bluuebunny/crossref_metadata_2025 huggingface dataset:
A modular vaccine platform enabled by decoration of bacterial outer membrane vesicles with biotinylated antigens
Authors: Weyant Kevin B. , Oloyede Ayomide , Pal Sukumar , Liao Julie , Jesus Mariela Rivera-De , Jaroentomeechai Thapakorn , Moeller Tyler D. , Hoang-Phou Steven , Gilmore Sean F. , Singh Riya , Pan Daniel C. , Putnam David , Locher Christopher , de la Maza Luis M. , Coleman Matthew A. , DeLisa Matthew P.
Published: January 2023

Engineered outer membrane vesicles (OMVs) derived from Gram-negative bacteria are a promising technology for the creation of non-infectious, nanoparticle vaccines against diverse pathogens. However, antigen display on OMVs can be difficult to control and highly variable due to bottlenecks in protein expression and localization to the outer membrane of the host cell, especially for bulky and/or complex antigens. Here, we describe a universal approach for avidin-based vaccine antigen crosslinking (AvidVax) whereby biotinylated antigens are linked to the exterior of OMVs whose surfaces are remodeled with multiple copies of a synthetic antigen-binding protein (SNAP) comprised of an outer membrane scaffold protein fused to a biotin-binding protein. We show that SNAP-OMVs can be readily decorated with a molecularly diverse array of biotinylated subunit antigens, including globular and membrane proteins, glycans and glycoconjugates, haptens, lipids, and short peptides. When the resulting OMV formulations are injected in mice, strong antigen-specific antibody responses are observed that depend on the physical coupling between the antigen and SNAP-OMV delivery vehicle. Overall, these results demonstrate AvidVax as a modular platform that enables rapid and simplified assembly of antigen-studded OMVs for application as vaccines against pathogenic threats.
Adipose-specific deletion of the cation channel TRPM7 inhibits TAK1 kinase-dependent inflammation and obesity in male mice
Authors: Zhong Weiting , Ma Mingming , Xie Jingwen , Huang Chengcui , Li Xiaoyan , Gao Min
Published: January 2023

Chronic inflammation of white adipose tissue is a key link between obesity and the associated metabolic syndrome. Transient receptor potential melastatin-like 7 (TRPM7) is known to be related to inflammation; however, the role of TRPM7 in adipocyte phenotype and function in obesity remains unclear. Here, we observe that the activation of adipocyte TRPM7 plays an essential role in pro-inflammatory responses. Adult male mice are used in our experiments. Adipocyte-specific deficiency in TRPM7 attenuates the pro-inflammatory phenotype, improves glucose homeostasis, and suppresses weight gain in mice fed a high-fat diet. Mechanistically, the pro-inflammatory effect of TRPM7 is dependent on Ca2+ signaling. Ca2+ influx initiated by TRPM7 enhances transforming growth factor-β activated kinase 1 activation via the co-regulation of calcium/calmodulin-dependent protein kinase II and tumor necrosis factor receptor-associated factor 6, leading to exacerbated nuclear factor kappa B signaling. Additionally, obese mice treated with TRPM7 inhibitor are protected against obesity and insulin resistance. Our results demonstrate TRPM7 as a factor in the development of adipose inflammation that regulates insulin sensitivity in obesity.
Molecular elucidation of drug-induced abnormal assemblies of the hepatitis B virus capsid protein by solid-state NMR
Authors: Lecoq Lauriane , Brigandat Louis , Huber Rebecca , Fogeron Marie-Laure , Wang Shishan , Dujardin Marie , Briday Mathilde , Wiegand Thomas , Callon Morgane , Malär Alexander , Durantel David , Burdette Dara , Berke Jan Martin , Meier Beat H. , Nassal Michael , Böckmann Anja
Published: January 2023

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a recent class of anti-HBV antivirals. CAMs disturb proper nucleocapsid assembly, by inducing formation of either aberrant assemblies (CAM-A) or of apparently normal but genome-less empty capsids (CAM-E). Classical structural approaches have revealed the CAM binding sites on the capsid protein (Cp), but conformational information on the CAM-induced off-path aberrant assemblies is lacking. Here we show that solid-state NMR can provide such information, including for wild-type full-length Cp183, and we find that in these assemblies, the asymmetric unit comprises a single Cp molecule rather than the four quasi-equivalent conformers typical for the icosahedral T = 4 symmetry of the normal HBV capsids. Furthermore, while in contrast to truncated Cp149, full-length Cp183 assemblies appear, on the mesoscopic level, unaffected by CAM-A, NMR reveals that on the molecular level, Cp183 assemblies are equally aberrant. Finally, we use a eukaryotic cell-free system to reveal how CAMs modulate capsid-RNA interactions and capsid phosphorylation. Our results establish a structural view on assembly modulation of the HBV capsid, and they provide a rationale for recently observed differences between in-cell versus in vitro capsid assembly modulation.
Mindset and perceived parental support of autonomy safeguard adolescents’ autonomous motivation during COVID-19 home-based learning
Authors: Benneker Ilona M. B. , Lee Nikki C. , van Atteveldt Nienke
Published: January 2023

