bluuebunny/crossref_metadata_2025 huggingface dataset:
Satellite Observations of the Impact of Individual Aircraft on Ice Crystal Number in Thin Cirrus Clouds
Authors: Marjani Sajedeh , Tesche Matthias , Bräuer Peter , Sourdeval Odran , Quaas Johannes
Published: February 2022

Contrails can persist in cloud‐free supersaturated air, increasing high‐cloud cover, and inside natural cirrus cloud, modifying the microphysical properties of them. The latter effect is almost unknown, partly because of the lack of height‐resolved measurements and the capability of measurements to penetrate inside the cloud. New retrievals of the ice crystal number concentration from combined satellite cloud radar and lidar measurements (CloudSat/CALIPSO; DARDAR‐Nice algorithm) now allow for satellite‐based assessment inside the clouds. We investigate this issue at intersections between the aircraft flight tracks and these retrieval profiles. Regions behind the aircraft inside the flight track were compared to the adjacent regions and to ahead of the aircraft, along the satellites' profiles, where DARDAR‐Nice identify geometrically thin cirrus clouds. This comparison revealed a statistically significant increase of 25% and 54% in the concentration of ice crystals with the minimum size of 5 μm around 300–540‐m beneath an aircraft's flight altitude.
Role of the Tropics in State‐Dependent Improvements of US West Coast NOAA Unified Forecast System Precipitation Forecasts
Authors: Hsiao Wei‐Ting , Barnes Elizabeth A. , Maloney Eric D. , Tulich Stefan N. , Dias Juliana , Kiladis George N.
Published: February 2022

Boreal‐wintertime hindcasts in the Unified Forecast System with the tropics nudged toward reanalysis improve United States (US) West Coast precipitation forecasts at Weeks 3–4 lead times when compared to those without nudging. To diagnose the origin of these improvements, a multivariate k‐means clustering method is used to group hindcasts into subsets by their initial conditions. One cluster characterized by an initially strong Aleutian Low demonstrates larger improvements at Weeks 3–4 with nudging compared to the others. The greater improvements with nudging for this cluster are related to model errors in simulating the interaction between the Aleutian Low and the teleconnection patterns associated with the Madden‐Julian oscillation (MJO) and El Niño‐Southern Oscillation (ENSO). Improving forecasts of tropical intraseasonal precipitation, especially during early MJO phases under non‐cold ENSO, may be important for producing better Weeks 3–4 precipitation forecasts for the US West Coast.
Latitudinal Variation of the Lifetime Maximum Intensity Location of Atlantic Tropical Cyclones Controlled by the Atlantic Multidecadal Oscillation
Authors: Kim Hyeong‐Seog , Park Doo‐Sun R. , Ho Chang‐Hoi , Moon Il‐Ju , Chan Johnny C. L.
Published: February 2022

The latitude of lifetime maximum intensity (LMI) location (ϕLMI) of Atlantic tropical cyclones (TCs) is related to the Atlantic Multidecadal Oscillation (AMO) with a significant negative correlation for 1948–2018. We objectively classify TC tracks into four patterns, to evaluate the effects of variations in dominant track patterns (track ϕLMI) and intra‐pattern ϕLMI (pure ϕLMI) on the total ϕLMI variation. During the warm phases of AMO, the prevailed south‐origin track patterns and equatorward pure ϕLMI shifts have almost equally contributed to the equatorward migration of the total ϕLMI. The negative anomaly of potential intensity in the subtropics is responsible for the equatorward shift of pure ϕLMI. Moreover, weak vertical wind shear in the tropics increases the south‐origin track patterns. These environmental conditions are associated with the east‐strong and west‐weak relative sea surface temperature warming during the warm phases that causes anomalous upward and downward motions in the eastern and western Atlantic, respectively.
Modeling the Deformation Regime of Thwaites Glacier, West Antarctica, Using a Simple Flow Relation for Ice Anisotropy (ESTAR)
Authors: McCormack F. S. , Warner R. C. , Seroussi H. , Dow C. F. , Roberts J. L. , Treverrow A.
Published: February 2022

Ice deformation dominates the evolution of ice shelf flow and the slow‐moving regions in the interior of ice sheets. However, deformation may be poorly represented in large‐scale ice sheet models that use the Glen flow relation, due to its questionable applicability to the steady‐state flow of anisotropic ice that prevails in ice sheets, having been derived from secondary creep rates of isotropic ice. We assess the deformation regimes of Thwaites Glacier, West Antarctica, using the Glen and “Empirical Scalar Tertiary Anisotropy Regime”, (ESTAR) flow relations, the latter being derived from steady‐state deformation rates of anisotropic ice. For grounded ice, the character of the flow relation determines the contribution of deformation to overall flow, with ESTAR producing greater bed‐parallel shear deformation than the standard Glen flow relation. The ESTAR experiments show larger basal shear stress maxima than the standard Glen experiment because ESTAR treats the responses to simple shear stresses and compression stresses differently, reducing the role of lateral and longitudinal stresses in momentum balance. On the Thwaites Glacier Tongue, ESTAR provides the best match to observed speeds by accounting for the differing effects of stresses on ice flow. Our results highlight the importance of the numerical description of anisotropy, particularly: In regions of transition from deformation‐dominated to sliding‐dominated flow; in the approach to the grounding line, and across ice shelves. Given the importance of these locations in determining mass flux into the ocean, our results have implications for projections of sea level change from Antarctic ice loss.
Comment on “Hydrometeorological Triggers of Periglacial Debris Flows in the Zermatt Valley (Switzerland) Since 1864” by Michelle Schneuwly‐Bollschweiler and Markus Stoffel
Authors: Heiser M. , Schlögl M. , Scheidl C. , Fuchs S.
Published: February 2022

