bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding Regional Background Ozone by Multiple Methods: A Case Study in the Shandong Region, China, 2018–2020
Authors: Wang F. T. , Zhang K. , Xue J. , Huang L. , Wang Y. J. , Chen H. , Wang S. Y. , Fu J. S. , Li L.
Published: November 2022

Uprising ground‐level ozone (O3) and its regional pollution in Northern China are attracting more attention. Besides local precursor emissions and photochemistry, background ozone and long‐range transport also contribute significantly to O3 concentrations. To quantify the regional background O3 concentrations and their temporal and spatial variations, multiple methods, including the principal component analysis (PCA) and the Texas Commission on Environmental Quality (TCEQ) method, were applied as a case study in Shandong province in Northern China, where serious O3 pollution occurred frequently yet the background contributions have not been well quantified. We used four methods to quantify the regional background O3: Method 1 is PCA analysis with only ambient O3 data as input; Method 2 is PCA analysis considering O3 and meteorological parameters; Method 3 combines multiple linear regression and the traditional PCA method; and Method 4 is based on TCEQ and consists of the lowest MAD8 O3 measured to represent regional background O3 concentrations. Results derived from multiple methods show an overall consistent trend with 2018–2020 averaged regional background O3 (MDA8) of 41.5 ppb, accounting for 79.4% of the total O3 in the region. From 2018 to 2020, the changes in regional MDA8 O3 estimated by Methods 1–4 are −1.8, 0.7, −2.4, and 0.4 ppb, respectively. Clear seasonal variations in the regional background O3 are observed, showing a pattern of summer > spring > autumn > winter. In addition, the regional ozone contribution at coastal cities was larger than that for inland cities with local O3 contribution gradually increasing from coastal areas to inland areas. The 3‐year average sea‐land breeze contribution to summertime O3 in the eastern coastal cities was estimated to be around 2.1%, while the local photochemistry to O3 in the inland cities was about 29.7% during ozone pollution episodes, with maximum contribution estimated up to 55.8%. Overall, our study provides insights into the regional background ozone and local photochemistry in Northern China.
Determining Emplacement Conditions and Vent Locations for Channelized Lava Flows Southwest of Arsia Mons
Authors: Flynn I. T. W. , Crown D. A. , Ramsey M. S.
Published: November 2022

The lava flow field southwest of Arsia Mons, Mars has complex volcanic geomorphology. Overlapping flows make observations of their total lengths and identification of their source vents impossible. Application of flow emplacement models, which rely upon physical parameters such as flow length, using only the exposed flow may produce inaccurate estimates of effusion rate, viscosity, and yield strength. We use an established terrestrial thermorheological model (PyFLOWGO), modified to Mars conditions, to estimate effusion rates, viscosities, yield strengths, and possible vent locations for five Mars flows. Our investigation found a range of effusion rates from 2,500 to 6,750 m3 s−1 (average of ∼4,960 m3 s−1). These results are an order of magnitude higher than terrestrial channelized basaltic flows. Corresponding modeled viscosities and yield strengths ranged from 9.4 × 103 to 6.6 × 105 Pa s (average of 5.5 × 104 Pa s) and 66 to 381 Pa (average of 209 Pa), respectively. A novel secondary application of PyFLOWGO that assumes upslope channel narrowing provided estimates of the entire channel length, which is on average four times longer than the exposed portions. Projecting these lengths upslope shows that four of the five flows may have a common vent location, which shares morphologic similarities to other Tharsis region vents. This modeling approach for partially‐exposed lava flows makes it possible to not only determine eruptive parameters, but also to estimate total channel lengths and thereby identify possible source vents.
Sex differences in preclinical models of hypertension
Authors: Olivera Sol , Graham Delyth
Published: November 2022

Hypertension remains the primary contributor in the development of cardiovascular disease which is rapidly increasing worldwide. High blood pressure affects men and women differently and understanding these sex differences is the ultimate unmet need for researchers in this field. Due to the inherent differences in hypertension prevalence, control and outcomes between men and women, novel research needs to be carried out to tackle these disparities and improve targeted treatment. Animal models of hypertension have provided valuable insights into the sexual dimorphism of blood pressure mechanisms. The availability of genetic and non-genetic hypertensive strains allows the opportunity to study diverse environmental and genetic factors that affect blood pressure, therefore presenting a valuable tool for researchers. Sex differences are present before birth and throughout life, which presents a challenge for the study of disease development in humans, but these complexities can be resolved with the use of in vivo models that display similarities to human disease. The aim of the present review is to provide an overview of the different available animal models of hypertension that present sexual dimorphisms and to discuss their relevance to humans.
Perceived stress as a predictor of eating behavior during the 3-year PREVIEW lifestyle intervention
Authors: Jalo Elli , Konttinen Hanna , Westerterp-Plantenga Margriet , Adam Tanja , Drummen Mathijs , Huttunen-Lenz Maija , Siig Vestentoft Pia , Martinez J. Alfredo , Handjiev Svetoslav , Macdonald Ian , Brand-Miller Jennie , Poppitt Sally , Swindell Nils , Lam Tony , Navas-Carretero Santiago , Handjieva-Darlenska Teodora , Taylor Moira , Muirhead Roslyn , Silvestre Marta P. , Raben Anne , Fogelholm Mikael
Published: November 2022

Background

To better support participants to achieve long-lasting results within interventions aiming for weight loss and maintenance, more information is needed about the maintenance of behavioral changes. Therefore, we examined whether perceived stress predicts the maintenance of changes in eating behavior (flexible and rigid restraint of eating, disinhibition, and hunger).

