bluuebunny/crossref_metadata_2025 huggingface dataset:
Explaining Orientation Adaptation in V1 by Updating the State of a Spatial Model
Authors: Gao Shaobing , Liu Xiao
Published: February 2022

In this work, we extend an influential statistical model based on the spatial classical receptive field (CRF) and non-classical receptive field (nCRF) interactions (Coen-Cagli et al.,2012) to explain the typical orientation adaptation effects observed in V1. If we assume that the temporal adaptation modifies the “state” of the model, the spatial statistical model can explain all of the orientation adaptation effects in the context of neuronal output using small and large grating observed in neurophysiological experiments in V1. The “state” of the model represents the internal parameters such as the prior and the covariance trained on a mixed dataset that totally determine the response of the model. These two parameters, respectively, reflect the probability of the orientation component and the connectivity among neurons between CRF and nCRF. Specifically, we have two key findings: First, neural adapted results using a small grating that just covers the CRF can be predicted by the change of the prior of our model. Second, the change of the prior can also predict most of the observed results using a large grating that covers both CRF and nCRF of a neuron. However, the prediction of the novel attractive adaptation using large grating covering both CRF and nCRF also necessitates the involvement of a connectivity change of the center-surround RFs. In addition, our paper contributes a new prior-based winner-take-all (WTA) working mechanism derived from the statistical-based model to explain why and how all of these orientation adaptation effects can be predicted by relying on this spatial model without modifying its structure, a novel application of the spatial model. The research results show that adaptation may link time and space by changing the “state” of the neural system according to a specific adaptor. Furthermore, different forms of stimulus used for adaptation can cause various adaptation effects, such as an a priori shift or a connectivity change, depending on the specific stimulus size.
Shuffling Improves the Acute and Carryover Effect of Subthalamic Coordinated Reset Deep Brain Stimulation
Authors: Wang Jing , Fergus Sinta P. , Johnson Luke A. , Nebeck Shane D. , Zhang Jianyu , Kulkarni Shivaputra , Bokil Hemant , Molnar Gregory F. , Vitek Jerrold L.
Published: February 2022

Coordinated reset deep brain stimulation (CR DBS) in the subthalamic nucleus (STN) has been demonstrated effective for the treatment of the motor signs associated with Parkinson's disease (PD). A critical CR parameter is an order in which stimulation is delivered across contacts. The relative effect of alternating vs. not alternating this order, i.e., shuffling vs. non-shuffling, however, has not been evaluated in vivo. The objective of this study is to compare the effect of shuffled vs. non-shuffled STN CR DBS on Parkinsonian motor signs. Two Parkinsonian non-human primates were implanted with a DBS lead in the STN. The effects of STN CR DBS with and without shuffling were compared with the traditional isochronal DBS (tDBS) using a within-subject design. For each stimulation setting, DBS was delivered for 2 or 4 h/day for 5 consecutive days. The severity of PD was assessed using a modified clinical rating scale immediately before, during, and 1 h after DBS, as well as on days following the discontinuation of the 5 days of daily stimulation, i.e., carryover effect. Shuffled STN CR DBS produced greater acute and carryover improvements on Parkinsonian motor signs compared with non-shuffled CR. Moreover, this difference was more pronounced when more effective stimulation intensity and burst frequency settings were used. tDBS showed limited carryover effects. Given the significant effect of shuffling on the effectiveness of CR DBS, it will be critical for future studies to further define the relative role of different CR parameters for the clinical implementation of this novel stimulation paradigm.
Correlation Between Thrombus Signal Intensity and Aneurysm Wall Thickness in Partially Thrombosed Intracranial Aneurysms Using 7T Magnetization-Prepared Rapid Acquisition Gradient Echo Magnetic Resonance Imaging
Authors: Sato Taku , Matsushige Toshinori , Chen Bixia , Gembruch Oliver , Dammann Philipp , Jabbarli Ramazan , Forsting Michael , Junker Andreas , Maderwald Stefan , Quick Harald H. , Ladd Mark E. , Sure Ulrich , Wrede Karsten H.
Published: February 2022

Objective

The objective of this study is to investigate the relationship between the thrombus signal intensity and aneurysm wall thickness in partially thrombosed intracranial aneurysms in vivo with magnetization-prepared rapid acquisition gradient echo (MPRAGE) taken using 7T magnetic resonance imaging (MRI) and correlate the findings to wall instability.

Methods

Sixteen partially thrombosed intracranial aneurysms were evaluated using a 7T whole-body MR system with nonenhanced MPRAGE. To normalize the thrombus signal intensity, its highest signal intensity was compared to that of the anterior corpus callosum of the same subject, and the signal intensity ratio was calculated. The correlation between the thrombus signal intensity ratio and the thickness of the aneurysm wall was analyzed. Furthermore, aneurysmal histopathological specimens from six tissue samples were compared with radiological findings to detect any correlation.