Generalizing properties of samples derived via data analysis to advance understanding of underlying processes constitutes the essence of statistical inference. This is especially true in geophysical research, where general findings often emerge from case studies. Consequently, statements about trends in case studies should naturally be grounded on a comprehensive and robust analysis of available data. Here, we focus on trends reported for a debris flow time series of a well‐known case study in the Zermatt Valley, Switzerland (Schneuwly‐Bollschweiler & Stoffel, 2012; https://doi.org/10.1029/2011jf002262). We elaborate that we were not able to confirm the findings of the original study with respect to changes in debris flow seasonality. On the contrary, we show that confusion between data analytic question types (exploratory vs. inferential) can lead to the confirmation of trends that do not necessarily hold beyond the data set, and we demonstrate how the reported effect could be an artifact of incomplete data. In doing so we employ a range of methods that can be used for adequately addressing the original question.
The Role of Mixed Convection and Hydrodynamic Dispersion During CO2 Dissolution in Saline Aquifers: A Numerical Study
Authors: Tsinober Avihai , Rosenzweig Ravid , Class Holger , Helmig Rainer , Shavit Uri
Published: February 2022

Dissolution trapping plays a significant role in CO2 geological storage. When CO2 dissolves in aquifer brines, the aqueous solution is heavier than the underlying resident brine. This results in convective instability in the form of CO2‐rich fingers, which accelerates dissolution. It was recently shown that background flow affects CO2 dissolution by suppressing the development of convective fingers. However, there was a discrepancy between computational results and measurements, with the computational results demonstrating a decrease in the dissolution rate and the laboratory measurements showing no significant effect. Here, we attempted to understand this difference by exploring the relations between the transport mechanisms that facilitate convective mixing. We investigated the role of background flow by using numerical simulations that were validated by laboratory measurements and analytical solutions. Simulations were generated for the same porous medium and fluid pair used in the experiments, keeping the Rayleigh number constant, while changing the background velocity and the Peclet number. Studying the flux components revealed three distinct regimes characterized by the Peclet to Rayleigh ratio Pe/Ra. When Pe/Ra < 0.77, natural convection dominated, and dissolution remained approximately constant. When the background flow was large (Pe/Ra > 2), dissolution was controlled by pure forced convection and increased with Pe/Ra. In the intermediate range (0.77 < Pe/Ra < 2), both natural convection and forced convection were important.
Growth differentiation factor 15 (GDF15) is associated with non-alcoholic fatty liver disease (NAFLD) in youth with overweight or obesity
Authors: Galuppo Brittany , Agazzi Cristiana , Pierpont Bridget , Chick Jennifer , Li Zhongyao , Caprio Sonia , Santoro Nicola
Published: February 2022

Objective

Growth differentiation factor 15 (GDF15) has been associated with food intake and weight regulation in response to metabolic stress. In animal models, it has been noted that it may play a role in the progression of non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease in children.

Design

In the current study, we explored the association of circulating plasma concentrations of GDF15 with NAFLD in youth with overweight/obesity, and whether changes in plasma concentrations in GDF15 parallel the changes in intrahepatic fat content (HFF%) over time.

Methods

Plasma GDF15 concentrations were measured by ELISA in 175 youth with overweight/obesity who underwent an oral glucose tolerance test (OGTT) and magnetic resonance imaging (MRI) to assess intrahepatic, visceral, and subcutaneous fat. Baseline fasting GDF15 concentrations were measured in twenty-two overweight/obese youth who progressed (n = 11) or regressed (n = 11) in HFF% by more than 30% of original over a 2-year period.

Results

Youth with NAFLD had significantly higher plasma concentrations of GDF15 than those without NAFLD, independent of age, sex, ethnicity, BMI z-score (BMIz), and visceral fat (P = 0.002). During the OGTT, there was a decline in plasma GDF15 concentrations from 0 to 60 min, but GDF15 concentrations returned to basal levels by the end of the study. There was a statistically significant association between change in HFF% and change in GDF15 (P = 0.008; r2 = 0.288) over ~2 years of follow-up.

Conclusions

These data suggest that plasma GDF15 concentrations change with change in intrahepatic fat content in youth with overweight/obesity and may serve as a biomarker for NAFLD in children.
Power signatures of habenular neuronal signals in patients with bipolar or unipolar depressive disorders correlate with their disease severity
Authors: Sonkusare Saurabh , Ding Qiong , Zhang Yingying , Wang Linbin , Gong Hengfen , Mandali Alekhya , Manssuer Luis , Zhao Yi-Jie , Pan Yixin , Zhang Chencheng , Li Dianyou , Sun Bomin , Voon Valerie
Published: February 2022

