracy of residents. SPS is an image-based search engine for pre-diagnosed cases along with related clinical reference content (https://eref.thieme.de). The reference database was constructed using 13,658 annotated regions of interest (ROIs) from 621 patients, comprising 69 lung diseases. For validation, 50 CT scans were evaluated by five radiology residents without SPS, and three months later with SPS. The residents could give a maximum of three diagnoses per case. A maximum of 3 points was achieved if the correct diagnosis without any additional diagnoses was provided. The residents achieved an average score of 17.6 ± 5.0 points without SPS. By using SPS, the residents increased their score by 81.8% to 32.0 ± 9.5 points. The improvement of the score per case was highly significant (p = 0.0001). The residents required an average of 205.9 ± 350.6 s per case (21.9% increase) when SPS was used. However, in the second half of the cases, after the residents became more familiar with SPS, this increase dropped to 7%. Residents’ average score in reading complex chest CT scans improved by 81.8% when the AI-driven SPS with integrated clinical reference content was used. The increase in time per case due to the use of the SPS was minimal.
Cyber-physical oil spill monitoring and detection for offshore petroleum risk management service
Authors: Wang Yuewei , Chen Xiaodao , Wang Lizhe
Published: March 2023

Petroleum industry has started to embrace the advanced petroleum cyber-physical system (CPS) technologies. Offshore petroleum CPS is particularly hard to build, mainly due to the difficulty in detecting and preventing offshore oil leaking. During the oil exploration and transportation process, the remote multi-sensing technology is typically employed for emerging service. It can be utilized for leak detection by enabling the underwater modeling of an offshore petroleum CPS. However, such a technology suffers from insufficient remote sensing resources and expensive computational overhead. In this work, a cross-entropy based leak detection technique is proposed to detect the oil leak, which facilitates the understanding of the oil leak induced marine pollution. Furthermore, a hierarchical parallel approach is proposed on the super computer Tianhe-2 to improve the efficiency of the proposed leak detection technique. Experimental results on Penglai oil spill events demonstrate that the proposed method can effectively identify the sources of oil spilling with accuracy up to $$100\%$$

100
%

.
Seroprevalence and socioeconomic impact of the first SARS-CoV-2 infection wave in a small town in Navarre, Spain
Authors: Ribes Marta , Montañà Júlia , Vidal Marta , Aguilar Ruth , Nicolás Patricia , Alfonso Uxue , Rodrigo Natalia , Carolis Carlo , Dobaño Carlota , Moncunill Gemma , Chaccour Carlos
Published: March 2023

The characterization of the antibody response to SARS-CoV-2 and its determinants are key for the understanding of COVID-19. The identification of vulnerable populations to the infection and to its socioeconomic impact is indispensable for inclusive policies. We conducted an age-stratified cross-sectional community-based seroprevalence survey between June 12th and 19th 2020—during the easing of lockdown—in Cizur, Spain. We quantified IgG, IgM and IgA levels against SARS-CoV-2 spike and its receptor-binding domain in a sample of 728 randomly selected, voluntarily registered inhabitants. We estimated a 7.9% seroprevalence in the general population, with the lowest seroprevalence among children under ten (n = 3/142, 2.1%) and the highest among adolescents (11–20 years old, n = 18/159, 11.3%). We found a heterogeneous immune-response profile across participants regarding isotype/antigen-specific seropositivity, although levels generally correlated. Those with technical education level were the most financially affected. Fifty-five percent had visited a supermarket and 43% a sanitary centre since mid-February 2020. When comparing by gender, men had left the household more frequently. In conclusion, few days after strict lockdown, the burden of SARS-CoV-2 infection was the lowest in children under 10. The findings also suggest that a wider isotype-antigen panel confers higher sensitivity. Finally, the economic impact biases should be considered when designing public health measures.
Neural correlates of gait adaptation in younger and older adults
Authors: Fettrow Tyler , Hupfeld Kathleen , Hass Chris , Pasternak Ofer , Seidler Rachael
Published: March 2023

Mobility decline is a major concern for older adults. A key component of maintaining mobility with advancing age is the ability to learn and adapt to the environment. The split-belt treadmill paradigm is an experimental protocol that tests the ability to adapt to a dynamic environment. Here we examined the magnetic resonance imaging (MRI) derived structural neural correlates of individual differences in adaptation to split-belt walking for younger and older adults. We have previously shown that younger adults adopt an asymmetric walking pattern during split-belt walking, particularly in the medial-lateral (ML) direction, but older adults do not. We collected T$$_1$$