Results

The mean thrombus signal intensity ratio was 0.57 (standard error of the mean [SEM] 0.06, range 0.25–1.01). The mean thickness of the aneurysm wall was 1.25 (SEM 0.08, range 0.84–1.55) mm. The thrombus signal intensity ratio significantly correlated with the aneurysm wall thickness (p < 0.01). The aneurysm walls with the high thrombus signal intensity ratio were significantly thicker. In histopathological examinations, three patients with a hypointense thrombus had fewer macrophages infiltrating the thrombus and a thin degenerated aneurysmal wall. In contrast, three patients with a hyperintense thrombus had abundant macrophages infiltrating the thrombus.

Conclusion

The thrombus signal intensity ratio in partially thrombosed intracranial aneurysms correlated with aneurysm wall thickness and histologic features, indicating wall instability.
A Quantitative Imaging Biomarker Supporting Radiological Assessment of Hippocampal Sclerosis Derived From Deep Learning-Based Segmentation of T1w-MRI
Authors: Rebsamen Michael , Radojewski Piotr , McKinley Richard , Reyes Mauricio , Wiest Roland , Rummel Christian
Published: February 2022

Purpose

Hippocampal volumetry is an important biomarker to quantify atrophy in patients with mesial temporal lobe epilepsy. We investigate the sensitivity of automated segmentation methods to support radiological assessments of hippocampal sclerosis (HS). Results from FreeSurfer and FSL-FIRST are contrasted to a deep learning (DL)-based segmentation method.

Materials and Methods

We used T1-weighted MRI scans from 105 patients with epilepsy and 354 healthy controls. FreeSurfer, FSL, and a DL-based method were applied for brain anatomy segmentation. We calculated effect sizes (Cohen's d) between left/right HS and healthy controls based on the asymmetry of hippocampal volumes. Additionally, we derived 14 shape features from the segmentations and determined the most discriminating feature to identify patients with hippocampal sclerosis by a support vector machine (SVM).

Results

Deep learning-based segmentation of the hippocampus was the most sensitive to detecting HS. The effect sizes of the volume asymmetries were larger with the DL-based segmentations (HS left d= −4.2, right = 4.2) than with FreeSurfer (left= −3.1, right = 3.7) and FSL (left= −2.3, right = 2.5). For the classification based on the shape features, the surface-to-volume ratio was identified as the most important feature. Its absolute asymmetry yielded a higher area under the curve (AUC) for the deep learning-based segmentation (AUC = 0.87) than for FreeSurfer (0.85) and FSL (0.78) to dichotomize HS from other epilepsy cases. The robustness estimated from repeated scans was statistically significantly higher with DL than all other methods.

Conclusion

Our findings suggest that deep learning-based segmentation methods yield a higher sensitivity to quantify hippocampal sclerosis than atlas-based methods and derived shape features are more robust. We propose an increased asymmetry in the surface-to-volume ratio of the hippocampus as an easy-to-interpret quantitative imaging biomarker for HS.
Cerebrospinal Fluid TNF-α and Orexin in Patients With Parkinson's Disease and Rapid Eye Movement Sleep Behavior Disorder
Authors: Yuan Yuan , Zhang Yimeng , Cheng Yueyang , Hou Yue , Huang Zhaoyang , Ma Jinghong , Li Ning , Zhan Shuqin
Published: February 2022

Background

Parkinson's disease (PD) pathological changes begin before motor symptoms appear. Rapid eye movement sleep behavior disorder (RBD) has the highest specificity and predictive value of any marker of prodromal PD. Tumor necrosis factor α (TNF-α) plays a part in the pathology of PD and disease conversion in isolated RBD (iRBD). TNF can also directly impair the hypocretin system in mice in vivo. As a result, we intend to investigate the effect of TNF-α on orexin levels in PD patients with RBD.

Method

Participants were recruited from the Department of Neurology of Xuanwu Hospital, Capital Medical University to engage in assessments on motor symptoms, sleep, cognition, etc. Then we collected blood and cerebrospinal fluid of all patients and 10 controls' cerebrospinal fluid. The levels of TNF-α in the serum and cerebrospinal fluid, as well as the level of orexin in the cerebrospinal fluid, were measured in the patients.

Results

The difference in TNF- levels in cerebrospinal fluid and serum between the three groups were not statistically significant. The levels of orexin in the three groups were not significantly lower than in the control group. UPDRS-III scores were significantly higher in the PD+RBD and PD-RBD groups than in the iRBD group. There was no statistically significant difference in H-Y stages, PSQI, or ESS scores between the PD+RBD and PD-RBD groups.