Methods

The present study was a secondary analysis of the PREVIEW intervention including participants with overweight (BMI ≥ 25 kg/m2) at baseline and high risk of type 2 diabetes (n = 1311). Intervention included a 2-month low-energy diet phase and a 34-month subsequent weight maintenance phase. The first 6 months were considered an active behavior change stage and the remaining 2.5 years were considered a behavior maintenance stage. Eating behavior was measured using the Three Factor Eating Questionnaire and stress using the Perceived Stress Scale. The associations between stress and eating behavior were analyzed using linear mixed effects models for repeated measurements.

Results

Perceived stress measured after the active behavior change stage (at 6 months) did not predict changes in eating behavior during the behavior maintenance stage. However, frequent high stress during this period was associated with greater lapse of improved flexible restraint (p = 0.026). The mean (SD) change in flexible restraint from 6 to 36 months was −1.1 (2.1) in participants with frequent stress and −0.7 (1.8) in participants without frequent stress (Cohen’s ds (95% CI) = 0.24 (0.04–0.43)). Higher perceived stress at 6 months was associated with less flexible restraint and more disinhibition and hunger throughout the behavior maintenance stage (all p < 0.001).

Conclusions

Perceived stress was associated with features of eating behavior that may impair successful weight loss maintenance. Future interventions should investigate, whether incorporating stress reduction techniques results in more effective treatment, particularly for participants experiencing a high stress level.
Cadmium-induced apoptosis of Leydig cells is mediated by excessive mitochondrial fission and inhibition of mitophagy
Authors: Yi Lingna , Shang Xue-Jun , Lv Linglu , Wang Yixiang , Zhang Jingjing , Quan Chao , Shi Yuqin , Liu Yunhao , Zhang Ling
Published: November 2022

Cadmium is one of the environmental and occupational pollutants and its potential adverse effects on human health have given rise to substantial concern. Cadmium causes damage to the male reproductive system via induction of germ-cell apoptosis; however, the underlying mechanism of cadmium-induced reproductive toxicity in Leydig cells remains unclear. In this study, twenty mice were divided randomly into four groups and exposed to CdCl2 at concentrations of 0, 0.5, 1.0 and 2.0 mg/kg/day for four consecutive weeks. Testicular injury, abnormal spermatogenesis and apoptosis of Leydig cells were observed in mice. In order to investigate the mechanism of cadmium-induced apoptosis of Leydig cells, a model of mouse Leydig cell line (i.e. TM3 cells) was subjected to treatment with various concentrations of CdCl2. It was found that mitochondrial function was disrupted by cadmium, which also caused a significant elevation in levels of mitochondrial superoxide and cellular ROS. Furthermore, while cadmium increased the expression of mitochondrial fission proteins (DRP1 and FIS1), it reduced the expression of mitochondrial fusion proteins (OPA1 and MFN1). This led to excessive mitochondrial fission, the release of cytochrome c and apoptosis. Conversely, cadmium-induced accumulation of mitochondrial superoxide was decreased by the inhibition of mitochondrial fission through the use of Mdivi-1 (an inhibitor of DRP1). Mdivi-1 also partially prevented the release of cytochrome c from mitochondria to cytosol and attenuated cell apoptosis. Finally, given the accumulation of LC3II and SQSTM1/p62 and the obstruction of Parkin recruitment into damaged mitochondria in TM3 cells, the autophagosome-lysosome fusion was probably inhibited by cadmium. Overall, these findings suggest that cadmium induces apoptosis of mouse Leydig cells via the induction of excessive mitochondrial fission and inhibition of mitophagy.
ALKBH5-mediated m6A modification of lincRNA LINC02551 enhances the stability of DDX24 to promote hepatocellular carcinoma growth and metastasis
Authors: Zhang Hongwei , Liu Yachong , Wang Wei , Liu Furong , Wang Weijian , Su Chen , Zhu He , Liao Zhibin , Zhang Bixiang , Chen Xiaoping
Published: November 2022

As the most important RNA epigenetic regulation in eukaryotic cells, N6-metheyladenosine (m6A) modification has been demonstrated to play significant roles in cancer progression. However, this modification in long intergenic non-coding RNAs (lincRNAs) and the corresponding functions remain elusive. Here, we showed a lincRNALINC02551was downregulated by AlkB Homolog 5 (ALKBH5) overexpression in a m6A-dependent manner in hepatocellular carcinoma (HCC). Functionally,LINC02551was required for the growth and metastasis of HCC. Mechanistically,LINC02551, a bona fide m6A target of ALKBH5, acted as a molecular adaptor that blocked the combination between DDX24 and a E3 ligase TRIM27 to decrease the ubiquitination and subsequent degradation of DDX24, ultimately facilitating HCC growth and metastasis. Thus, ALKBH5-mediatedLINC02551m6A methylation was required for HCC growth and metastasis.
SMG6 regulates DNA damage and cell survival in Hippo pathway kinase LATS2-inactivated malignant mesothelioma
Authors: Suzuki Koya , Tange Masaki , Yamagishi Ryota , Hanada Hiroyuki , Mukai Satomi , Sato Tatsuhiro , Tanaka Takeshi , Akashi Tomohiro , Kadomatsu Kenji , Maeda Tohru , Miida Takashi , Takeuchi Ichiro , Murakami Hiroshi , Sekido Yoshitaka , Murakami-Tonami Yuko
Published: November 2022