1

-weighted and diffusion-weighted MRI scans to quantify brain morphological characteristics (i.e. in the gray matter and white matter) on these same participants. We investigated two distinct questions: (1) Are there structural brain metrics that are associated with the ability to adopt asymmetry during split-belt walking; and (2) Are there different brain-behavior relationships for younger and older adults? Given the growing evidence that indicates the brain has a critical role in the maintenance of gait and balance, we hypothesized that brain areas commonly associated with locomotion (i.e. basal ganglia, sensorimotor cortex, cerebellum) would be associated with ML asymmetry and that older adults would show more associations between split-belt walking and prefrontal brain areas. We identified multiple brain-behavior associations. More gray matter volume in the superior frontal gyrus and cerebellar lobules VIIB and VIII, more sulcal depth in the insula, more gyrification in the pre/post central gyri, and more fractional anisotropy in the corticospinal tract and inferior longitudinal fasciculus corresponded to more gait asymmetry. These associations did not differ between younger and older adults. This work progresses our understanding of how brain structure is associated with balance during walking, particularly during adaptation.
Revealing the hidden signature of fault slip history in the morphology of degrading scarps
Authors: Holtmann Regina , Cattin Rodolphe , Simoes Martine , Steer Philippe
Published: March 2023

Active faults accommodate tectonic plate motion through different slip modes, some stable and aseismic, others characterized by the occurrence of large earthquakes after long periods of inactivity. Although the slip mode estimation is of primary importance to improve seismic hazard assessment, this parameter inferred today from geodetic observations needs to be better constrained over many seismic cycles. From an analytical formulation developed for analyzing fault scarp formation and degradation in loosely consolidated material, we show that the final topographic shape generated by one earthquake rupture or by creep (i.e., continuous slip) deviates by as much as 10–20%, despite a similar cumulated slip and a constant diffusion coefficient. This result opens up the theoretical possibility of inverting, not only the cumulated slip or averaged slip rate, but also the number of earthquakes and their sizes from scarp morphologies. This approach is all the more relevant as the number of rupture events is limited. Estimating the fault slip history beyond a dozen earthquakes becomes very difficult as the effect of erosion on scarp morphology prevails. Our modeling also highlights the importance of trade-offs between fault slip history and diffusive processes. An identical topographic profile can be obtained either with a stable fault creep associated with rapid erosion, or a single earthquake rupture followed by slow erosion. These inferences, derived from the simplest possible diffusion model, are likely to be even more pronounced in nature.
Risk and prognosis of secondary esophagus cancer after radiotherapy for breast cancer
Authors: Sun Qianhui , Chen Yunru , Li Tingting , Ni Baoyi , Zhu Xiaoyu , Xu Bowen , Li Jie
Published: March 2023

Although radiation therapy (RT) improves locoregional recurrence and overall survival in breast cancer (BC), it is not yet clear whether RT affects the risk of patients with BC developing second esophageal cancer (SEC). We enrolled patients with BC as their first primary cancer from nine registries in the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2018. Fine–Gray competing risk regressions were assessed to determine the cumulative incidence of SECs. The standardized incidence ratio (SIR) was used to compare the prevalence of SECs among BC survivors to that in the general population of the US. Kaplan–Meier survival analysis was applied to calculate the 10-year overall survival (OS) and cancer-specific survival (CSS) rates for SEC patients. Among the 523,502 BC patients considered herein, 255,135 were treated with surgery and RT, while 268,367 had surgery without radiotherapy. In a competing risk regression analysis, receiving RT was associated with a higher risk of developing an SEC in BC patients than that in the patients not receiving RT (P = .003). Compared to the general population of the US, the BC patients receiving RT showed a greater incidence of SEC (SIR, 1.52; 95% confidence interval [CI], 1.34–1.71, P < .05). The 10-year OS and CSS rates of SEC patients after RT were comparable to those of the SEC patients after no RT. Radiotherapy was related to an increased risk of developing SECs in patients with BC. Survival outcomes for patients who developed SEC after RT were similar to those after no RT.
Smoking and passive smoking increases mortality through mediation effect of cadmium exposure in the United States
Authors: Kim Joon , Song Hangyul , Lee Junghoon , Kim Yoon Jung , Chung Hye Soo , Yu Jae Myung , Jang Gyuho , Park Raekil , Chung Wankyo , Oh Chang-Myung , Moon Shinje
Published: March 2023