Conclusion

Our findings suggest that TNF-α may not have a significant effect on the orexinergic system in patients with Parkinson's disease and iRBD. As a result, it is necessary to investigate the changes in TNF-α and orexin levels in different disease stages and to enlarge the sample size to determine whether TNF-α affects the function of the orexin system, which may be related to the occurrence of RBD and disease progression in Parkinson's disease.
Gestational Bisphenol A Exposure Impacts Embryonic Hypothalamic Microglia Numbers, Ramification, and Phagocytic Cups
Authors: Rosin Jessica M. , Tretiakov Nikol , Hanniman Emily , Hampton Kiana , Kurrasch Deborah M.
Published: February 2022

Microglia are a resident population of phagocytic immune cells that reside within the central nervous system (CNS). During gestation, they are highly sensitive to their surrounding environment and can alter their physiology to respond to perceived neural insults, potentially leading to adverse influences on nearby neural progenitors. Given that bisphenol A (BPA) itself can impact developing brains, and that microglia express estrogen receptors to which BPA can bind, here we asked whether fetal microglia are responsive to gestational BPA exposure. Accordingly, we exposed pregnant dams to control or 50 mg of BPA per kg diet during gestation to investigate the impact of maternal BPA on embryonic hypothalamic microglia. Gestational BPA exposure from embryonic day 0.5 (E0.5) to E15.5 resulted in a significant increase in the number of microglia present in the hypothalamus of both male and female embryos. Staining for microglial activation using CD68 showed no change between control and prenatal BPA-exposed microglia, regardless of sex. Similarly, analysis of cultured embryonic brains demonstrated that gestational BPA exposure failed to change the secretion of cytokines or chemokines, regardless of embryo sex or the dose (50 μg of BPA per kg or 50 mg of BPA per kg maternal diet) of BPA treatment. In contrast, live-cell imaging of microglia dynamics in E15.5 control and gestationally-exposed BPA hypothalamic slices showed increased ramification of microglia exposed to BPA. Moreover, live-cell imaging also revealed a significant increase in the number of microglial phagocytic cups visible following exposure to gestational BPA. Together, these results suggest that gestational BPA exposure impacts embryonic hypothalamic microglia, perhaps leading them to alter their interactions with developing neural programs.
Small-Molecule Bi-DOTA Complex for High-Performance CT and Spectral CT Bioimaging
Authors: Dai Guidong , Zhang Yu , Wang Ximei , Wang Xingyu , Jia Juan , Jia Fei , Yang Lu , Yang Chunmei
Published: February 2022

Objectives

It is necessary to develop a high-performance and biocompatible contrast agent to accurately diagnose various diseases via in vivo computed tomography (CT) imaging. Here, we synthesized a small molecular Bi-DOTA complex as a high-performance contrast agent for in vitro and in vivo CT bioimaging.

Materials and Methods

In our study, Bi-DOTA was fabricated through a facile and one-pot synthesis strategy. The formed Bi-DOTA complex was characterized via different techniques. Furthermore, Bi-DOTA was used for in vitro and in vivo CT bioimaging to verify its X-ray attenuation ability, especially in vivo kidney imaging, gastrointestinal tract CT imaging, and spectral CT imaging.

Results

A small molecular Bi-DOTA complex with a molecular mass of 0.61 kDa was synthesized successfully, which exhibited outstanding dispersion, good biocompatibility, and superior X-ray attenuation ability. Meanwhile, we showed that the obtained contrast agent was quite biocompatible and safe in the given concentration range as confirmed by in vitro and in vivo cytotoxicity assay. Also, the proposed contrast agent can be rapidly excreted from the body via the urinary system, avoiding the potential side effects caused by long-term retention in vivo. Importantly, Bi-DOTA was successfully used in high-quality in vitro CT imaging, in vivo kidney imaging, gastrointestinal tract CT imaging, and spectral CT imaging.

Conclusions

These superiorities allowed Bi-DOTA to be used as an efficient CT contrast agent and laid down a new way of designing high-performance CT contrast agents with great clinical transformation potential.
Rare Case of Cystic Lymphangioma Transforming Into Lymphangiosarcoma: A Case Report
Authors: Yu Huili , Mao Qinxiang , Zhou Lingyan , Li Jiawei , Xu Xunhua
Published: February 2022

Cystic lymphangioma (CL) is a rare benign tumor that mainly occurs in the neck and axilla and usually occurs in children, whereas lymphangiosarcoma (LAS) is a rare invasive tumor, usually secondary to chronic lymphedema caused by various causes, with a rare malignant transformation from CL. We presented the case of a 63-year-old woman who underwent four surgical excisions for multiple recurrence of CL in the right groin. The changes of imaging and pathological examination revealed the unusual process of its gradual malignant transformation into LAS. We followed up the patient for 16 years, and she eventually died of LAS complications.
Chidamide Reverses Fluzoparib Resistance in Triple-Negative Breast Cancer Cells
Authors: Li Xinyang , Yuan Xiang , Wang Ziming , Li Jing , Liu Zhiwei , Wang Yukun , Wei Limin , Li Yuanpei , Wang Xinshuai
Published: February 2022

Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance is a new challenge for antitumor therapy. The purpose of this study was to investigate the reversal effects of chidamide on fluzoparib resistance, a PARPi, and its mechanism of action. A fluzoparib-resistant triple-negative breast cancer (TNBC) cell line was constructed, and the effects of chidamide and fluzoparib on drug-resistant cells were studied in vitro and in vivo. The effects of these drugs on cell proliferation, migration, invasiveness, the cell cycle, and apoptosis were detected using an MTT assay, wound-healing and transwell invasion assays, and flow cytometry. Bioinformatics was used to identify hub drug resistance genes and Western blots were used to assess the expression of PARP, RAD51, MRE11, cleaved Caspase9, and P-CDK1. Xenograft models were established to analyze the effects of these drugs on nude mice. In vivo results showed that chidamide combined with fluzoparib significantly inhibited the proliferation, migration, and invasiveness of drug-resistant cells and restored fluzoparib sensitivity to drug-resistant cells. The combination of chidamide and fluzoparib significantly inhibited the expression of the hub drug resistance genes RAD51 and MRE11, arrested the cell cycle at the G2/M phase, and induced cell apoptosis. The findings of this work show that chidamide combined with fluzoparib has good antineoplastic activity and reverses TNBC cell resistance to fluzoparil by reducing the expression levels of RAD51 and MRE11.
Downregulation of Methyltransferase-Like 14 Promotes Ovarian Cancer Cell Proliferation Through Stabilizing TROAP mRNA
Authors: Li Yize , Peng Hongyan , Jiang Peng , Zhang Jiarui , Zhao Yongmei , Feng Xuelian , Pang Cui , Ren Jingyi , Zhang Hongmei , Bai Wendong , Liu Wenchao
Published: February 2022

Altered expression levels of the proteins that regulate N6-methyladenosine (m6A) RNA methylation, including methyltransferase-like 14 (METTL14), are associated with cancer development. Based on our analysis of m6A methylation regulators using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, we focused on the regulatory role of METTL14 in ovarian cancer. We performed bioinformatics and survival analyses with these datasets and also used METTL14-overexpressing SKOV-3 ovarian cancer cells for in vitro studies. Trophinin associated protein (TROAP) siRNA and treatment with or without actinomycin D was used in the cells for qRT-PCR, western blot, cDNA microarray, cell viability, colony formation, luciferase gene reporter, methylated RNA immunoprecipitation (MeRIP)-qPCR, total RNA methylation, and RNA stability assays. Additionally, ovarian cancer and normal tissue samples were analyzed by immunohistochemistry, qRT-PCR, and western blot assays. The TCGA and GEO data confirmed copy number variations (CNVs) of these m6A RNA methylation regulators in ovarian cancer tissues. Furthermore, reduced METTL14 expression was associated with alterations in CNVs as well as poor patient survival in ovarian cancer. Moreover, the METTL14 and m6A RNA methylation levels were both significantly reduced in ovarian cancer tissues than in normal tissues. Restoration of METTL14 expression suppresses ovarian cancer cell proliferation by inhibition of TROAP expression. Further in vivo and in vitro experiments confirmed that METTL14 is a negative regulator of ovarian cancer cell proliferation via TROAP expression and that m6A RNA methylation regulates TROAP mRNA stability. In conclusion, METTL14 overexpression decreased ovarian cancer proliferation by inhibition of TROAP expression via an m6A RNA methylation-dependent mechanism.
In Vivo Targeting Replication Protein A for Cancer Therapy
Authors: VanderVere-Carozza Pamela S. , Gavande Navnath S. , Jalal Shadia I. , Pollok Karen E. , Ekinci Elmira , Heyza Joshua , Patrick Steve M. , Masters Andi , Turchi John J. , Pawelczak Katherine S.
Published: February 2022

Replication protein A (RPA) plays essential roles in DNA replication, repair, recombination, and the DNA damage response (DDR). Retrospective analysis of lung cancer patient data demonstrates high RPA expression as a negative prognostic biomarker for overall survival in smoking-related lung cancers. Similarly, relative expression of RPA is a predictive marker for response to chemotherapy. These observations are consistent with the increase in RPA expression serving as an adaptive mechanism that allows tolerance of the genotoxic stress resulting from carcinogen exposure. We have developed second-generation RPA inhibitors (RPAis) that block the RPA–DNA interaction and optimized formulation for in vivo analyses. Data demonstrate that unlike first-generation RPAis, second-generation molecules show increased cellular permeability and induce cell death via apoptosis. Second-generation RPAis elicit single-agent in vitro anticancer activity across a broad spectrum of cancers, and the cellular response suggests existence of a threshold before chemical RPA exhaustion induces cell death. Chemical RPA inhibition potentiates the anticancer activity of a series of DDR inhibitors and traditional DNA-damaging cancer therapeutics. Consistent with chemical RPA exhaustion, we demonstrate that the effects of RPAi on replication fork dynamics are similar to other known DDR inhibitors. An optimized formulation of RPAi NERx 329 was developed that resulted in single-agent anticancer activity in two non-small cell lung cancer models. These data demonstrate a unique mechanism of action of RPAis eliciting a state of chemical RPA exhaustion and suggest they will provide an effective therapeutic option for difficult-to-treat lung cancers.
Clinical Significance of Circulating Cell-Free DNA Detection in Multiple Myeloma: A Meta-Analysis
Authors: Ye Xueshi , Li Wanli , Zhang Lifei , Yu Junyao
Published: February 2022