During school closures throughout the COVID-19 pandemic, less support from peers and teachers may have required more autonomous motivation from adolescents. Little is known about factors that could shield against these negative effects. Driven by two influential motivational theories, we examined how mindset, feelings of school burnout and the three basic psychological needs of the self-determination theory, could predict changes in autonomous motivation when controlling for pre-pandemic levels of motivation. The results from a sample of Dutch adolescents (Mage = 14.63 years) and their parents (Mage = 48.65 years) showed that endorsing a growth mindset was positively associated with autonomous motivation during the school closures, while feelings of school burnout were negatively associated with autonomous motivation. Additionally, perceived parental autonomy support (i.e. a measure of the basic psychological need of autonomy) related to more autonomous motivation during home-based learning. Our findings highlight the personal and family factors that influence how adolescents respond to home-based learning and suggest ways to keep adolescents motivated and diminish possible negative consequences during future home-based learning situations.
Influence of the ultra-fine fly ash dosages on the mechanical properties of the sulfoaluminate cement-based high water backfilling material
Authors: Sun Yaohui , Xie Shengrong , Wu Chaowen , Cui Junqi , Chen Dongdong , Guo Fangfang , Jiang Zaisheng , Ren Yuxin , Lu Weiyong
Published: January 2023

To reduce the filling cost of high-water backfilling material (HWBM) in mining backfill and improve the recycling utilization of the industrial waste such as the coal fly ash. The ultra-fine fly ash (UFA) was added to the HWBM as a partial replacement in this work. Therefore, a series of experiments were performed to investigate the effect of UFA on the mechanical properties of the HWBM at the different curing conditions, then the hydration mechanism of the HWBM blended with UFA was analyzed by XRD and SEM method. The result indicates that the strength of the HWBM decreased with the increasing of UFA dosages, but the addition of UFA can improve the residual strength of the initial HWBM. Additionally, when the HWBM was cured at the laboratory air condition, its carbonation process was restrained obviously as the UFA dosages were less than 15% at the ages of 28 days, which indicates the UFA can improve the weathering resistance of the HWBM with the curing ages increasing effectively. The XRD and SEM results also shows that the degree of crystallinity of the HWBM increased when UFA dosages were less than 15% effectively, while there were few obvious changes on types of hydration products. It indicates that the main affects of UFA on the performance of HWBM is filler and dilution, which reduced the contact area between hydration products of HWBM and CO2 in the air, further improved the carbonation resistance of HWBM.
Using Bayesian networks with Tabu-search algorithm to explore risk factors for hyperhomocysteinemia
Authors: Song Wenzhu , Qin Zhiqi , Hu Xueli , Han Huimin , Li Aizhong , Zhou Xiaoshaung , Li Yafeng , Li Rongshan
Published: January 2023

Hyperhomocysteinemia (HHcy) is a condition closely associated with cardiovascular and cerebrovascular diseases. Detecting its risk factors and taking some relevant interventions still represent the top priority to lower its prevalence. Yet, in discussing risk factors, Logistic regression model is usually adopted but accompanied by some defects. In this study, a Tabu Search-based BNs was first constructed for HHcy and its risk factors, and the conditional probability between nodes was calculated using Maximum Likelihood Estimation. Besides, we tried to compare its performance with Hill Climbing-based BNs and Logistic regression model in risk factor detection and discuss its prospect in clinical practice. Our study found that Age, sex, α1-microgloblobumin to creatinine ratio, fasting plasma glucose, diet and systolic blood pressure represent direct risk factors for HHcy, and smoking, glycosylated hemoglobin and BMI constitute indirect risk factors for HHcy. Besides, the performance of Tabu Search-based BNs is better than Hill Climbing-based BNs. Accordingly, BNs with Tabu Search algorithm could be a supplement for Logistic regression, allowing for exploring the complex network relationship and the overall linkage between HHcy and its risk factors. Besides, Bayesian reasoning allows for risk prediction of HHcy, which is more reasonable in clinical practice and thus should be promoted.
Lymphatic insufficiency leads to distinct myocardial infarct content assessed by magnetic resonance TRAFFn, T1ρ and T2 relaxation times
Authors: Ylä-Herttuala Elias , Vuorio Taina , Kettunen Sanna , Laidinen Svetlana , Ylä-Herttuala Seppo , Liimatainen Timo
Published: January 2023

The role of cardiac lymphatics in the pathogenesis of myocardial infarction (MI) is unclear. Lymphatic system regulates cardiac physiological processes such as edema and tissue fluid balance, which affect MI pathogenesis. Recently, MI and fibrosis have been assessed using endogenous contrast in magnetic resonance imaging (MRI) based on the relaxation along a fictitious field with rank n (RAFFn). We extended the RAFFn applications to evaluate the effects of lymphatic insufficiency on MI with comparison to longitudinal rotating frame (T1ρ) and T2relaxation times. MI was induced in transgenic (TG) mice expressing soluble decoy VEGF receptor 3 that reduces lymphatic vessel formation and their wild-type (WT) control littermates for comparison. The RAFFn relaxation times with rank 2 (TRAFF2), and rank 4 (TRAFF4), T1ρand T2were acquired at time points 0, 3, 7, 21 and 42 days after the MI at 9.4 T. Infarct sizes were determined based on TRAFF2, TRAFF4, T1ρand T2relaxation time maps. The area of differences (AOD) was calculated based on the MI areas determined on T2and TRAFF2, TRAFF4or T1ρrelaxation time maps. Hematoxylin–eosin and Sirius red stained histology sections were prepared to confirm MI locations and sizes. MI was detected as increased TRAFF2, TRAFF4, T1ρand T2relaxation times. Infarct sizes were similar on all relaxation time maps during the experimental period. Significantly larger AOD values were found together with increased AOD values in the TG group compared to the WT group. Histology confirmed these findings. The lymphatic deficiency was found to increase cardiac edema in MI. The combination of TRAFF2(or TRAFF4) and T2characterizes MI and edema in the myocardium in both lymphatic insufficiency and normal mice without any contrast agents.
Application of 3D printing technology for pre-operative evaluation, education and informed consent in pediatric retroperitoneal tumors
Authors: Youn Joong Kee , Park Sang Joon , Choi Young-Hun , Han Ji-Won , Ko Dayoung , Byun Jeik , Yang Hee-Beom , Kim Hyun-Young
Published: January 2023