Many genes responsible for Malignant mesothelioma (MM) have been identified as tumor suppressor genes and it is difficult to target these genes directly at a molecular level. We searched for the gene which showed synthetic lethal phenotype with LATS2, one of the MM causative genes and one of the kinases in the Hippo pathway. Here we showed that knockdown of SMG6 results in synthetic lethality in LATS2-inactivated cells. We found that this synthetic lethality required the nuclear translocation of YAP1 and TAZ. Both are downstream factors of the Hippo pathway. We also demonstrated that this synthetic lethality did not require SMG6 in nonsense-mediated mRNA decay (NMD) but in regulating telomerase reverse transcriptase (TERT) activity. In addition, the RNA-dependent DNA polymerase (RdDP) activity of TERT was required for this synthetic lethal phenotype. We confirmed the inhibitory effects of LATS2 and SMG6 on cell proliferation in vivo. The result suggests an interaction between the Hippo and TERT signaling pathways. We also propose that SMG6 and TERT are novel molecular target candidates for LATS2-inactivated cancers such as MM.
Structure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor
Authors: Zhao Li-Hua , Lin Jingyu , Ji Su-Yu , Zhou X. Edward , Mao Chunyou , Shen Dan-Dan , He Xinheng , Xiao Peng , Sun Jinpeng , Melcher Karsten , Zhang Yan , Yu Xiao , Xu H. Eric
Published: November 2022

The ability to couple with multiple G protein subtypes, such as Gs, Gi/o, or Gq/11, by a given G protein-coupled receptor (GPCR) is critical for many physiological processes. Over the past few years, the cryo-EM structures for all 15 members of the medically important class B GPCRs, all in complex with Gs protein, have been determined. However, no structure of class B GPCRs with Gq/11 has been solved to date, limiting our understanding of the precise mechanisms of G protein coupling selectivity. Here we report the structures of corticotropin releasing factor receptor 2 (CRF2R) bound to Urocortin 1 (UCN1), coupled with different classes of heterotrimeric G proteins, G11 and Go. We compare these structures with the structure of CRF2R in complex with Gs to uncover the structural differences that determine the selective coupling of G protein subtypes by CRF2R. These results provide important insights into the structural basis for the ability of CRF2R to couple with multiple G protein subtypes.
Hi-TrAC reveals division of labor of transcription factors in organizing chromatin loops
Authors: Liu Shuai , Cao Yaqiang , Cui Kairong , Tang Qingsong , Zhao Keji
Published: November 2022

The three-dimensional genomic structure plays a critical role in gene expression, cellular differentiation, and pathological conditions. It is pivotal to elucidate fine-scale chromatin architectures, especially interactions of regulatory elements, to understand the temporospatial regulation of gene expression. In this study, we report Hi-TrAC as a proximity ligation-free, robust, and sensitive technique to profile genome-wide chromatin interactions at high-resolution among regulatory elements. Hi-TrAC detects chromatin looping among accessible regions at single nucleosome resolution. With almost half-million identified loops, we reveal a comprehensive interaction network of regulatory elements across the genome. After integrating chromatin binding profiles of transcription factors, we discover that cohesin complex and CTCF are responsible for organizing long-range chromatin loops, related to domain formation; whereas ZNF143 and HCFC1 are involved in structuring short-range chromatin loops between regulatory elements, which directly regulate gene expression. Thus, we introduce a methodology to identify a delicate and comprehensive network of cis-regulatory elements, revealing the complexity and a division of labor of transcription factors in organizing chromatin loops for genome organization and gene expression.
Anisotropic dislocation-domain wall interactions in ferroelectrics
Authors: Zhuo Fangping , Zhou Xiandong , Gao Shuang , Höfling Marion , Dietrich Felix , Groszewicz Pedro B. , Fulanović Lovro , Breckner Patrick , Wohninsland Andreas , Xu Bai-Xiang , Kleebe Hans-Joachim , Tan Xiaoli , Koruza Jurij , Damjanovic Dragan , Rödel Jürgen
Published: November 2022

Dislocations are usually expected to degrade electrical, thermal and optical functionality and to tune mechanical properties of materials. Here, we demonstrate a general framework for the control of dislocation–domain wall interactions in ferroics, employing an imprinted dislocation network. Anisotropic dielectric and electromechanical properties are engineered in barium titanate crystals via well-controlled line-plane relationships, culminating in extraordinary and stable large-signal dielectric permittivity (≈23100) and piezoelectric coefficient (≈2470 pm V–1). In contrast, a related increase in properties utilizing point-plane relation prompts a dramatic cyclic degradation. Observed dielectric and piezoelectric properties are rationalized using transmission electron microscopy and time- and cycle-dependent nuclear magnetic resonance paired with X-ray diffraction. Succinct mechanistic understanding is provided by phase-field simulations and driving force calculations of the described dislocation–domain wall interactions. Our 1D-2D defect approach offers a fertile ground for tailoring functionality in a wide range of functional material systems.
Diffusion MRI anisotropy in the cerebral cortex is determined by unmyelinated tissue features
Authors: Reveley Colin , Ye Frank Q. , Mars Rogier B. , Matrov Denis , Chudasama Yogita , Leopold David A.
Published: November 2022