Circulating cell-free DNA (cfDNA) detection, a non-invasive method, appears promising for genetic analyses as well as quantitative assessment of tumor burden in patients with cancer. Although the analysis of cfDNA for clinical prognosis and monitoring disease burden in multiple myeloma (MM) has been recently studied, the results are unclear. In this meta-analysis, we explored the clinical significance of circulating cfDNA detection in patients with MM. We searched PubMed, Embase, and the Cochrane Library for eligible studies published up until July 25, 2021. Diagnostic accuracy variables were calculated and analyzed using Meta-Disc, and prognostic data were analyzed using Review Manager. Overall, seven studies comprising 235 myeloma patients met our inclusion criteria. The overall sensitivity and specificity of cfDNA to detect minimal residual disease (MRD) were 0.58 and 0.91, respectively. Moreover, higher levels of cfDNA were associated with worse progression-free survival as well as with poor overall survival. Our meta-analysis revealed that ctDNA detection has an obvious advantage in terms of MRD detection specificity, but it showed no superiority over bone marrow assessment in terms of MRD detection sensitivity, and higher levels of cfDNA were indicative of worse prognosis in patients with MM. cfDNA detection is a non-invasive method and thus shows promise as a good alternative to BM biopsies for monitoring clonal evolution and tumor burden so as to guide the treatment of patients with MM.
Cost-Utility Analysis of Once-Weekly Semaglutide, Dulaglutide, and Exenatide for Type 2 Diabetes Patients Receiving Metformin-Based Background Therapy in China
Authors: Hu Shanshan , Wang Shuowen , Qi Chendong , Gu Shengying , Shi Chenyang , Mao Lin , Fan Guorong
Published: February 2022

Introduction: The substantial financial burden associated with type 2 diabetes (T2D) over a lifetime cannot be neglected. Therefore, the objective of this study was to evaluate the pharmacoeconomic value of three once-weekly GLP-1 RAs, namely subcutaneous semaglutide (sc. SEMA), dulaglutide (DULA), and extended-release exenatide (e-r EXEN), in treating patients with T2D that cannot be controlled with metformin-based background therapy, and to find a suitable price reduction for non-cost-effective medications, to provide reasonable recommendations to the administration for adjusting drug prices.

Methods: The baseline characteristics of the simulation patient cohort were sourced from a comprehensive meta-analysis synthesizing 453 trials evaluating 21 hypoglycemic agents from nine categories of drugs. The UKPDS OM2 was applied to project the long-term effectiveness and costs from a Chinese health care provider’s perspective. After cost-utility analysis, the reasonable price adjustment of non-cost-effective options was explored via binary search. Uncertainty was measured by means of sensitivity analysis.

Results: After a 40-year simulation, the sc. SEMA, DULA, and e-r EXEN groups yielded 9.6315, 9.5968, and 9.5895 quality-adjusted life years (QALYs), respectively. In terms of expenditure, the total costs for the sc. SEMA, DULA, and e-r EXEN groups were $42012.47, $24931.27, and $40264.80, respectively. DULA was dominant over e-r EXEN due to the higher QALYs and lower total costs. The ICURs of sc. SEMA vs. DULA and sc. SEMA vs. e-r EXEN were $492994.72/QALY and $41622.69/QALY (ICUR > λ), respectively, indicating that sc. SEMA was not more cost-effective than DULA or e-r EXEN. The INMB and absolute NMB yielded the same conclusions which were robust to one-way, scenario, and probabilistic sensitivity analyses. After several assumptions in the binary search, sc. SEMA and e-r EXEN appear to become cost-effective when their annual costs are decreased by 57.67% and 70.34%, respectively, with DULA as a counterpart.

Conclusion: From the cost-utility analysis, DULA appears to be the most cost-effective option among sc. SEMA, DULA, and e-r EXEN for the treatment of patients with T2D receiving metformin-based background therapy. With a 57.67% or 70.34% reduction in cost, sc. SEMA or e-r EXEN, respectively, would become as cost-effective as DULA in China.
Assessment of Fibrotic Liver Regeneration After Partial Hepatectomy With Intravoxel Incoherent Motion Diffusion-Weighted Imaging: An Experimental Study in a Rat Model With Carbon Tetrachloride Induced Liver Injury
Authors: Xie Shuangshuang , Qiu Caixin , Sun Yajie , Yu Yongquan , Hu Zhandong , Zhang Kun , Chen Lihua , Cheng Yue , Bao Mingzhu , Zhang Quansheng , Zhu Jinxia , Grimm Robert , Shen Wen
Published: February 2022

Purpose

To determine whether intravoxel incoherent motion (IVIM) parameters correlate with liver regeneration and function recovery after partial hepatectomy (PH) in rats with carbon tetrachloride (CCl4)-induced liver fibrosis.