The habenula is an epithalamic structure implicated in negative reward mechanisms and plays a downstream modulatory role in regulation of dopaminergic and serotonergic functions. Human and animal studies show its hyperactivity in depression which is curtailed by the antidepressant response of ketamine. Deep brain stimulation of habenula (DBS) for major depression have also shown promising results. However, direct neuronal activity of habenula in human studies have rarely been reported. Here, in a cross-sectional design, we acquired both spontaneous resting state and emotional task-induced neuronal recordings from habenula from treatment resistant depressed patients undergoing DBS surgery. We first characterise the aperiodic component (1/f slope) of the power spectrum, interpreted to signify excitation-inhibition balance, in resting and task state. This aperiodicity for left habenula correlated between rest and task and which was significantly positively correlated with depression severity. Time-frequency responses to the emotional picture viewing task show condition differences in beta and gamma frequencies for left habenula and alpha for right habenula. Notably, alpha activity for right habenula was negatively correlated with depression severity. Overall, from direct habenular recordings, we thus show findings convergent with depression models of aberrant excitatory glutamatergic output of the habenula driving inhibition of monoaminergic systems.
Changes in gut viral and bacterial species correlate with altered 1,2-diacylglyceride levels and structure in the prefrontal cortex in a depression-like non-human primate model
Authors: Wu Jing , Chai Tingjia , Zhang Hanping , Huang Yu , Perry Seth W. , Li Yifan , Duan Jiajia , Tan Xunmin , Hu Xi , Liu Yiyun , Pu Juncai , Wang Haiyang , Song Jinlin , Jin Xin , Ji Ping , Zheng Peng , Xie Peng
Published: February 2022

Major depressive disorder (MDD) is a debilitating mental disease, but its underlying molecular mechanisms remain obscure. Our previously established model of naturally occurring depression-like (DL) behaviors in Macaca fascicularis, which is characterized by microbiota-gut–brain (MGB) axis disturbances, can be used to interrogate how a disturbed gut ecosystem may impact the molecular pathology of MDD. Here, gut metagenomics were used to characterize how gut virus and bacterial species, and associated metabolites, change in depression-like monkey model. We identified a panel of 33 gut virus and 14 bacterial species that could discriminate the depression-like from control macaques. In addition, using lipidomic analyses of central and peripheral samples obtained from these animals, we found that the DL macaque were characterized by alterations in the relative abundance, carbon-chain length, and unsaturation degree of 1,2-diacylglyceride (DG) in the prefrontal cortex (PFC), in a brain region-specific manner. In addition, lipid-reaction analysis identified more active and inactive lipid pathways in PFC than in amygdala or hippocampus, with DG being a key nodal player in these lipid pathways. Significantly, co-occurrence network analysis showed that the DG levels may be relevant to the onset of negative emotions behaviors in PFC. Together our findings suggest that altered DG levels and structure in the PFC are hallmarks of the DL macaque, thus providing a new framework for understanding the gut microbiome’s role in depression.
Associations between diagnostic time intervals and health-related quality of life, clinical anxiety and depression in adolescents and young adults with cancer: cross-sectional analysis of the BRIGHTLIGHT cohort
Authors: Forster Alice S. , Herbert Annie , Koo Minjoung Monica , Taylor Rachel M. , Gibson Faith , Whelan Jeremy S. , Lyratzopoulos Georgios , Fern Lorna A.
Published: February 2022

Background

The association of diagnostic intervals and outcomes is poorly understood in adolescents and young adults with cancer (AYA). We investigated associations between diagnostic intervals and health-related quality of life (HRQoL), anxiety and depression in a large AYA cohort.

Methods

Participants aged 12–24 completed interviews post-diagnosis, providing data on diagnostic experiences and the patient-reported outcomes (PROs) HRQoL, anxiety and depression. Demographic and cancer information were obtained from clinical and national records. Six diagnostic intervals were considered. Relationships between intervals and PROs were examined using regression models.

Results

Eight hundred and thirty participants completed interviews. In adjusted models, across 28 of 30 associations, longer intervals were associated with poorer PROs. Patient intervals (symptom onset to first seeing a GP) of ≥1 month were associated with greater depression (adjusted odds ratio (aOR):1.7, 95% Confidence Interval (CI):1.1–2.5) compared to <1 month. ≥3 pre-referral GP consultations were associated with greater anxiety (aOR:1.6, CI:1.1–2.3) compared to 1–2 consultations. Symptom onset to first oncology appointment intervals of ≥2 months was associated with impaired HRQoL (aOR:1.8, CI:1.2–2.5) compared to <2 months.

Conclusions

Prolonged diagnostic intervals in AYA are associated with an increased risk of impaired HRQoL, anxiety and depression. Identifying and delivering interventions for this high-risk group is a priority.
ERK1/2 inhibits Cullin 3/SPOP-mediated PrLZ ubiquitination and degradation to modulate prostate cancer progression
Authors: Fan Yizeng , Hou Tao , Dan Weichao , Zhu Yasheng , Liu Bo , Wei Yi , Wang Zixi , Gao Yang , Zeng Jin , Li Lei
Published: February 2022

The gene encoding the E3 ubiquitin ligase substrate-binding adaptor SPOP is frequently mutated in prostate cancer (PCa), but how SPOP functions as a tumor suppressor and contributes to PCa pathogenesis remains poorly understood. Prostate Leucine Zipper (PrLZ) serves as a prostate-specific and androgen-responsive gene, which plays a pivotal role in the malignant progression of PCa. However, the upstream regulatory mechanism of PrLZ protein stability and its physiological contribution to PCa carcinogenesis remain largely elusive. Here we report that PrLZ can be degraded by SPOP. PrLZ abundance is elevated in SPOP-mutant expressing PCa cell lines and patient specimens. Meanwhile, ERK1/2 might regulate SPOP-mediated PrLZ degradation through phosphorylating PrLZ at Ser40, which blocks the interaction between SPOP and PrLZ. In addition, we identify IL-6 might act as an upstream PrLZ degradation regulator via promoting its phosphorylation by ERK1/2, leading to its impaired recognition by SPOP. Thus, our study reveals a novel SPOP substrate PrLZ which might be controlled by ERK1/2-mediated phosphorylation, thereby facilitating to explore novel drug targets and improve therapeutic strategy for PCa.
High-throughput identification and quantification of single bacterial cells in the microbiota
Authors: Jin Jianshi , Yamamoto Reiko , Takeuchi Tadashi , Cui Guangwei , Miyauchi Eiji , Hojo Nozomi , Ikuta Koichi , Ohno Hiroshi , Shiroguchi Katsuyuki
Published: February 2022