Diffusion magnetic resonance imaging (dMRI) is commonly used to assess the tissue and cellular substructure of the human brain. In the white matter, myelinated axons are the principal neural elements that shape dMRI through the restriction of water diffusion; however, in the gray matter the relative contributions of myelinated axons and other tissue features to dMRI are poorly understood. Here we investigate the determinants of diffusion in the cerebral cortex. Specifically, we ask whether myelinated axons significantly shape dMRI fractional anisotropy (dMRI-FA), a measure commonly used to characterize tissue properties in humans. We compared ultra-high resolution ex vivo dMRI data from the brain of a marmoset monkey with both myelin- and Nissl-stained histological sections obtained from the same brain after scanning. We found that the dMRI-FA did not match the spatial distribution of myelin in the gray matter. Instead dMRI-FA was more closely related to the anisotropy of stained tissue features, most prominently those revealed by Nissl staining and to a lesser extent those revealed by myelin staining. Our results suggest that unmyelinated neurites such as large caliber apical dendrites are the primary features shaping dMRI measures in the cerebral cortex.
A biomimetic electrostatic assistance for guiding and promoting N-terminal protein chemical modification
Authors: Ollivier Nathalie , Sénéchal Magalie , Desmet Rémi , Snella Benoît , Agouridas Vangelis , Melnyk Oleg
Published: November 2022

The modification of protein electrostatics by phosphorylation is a mechanism used by cells to promote the association of proteins with other biomolecules. In this work, we show that introducing negatively charged phosphoserines in a reactant is a powerful means for directing and accelerating the chemical modification of proteins equipped with oppositely charged arginines. While the extra charged amino acid residues induce no detectable affinity between the reactants, they bring site-selectivity to a reaction that is otherwise devoid of such a property. They also enable rate accelerations of four orders of magnitude in some cases, thereby permitting chemical processes to proceed at the protein level in the low micromolar range, using reactions that are normally too slow to be useful in such dilute conditions.
Anomalous universal conductance as a hallmark of non-locality in a Majorana-hosted superconducting island
Authors: Hao Yiru , Zhang Gu , Liu Donghao , Liu Dong E.
Published: November 2022

The non-local feature of topological states of matter is the key for the topological protection of quantum information and enables robust non-local manipulation in quantum information. Here we propose to manifest the non-local feature of a Majorana-hosted superconducting island by measuring the temperature dependence of Coulomb blockade peak conductance in different regimes. In the low-temperature regime, we discover a coherent double Majorana-assisted teleportation (MT) process, where any independent tunneling process always involves two coherent non-local MTs; and we also find an anomalous universal scaling behavior, i.e., a crossover from a $${[\max (T,eV)]}^{6}$$

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)

]

6

power-law to a $${[\max (T,eV)]}^{3}$$

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(

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]

3

power-law conductance behavior when energy scale increases — in stark contrast to the usual exponential suppression due to certain local transport. In the high-temperature regime, the conductance is instead proportional to the temperature inverse, indicating a non-monotonic temperature-dependence of the conductance. Both the anomalous power law and non-monotonic temperature-dependence of the conductance can be distinguished from the conductance peak in the traditional Coulomb block, and therefore, together serve as a hallmark for the non-local feature in the Majorana-hosted superconducting island.
Stokes meta-hologram toward optical cryptography
Authors: Guo Xuyue , Li Peng , Zhong Jinzhan , Wen Dandan , Wei Bingyan , Liu Sheng , Qi Shuxia , Zhao Jianlin
Published: November 2022

Optical cryptography manifests itself a powerful platform for information security, which involves encrypting secret images into visual patterns. Recently, encryption schemes demonstrated on metasurface platform have revolutionized optical cryptography, as the versatile design concept allows for unrestrained creativity. Despite rapid progresses, most efforts focus on the functionalities of cryptography rather than addressing performance issues, such as deep security, information capacity, and reconstruction quality. Here, we develop an optical encryption scheme by integrating visual cryptography with metasurface-assisted pattern masking, referred to as Stokes meta-hologram. Based on spatially structured polarization pattern masking, Stokes meta-hologram allows multichannel vectorial encryption to mask multiple secret images into unrecognizable visual patterns, and retrieve them following Stokes vector analysis. Further, an asymmetric encryption scheme based on Stokes vector rotation transformation is proposed to settle the inherent problem of the need to share the key in symmetric encryption. Our results show that Stokes meta-hologram can achieve optical cryptography with effectively improved security, and thereby paves a promising pathway toward optical and quantum security, optical communications, and anticounterfeiting.
Ultrasensitive probing of plasmonic hot electron occupancies
Authors: Budai Judit , Pápa Zsuzsanna , Petrik Péter , Dombi Péter
Published: November 2022

Non-thermal and thermal carrier populations in plasmonic systems raised significant interest in contemporary fundamental and applied physics. Although the theoretical description predicts not only the energies but also the location of the generated carriers, the experimental justification of these theories is still lacking. Here, we demonstrate experimentally that upon the optical excitation of surface plasmon polaritons, a non-thermal electron population appears in the topmost domain of the plasmonic film directly coupled to the local fields. The applied all-optical method is based on spectroscopic ellipsometric determination of the dielectric function, allowing us to obtain in-depth information on surface plasmon induced changes of the directly related electron occupancies. The ultrahigh sensitivity of our method allows us to capture the signatures of changes induced by electron-electron scattering processes with ultrafast decay times. These experiments shed light on the build-up of plasmonic hot electron population in nanoscale media.
RNA-binding proteins of KHDRBS and IGF2BP families control the oncogenic activity of MLL-AF4
Authors: Okuda Hiroshi , Miyamoto Ryo , Takahashi Satoshi , Kawamura Takeshi , Ichikawa Juri , Harada Ibuki , Tamura Tomohiko , Yokoyama Akihiko
Published: November 2022