Methods

Sixty-two adult Sprague-Dawley rats were divided into the control group and the fibrosis group with CCl4 injection for 8 weeks. At the end of the 8th week, all rats received left lateral lobe liver resection. Within each group, IVIM imaging (n = 10/group) and histologic and biochemical analyses (n = 3/group/time point) were performed pre- and post-PH (on days 1, 2, 3, 5, 7, 14, and 21). Differences in liver IVIM parameters and correlation between IVIM parameters and Ki-67 indices, hepatocyte diameter, alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) values were analyzed.

Results

Post-PH, liver true diffusion coefficient (D) values decreased and pseudodiffusion coefficient (D*) and perfusion fraction (PF) values increased, then recovered to pre-PH levels gradually in both fibrosis and control rats. PF in fibrosis group were significantly higher than in controls from 3 to 21 days (P < 0.05). In fibrosis rats, both Ki-67 indices and hepatocyte diameters increased, and a strong correlation was found between PF and Ki-67 indices (r = −0.756; P = 0.03), D* and PF values and ALT, AST, and TBil values (r = −0.762 to −0.905; P < 0.05). In control rats, only hepatocyte diameters increased, and all IVIM parameters correlated well with hepatocyte diameters, ALT, AST and TBil values (r = 0.810 to −1.000; P < 0.05).

Conclusion

The regeneration pattern in fibrotic liver tissue was different compared with control livers. IVIM parameters can monitor liver regeneration and functional recovery non-invasively after PH.
Reduced Expression of Prion Protein With Increased Interferon-β Fail to Limit Creutzfeldt-Jakob Disease Agent Replication in Differentiating Neuronal Cells
Authors: Aguilar Gerard , Pagano Nathan , Manuelidis Laura
Published: February 2022

Immortalized uninfected septal (SEP) neurons proliferate but after physiological mitotic arrest they express differentiated neuronal characteristics including enhanced cell-to-cell membrane contacts and ≥ 8 fold increases in host prion protein (PrP). We compared proliferating uninfected and Creutzfeldt-Jakob Disease (CJD) agent infected cells with their arrested counterparts over 33 days by quantitative mRNA and protein blot analyses. Surprisingly, uninfected arrested cells increased interferon-β (IFN-β) mRNA by 2.5–8 fold; IFN-β mRNA elevations were not previously associated with neuronal differentiation. SEP cells with high CJD infectivity titers produced a much larger 40–68-fold increase in IFN-β mRNA, a classic host anti-viral response that is virucidal for RNA but not DNA viruses. High titers of CJD agent also induced dramatic decreases in host PrP, a protein needed for productive agent replication. Uninfected arrested cells produced large sustained 20–30-fold increases in PrP mRNA and protein, whereas CJD arrested cells showed only transient small 5-fold increases in PrP. A > 10-fold increase in infectivity, but not PrP misfolding, induced host PrP reductions that can limit CJD agent replication. In contrast to neuronal lineage cells, functionally distinct migratory microglia with high titers of CJD agent do not induce an IFN-β mRNA response. Because they have 1/50th of PrP of an average brain cell, microglia would be unable to produce the many new infectious particles needed to induce a large IFN-β response by host cells. Instead, microglia and related cells can be persistent reservoirs of infection and spread. Phase separations of agent-associated molecules in neurons, microglia and other cell types can yield new insights into the molecular structure, persistent, and evasive behavior of CJD-type agents.
iTRAQ Proteomic Analysis of Interactions Between 20E and Phospholipase C in Apolygus lucorum (Meyer-Dür)
Authors: Tan Yong-An , Zhao Xu-Dong , Zhao Jing , Zhu-Salzman Keyan , Ji Qin-Qin , Xiao Liu-Bin , Hao De-Jun
Published: February 2022

Polyphagous Apolygus lucorum has become the dominant insect in Bacillus thuringiensis (Bt) cotton fields. Hormone 20-hydroxyecdysone (20E) regulates multiple insect development and physiology events. 20E responses are controlled by pathways triggered by phospholipase C (PLC)-associated proteins. However, 20E-modulated genes and related proteins that can be affected by PLC still remain unknown. Here, isobaric tag for relative and absolute quantitation (iTRAQ) and immunoblotting techniques were used to compare differentially expressed proteins (DEPs) in A. lucorum in response to the treatment of 20E and the PLC inhibitor U73122 as well as their combination. A total of 1,624 non-redundant proteins and 97, 248, 266 DEPs were identified in the 20E/control, U73122/control, and 20E + U73122/control groups, respectively. Only 8 DEPs, including pathogenesis-related protein 5-like, cuticle protein 19.8, trans-sialidase, larval cuticle protein A2B-like, cathepsin L1, hemolymph juvenile hormone-binding protein, ATP-dependent RNA helicase p62-like, and myosin-9 isoform X1, were detected in all three groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEPs were involved in diverse signaling pathways. The results were validated by immunoblotting, which highlighted the reliability of proteomics analysis. These findings provided novel insights into the function of PLC in 20E signaling pathway in A. lucorum.
Microautophagy Mediates Vacuolar Delivery of Storage Proteins in Maize Aleurone Cells
Authors: Ding Xinxin , Zhang Xiaoguo , Paez-Valencia Julio , McLoughlin Fionn , Reyes Francisca C. , Morohashi Kengo , Grotewold Erich , Vierstra Richard D. , Otegui Marisa S.
Published: February 2022