To investigate usefulness of 3D printing for preoperative evaluations, student and resident education, and communication with parents or guardians of patients with pediatric retroperitoneal tumors. Ten patients planning retroperitoneal tumor resection between March and November 2019 were included. Preoperative computed tomography (CT) images were used for 3D reconstruction and printing. Surveyed items were understanding of preoperative lesions with 3 different modules (CT, 3D reconstruction, and 3D printing) by students, residents, and specialists; satisfaction of specialists; and comprehension by guardians after preoperative explanations with each module. The median age at operation was 4.2 years (range, 1.8–18.1), and 8 patients were diagnosed with neuroblastoma. The 3D printing was the most understandable module for all groups (for students, residents, and specialists, P = 0.002, 0.027, 0.013, respectively). No significant intraoperative adverse events or immediate postoperative complications occurred. All specialists stated that 3D printing enhanced their understanding of cases. Guardians answered that 3D printing were the easiest to comprehend among the 3 modules (P = 0.007). Use of 3D printing in treatment of pediatric patients with retroperitoneal tumors was useful for preoperative planning, education, and parental explaining with obtaining informed consents.
Privacy-preserving cancer type prediction with homomorphic encryption
Authors: Sarkar Esha , Chielle Eduardo , Gursoy Gamze , Chen Leo , Gerstein Mark , Maniatakos Michail
Published: January 2023

Cancer genomics tailors diagnosis and treatment based on an individual’s genetic information and is the crux of precision medicine. However, analysis and maintenance of high volume of genetic mutation data to build a machine learning (ML) model to predict the cancer type is a computationally expensive task and is often outsourced to powerful cloud servers, raising critical privacy concerns for patients’ data. Homomorphic encryption (HE) enables computation on encrypted data, thus, providing cryptographic guarantees to protect privacy. But restrictive overheads of encrypted computation deter its usage. In this work, we explore the challenges of privacy preserving cancer type prediction using a dataset consisting of more than 2 million genetic mutations from 2713 patients for several cancer types by building a highly accurate ML model and then implementing its privacy preserving version in HE. Our solution for cancer type inference encodes somatic mutations based on their impact on the cancer genomes into the feature space and then uses statistical tests for feature selection. We propose a fast matrix multiplication algorithm for HE-based model. Our final model achieves 0.98 micro-average area under curve improving accuracy from 70.08 to 83.61% , being 550 times faster than the standard matrix multiplication-based privacy-preserving models. Our tool can be found athttps://github.com/momalab/octal-candet.
CT Hounsfield unit is a reliable parameter for screws loosening or cages subsidence in minimally invasive transforaminal lumbar interbody fusion
Authors: Yao Yu-Cheng , Chao Hsien , Kao Kun-Yu , Lin Hsi-Hsien , Wang Shih-Tien , Chang Ming-Chau , Liu Chien-Lin , Chou Po-Hsin
Published: January 2023

Retrospective cohort study. To validate computed tomography (CT) radiodensity in Hounsfield units (HU) as a prognostic marker for pedicle screw loosening or cage subsidence in minimally invasive transforaminal lumbar interbody fusion (MI-TLIF). The retrospective study involved 198 patients treated with MI-TLIF. Screw loosening (SL), cage subsidence (CS), and fusion status were assessed by plain radiographs. The risk factors of SL and CS were identified using logistic regression. A total of 258 levels and 930 screws were analyzed. During a 2-year follow-up, 16.2% and 24.7% of patients had CS and SL respectively. The cut-off value of L1 HU for predicting SL or CS was 117. The L1 HU < 117 and BMI ≥ 25 were two independent risk factors. The risk of SL or CS was 4.1 fold in patients L1 HU < 117 and 2.6 fold in patients with BMI ≥ 25. For patients concurrently having BMI ≥ 25 and pre-op L1 HU < 117, the risk was 4.3 fold. Fusion rate and clinical outcome were comparable in patients with SL or CS. L1 HU < 117 and BMI > 25 were two independent risk factors that can be screened preoperatively for preventing SL or CS and lead to better management of patients undergoing MI-TLIF.
Centralized Space Learning for open-set computer-aided diagnosis
Authors: Yu Zhongzhi , Shi Yemin
Published: January 2023

In computer-aided diagnosis (CAD), diagnosing untrained diseases as known categories will cause serious medical accidents, which makes it crucial to distinguish the new class (open set) meanwhile preserving the known classes (closed set) performance so as to enhance the robustness. However, how to accurately define the decision boundary between known and unknown classes is still an open problem, as unknown classes are never seen during the training process, especially in medical area. Moreover, manipulating the latent distribution of known classes further influences the unknown’s and makes it even harder. In this paper, we propose the Centralized Space Learning (CSL) method to address the open-set recognition problem in CADs by learning a centralized space to separate the known and unknown classes with the assistance of proxy images generated by a generative adversarial network (GAN). With three steps, including known space initialization, unknown anchor generation and centralized space refinement, CSL learns the optimized space distribution with unknown samples cluster around the center while the known spread away from the center, achieving a significant identification between the known and the unknown. Extensive experiments on multiple datasets and tasks illustrate the proposed CSL’s practicability in CAD and the state-of-the-art open-set recognition performance.
Developing a metabolic clearance rate framework as a translational analysis approach for hyperpolarized 13C magnetic resonance imaging
Authors: Grist James T. , Bøgh Nikolaj , Hansen Esben Søvsø , Schneider Anna M. , Healicon Richard , Ball Vicky , Miller Jack J. J. J. , Smart Sean , Couch Yvonne , Buchan Alastair M. , Tyler Damian J. , Laustsen Christoffer
Published: January 2023