Chromosomal translocation generates the MLL-AF4 fusion gene, which causes acute leukemia of multiple lineages. MLL-AF4 is a strong oncogenic driver that induces leukemia without additional mutations and is the most common cause of pediatric leukemia. However, establishment of a murine disease model via retroviral transduction has been difficult owning to a lack of understanding of its regulatory mechanisms. Here, we show that MLL-AF4 protein is post-transcriptionally regulated by RNA-binding proteins, including those of KHDRBS and IGF2BP families. MLL-AF4 translation is inhibited by ribosomal stalling, which occurs at regulatory sites containing AU-rich sequences recognized by KHDRBSs. Synonymous mutations disrupting the association of KHDRBSs result in proper translation of MLL-AF4 and leukemic transformation. Consequently, the synonymous MLL-AF4 mutant induces leukemia in vivo. Our results reveal that post-transcriptional regulation critically controls the oncogenic activity of MLL-AF4; these findings might be valuable in developing novel therapies via modulation of the activity of RNA-binding proteins.
Autoinducer-2 and bile salts induce c-di-GMP synthesis to repress the T3SS via a T3SS chaperone
Authors: Li Shuyu , Sun Hengxi , Li Jianghan , Zhao Yujiao , Wang Ruiying , Xu Lei , Duan Chongyi , Li Jialin , Wang Zhuo , Liu Qinmeng , Wang Yao , Ouyang Songying , Shen Xihui , Zhang Lei
Published: November 2022

Cyclic di-GMP (c-di-GMP) transduces extracellular stimuli into intracellular responses, coordinating a plethora of important biological processes. Low levels of c-di-GMP are often associated with highly virulent behavior that depends on the type III secretion system (T3SS) effectors encoded, whereas elevated levels of c-di-GMP lead to the repression of T3SSs. However, extracellular signals that modulate c-di-GMP metabolism to control T3SSs and c-di-GMP effectors that relay environmental stimuli to changes in T3SS activity remain largely obscure. Here, we show that the quorum sensing signal autoinducer-2 (AI-2) induces c-di-GMP synthesis via a GAPES1 domain-containing diguanylate cyclase (DGC) YeaJ to repress T3SS-1 gene expression inSalmonella entericaserovar Typhimurium. YeaJ homologs capable of sensing AI-2 are present in many other species belonging toEnterobacterales. We also reveal that taurocholate and taurodeoxycholate bind to the sensory domain of the DGC YedQ to induce intracellular accumulation of c-di-GMP, thus repressing the expression of T3SS-1 genes. Further, we find that c-di-GMP negatively controls the function of T3SSs through binding to the widely conserved CesD/SycD/LcrH family of T3SS chaperones. Our results support a model in which bacteria sense changes in population density and host-derived cues to regulate c-di-GMP synthesis, thereby modulating the activity of T3SSs via a c-di-GMP-responsive T3SS chaperone.
Granular piston-probing in microgravity: powder compression, from densification to jamming
Authors: D’Angelo Olfa , Horb Anabelle , Cowley Aidan , Sperl Matthias , Kranz W. Till
Published: November 2022

The macroscopic response of granular solids is determined by the microscopic fabric of force chains, which, in turn, is intimately linked to the history of the solid. To query the influence of gravity on powder flow behavior, a granular material is subjected to compression by a piston in a closed container, on-ground and in microgravity (on parabolic flights). Results show that piston-probing densifies the packing, eventually leading to jamming of the material compressed by the piston, regardless of the gravitational environment. The onset of jamming is found to appear at lower packing fraction in microgravity ($${\varphi }_{J}^{\mu -{{{\rm{g}}}}}=0.567\pm 0.014$$

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μ
−
g

=
0.567
±
0.014

) than on-ground ($${\varphi }_{J}^{{{{\rm{gnd}}}}}=0.579\pm 0.014$$

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gnd

=
0.579
±
0.014

). We interpret these findings as the manifestation of a granular fabric altered by the gravitational force field: in absence of a secondary load (due to gravitational acceleration) to stimulate reorganization in a different direction to the major compression stress, the particles’ configuration becomes stable at lower density, as the particles have no external drive to promote reorganization into a denser packing. This is coupled with a change in interparticular force balance which takes place under low gravity, as cohesive interactions become predominant. We propose a combination of microscopic and continuum arguments to rationalize our results.
Pre- and post-surgery brain tumor multimodal magnetic resonance imaging data optimized for large scale computational modelling
Authors: Aerts Hannelore , Colenbier Nigel , Almgren Hannes , Dhollander Thijs , Daparte Javier Rasero , Clauw Kenzo , Johri Amogh , Meier Jil , Palmer Jessica , Schirner Michael , Ritter Petra , Marinazzo Daniele
Published: November 2022