The molecular machinery orchestrating microautophagy, whereby eukaryotic cells sequester autophagic cargo by direct invagination of the vacuolar/lysosomal membrane, is still largely unknown, especially in plants. Here, we demonstrate microautophagy of storage proteins in the maize aleurone cells of the endosperm and analyzed proteins with potential regulatory roles in this process. Within the cereal endosperm, starchy endosperm cells accumulate storage proteins (mostly prolamins) and starch whereas the peripheral aleurone cells store oils, storage proteins, and specialized metabolites. Although both cell types synthesize prolamins, they employ different pathways for their subcellular trafficking. Starchy endosperm cells accumulate prolamins in protein bodies within the endoplasmic reticulum (ER), whereas aleurone cells deliver prolamins to vacuoles via an autophagic mechanism, which we show is by direct association of ER prolamin bodies with the tonoplast followed by engulfment via microautophagy. To identify candidate proteins regulating this process, we performed RNA-seq transcriptomic comparisons of aleurone and starchy endosperm tissues during seed development and proteomic analysis on tonoplast-enriched fractions of aleurone cells. From these datasets, we identified 10 candidate proteins with potential roles in membrane modification and/or microautophagy, including phospholipase-Dα5 and a possible EUL-like lectin. We found that both proteins increased the frequency of tonoplast invaginations when overexpressed in Arabidopsis leaf protoplasts and are highly enriched at the tonoplast surface surrounding ER protein bodies in maize aleurone cells, thus supporting their potential connections to microautophagy. Collectively, this candidate list now provides useful tools to study microautophagy in plants.
Parental Autonomy Support, Parental Psychological Control and Chinese University Students’ Behavior Regulation: The Mediating Role of Basic Psychological Needs
Authors: Wei Songqin , Teo Timothy , Malpique Anabela , Lausen Adi
Published: February 2022

The present research examined relationships between parental autonomy support, parental psychological control, and Chinese emerging adults’ autonomous regulation in their university studies as well as dysregulation in social media engagement. A total of 287 (102 female and 185 male) Chinese university students reported on their perceived parenting styles, psychological needs, and behavior regulation. Results showed that basic psychological need satisfaction was positively associated with parental autonomy support and autonomous regulation of learning; need frustration was positively correlated with parental psychological control and dysregulation in social media engagement. More importantly, psychological need frustration was a mediator of the relation between parental psychological control and dysregulation in social media engagement. Our findings suggest that students living in an autonomy-supportive familial environment tend to have satisfied psychological needs as well as autonomous learning behavior. Impairment of psychological needs could be one of the mechanisms through which psychologically controlling parenting was linked to dysregulation of social media use in Chinese culture.
Enjoyment as a Predictor of Exercise Habit, Intention to Continue Exercising, and Exercise Frequency: The Intensity Traits Discrepancy Moderation Role
Authors: Teixeira Diogo S. , Rodrigues Filipe , Cid Luis , Monteiro Diogo
Published: February 2022

Given the need to explore the factors that can account for a better understanding of the intention-behavior gap in exercise practice in health club settings, and considering the emergence of hedonic assumptions related to exercise adherence, this cross-sectional study aimed to test the moderation effect of the intensity traits agreement/disagreement in three relevant outcomes of exercise enjoyment: exercise habit, intention to continue exercising, and exercise frequency. A sample consisted of 273 exercisers (male = 127; Mage = 36.21; SD = 11.29) enrolled in nine health clubs who voluntarily fulfilled a battery of questionnaires. All analyses were performed using SPSS v. 23.0/PROCESS v. 3.5. The results of the study presented a moderation effect of exercise intensity traits agreement on three relevant enjoyment outcomes: exercise habit, intention to continue exercising, and exercise frequency. No relevant results emerged from intensity traits disagreement. The results suggest that assessing and tailoring exercise prescription and supervision in order to customize exercise intensity may influence future exercise participation.
The Pandemic and the “Perpetual Foreigner”: How Threats Posed by the COVID-19 Pandemic Relate to Stereotyping of Asian Americans
Authors: Daley Jordan S. , Gallagher Natalie M. , Bodenhausen Galen V.
Published: February 2022