Cigarette smoking is one of the leading causes of preventable and premature death worldwide. Even worse, many people are generally exposed to passive smoking, which leads to several respiratory diseases and related mortalities. Considering, more than 7000 compounds are included in cigarettes, their combustion results intoxicants that have deleterious effects on health. However, there is a lack of research analyzing the effects of smoking and passive smoking on all-cause and disease-specific mortality through its chemical compounds including heavy metals. Thus, this study aimed to evaluate the effect of smoking and passive smoking on all-cause and disease-specific mortality mediated by cadmium, one of the representative smoking-related heavy metals using data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 in the United States. We found that current smoking and passive smoking was related to increased risk of all-cause, CVD-related, and cancer-related mortality. Notably, passive smoking showed a synergistic effect with smoking status on the risk of mortality. In particular, current smokers with passive smoking had the highest risk of all-cause and disease-specific deaths. In addition, the accumulation of cadmium in the blood due to smoking and passive smoking mediates the increased risk of all-cause mortality. Further studies are needed to monitor and treat cadmium toxicity to improve smoking-related mortality rates.
The effect of herbicides on morphological features of pollen grains in Prunus serotina Ehrh. in the context of elimination of this invasive species from European forests
Authors: Wrońska–Pilarek Dorota , Maciejewska–Rutkowska Irmina , Lechowicz Kacper , Bocianowski Jan , Hauke–Kowalska Maria , Baranowska Marlena , Korzeniewicz Robert
Published: March 2023

Prunus serotinaEhrh. is an alien invasive neophyte widespread in European forests. So far, no effective methods of its elimination have been developed. For this reason, the aim of our study was to determine how herbicides affect the morphological characteristics of pollen grains. This knowledge may be crucial to control this invasive species. The current study was carried out in a research area of 2.7 ha located in the Zielonka Forest near Poznań, Poland (N 52°31′58.016″, E 17°05′55.588″). We tested morphological differences among ten features ofP. serotinapollen, based on the samples collected from 15 control trees compared to the 50 trees treated with five different herbicides. In total 1950 pollen grains were measured. We confirmed the adopted hypotheses of long-term herbicide influence onP. serotinapollen. Pollen grains from the control trees had a longer equatorial axis, were more elongated in shape and had the largest range of exine thickness compared to the pollen from the herbicide-treated samples. Exine thickness in the control sample was on average 0.74 µm, ranging from 0.42 to 1.19 µm. The average values and the ranges of this trait in the samples treated with herbicides were larger (e.g. average exine thickness was from 0.90 to 0.95 µm). There were differences in the P/E ranges of variability between the control and herbicide-treated samples. In the control sample the P/E ratio was 1.32–2.04 and elongated forms of pollen shapes prevailed, while in the herbicide-treated samples it ranged from 1.03 to 1.47. The share of deformed pollen grains in the herbicide-treated samples was lower than expected, ranging from 8.7 to 25.3%, while in the control samples it was 6%. Logo and Mustang turned out to be the most effective among the herbicides used in the described research. The two used application methods were found to have an effect on pollen quality.
Detached, wetted strawberries take up substantial water in the calyx region
Authors: Hurtado Grecia , Knoche Moritz
Published: March 2023

In strawberry, surface disorders like ‘water soaking’, ‘cracking’ and ‘shrivel’ impair fruit quality of this high value crop. Water movement through the fruit surface is implicated a role in these disorders. The objective was to identify the pathways of water uptake and water loss (transpiration) and to identify factors affecting these flows. Water movement was quantified gravimetrically in detached fruit. Cumulative transpiration and uptake increased linearly with time. During ripening, fruit osmotic potential and water potential became slightly more negative. Rates of transpiration and water uptake and their corresponding permeances were constant during early ripening but increased as the fruit turned red. The permeance for osmotic water uptake was more than 10-times that for transpiration. Sealing selected regions of the fruit surface with silicone rubber allowed identification of the petal and staminal abscission zones in the calyx region and cuticular microcracks of the calyx region and receptacle as high flux pathways particularly for water uptake (osmotic). These results were confirmed by acridine orange infiltration and fluorescence microscopy. Increasing the relative humidity (RH) decreased the rate of transpiration, while increasing temperature increased both transpiration and water uptake. There was no effect of storing fruit (2 °C, ~ 80% RH) for up to 10 days. Our results identify petal and staminal abscission zones and cuticular microcracks as high flux pathways for water uptake.
Enhancing reading accuracy through visual search training using symbols
Authors: Vialatte Audrey , Aguera Pierre-Emmanuel , Bedoin Nathalie , Witko Agnès , Chabanat Eric , Pisella Laure
Published: March 2023