Hyperpolarized carbon-13 magnetic resonance imaging is a promising technique for in vivo metabolic interrogation of alterations between health and disease. This study introduces a formalism for quantifying the metabolic information in hyperpolarized imaging. This study investigated a novel perfusion formalism and metabolic clearance rate (MCR) model in pre-clinical stroke and in the healthy human brain. Simulations showed that the proposed model was robust to perturbations in T1, transmit B1, and kPL. A significant difference in ipsilateral vs contralateral pyruvate derived cerebral blood flow (CBF) was detected in rats (140 ± 2 vs 89 ± 6 mL/100 g/min, p < 0.01, respectively) and pigs (139 ± 12 vs 95 ± 5 mL/100 g/min, p = 0.04, respectively), along with an increase in fractional metabolism (26 ± 5 vs 4 ± 2%, p < 0.01, respectively) in the rodent brain. In addition, a significant increase in ipsilateral vs contralateral MCR (0.034 ± 0.007 vs 0.017 ± 0.02/s, p = 0.03, respectively) and a decrease in mean transit time (31 ± 8 vs 60 ± 2 s, p = 0.04, respectively) was observed in the porcine brain. In conclusion, MCR mapping is a simple and robust approach to the post-processing of hyperpolarized magnetic resonance imaging.
Prediction of heavy metal biosorption mechanism through studying isotherm kinetic equations
Authors: Fadl Mostafa G.
Published: January 2023

The kinetic constants for free and immobilized cells were determined by measuring reaction rates at different metal concentrations at the optimum reaction conditions. (Kmax and Vmax) were calculated from the slope and intercept of the straight lines. The pseudo-second-order rate constants are derived based on the sorption capacity of the solid phase, where K2 is the rate constant for the pseudo-second-order model. Determined experimentally by plotting t/q against t. The mean free vitality of adsorption (E) was figured as 2.62 kJ mol−1 and the extent of E communicated gives data on the adsorption mechanism. An E value ranging from 1 to 8 indicates physisorption and 8–16 kJ mol−1 predicts ion exchange. Thus, the evaluated value of 2.62 kJ mol−1 predicts the phenomenon of physisorption, which suggests that metal ions were favorably adsorbed by this biosorbent in a multi-layer fashion. The overall result suggested that 98.2% of U (VI) by biosorption of U in the mechanism of adsorption will include chemisorption mechanistic pathway: Langmuir, Freundlich, equations and the values of Kf 5.791 where KL 3.9 were determined from the linear plot of log qe vs. log Ce at 30 °C, indicating that metal ions were favorably adsorbed by this biosorbent in a multi-layer fashion and instrumentation of beads characterizing novel Binding sites using FTIR & SEM beside change in peaks position which assigned for its groups confirm biosorption of metal.
A selective laser-based sensor for fugitive methane emissions
Authors: Mhanna Mhanna , Sy Mohamed , Farooq Aamir
Published: January 2023

A mid-infrared laser-based sensor is reported for the quantification of fugitive methane emissions. The sensor is based on a distributed feedback inter-band cascade laser operating near 3.3 μm. Wavelength tuning with cepstral analysis is employed to isolate methane absorbance from (1) fluctuations in the baseline laser intensity, and (2) interfering species. Cepstral analysis creates a modified form of the time-domain molecular free-induction-decay (m-FID) signal to temporally separate optical and molecular responses. The developed sensor is insensitive to baseline laser intensity imperfections and spectral interference from other species. Accurate measurements of methane in the presence of a representative interfering species, benzene, are performed by careful selection of the scan index (ratio of laser tuning range to spectral linewidth) and initial and final time of m-FID signal fitting. The minimum detection limit of the sensor is ~ 110 ppm which can be enhanced with an optical cavity. The proposed sensing strategy can be utilized to measure methane leaks in harsh environments and in the presence of interfering species in environment-monitoring applications.
TPPU inhibits inflammation-induced excessive autophagy to restore the osteogenic differentiation potential of stem cells and improves alveolar ridge preservation
Authors: Dang Haixia , Chen Weixian , Chen Lan , Huo Xinru , Wang Fu
Published: January 2023