The bacterial microbiota works as a community that consists of many individual organisms, i.e., cells. To fully understand the function of bacterial microbiota, individual cells must be identified; however, it is difficult with current techniques. Here, we develop a method, Barcoding Bacteria for Identification and Quantification (BarBIQ), which classifies single bacterial cells into taxa–named herein cell-based operational taxonomy units (cOTUs)–based on cellularly barcoded 16S rRNA sequences with single-base accuracy, and quantifies the cell number for each cOTU in the microbiota in a high-throughput manner. We apply BarBIQ to murine cecal microbiotas and quantify in total 3.4 × 105 bacterial cells containing 810 cOTUs. Interestingly, we find location-dependent global differences in the cecal microbiota depending on the dietary vitamin A deficiency, and more differentially abundant cOTUs at the proximal location than the distal location. Importantly, these location differences are not clearly shown by conventional 16S rRNA gene-amplicon sequencing methods, which quantify the 16S rRNA genes, not the cells. Thus, BarBIQ enables microbiota characterization with the identification and quantification of individual constituent bacteria, which is a cornerstone for microbiota studies.
Multi-parameter photon-by-photon hidden Markov modeling
Authors: Harris Paul David , Narducci Alessandra , Gebhardt Christian , Cordes Thorben , Weiss Shimon , Lerner Eitan
Published: February 2022

Single molecule Förster resonance energy transfer (smFRET) is a unique biophysical approach for studying conformational dynamics in biomacromolecules. Photon-by-photon hidden Markov modeling (H2MM) is an analysis tool that can quantify FRET dynamics of single biomolecules, even if they occur on the sub-millisecond timescale. However, dye photophysical transitions intertwined with FRET dynamics may cause artifacts. Here, we introduce multi-parameter H2MM (mpH2MM), which assists in identifying FRET dynamics based on simultaneous observation of multiple experimentally-derived parameters. We show the importance of using mpH2MM to decouple FRET dynamics caused by conformational changes from photophysical transitions in confocal-based smFRET measurements of a DNA hairpin, the maltose binding protein, MalE, and the type-III secretion system effector, YopO, from Yersinia species, all exhibiting conformational dynamics ranging from the sub-second to microsecond timescales. Overall, we show that using mpH2MM facilitates the identification and quantification of biomolecular sub-populations and their origin.
Virtual intracranial EEG signals reconstructed from MEG with potential for epilepsy surgery
Authors: Cao Miao , Galvis Daniel , Vogrin Simon J. , Woods William P. , Vogrin Sara , Wang Fan , Woldman Wessel , Terry John R. , Peterson Andre , Plummer Chris , Cook Mark J.
Published: February 2022

Modelling the interactions that arise from neural dynamics in seizure genesis is challenging but important in the effort to improve the success of epilepsy surgery. Dynamical network models developed from physiological evidence offer insights into rapidly evolving brain networks in the epileptic seizure. A limitation of previous studies in this field is the dependence on invasive cortical recordings with constrained spatial sampling of brain regions that might be involved in seizure dynamics. Here, we propose virtual intracranial electroencephalography (ViEEG), which combines non-invasive ictal magnetoencephalographic imaging (MEG), dynamical network models and a virtual resection technique. In this proof-of-concept study, we show that ViEEG signals reconstructed from MEG alone preserve critical temporospatial characteristics for dynamical approaches to identify brain areas involved in seizure generation. We show the non-invasive ViEEG approach may have some advantage over intracranial electroencephalography (iEEG). Future work may be designed to test the potential of the virtual iEEG approach for use in surgical management of epilepsy.
Randomized controlled trial for time-restricted eating in healthy volunteers without obesity
Authors: Xie Zhibo , Sun Yuning , Ye Yuqian , Hu Dandan , Zhang Hua , He Zhangyuting , Zhao Haitao , Yang Huayu , Mao Yilei
Published: February 2022

Time-restricted feeding (TRF) improves metabolic health. Both early TRF (eTRF, food intake restricted to the early part of the day) and mid-day TRF (mTRF, food intake restricted to the middle of the day) have been shown to have metabolic benefits. However, the two regimens have yet to be thoroughly compared. We conducted a five-week randomized trial to compare the effects of the two TRF regimens in healthy individuals without obesity (ChiCTR2000029797). The trial has completed. Ninety participants were randomized to eTRF (n=30), mTRF (n=30), or control groups (n=30) using a computer-based random-number generator. Eighty-two participants completed the entire five-week trial and were analyzed (28 in eTRF, 26 in mTRF, 28 in control groups). The primary outcome was the change in insulin resistance. Researchers who assessed the outcomes were blinded to group assignment, but participants and care givers were not. Here we show that eTRF was more effective than mTRF at improving insulin sensitivity. Furthermore, eTRF, but not mTRF, improved fasting glucose, reduced total body mass and adiposity, ameliorated inflammation, and increased gut microbial diversity. No serious adverse events were reported during the trial. In conclusion, eTRF showed greater benefits for insulin resistance and related metabolic parameters compared with mTRF. Clinical Trial Registration URL: http://www.chictr.org.cn/showproj.aspx?proj=49406.
Effects of preoperative sagittal spinal imbalance on pain after lateral lumbar interbody fusion
Authors: Hiyama Akihiko , Katoh Hiroyuki , Sakai Daisuke , Sato Masato , Watanabe Masahiko
Published: February 2022