We present a dataset of magnetic resonance imaging (MRI) data (T1, diffusion, BOLD) acquired in 25 brain tumor patients before the tumor resection surgery, and six months after the surgery, together with the tumor masks, and in 11 controls (recruited among the patients’ caregivers). The dataset also contains behavioral and emotional scores obtained with standardized questionnaires. To simulate personalized computational models of the brain, we also provide structural connectivity matrices, necessary to perform whole-brain modelling with tools such as The Virtual Brain. In addition, we provide blood-oxygen-level-dependent imaging time series averaged across regions of interest for comparison with simulation results. An average resting state hemodynamic response function for each region of interest, as well as shape maps for each voxel, are also contributed.
Incidence, risk factors and prognosis of acute kidney injury in patients treated with immune checkpoint inhibitors: a retrospective study
Authors: Ji Ming-Su , Wu Rilige , Feng Zhe , Wang Yuan-Da , Wang Yong , Zhang Li , Sun Xue-Feng , Chen Xiang-Mei , He Kun-Lun , Cai Guang-Yan
Published: November 2022

Immune checkpoint inhibitors (ICIs) change the prognosis of many cancer patients. With the increasing use of ICIs, immune-related adverse events are occurring, including acute kidney injury (AKI). This study aimed to assess the incidence of AKI during ICI treatment and its risk factors and impact on mortality. Patients treated with ICIs at the First Medical Center of the Chinese PLA General Hospital from January 1, 2014, to December 30, 2019, were consecutively enrolled, and risk factors affecting AKI development in patients treated with ICIs were analyzed using univariate and multivariate logistic regression. Medical record surveys and telephone inquiry were used for follow-up, and Kaplan–Meier survival analysis and Cox regression were used to analyze independent risk factors for death. Among 1615 patients, 114 (7.1%) had AKI. Multivariate logistic regression analysis showed that anemia, Alb < 30 g/L, antibiotic use, diuretic use, NSAID use and proton pump inhibitor use were independent risk factors for AKI development in patients treated with ICIs. Stage 2 or 3 AKI was an independent risk factor for nonrecovery of renal function after AKI onset. Multivariate Cox regression analysis showed that anemia, Alb < 30 g/L, AKI occurrence, and diuretic use were independent risk factors for death in patients treated with ICIs, while high baseline BMI, other tumor types, ACEI/ARB use, and chemotherapy use were protective factors for patient death. AKI occurs in 7.1% of patients treated with ICIs. Anemia, Alb < 30 g/L, and combined medication use are independent risk factors for AKI in patients treated with ICIs. Anemia, Alb < 30 g/L, AKI occurrence, and diuretic use were independent risk factors for death in patients treated with ICIs.
Brain activity during shadowing of audiovisual cocktail party speech, contributions of auditory–motor integration and selective attention
Authors: Wikman Patrik , Ylinen Artturi , Leminen Miika , Alho Kimmo
Published: November 2022

Selective listening to cocktail-party speech involves a network of auditory and inferior frontal cortical regions. However, cognitive and motor cortical regions are differentially activated depending on whether the task emphasizes semantic or phonological aspects of speech. Here we tested whether processing of cocktail-party speech differs when participants perform a shadowing (immediate speech repetition) task compared to an attentive listening task in the presence of irrelevant speech. Participants viewed audiovisual dialogues with concurrent distracting speech during functional imaging. Participants either attentively listened to the dialogue, overtly repeated (i.e., shadowed) attended speech, or performed visual or speech motor control tasks where they did not attend to speech and responses were not related to the speech input. Dialogues were presented with good or poor auditory and visual quality. As a novel result, we show that attentive processing of speech activated the same network of sensory and frontal regions during listening and shadowing. However, in the superior temporal gyrus (STG), peak activations during shadowing were posterior to those during listening, suggesting that an anterior–posterior distinction is present for motor vs. perceptual processing of speech already at the level of the auditory cortex. We also found that activations along the dorsal auditory processing stream were specifically associated with the shadowing task. These activations are likely to be due to complex interactions between perceptual, attention dependent speech processing and motor speech generation that matches the heard speech. Our results suggest that interactions between perceptual and motor processing of speech relies on a distributed network of temporal and motor regions rather than any specific anatomical landmark as suggested by some previous studies.
People’s perceptions and experience of managing life after recurrent pancreatitis: a qualitative study in eastern China
Authors: Chen Lin , Zhou Xingxing , Tu Xiamin , Cheng Hongmei , Duan Zhaotao , Lu Guotao , Yuan Yuan
Published: November 2022

There is a high rate of recurrent hypertriglyceridemic acute pancreatitis (HTG-RAP) and risk of developing into chronic pancreatitis among recurrent hypertriglyceridemic acute pancreatitis. The key to avoiding recurrence is home-based self-management. However, self-management has proven to be difficult. Exploring experiences and perceptions of home-based self-management among patients with HTG-RAP could inform intervention development and policy making in primary care. To explore experiences and perceptions of home-based self-management among patients with HTG-RAP. This is primarily a qualitative study involving patients from eastern China. The study was designed using semi-structured interviews combined with open interviews among individuals and focus groups. Interviews with patients (n = 25) and relatives (n = 2) were conducted from October to December, 2021. Data were analyzed using the thematic analysis approach. Five themes were identified: (1) pity, (2) sense of uncertainty, (3) contradiction, (4) the way to cope, and (5) benefits. The themes constituted a continuous process where a final coping strategy was confirmed. Patients expressed sorrow, struggle, pity, adaptation, and benefits. The disease still bothered them without attack, both mentally and physically. These key points deserve considerable attention to improve the quality of life of patients and lifestyle modification. Patients with pancreatitis were more likely to manage the disease but under a tough process, and during the struggle, they experienced a continuous and contradictory period. Ultimately, the final condition was reached.
Decreased expression of miR-23b is associated with poor survival of endometrial cancer patients
Authors: Klicka Klaudia , Grzywa Tomasz M. , Klinke Alicja , Mielniczuk Aleksandra , Wejman Jarosław , Ostrowska Joanna , Gondek Agata , Włodarski Paweł K.
Published: November 2022