Inflammation-induced autophagy is a double-edged sword. Dysfunction of autophagy impairs the differentiation capacity of mesenchymal stem cells and enhances inflammation-induced bone loss. Tooth extraction with periodontal and/or endodontic lesions exacerbates horizontal and vertical resorption of alveolar bone during the healing period. Alveolar socket preservation (ASP) procedure following tooth extraction has important clinical implications for future prosthodontic treatments. Studies have shown that epoxyeicosatrienoic acids (EETs) have significant anti-inflammatory effects and participate in autophagy. However, whether EETs can minimize alveolar bone resorption and contribute to ASP by regulating autophagy levels under inflammatory conditions remain elusive. Here, we figured out that LPS-induced inflammatory conditions increased the inflammatory cytokine and inhibited osteogenic differentiation of human dental pulp stem cells (hDPSCs), and led to excessive autophagy of hDPSCs. Moreover, we identified that increased EETs levels using TPPU, a soluble epoxide hydrolase inhibitor, reversed these negative outcomes. We further demonstrated the potential of TPPU to promote early healing of extraction sockets and ASP, and speculated that it was related to autophagy. Taken together, these results suggest that targeting inhibition of soluble epoxide hydrolase using TPPU plays a protective role in the differentiation and autophagy of mesenchymal stem cells and provides potential feasibility for applying TPPU for ASP, especially under inflammatory conditions.
Magnetic and electronic properties unveil polaron formation in Eu$$_5$$In$$_2$$Sb$$_6$$
Authors: Ale Crivillero M. Victoria , Rößler Sahana , Granovsky S. , Doerr M. , Cook M. S. , Rosa Priscila F. S. , Müller J. , Wirth S.
Published: January 2023

The intermetallic compound Eu$$_5$$

5

In$$_2$$

2

Sb$$_6$$

6

, an antiferromagnetic material with nonsymmorphic crystalline structure, is investigated by magnetic, electronic transport and specific heat measurements. Being a Zintl phase, insulating behavior is expected. Our thermodynamic and magnetotransport measurements along different crystallographic directions strongly indicate polaron formation well above the magnetic ordering temperatures. Pronounced anisotropies of the magnetic and transport properties even above the magnetic ordering temperature are observed despite the Eu$$^{2+}$$

2
+

configuration which testify to complex and competing magnetic interactions between these ions and give rise to intricate phase diagrams discussed in detail. Our results provide a comprehensive framework for further detailed study of this multifaceted compound with possible nontrivial topology.
Network-based validation of the psychometric questionnaire EDI-3 for the assessment of eating disorders
Authors: Punzi Clara , Tieri Paolo , Girelli Laura , Petti Manuela
Published: January 2023

Assessing the validity of a psychometric test is fundamental to ensure a reliable interpretation of its outcomes. Few attempts have been made recently to complement classical approaches (e.g., factor models) with a novel technique based on network analysis. The objective of the current study is to carry out a network-based validation of the Eating Disorder Inventory 3 (EDI-3), a questionnaire designed for the assessment of eating disorders. Exploiting a reliable, open source sample of 1206 patients diagnosed with an eating disorder, we set up a robust validation process encompassing detection and handling of redundant EDI-3 items, estimation of the cross-sample psychometric network, resampling bootstrap procedure and computation of the median network of the replica samples. We then employed a community detection algorithm to identify the topological clusters, evaluated their coherence with the EDI-3 subscales and replicated the full validation analysis on the subpopulations corresponding to patients diagnosed with either anorexia nervosa or bulimia nervosa. Results of the network-based analysis, and particularly the topological community structures, provided support for almost all the composite scores of the EDI-3 and for 2 single subscales: Bulimia and Maturity Fear. A moderate instability of some dimensions led to the identification of a few multidimensional items that should be better located in the intersection of multiple psychological scales. We also found that, besides symptoms typically attributed to eating disorders, such as drive for thinness, also non-specific symptoms like low self-esteem and interoceptive deficits play a central role in both the cross-sample and the diagnosis-specific networks. Our work adds insights into the complex and multidimensional structure of EDI-3 by providing support to its network-based validity on both mixed and diagnosis-specific samples. Moreover, we replicated previous results that reinforce the transdiagnostic theory of eating disorders.
Laterality of blood perfusion in the lower extremities after drinking saline at different temperatures
Authors: Jia Shuyong , Wang Qizhen , Li Hongyan , Song Xiaojing , Wang Shuyou , Zhang Weibo , Wang Guangjun
Published: January 2023

Skin blood flux (SkBF) changes caused by drinking cold water are generally associated with vagal tone and osmotic factors in the digestive system. However, there is still a lack of relevant research on whether there are left and right differences in these SkBF change. In the current study, a total of 60 subjects were recruited. Skin blood perfusion of the bilateral lower extremities was recorded simultaneously before and after drinking saline of different temperatures saline by using Laser Doppler flowmetry (LDF). The electrogastrogram (EGG) was also monitored, and the dominant frequency of the EGG and heart rate variability were analyzed. The results indicated that after drinking saline, the laterality index of SkBF at the lower extremities was different and the laterality index changes of SkBF were mainly reflected in the frequency interval V (0.4–1.6 Hz). There was a weak negative correlation between the laterality index of endothelial NO-dependent component and change rate of root mean square of successive differences (RMSSD) after drinking 4 °C saline. However, after drinking 30 °C saline, there was a weak positive correlation between neurogenic component and RMSSD The distribution and regulation of bilateral blood flow are not symmetrical but exhibit a certain laterality.
Development of MRI-based radiomics predictive model for classifying endometrial lesions
Authors: Liu Jiaqi , Li Shiyun , Lin Huashan , Pang Peiei , Luo Puying , Fan Bing , Yu Juhong
Published: January 2023