Sagittal misalignment has been associated with negative quality of life (QOL). However, there is no report on whether differences in preoperative sagittal misalignment in patients with lumbar degenerative diseases affect postoperative results after lateral lumbar interbody fusion (LLIF). We investigated whether preoperative sagittal alignment influences the correction of alignment after surgery and whether the preoperative sagittal alignment affects the rating of low back pain, leg pain, and leg numbness. The subjects were 81 patients (48 male, 33 females, average age at surgery 70.2 years) who underwent anterior–posterior combined surgery with LLIF and percutaneous pedicle screws from May 2018 to July 2020. Cluster analysis was performed using the preoperative sagittal vertical axis (SVA) value, and patients were classified into two groups (group 1; n = 30, SVA = 129.0 ± 53.4 mm, group 2; n = 51, SVA = 30.8 ± 23.5 mm). Baseline demographics and treatment data were compared between groups. Sagittal and pelvic parameters and pain scores, such as low back pain, leg pain, and leg numbness, were also compared. Operative time, blood loss, and length of hospital stay did not differ significantly between groups. The changes (Δ) in SVA and lumbar lordosis (LL) for all patients from before to after surgery were not significant (ΔSVA; p = 0.218, ΔLL; p = 0.189, respectively). The SVA, LL, and PI − LL changed significantly after the surgery in group 1, but no marked improvement in sagittal imbalance was obtained after LLIF surgery. The improvement in each pain score from before to after the surgery did not differ significantly between groups. LLIF surgery has a limited chance of recovering sagittal imbalance. However, postoperative low back pain, leg pain, and leg numbness may be improved by LLIF surgery, regardless of the preoperative sagittal alignment.
Pemafibrate suppresses NLRP3 inflammasome activation in the liver and heart in a novel mouse model of steatohepatitis-related cardiomyopathy
Authors: Kanno Kotaro , Koseki Masahiro , Chang Jiuyang , Saga Ayami , Inui Hiroyasu , Okada Takeshi , Tanaka Katsunao , Asaji Masumi , Zhu Yinghong , Ide Seiko , Saito Shigeyoshi , Higo Tomoaki , Okuzaki Daisuke , Ohama Tohru , Nishida Makoto , Kamada Yoshihiro , Ono Masafumi , Saibara Toshiji , Yamashita Shizuya , Sakata Yasushi
Published: February 2022

Although patients with nonalcoholic fatty liver disease have been reported to have cardiac dysfunction, and appropriate model has not been reported. We established a novel mouse model of diet-induced steatohepatitis-related cardiomyopathy and evaluated the effect of pemafibrate. C57Bl/6 male mice were fed a (1) chow diet (C), (2) high-fat, high-cholesterol, high-sucrose, bile acid diet (NASH diet; N), or (3) N with pemafibrate 0.1 mg/kg (NP) for 8 weeks. In the liver, macrophage infiltration and fibrosis in the liver was observed in the N group compared to the C group, suggesting steatohepatitis. Free cholesterol accumulated, and cholesterol crystals were observed. In the heart, free cholesterol similarly accumulated and concentric hypertrophy was observed. Ultrahigh magnetic field magnetic resonance imaging revealed that the left ventricular (LV) ejection fraction (EF) was attenuated and LV strain was focally impaired. RNA sequencing demonstrated that the NOD-like receptor and PI3 kinase-Akt pathways were enhanced. mRNA and protein expression of inflammasome-related genes, such as Caspase-1, NLRP3, and IL-1β, were upregulated in both the liver and heart. In the NP compared to the N group, steatohepatitis, hepatic steatosis, and cardiac dysfunction were suppressed. Sequential administration of pemafibrate after the development of steatohepatitis-related cardiomyopathy recovered hepatic fibrosis and cardiac dysfunction.
Deep learning for fully automatic detection, segmentation, and Gleason grade estimation of prostate cancer in multiparametric magnetic resonance images
Authors: Pellicer-Valero Oscar J. , Marenco Jiménez José L. , Gonzalez-Perez Victor , Casanova Ramón-Borja Juan Luis , Martín García Isabel , Barrios Benito María , Pelechano Gómez Paula , Rubio-Briones José , Rupérez María José , Martín-Guerrero José D.
Published: February 2022

Although the emergence of multi-parametric magnetic resonance imaging (mpMRI) has had a profound impact on the diagnosis of prostate cancers (PCa), analyzing these images remains still complex even for experts. This paper proposes a fully automatic system based on Deep Learning that performs localization, segmentation and Gleason grade group (GGG) estimation of PCa lesions from prostate mpMRIs. It uses 490 mpMRIs for training/validation and 75 for testing from two different datasets: ProstateX and Valencian Oncology Institute Foundation. In the test set, it achieves an excellent lesion-level AUC/sensitivity/specificity for the GGG$$\ge$$
≥
2 significance criterion of 0.96/1.00/0.79 for the ProstateX dataset, and 0.95/1.00/0.80 for the IVO dataset. At a patient level, the results are 0.87/1.00/0.375 in ProstateX, and 0.91/1.00/0.762 in IVO. Furthermore, on the online ProstateX grand challenge, the model obtained an AUC of 0.85 (0.87 when trained only on the ProstateX data, tying up with the original winner of the challenge). For expert comparison, IVO radiologist’s PI-RADS 4 sensitivity/specificity were 0.88/0.56 at a lesion level, and 0.85/0.58 at a patient level. The full code for the ProstateX-trained model is openly available at https://github.com/OscarPellicer/prostate_lesion_detection. We hope that this will represent a landmark for future research to use, compare and improve upon.
Determinants of interchain coupling properties of Te atomic chains
Authors: Han Jie , Li Quan Ming , Gao Wang
Published: February 2022