Children with reading disorders present with inaccurate and/or delayed printed word identification. Regarding visual-attentional processing, printed words are letter strings, and each letter is a symbol made of separable features. Simultaneous processing of separable features has been evidenced to be specifically impaired in visual search tasks using symbols in poor readers as well as in a patient with superior parietal lobules (SPL) lesion. Additionally, activation in the SPL has been shown to be abnormally low in dyslexic readers displaying a reduced span of letter strings processing. This deficit has been assumed to impair visual-attentional sampling of printed words. An experiment conducted with 21 dyslexic children tested the hypothesis that a training program based on visual symbol search may stimulate the SPL, leading to a potential benefit transferred to reading performance. We designed the VisioCogLetters serious game and introduced it at random for one month (10 min every day) between four monthly reading sessions. No training was provided between the other (control) reading sessions. Reading accuracy increased without any speed-accuracy trade-off specifically in the session after training. Moreover, the percentage of improvement correlated with the individual time spent at home on training. These results show that improved visual search skills on symbols can translate into enhanced reading performance, and pave a new avenue for future rehabilitation tools.
Cleaner production of essential oils from Indian basil, lemongrass and coriander leaves using ultrasonic and ohmic heating pre-treatment systems
Authors: Kumar Rajeev , Chopra Sangeeta , Choudhary Anil K. , Mani Indra , Yadav Shruti , Barua Sukanya
Published: March 2023

Indian basil (Ocimum basillicum), lemongrass (Cymbopogon flexuosus) and coriander (Coriandrum sativum) leaves are a good source of aromatic oils; however, their extraction volume is low. Hence, two pre-treatment systems (ohmic-heating and ultrasonic) were devised for extraction of essential oils (EO) from the leaves of these three plant spp., which consequently enhanced the EO yield and saved the time and energy. First of all, an experimental set-up was developed for ohmic-heating pre-treatment which was subjected to the optimization of electric conductivity of lemongrass and coriander leaves at 26.25 V/cm and for Indian basil at 22.5 V/cm voltage gradient. An Experimental setup was also developed for ohmic heating-assisted hydro-distillation (OHD). Finally, conventional Clevenger hydro-distillation (CHD), OHD, ultrasonic-assisted conventional hydro-distillation (UACHD) and ultrasonic-assisted ohmic-heating hydro-distillation (UAOHD) methods were evaluated for their effectiveness in the extraction of the EOs. The OHD took 3.5 h time with 410 W power consumption compared to 5 h time and 500 W power consumption in CHD of sleeted leaves. Likewise, a saving of ~ 86% in time and 74% in energy consumption was observed for EO extraction through UAOHD over CHD. Quantity of EOs extracted from all three aromatic plant spp. leaves followed the trend of UAOHD > UACHD > OHD > CHD methods, respectively. Overall, ultrasonic pre-treatment coupled with ohmic-heating assisted hydro-distillation (UAOHD) proved as an innovative and effective clean EO extraction technology which took shorter extraction time and lesser energy consumption with better EO yield over the UACHD, OHD and CHD methods from the leaves of Indian basil, lemongrass and coriander.
Spectrum of BRCA1 interacting helicase 1 aberrations and potential prognostic and therapeutic implication: a pan cancer analysis
Authors: Long Guo , Hu Kuan , Zhang Xiaofang , Zhou Ledu , Li Juanni
Published: March 2023

BRCA1 interacting helicase 1 (BRIP1) alteration was crucial in tumors and it was a potential therapeutic target in ovarian serous cystadenocarcinoma (OV). Although a small number of studies had focused on BRIP1, an extensive study of BRIP1 genetic mutation and its clinical application in different cancer types had not been analyzed. In the current study, we analyzed BRIP1 abnormal expression, methylation, mutation, and their clinical application via several extensive datasets, which covered over 10,000 tumor samples across more than 30 cancer types. The total mutation rate of BRIP1 was rare in pan cancer. Its alteration frequency, oncogenic effects, mutation, and therapeutic implications were different in each cancer. 242 BRIP1 mutations were found across 32 cancer types. UCEC had the highest alteration (mutation and CNV) frequency. In addition, BRIP1 was a crucial oncogenic factor in OV and BRCA. BRIP1 mutation in PRAD was targetable, and FDA had approved a new drug. Moreover, Kaplan–Meier curve analysis showed that BRIP1 expression and genetic aberrations were closely related to patient survival in several cancers, indicating their potential for application as new tumor markers and therapeutic targets. The current study profiled the total BRIP1 mutation spectrum and offered an extensive molecular outlook of BRIP1 in a pan cancer analysis. And it suggested a brand-new perspective for clinical cancer therapy.
The occurrence of pristine and functionalized fullerenes as constituents of airborne aerosols
Authors: dos Santos Fábio N. , Nascimento Madson M. , da Rocha Gisele O. , de Andrade Jailson B.
Published: March 2023