An unbiased and accurate diagnosis of benign and malignant endometrial lesions is essential for the gynecologist, as each type might require distinct treatment. Radiomics is a quantitative method that could facilitate deep mining of information and quantification of the heterogeneity in images, thereby aiding clinicians in proper lesion diagnosis. The aim of this study is to develop an appropriate predictive model for the classification of benign and malignant endometrial lesions, and evaluate potential clinical applicability of the model. 139 patients with pathologically-confirmed endometrial lesions from January 2018 to July 2020 in two independent centers (center A and B) were finally analyzed. Center A was used for training set, while center B was used for test set. The lesions were manually drawn on the largest slice based on the lesion area by two radiologists. After feature extraction and feature selection, the possible associations between radiomics features and clinical parameters were assessed by Uni- and multi- variable logistic regression. The receiver operator characteristic (ROC) curve and DeLong validation were employed to evaluate the possible predictive performance of the models. Decision curve analysis (DCA) was used to evaluate the net benefit of the radiomics nomogram. A radiomics prediction model was established from the 15 selected features, and were found to be relatively high discriminative on the basis of the area under the ROC curve (AUC) for both the training and the test cohorts (AUC = 0.90 and 0.85, respectively). The radiomics nomogram also showed good performance of discrimination for both the training and test cohorts (AUC = 0.91 and 0.86, respectively), and the DeLong test shows that AUCs were significantly different between clinical parameters and nomogram. The result of DCA demonstrated the clinical usefulness of this novel nomogram method. The predictive model constructed based on MRI radiomics and clinical parameters indicated a highly diagnostic efficiency, thereby implying its potential clinical usefulness for the precise identification and prediction of endometrial lesions.
The association of postoperative global femoral offset with total hip arthroplasty outcomes
Authors: Hirano Yuki , Imai Norio , Nozaki Asami , Horigome Yoji , Suzuki Hayato , Kawashima Hiroyuki
Published: January 2023

Global femoral offset (GFO) and femoral offset (FO) reportedly affect outcomes following total hip arthroplasty (THA). However, FO assessed using plain radiography is affected by internal and external rotations of the hip joint. We investigated the relationship between leg length discrepancy and Harris hip score (HHS), and their influence on acetabular offset (AO), FO, GFO, anterior femoral offset, and outcomes after THA. We retrospectively evaluated 140 patients with hip osteoarthritis who underwent THA. A three-dimensional (3D) pelvis and femur model created from computed tomography (data using ZedHip software was used to investigate these parameters. The modified (m)HHS scores were significantly improved from 49.0 to 88.8 in total mHHS, 20.0–44.5 in pain, and 28.9–44.4 points in function. Significant correlations were found between the differences in AO, FO, GFO, and pain score in binominal, with maximum values of − 1.24, + 1.54, and + 0.90 mm/100 cm body height, respectively. The maximum value of GFO and mHHS in binominal was + 1.17 mm/100 cm body height (BH). The optimal range of difference of GFO was − 1.75 to 4.09 mm/100 cm BH. This is the first report using a 3D method for assessing FO. Preoperative planning using the system could improve postoperative function.
Psychological measures of stress and biomarkers of inflammation, aging, and endothelial dysfunction in breast cancer survivors on aromatase inhibitors
Authors: Blaes Anne H. , Nair Chandini , Everson-Rose Susan , Jewett Patricia , Wolf Jack , Zordoky Beshay
Published: January 2023

The use of aromatase inhibitors (AIs) is associated with higher rates of cardiovascular events and lower endothelial function in breast cancer survivors. Psychosocial stress is associated with higher levels of inflammatory and aging markers, and lower endothelial function in otherwise healthy subjects. These associations among breast cancer survivors on AIs are not well defined. A cross-sectional study of 30 breast cancer survivors on AIs was performed to assess the associations between self-reported scores of psychosocial measures of depression, anxiety, and stress assessed by validated questionnaires with markers of inflammation (CRP; IL-6; IL-18), aging (p16INK4a), and endothelial function (ICAM-1, EndoPAT ratio). Significant positive correlations were observed between psychosocial measures and inflammatory markers including CRP, IL-6, and ICAM-1. However, no psychosocial scores were related to endothelial function or gene expression of the aging biomarker p16INK4a. Overall, survivors had endothelial dysfunction with reduced EndoPAT ratios. Psychosocial stress is associated with greater inflammation in breast cancer survivors on AIs, corroborating previous studies in cancer-free populations. The lack of association between psychosocial stress and either endothelial function or aging biomarkers could be due to the already low endothelial function and accelerated aging in our cohort of breast cancer survivors on AIs, though our small sample size limits conclusions. Further work in a larger and more diverse cohort of patients is needed to further understand the relationships among inflammation, aging and endothelial function in breast cancer survivors.
A novel ultrasound image diagnostic method for thyroid nodules
Authors: Zheng Zhiqiang , Su Tianyi , Wang Yuhe , Weng Zhi , Chai Jun , Bu Wenjin , Xu Jinjin , Chen Jiarui
Published: January 2023