The coupling effect of one-dimensional (1D) materials is of great significance for the practical application of 1D materials in high-density memory devices and ultra-micro nanometer array lasers. However, the determinants of the coupling effect remain debated. Here, using first principles methods, we investigate the effects of chirality, size and stacking mode on the stability and electronic properties of few-chain Te nanowires. We find that the stacking mode and size play a dominant role in the stability of the nanowires, while the chirality and size have a key effect on the electronic structures. These phenomena are mainly due to the quantum size effect and the special helical structure of the Te chain. Our findings provide the means for adjusting the band gap and the candidates for constructing n-type spin devices, which serve as a basis for the research and manufacture of new nano electronic devices.
Fatigue-free visual perception of high-density super-multiview augmented reality images
Authors: Lim Sungjin , Jeon Hosung , Jung Minwoo , Lee Chulwoong , Moon Woonchan , Kim Kwangsoo , Kim Hwi , Hahn Joonku
Published: February 2022

It is well known that wearing virtual reality (VR) and augmented reality (AR) devices for long periods can cause visual fatigue and motion sickness due to vergence-accommodation conflict (VAC). VAC is considered the main obstacle to the development of advanced three-dimensional VR and AR technology. In this paper, we present a novel AR high-density super-multiview (HDSMV) display technique capable of eliminating VAC in wide range. The designed binocular time-sequential AR HDSMV projection, which delivers 11 views to each eye pupil, is experimentally demonstrated, confirming that VAC is eliminated over a wide-range of viewer’s focus distance. It is believed that the proposed time-sequential AR HDSMV method will pave the way for the development of VAC-free AR technology.
Shared mechanisms underlie mental imagery and motor planning
Authors: Bennet Rotem , Reiner Miriam
Published: February 2022

Many studies have associated mental imagery with motor control mechanisms by showing mutually active brain areas and functions, as well as similar temporal patterns of imagining and executing the same motor actions. One of the main conjectured mutual mechanisms is the Cerebellar forward-model, commonly believed to generate sensory predictions as part of both motor control and mental imagery processes. Nevertheless, trials to associate one’s overall individual mental and motor capacities have shown only mild and inconsistent correlations, hence challenging the mutual mechanism assumption. We hypothesized that one cause to this inconsistency is the forward-model’s dominance in the motor-planning stage only when adapting to novel sensorimotor environments, while the inverse-model is gradually taking the lead along the adaptation, and therefore biasing most attempts to measure motor-mental overlapping functions and correlate these measurements under regular circumstances. Our current study aimed to tackle and explore this gap using immersive virtual embodiment, by applying an experience of a fundamental sensorimotor conflict, thereby manipulating the sensory prediction mechanism, and presumably forcing an increased involvement of the forward-model in the motor planning stage throughout the experiment. In the study, two groups of subjects (n = 48) performed mental and manual rotation within an immersive, motion-captured, virtual reality environment, while the sensorimotor dynamics of only the test group were altered by physical-virtual speed re-mapping making the virtual hand move twice as fast as the physical hand controlling it. Individual mental imagery capacities were assessed before and after three blocks of manual-rotation, where motor planning durations were measured as the time until motion onset. The results show that virtual sensorimotor alteration extremely increases the correlation of mental imagery and motor planning (r = 0.9, p < .0001) and leads to higher mental imagery performance improvement following the physical blocks. We particularly show that virtual embodiment manipulation affects the motor planning stage to change and functionally overlap with imagery mechanisms, rather than the other way around, which supports our conjecture of an increased sensory-prediction forward-model involvement. Our results shed new light on the embodied nature of mental imagery, support the view of the predictive forward-model as a key mechanism mutually underlying motor control and imagery, and suggest virtual sensorimotor alteration as a novel methodology to increase physical-mental convergence. These findings also suggest the applicability of using existing motion-tracked virtual environments for continuous cognitive evaluation and treatment, through kinematic analysis of ongoing natural motor behaviors.
Protein and miRNA profile of circulating extracellular vesicles in patients with primary sclerosing cholangitis
Authors: Povero Davide , Tameda Masahiko , Eguchi Akiko , Ren Wenhua , Kim Jihoon , Myers Robert , Goodman Zachary D. , Harrison Stephen A. , Sanyal Arun J. , Bosch Jaime , Ohno-Machado Lucila , Feldstein Ariel E.
Published: February 2022