We investigated if pristine and functionalized fullerenes could be actual constituents of fine atmospheric aerosols. Comprehensive profiles of fullerenes from 1 µL extracts were made through matrix laser desorption ionization Time-of-Flight Mass Spectrometry (MALDI-MS) within a few minutes. The ion with m/z 720, corresponding to [C60]−•, was identified as fullerene after 1 µL of α-cyano-4-hydroxycinnamic acid matrix solution was spotted over the dried extracts. The ions with the m/z corresponding to C70, C76, C84, C100, C118, C128, and C130 were also attributed to other fullerene species detected within the samples. The ion m/z 878 was found to be the fullerene derivative diethyl methano[60]fullerene dicarboxylate. Since ions of fragmented fullerene molecules were not detected even at high laser energies, we considered the fullerenes’ occurring as original constituents of real atmospheric particle matrices instead of being formed as artifacts of the laser action on samples. Therefore, this protocol would be helpful in the understanding of the distribution of either pristine or functionalized fullerenes in the environment and their participation in atmospheric chemistry under typical conditions, as well as its application in vitro and in vivo (eco)toxicity studies.
Muscle prestimulation tunes velocity preflex in simulated perturbed hopping
Authors: Izzi Fabio , Mo An , Schmitt Syn , Badri-Spröwitz Alexander , Haeufle Daniel F. B.
Published: March 2023

Muscle fibres possess unique visco-elastic properties, which generate a stabilising zero-delay response to unexpected perturbations. This instantaneous response—termed “preflex”—mitigates neuro-transmission delays, which are hazardous during fast locomotion due to the short stance duration. While the elastic contribution to preflexes has been studied extensively, the function of fibre viscosity due to the force–velocity relation remains unknown. In this study, we present a novel approach to isolate and quantify the preflex force produced by the force–velocity relation in musculo-skeletal computer simulations. We used our approach to analyse the muscle response to ground-level perturbations in simulated vertical hopping. Our analysis focused on the preflex-phase—the first 30 ms after impact—where neuronal delays render a controlled response impossible. We found that muscle force at impact and dissipated energy increase with perturbation height, helping reject the perturbations. However, the muscle fibres reject only 15% of step-down perturbation energy with constant stimulation. An open-loop rising stimulation, observed in locomotion experiments, amplified the regulatory effects of the muscle fibre’s force–velocity relation, resulting in 68% perturbation energy rejection. We conclude that open-loop neuronal tuning of muscle activity around impact allows for adequate feed-forward tuning of muscle fibre viscous capacity, facilitating energy adjustment to unexpected ground-level perturbations.
Targeting Tn-positive tumors with an afucosylated recombinant anti-Tn IgG
Authors: Matsumoto Yasuyuki , Jia Nan , Heimburg-Molinaro Jamie , Cummings Richard D.
Published: March 2023

The aberrant expression of the Tn antigen (CD175) on surface glycoproteins of human carcinomas is associated with tumorigenesis, metastasis, and poor survival. To target this antigen, we developed Remab6, a recombinant, human chimeric anti-Tn-specific monoclonal IgG. However, this antibody lacks antibody-dependent cell cytotoxicity (ADCC) effector activity, due to core fucosylation of its N-glycans. Here we describe the generation of an afucosylated Remab6 (Remab6-AF) in HEK293 cells in which the FX gene is deleted (FXKO). These cells cannot synthesize GDP-fucose through the de novo pathway, and lack fucosylated glycans, although they can incorporate extracellularly-supplied fucose through their intact salvage pathway. Remab6-AF has strong ADCC activity against Tn+ colorectal and breast cancer cell lines in vitro, and is effective in reducing tumor size in an in vivo xenotransplant mouse model. Thus, Remab6-AF should be considered as a potential therapeutic anti-tumor antibody against Tn+ tumors.