The incidence of thyroid nodules is increasing year by year. Accurate determination of benign and malignant nodules is an important basis for formulating treatment plans. Ultrasonography is the most widely used methodology in the diagnosis of benign and malignant nodules, but diagnosis by doctors is highly subjective, and the rates of missed diagnosis and misdiagnosis are high. To improve the accuracy of clinical diagnosis, this paper proposes a new diagnostic model based on deep learning. The diagnostic model adopts the diagnostic strategy of localization-classification. First, the distribution laws of the nodule size and nodule aspect ratio are obtained through data statistics, a multiscale localization network structure is a priori designed, and the nodule aspect ratio is obtained from the positioning results. Then, uncropped ultrasound images and nodule area image are correspondingly input into a two-way classification network, and an improved attention mechanism is used to enhance the feature extraction performance. Finally, the deep features, the shallow features, and the nodule aspect ratio are fused, and a fully connected layer is used to complete the classification of benign and malignant nodules. The experimental dataset consists of 4021 ultrasound images, where each image has been labeled under the guidance of doctors, and the ratio of the training set, validation set, and test set sizes is close to 3:1:1. The experimental results show that the accuracy of the multiscale localization network reaches 93.74%, and that the accuracy, specificity, and sensitivity of the classification network reach 86.34%, 81.29%, and 90.48%, respectively. Compared with the champion model of the TNSCUI 2020 classification competition, the accuracy rate is 1.52 points higher. Therefore, the network model proposed in this paper can effectively diagnose benign and malignant thyroid nodules.
Coronary artery disease patient-derived iPSC-hepatocytes have distinct miRNA profile that may alter lipid metabolism
Authors: Alexanova Anna , Raitoharju Emma , Valtonen Joona , Aalto-Setälä Katriina , Viiri Leena E.
Published: January 2023

Metabolic dysfunction, partly driven by altered liver function, predisposes to coronary artery disease (CAD), but the role of liver in vulnerable atherosclerotic plaque development remains unclear. Here we produced hepatocyte-like cells (HLCs) from 27 induced pluripotent stem cell (iPSC) lines derived from 15 study subjects with stable CAD (n = 5), acute CAD (n = 5) or healthy controls (n = 5). We performed a miRNA microarray screening throughout the differentiation, as well as compared iPSC-HLCs miRNA profiles of the patient groups to identify miRNAs involved in the development of CAD. MicroRNA profile changed during differentiation and started to resemble that of the primary human hepatocytes. In the microarray, 35 and 87 miRNAs were statistically significantly deregulated in the acute and stable CAD patients, respectively, compared to controls. Down-regulation of miR-149-5p, -92a-3p and -221-3p, and up-regulation of miR-122-5p was verified in the stable CAD patients when compared to other groups. The predicted targets of deregulated miRNAs were enriched in pathways connected to insulin signalling, inflammation and lipid metabolism. The iPSC-HLCs derived from stable CAD patients with extensive lesions had a distinct genetic miRNA profile possibly linked to metabolic dysfunction, potentially explaining the susceptibility to developing CAD. The iPSC-HLCs from acute CAD patients with only the acute rupture in otherwise healthy coronaries did not present a distinct miRNA profile, suggesting that hepatic miRNAs do not explain susceptibility to plaque rupture.
Generation of Gαi knock-out HEK293 cells illuminates Gαi-coupling diversity of GPCRs
Authors: Ono Yuki , Kawakami Kouki , Nakamura Gaku , Ishida Satoru , Aoki Junken , Inoue Asuka
Published: January 2023

G-protein-coupled receptors (GPCRs) are pivotal cell membrane proteins that sense extracellular molecules and activate cellular responses. The G-protein α subunit i (Gαi) family represents the most common GPCR-coupling partner and consists of eight subunits with distinct signaling properties. However, analyzing the coupling pattern has been challenging owing to endogenous expression of the Gαi subunits in virtually all cell lines. Here, we generate a HEK293 cell line lacking all Gαi subunits, which enables the measurement of GPCR-Gαi coupling upon transient re-expression of a specific Gαi subunit. We profile Gαi-coupling selectivity across 11 GPCRs by measuring ligand-induced inhibitory activity for cAMP accumulation. The coupling profiles are then classified into three clusters, representing those preferentially coupled to Gαz, those to Gαo, and those with unapparent selectivity. These results indicate that individual Gαi-coupled GPCRs fine-tune Gαi signaling by exerting coupling preference at the Gαi-subunit level.
Multivariate EEG activity reflects the Bayesian integration and the integrated Galilean relative velocity of sensory motion during sensorimotor behavior
Authors: Jeong Woojae , Kim Seolmin , Park JeongJun , Lee Joonyeol
Published: January 2023

Humans integrate multiple sources of information for action-taking, using the reliability of each source to allocate weight to the data. This reliability-weighted information integration is a crucial property of Bayesian inference. In this study, participants were asked to perform a smooth pursuit eye movement task in which we independently manipulated the reliability of pursuit target motion and the direction-of-motion cue. Through an analysis of pursuit initiation and multivariate electroencephalography activity, we found neural and behavioral evidence of Bayesian information integration: more attraction toward the cue direction was generated when the target motion was weak and unreliable. Furthermore, using mathematical modeling, we found that the neural signature of Bayesian information integration had extra-retinal origins, although most of the multivariate electroencephalography activity patterns during pursuit were best correlated with the retinal velocity errors accumulated over time. Our results demonstrated neural implementation of Bayesian inference in human oculomotor behavior.
A design of experiments screen reveals that Clostridium novyi-NT spore germinant sensing is stereoflexible for valine and its analogs
Authors: Sundaresan Ajitha , Le Ngoc Mai , Wew Marvell Ung , Ramkumar Varsha , Raninga Prahlad , Sum Rongji , Cheong Ian
Published: January 2023