Endometrial cancer (EC) is one of the most common types of cancer of the female reproductive system. EC is classified into two types (EC1 and EC2). MiRNAs are single-stranded RNA molecules that regulate gene expression posttranscriptionally. They have aberrant expression profiles in cancer, including EC. This study aimed to assess the level of expression of a panel of 16 miRNAs in both types of EC and healthy endometrium (HE). A total of 45 patients were enrolled into the study, 18 patients diagnosed with EC1, 12 diagnosed with EC2, and 15 HE controls. Tumor tissues or healthy endometrial tissues were dissected from archival formalin-fixed paraffin-embedded (FFPE) using laser capture microdissection (LCM). RNA was isolated from collected material and the expression of selected miRNAs was determined using the real-time qPCR. We found that miR-23b, miR-125b-5p, miR-199a-3p, miR-221-3p, and miR-451a were downregulated in EC in comparison to HE. Moreover, the expression of miR-34a-5p and miR-146-5p was higher in EC1 compared to EC2. Analysis of The Cancer Genome Atlas (TCGA) database confirmed decreased levels of miR-23b, miR-125b-5p, and miR-199a-3p in EC. Decreased miR-23b expression was associated with worse survival of EC patients.
Molecular profile and its clinical impact of IDH1 mutated versus IDH1 wild type intrahepatic cholangiocarcinoma
Authors: Rimini Margherita , Fabregat-Franco Carles , Burgio Valentina , Lonardi Sara , Niger Monica , Scartozzi Mario , Rapposelli Ilario Giovanni , Aprile Giuseppe , Ratti Francesca , Pedica Federica , Verdaguer Helena , Rizzato Mario , Nichetti Federico , Lai Eleonora , Cappetta Alessandro , Macarulla Teresa , Fassan Matteo , De Braud Filippo , Pretta Andrea , Simionato Francesca , De Cobelli Francesco , Aldrighetti Luca , Fornaro Lorenzo , Cascinu Stefano , Casadei-Gardini Andrea
Published: November 2022

IDH1-mutated cholangiocarcinomas (CCAs) are an interesting group of neoplasia with particular behavior and therapeutic implications. The aim of the present work is to highlight the differences characterizing IDH1m and IDH1wt CCAs in terms of genomic landscape. 284 patients with iCCA treated for resectable, locally advanced or metastatic disease were selected and studied with the FOUNDATION Cdx technology. A comparative genomic analysis and survival analyses for the most relevant altered genes were performed between IDH1m and IDH1wt patients. Overall, 125 patients were IDH1m and 122 IDH1wt. IDH1m patients showed higher mutation rates compared to IDH1wt in CDKN2B and lower mutation rates in several genes including TP53, FGFR2, BRCA2, ATM, MAP3K1, NOTCH2, ZNF703, CCND1, NBN, NF1, MAP3KI3, and RAD21. At the survival analysis, IDH1m and IDH1wt patients showed no statistically differences in terms of survival outcomes, but a trend in favor of IDH1wt patients was observed. Differences in prognostic values of the most common altered genes were reported. In surgical setting, in IDH1m group the presence of CDKN2A and CDKN2B mutations negatively impact DFS, whereas the presence of CDKN2A, CDKN2B, and PBRM1 mutations negatively impact OS. In advanced setting, in the IDH1m group, the presence of KRAS/NRAS and TP53 mutations negatively impact PFS, whereas the presence of TP53 and PIK3CA mutations negatively impact OS; in the IDH1wt group, only the presence of MTAP mutation negatively impact PFS, whereas the presence of TP53 mutation negatively impact OS. We highlighted several molecular differences with distinct prognostic implications between IDH1m and IDH1wt patients.
Finding the best hardware configuration for 2D SLAM in indoor environments via simulation based on Google Cartographer
Authors: Sobczak Łukasz , Filus Katarzyna , Domańska Joanna , Domański Adam
Published: November 2022

One of the most challenging topics in robotics is simultaneous localization and mapping (SLAM) in the indoor environments. Due to the fact that Global Navigation Satellite Systems cannot be successfully used in such environments, different data sources are used for this purpose, among others light detection and ranging (LiDARs ), which have advanced from numerous other technologies. Other embedded sensors can be used along with LiDARs to improve SLAM accuracy, e.g. the ones available in the Inertial Measurement Units and wheel odometry sensors. Evaluation of different SLAM algorithms and possible hardware configurations in real environments is time consuming and expensive. In our study, we evaluate the accuracy of mapping and localization (based on Absolute Trajectory Error and Relative Pose Error). Our use case is a robot used for room decontamination. The results for a small room show that for our robot the best hardware configuration consists of three LiDARs 2D, IMU and wheel odometry sensors. On the other hand, for long hallways, a configuration with one LiDAR 3D sensor and IMU works better and more stable. We also described a general approach together with tools and procedures that can be used to find the best sensor setup in simulation.
The use of machine learning modeling, virtual screening, molecular docking, and molecular dynamics simulations to identify potential VEGFR2 kinase inhibitors
Authors: Salimi Abbas , Lim Jong Hyeon , Jang Jee Hwan , Lee Jin Yong
Published: November 2022