Primary sclerosing cholangitis (PSC) is an idiopathic and heterogenous cholestatic liver disease characterized by chronic inflammation and fibrosis of the biliary tree. Currently, no effective therapies are available for this condition, whose incidence is rising. At present, specificity and sensitivity of current serum markers used to diagnose PSC are limited and often unreliable. In this study, we characterize circulating extracellular vesicles and provide supporting data on their potential use as novel surrogate biomarkers for PSC. EVs are membrane surrounded structures, 100–1000 nm in size, released by cells under various conditions and which carry a variety of bioactive molecules, including small non-coding RNAs, lipids and proteins. In recent years, a large body of evidence has pointed to diagnostic implications of EVs and relative cargo in various human diseases. We isolated EVs from serum of well-characterized patients with PSC or control subjects by differential centrifugation and size-exclusion chromatography. A complete characterization identified elevated levels of circulating EVs in PSC patients compared to healthy control subjects (2000 vs. 500 Calcein-FITC + EVs/μL). Tissue and cell specificity of circulating EVs was assessed by identification of liver-specific markers and cholangiocyte marker CK-19. Further molecular characterization identified 282 proteins that were differentially regulated in PSC-derived compared to healthy control-EVs. Among those, IL-13Ra1 was the most significantly and differentially expressed protein in PSC-derived EVs and correlated with the degree of liver fibrosis. In addition to protein profiling, we performed a miRNA-sequencing analysis which identified 11 among established, liver-specific (e.g., miR-122 and miR-192) and novel miRNAs. One of the newly identified miRNAs, miR-4645-3p, was significantly up-regulated fourfold in PSC-derived EVs compared to circulating EVs isolated from healthy controls. This study provides supporting evidence of the potential role of circulating EVs and associated protein and miRNA cargo as surrogate noninvasive and reliable biomarker for PSC.
Min-entropy estimation for semiconductor superlattice true random number generators
Authors: Liu Jing , Xie Jianguo , Chao Lu , Wu Han , Ding Peng , Chen Xiaoming , Feng Huamin
Published: February 2022

Semiconductor superlattice true random number generator (SSL-TRNG) has an outstanding practical property on high-throughput and high-security cryptographic applications. Security in random number generators is closely related to the min-entropy of the raw output because feeding cryptographic applications with insufficient entropy leads to poor security and vulnerability to malicious attacks. However, no research has focused on the min-entropy estimation based on the stochastic model for SSL-TRNG, which is a highly recommended method for evaluating the security of a specific TRNG structure. A min-entropy estimation method is proposed in this paper for the SSL-TRNG by extending the Markov stochastic model derived from the memory effects. By calculating the boundary of the transition matrix, the min-entropy result is the average value of each sample (1 bit) is 0.2487. Moreover, the experimental results show that the estimator is accurate enough to adjust compression rate dynamically in post-processing to reach the required security level, estimating entropy on the fly rather than off-line.
A multiparametric fluorescence assay for screening aptamer–protein interactions based on microbeads
Authors: Schmidt Carsten , Kammel Anne , Tanner Julian A. , Kinghorn Andrew B. , Khan Muhammad Moman , Lehmann Werner , Menger Marcus , Schedler Uwe , Schierack Peter , Rödiger Stefan
Published: February 2022

For improving aptamer-ligand binding we have developed a screening system that defines optimal binding buffer composition. Using multiplex assays, one buffer system is needed which guarantees the specific binding of all aptamers. We investigated nine peer-reviewed DNA aptamers. Non-specific binding of aptamers is an obstacle. To address this, we investigated 16 proteins as specificity controls bound covalently to encoded microbeads in a multiplex assay. Increasing the NaCl concentration decreased the binding for all aptamers. Changing pH values by one unit higher or lower did not influence the aptamer binding significantly. However, pH < 5 led to non-specific binding for all aptamers. The PfLDH-aptamer selected in the absence of divalent cations exhibited doubling of its binding signal by the addition of Ca2+ and Mg2+. We confirmed Ca2+ and Mg2+ dependency of the aptamers for streptavidin and thrombin by observing a 90% and 50% binding decrease, respectively. We also achieved a doubling of binding for the streptavidin aptamer when replacing Ca2+ and Mg2+ by Mn2+. A buffer suitable for all aptamers can have considerable variations in pH or ionic strength, but divalent cations (Ca2+, Mg2+, Mn2+) are essential.
Heteroscedastic sparse Gaussian process regression-based stochastic material model for plastic structural analysis
Authors: Chen Baixi , Shen Luming , Zhang Hao
Published: February 2022

Describing the material flow stress and the associated uncertainty is essential for the plastic stochastic structural analysis. In this context, a data-driven approach-heteroscedastic sparse Gaussian process regression (HSGPR) with enhanced efficiency is introduced to model the material flow stress. Different from other machine learning approaches, e.g. artificial neural network (ANN), which only estimate the deterministic flow stress, the HSGPR model can capture the flow stress and its uncertainty simultaneously from the dataset. For validating the proposed model, the experimental data of the Al 6061 alloy is used here. Without setting a priori assumption on the mathematical expression, the proposed HSGPR-based flow stress model can produce a better prediction of the experimental stress data than the ANN model, the conventional GPR model, and Johnson Cook model at elevated temperatures. After the HSGPR-based flow stress model is implemented into finite element analysis, two numerical examples with synthetic material properties are performed to demonstrate the model’s capability in stochastic plastic structural analysis. The results have shown that with sufficient data, the distribution of the structural load carrying capacity at elevated temperatures and the variation of load–displacement curves during the loading and unloading processes can be accurately predicted by the HSGPR-based flow stress model.
Histopathology and surgical outcome of symptomatic treatment-related changes after gamma knife radiosurgery in patients with brain metastases
Authors: Kim Jeong-Hwa , Choi Jung-Won , Kong Doo-Sik , Seol Ho Jun , Nam Do-Hyun , Ryu Jae-Wook , Kim Sung-Tae , Suh Yeon-Lim , Lee Jung-Il
Published: February 2022