Although Clostridium novyi-NT is an anti-cancer bacterial therapeutic which germinates within hypoxic tumors to kill cancer cells, the actual germination triggers for C. novyi-NT are still unknown. In this study, we screen candidate germinants using combinatorial experimental designs and discover by serendipity that D-valine is a potent germinant, inducing 50% spore germination at 4.2 mM concentration. Further investigation revealed that five D-valine analogs are also germinants and four of these analogs are enantiomeric pairs. This stereoflexible effect of L- and D-amino acids shows that spore germination is a complex process where enantiomeric interactions can be confounders. This study also identifies L-cysteine as a germinant, and hypoxanthine and inosine as co-germinants. Several other amino acids promote (L-valine, L-histidine, L-threonine and L-alanine) or inhibit (L-arginine, L-glycine, L-lysine, L-tryptophan) germination in an interaction-dependent manner. D-alanine inhibits all germination, even in complex growth media. This work lays the foundation for improving the germination efficacy of C. novyi-NT spores in tumors.
Transcription factor EB regulates phosphatidylinositol-3-phosphate levels that control lysosome positioning in the bladder cancer model
Authors: Mathur Pallavi , De Barros Santos Camilla , Lachuer Hugo , Patat Julie , Latgé Bruno , Radvanyi François , Goud Bruno , Schauer Kristine
Published: January 2023

Lysosomes orchestrate degradation and recycling of exogenous and endogenous material thus controlling cellular homeostasis. Little is known how this organelle changes during cancer. Here we investigate the intracellular landscape of lysosomes in a cellular model of bladder cancer. Employing standardized cell culture on micropatterns we identify a phenotype of peripheral lysosome positioning prevailing in bladder cancer cell lines but not normal urothelium. We show that lysosome positioning is controlled by phosphatidylinositol-3-phosphate (PtdIns3P) levels on endomembranes which recruit FYVE-domain containing proteins for lysosomal dispersion. We identify transcription factor EB (TFEB) as an upstream regulator of PtdIns3P production by VPS34 that is activated in aggressive bladder cancer cells with peripheral lysosomes. This conceptually clarifies the dual role of TFEB as regulator of endosomal maturation and autophagy, two distinct processes controlled by PtdIns3P. Altogether, our findings uncover peripheral lysosome positioning, resulting from PtdIns3P production downstream of TFEB activation, as a potential biomarker for bladder cancer.
circRNA432 enhances the coelomocyte phagocytosis via regulating the miR-2008-ELMO1 axis in Vibrio splendidus-challenged Apostichopus japonicus
Authors: Fu Xianmu , Guo Ming , Liu Jiqing , Li Chenghua
Published: January 2023

Circular RNAs (circRNAs) are a kind of extensive and diverse covalently closed circular endogenous RNA, which exert crucial functions in immune regulation in mammals. However, the functions and mechanisms of circRNAs in invertebrates are largely unclarified. In our previous work, 261 differentially expressed circRNAs including circRNA432 (circ432) were identified from skin ulcer syndrome (SUS) diseased sea cucumber Apostichopus japonicus by RNA-seq. To better address the functional role of sea cucumber circRNAs, circ432 was first found to be significantly induced by Vibrio splendidus challenge and LPS exposure in this study. Knock-down circ432 could depress the V. splendidus-induced coelomocytes phagocytosis. Moreover, circ432 is validated to serve as the sponge of miR-2008, a differential expressed miRNA in SUS-diseased sea cucumbers, by Argonaute 2-RNA immunoprecipitation (AGO2-RIP) assay, luciferase reporter assay and RNA fluorescence in situ hybridization (FISH) in vitro. Engulfment and cell motility protein 1 (AjELMO1) is further demonstrated to be the target of miR-2008, and silencing AjELMO1 inhibits the V. splendidus-induced coelomocytes phagocytosis, and this phenomenon could be further suppressed by supplementing with miR-2008 mimics, suggesting that circ432 might regulate coelomocytes phagocytosis via miR-2008-AjELMO1 axis. We further confirm that the depressed coelomocytes’ phagocytosis by circ432 silencing is consistent with the decreased abundance of AjELMO1, and could be recovered by miR-2008 inhibitors transfection. All our results provide the evidence that circ432 is involved in regulating pathogen-induced coelomocyte phagocytosis via sponge miR-2008 and promotes the abundance of AjELMO1. These findings will enrich the regulatory mechanism of phagocytosis in echinoderm and provide theoretical data for SUS disease prevention and control in sea cucumbers.
Targeted inhibition of RBPJ transcription complex alleviates the exhaustion of CD8+ T cells in hepatocellular carcinoma
Authors: Pan Banglun , Wang Zengbin , Zhang Xiaoxia , Shen Shuling , Ke Xiaoling , Qiu Jiacheng , Yao Yuxin , Wu Xiaoxuan , Wang Xiaoqian , Tang Nanhong
Published: January 2023

Impaired function of CD8+ T cells in hepatocellular carcinoma (HCC) is an important reason for acquired resistance. Compared with single-target inhibitors, small-molecule compounds that could both inhibit tumor cells and alleviate T cell exhaustion are more promising to reduce resistance. In this study, we screened immunosuppressive targets in HCC by combining cancer–immunity cycle score with weighted gene co-expression network and system analysis. Through in vitro and in vivo validation experiments, we found that one of the screened molecules, recombination signal binding protein for immunoglobulin kappa J region (RBPJ), was negatively correlated with CD8+ T cell mediated killing function. More importantly, its transcription complex inhibitor RIN1 not only inhibited the malignant biological behaviors of HCC cells by inhibiting mTOR pathway, but also reduced the expression of PD-L1 and L-kynurenine synthesis in HCC cells, thus alleviating T cell exhaustion. Meanwhile, the combination of RIN1 and anti-PD-1/PD-L1 antibodies could further activate CD8+ T cells. In short, RBPJ is an important factor regulating the function of T cells. Target inhibition of RBPJ transcription complex by small molecule compound may be a new strategy for immunotherapy of HCC.