Targeting the signaling pathway of the Vascular endothelial growth factor receptor-2 is a promising approach that has drawn attention in the quest to develop novel anti-cancer drugs and cardiovascular disease treatments. We construct a screening pipeline using machine learning classification integrated with similarity checks of approved drugs to find new inhibitors. The statistical metrics reveal that the random forest approach has slightly better performance. By further similarity screening against several approved drugs, two candidates are selected. Analysis of absorption, distribution, metabolism, excretion, and toxicity, along with molecular docking and dynamics are performed for the two candidates with regorafenib as a reference. The binding energies of molecule1, molecule2, and regorafenib are − 89.1, − 95.3, and − 87.4 (kJ/mol), respectively which suggest candidate compounds have strong binding to the target. Meanwhile, the median lethal dose and maximum tolerated dose for regorafenib, molecule1, and molecule2 are predicted to be 800, 1600, and 393 mg/kg, and 0.257, 0.527, and 0.428 log mg/kg/day, respectively. Also, the inhibitory activity of these compounds is predicted to be 7.23 and 7.31, which is comparable with the activity of pazopanib and sorafenib drugs. In light of these findings, the two compounds could be further investigated as potential candidates for anti-angiogenesis therapy.
Phototoxic effects of nonlinear optical microscopy on cell cycle, oxidative states, and gene expression
Authors: Zhang Xinyi , Dorlhiac Gabriel , Landry Markita P. , Streets Aaron
Published: November 2022

Nonlinear optical imaging modalities, such as stimulated Raman scattering (SRS) microscopy, use pulsed-laser excitation with high peak intensity that can perturb the native state of cells. In this study, we used bulk RNA sequencing, quantitative measurement of cell proliferation, and fluorescent measurement of the generation of reactive oxygen species to assess phototoxic effects of near-IR pulsed laser radiation, at different time scales, for laser excitation settings relevant to SRS imaging. We define a range of laser excitation settings for which there was no significant change in mouse Neuro2A cells after laser exposure. This study provides guidance for imaging parameters that minimize photo-induced perturbations in SRS microscopy to ensure accurate interpretation of experiments with time-lapse imaging or with paired measurements of imaging and sequencing on the same cells.
Dual-energy X-ray absorptiometry measures of lean body mass as a biomarker for progression in boys with Duchenne muscular dystrophy
Authors: Sherlock Sarah P. , Palmer Jeffrey , Wagner Kathryn R. , Abdel-Hamid Hoda Z. , Tian Cuixia , Mah Jean K. , Muntoni Francesco , Guglieri Michela , Butterfield Russell J. , Charnas Lawrence , Marraffino Shannon
Published: November 2022

We evaluated whether whole-body dual-energy X-ray absorptiometry (DXA) measures of lean body mass can be used as biomarkers for disease progression and treatment effects in patients with Duchenne muscular dystrophy. This post hoc analysis utilized data from a randomized, 2-period study of domagrozumab versus placebo in 120 ambulatory boys with DMD. DXA measures of lean body mass were obtained from the whole body (excluding head), arms, legs and appendicular skeleton at baseline and every 16 weeks. Treatment effects on DXA measures for domagrozumab versus placebo were assessed at Week 49. At Week 49, domagrozumab statistically significantly increased lean body mass versus placebo in the appendicular skeleton (p = 0.050) and arms (p < 0.001). The relationship between lean body mass at Week 49 and functional endpoints at Week 97 was evaluated. Changes in lean body mass at Week 49 in all regions except arms were significantly correlated with percent change from baseline in 4-stair climb (4SC) at Week 97. DXA-derived percent lean mass at Week 49 also correlated with 4SC and North Star Ambulatory Assessment at Week 97. These data indicate that whole-body DXA measures can be used as biomarkers for treatment effects and disease progression in patients with DMD, and warrant further investigation.

Trial registration: ClinicalTrials.gov, NCT02310763; registered 8 December 2014.
Long term environmental variability modulates the epigenetics of maternal traits of kelp crabs in the coast of Chile
Authors: Baldanzi Simone , Saldías Gonzalo S. , Vargas Cristian A. , Porri Francesca
Published: November 2022

The methylation of DNA is an environmentally inducible epigenetic mechanism reflecting the short‐term ecological and environmental background of populations. Marine invertebrate populations, which spread along a latitudinal cline, are particularly suitable for profiling DNA methylation, due to the heterogenous environmental conditions experienced. We used the MSAP (Methylation Sensitive Amplified Polymorphism) technique to investigate the natural variation in DNA methylation of different female’s tissues (muscle, gonads, and gills) and early-stage eggs from five populations of the kelp crabTaliepus dentatus, distributed along a latitudinal cline in the coast of Chile. We assessed whether, (1) the distribution of DNA methylation profiles can be associated with the temporal variability of long term (18 years) climatologies (sea surface temperature, turbidity and productivity) and (2) the epigenetic diversity of eggs is related to the population-level phenotypic variability of several maternal investment traits (egg volume, egg weight, egg lipids and fecundity). The DNA methylation of eggs correlated positively and negatively with the long term variability in productivity and sea surface temperature, respectively. Furthermore, the diversity of DNA methylation of eggs correlated positively with the population-level phenotypic variability of several maternal investment traits, suggesting a key role of epigenetic mechanisms in generating phenotypic variability at population level for this species. We provide evidence of a strong link between the temporal variability of long term climatologies with the epigenetic profiles of key early ontogenetic traits associated with the maternal investment of kelp crabs. These modulating mechanisms can hence contribute early to phenotypic variability at population levels in response to local and past environmental fluctuation.