A late-onset treatment-related changes (TRCs), which represent radiographic radiation necrosis (RN), frequently occur after stereotactic radiosurgery (SRS) for brain metastases and often need surgical treatment. This study aimed to validate the true pathology and investigate clinical implication of surgically resected TRCs on advanced magnetic resonance imaging (MRI). Retrospective analyses of 86 patients who underwent surgical resection after radiosurgery of brain metastases were performed. Fifty-four patients displayed TRCs on preoperative MRI, comprising pure RN in 19 patients (TRC-RN group) and mixed viable tumor cells in 35 patients (TRC-PD group). Thirty-two patients revealed the consistent diagnosis of progressive disease in both MRI and histopathology (PD–PD group). The TRC-PD group showed larger prescription isodose volume (9.4 cm3) than the TRC-RN (4.06 cm3, p = 0.014) group and a shorter time interval from SRS to preoperative MRI diagnosis (median 4.07 months) than the PD–PD group (median 8.77 months, p = 0.004). Progression-free survival was significantly different among the three groups (p < 0.001), but not between TRC-RN and TRC-PD (post hoc test, p = 1.00), while no difference was observed in overall survival (p = 0.067). Brain metastases featured as TRCs after SRS frequently contained viable tumor cells. However, this histologic heterogeneity had a minor impact on benign local prognosis of TRCs after surgical resection.
Tumor cell enrichment by tissue suspension enables detection of mutations with low variant allele frequency and estimation of germline mutations
Authors: Hatakeyama Keiichi , Muramatsu Koji , Nagashima Takeshi , Kawanishi Yuichi , Fukumura Ryutaro , Ohshima Keiichi , Shimoda Yuji , Kenmotsu Hirotsugu , Mochizuki Tohru , Urakami Kenichi , Akiyama Yasuto , Sugino Takashi , Yamaguchi Ken
Published: February 2022

Targeted sequencing offers an opportunity to select specific drugs for cancer patients based on alterations in their genome. However, accurate sequencing cannot be performed in cancers harboring diffuse tumor cells because of low tumor content. We performed tumor cell enrichment using tissue suspension of formalin-fixed, paraffin-embedded (FFPE) tissue sections with low tumor cell content. The enriched fractions were used to efficiently identify mutations by sequencing a target panel of cancer-related genes. Tumor-enriched and residual fractions were isolated from FFPE tissue sections of intestinal and diffuse gastric cancers harboring diffuse tumor cells and DNA of suitable quality was isolated for next-generation sequencing. Sequencing of a target panel of cancer-related genes using the tumor-enriched fraction increased the number of detectable mutations and variant allele frequency. Furthermore, mutation analysis of DNA isolated from tumor-enriched and residual fractions allowed us to estimate germline mutations without a blood reference. This approach of tumor cell enrichment will not only enhance the success rate of target panel sequencing, but can also improve the accuracy of detection of somatic mutations in archived specimens.
Mechanoporation enables rapid and efficient radiolabeling of stem cells for PET imaging
Authors: Jung Kyung Oh , Theruvath Ashok Joseph , Nejadnik Hossein , Liu Anna , Xing Lei , Sulchek Todd , Daldrup-Link Heike E. , Pratx Guillem
Published: February 2022

Regenerative medicine uses the patient own stem cells to regenerate damaged tissues. Molecular imaging techniques are commonly used to image the transplanted cells, either right after surgery or at a later time. However, few techniques are fast or straightforward enough to label cells intraoperatively. Adipose tissue-derived stem cells (ADSCs) were harvested from knee joints of minipigs. The cells were labeled with PET contrast agent by flowing mechanoporation using a microfluidic device. While flowing through a series of microchannels, cells are compressed repeatedly by micro-ridges, which open transient pores in their membranes and induce convective transport, intended to facilitate the transport of 68Ga-labeled and lipid-coated mesoporous nanoparticles (MSNs) into the cells. This process enables cells to be labeled in a matter of seconds. Cells labeled with this approach were then implanted into cartilage defects, and the implant was imaged using positron emission tomography (PET) post-surgery. The microfluidic device can efficiently label millions of cells with 68Ga-labeled MSNs in as little as 15 min. The method achieved labeling efficiency greater than 5 Bq/cell on average, comparable to 30 min-long passive co-incubation with 68Ga-MSNs, but with improved biocompatibility due to the reduced exposure to ionizing radiation. Labeling time could also be accelerated by increasing throughput through more parallel channels. Finally, as a proof of concept, ADSCs were labeled with 68Ga-MSNs and quantitatively assessed using clinical PET/MR in a mock transplant operation in pig knee joints. MSN-assisted mechanoporation is a rapid, effective and straightforward approach to label cells with 68Ga. Given its high efficiency, this labeling method can be used to track small cells populations without significant effects on viability. The system is applicable to a variety of cell tracking studies for cancer therapy, regenerative therapy, and immunotherapy.
Mutations in the stator protein PomA affect switching of rotational direction in bacterial flagellar motor
Authors: Terashima Hiroyuki , Hori Kiyoshiro , Ihara Kunio , Homma Michio , Kojima Seiji
Published: February 2022

The flagellar motor rotates bi-directionally in counter-clockwise (CCW) and clockwise (CW) directions. The motor consists of a stator and a rotor. Recent structural studies have revealed that the stator is composed of a pentameric ring of A subunits and a dimer axis of B subunits. Highly conserved charged and neighboring residues of the A subunit interacts with the rotor, generating torque through a gear-like mechanism. The rotational direction is controlled by chemotaxis signaling transmitted to the rotor, with less evidence for the stator being involved. In this study, we report novel mutations that affect the switching of the rotational direction at the putative interaction site of the stator to generate rotational force. Our results highlight an aspect of flagellar motor function that appropriate switching of the interaction states between the stator and rotor is critical for controlling the rotational direction.