We examined the “othering” of Asian Americans in the context of the COVID-19 pandemic. Given past evidence that pathogen-related threat perceptions can exacerbate intergroup biases, as well as salient public narratives blaming the Chinese for the pandemic, we assessed whether individuals experiencing a greater sense of threat during the pandemic were more likely to apply the “perpetual foreigner” stereotype to Asian Americans. Over a seven-week period, we recruited 1,323 White Americans to complete a measure of the perceived Americanness of Asian, Black, and White targets. Asian targets were consistently perceived as less American than White targets, across variations in subjective health threat and regional case counts. The direct and indirect connections of political ideology to the observed patterns were examined, revealing that White participants who blamed China for the pandemic were more likely to apply the perpetual foreigner stereotype to Asian Americans. These results indicate that the othering of Asian Americans is pervasive among White Americans and that variables related to social conditions surrounding the COVID-19 pandemic can predict the potency of this association.
Functional Genomic Analysis of Amphetamine Sensitivity in Drosophila
Authors: Karam Caline S. , Williams Brenna L. , Morozova Irina , Yuan Qiaoping , Panarsky Rony , Zhang Yuchao , Hodgkinson Colin A. , Goldman David , Kalachikov Sergey , Javitch Jonathan A.
Published: February 2022

Abuse of psychostimulants, including amphetamines (AMPHs), is a major public health problem with profound psychiatric, medical, and psychosocial complications. The actions of these drugs at the dopamine transporter (DAT) play a critical role in their therapeutic efficacy as well as their liability for abuse and dependence. To date, however, the mechanisms that mediate these actions are not well-understood, and therapeutic interventions for AMPH abuse have been limited. Drug exposure can induce broad changes in gene expression that can contribute to neuroplasticity and effect long-lasting changes in neuronal function. Identifying genes and gene pathways perturbed by drug exposure is essential to our understanding of the molecular basis of drug addiction. In this study, we used Drosophila as a model to examine AMPH-induced transcriptional changes that are DAT-dependent, as those would be the most relevant to the stimulatory effects of the drug. Using this approach, we found genes involved in the control of mRNA translation to be significantly upregulated in response to AMPH in a DAT-dependent manner. To further prioritize genes for validation, we explored functional convergence between these genes and genes we identified in a genome-wide association study of AMPH sensitivity using the Drosophila Genetic Reference Panel. We validated a number of these genes by showing that they act specifically in dopamine neurons to mediate the behavioral effects of AMPH. Taken together, our data establish Drosophila as a powerful model that enables the integration of behavioral, genomic and transcriptomic data, followed by rapid gene validation, to investigate the molecular underpinnings of psychostimulant action.
Influencing Factors on College Students' Willingness to Spread Internet Public Opinion: Analysis Based on COVID-19 Data in China
Authors: Ye Pinghao , Liu Liqiong , Tan Joseph
Published: February 2022

Following COVID-19 outbreak, Internet public opinion has tended to proliferate. From a theoretical perspective, however, the spread law of Internet public opinion in major epidemic prevention and control may provide optimization strategies on how best to channel Internet public opinion. Specifically, this article aims at exploring key factors affecting our theoretical understanding on the spread of Internet public opinion on a major epidemic situation amongst college students. A questionnaire survey on college students was conducted via online research data collection platform located in Changsha, China, amassing three hundred and nineteen valid questionnaires. Smart PLS was applied to verify a theoretical model vis-à-vis the reliability and validity of the measuring instrument. Results show that adult attachment and social motivation have significant positive influences on the consciousness of social participation. Evidently, adult attachment, emotional orientation and risk perception also have significant positive influences on emotional motivation. Emotional motivation plays a mediating role in the relationship between affective disposition and dissemination willingness. Additionally, social motivation, consciousness of social participation and emotional motivation significantly influence one's dissemination willingness in a positive way. The consciousness of social participation plays a mediating role in the relationship between social motivation and dissemination willingness. Social motivation plays a moderating role in the relationship between risk perception and dissemination willingness. Altogether, theoretical rationalization to enhance understanding and guide the initiation and spread of Internet public opinion of major public health emergencies accurately has now been provided by this work.
Building Emergent Cycling Infrastructure During the COVID-19 Pandemic: The Case of Zapopan, México
Authors: Ohlund Hannah , El-Samra Siba , Amezola Diana , Soto Morfín Jesús Carlos , López Zaragoza Carlos , Aguilar Gónzalez Sonia
Published: February 2022

The COVID-19 pandemic has led to strict measures intended to limit people's movement and slow viral spread. The subsequent need for social distancing when traveling has driven many cities to reduce public transport services, as urban residents simultaneously stay at home and avoid crowded spaces. As a result, cities are turning to cycling to meet the mobility needs of their inhabitants, particularly those who lack access to a private vehicle. Infrastructure plays a critical role in encouraging cycling by protecting cyclists and providing safe and comfortable conditions for users of various confidence levels. Due to the pandemic, this infrastructure has been rapidly constructed, in many cases, as pop-up or temporary installations. In this article, we present and examine the design methods and community response to an emergent bike lane along Avenida Guadalupe in Zapopan, México during the COVID-19 pandemic. Through this examination, the paper distills and highlights the key features of a successful emergent bike lane in the urban Global South and identifies gaps in need of filling. The emergent intervention is 4.2 km and includes a number of traffic calming elements such as bollards and markings, connecting the peripheral part of the city to the existing cycle infrastructure. This case study shall contribute to a greater understanding of emergency mobility planning practices during crises such as the COVID-19 pandemic, as well as future directions for the expansion of cycling infrastructure and networks, especially in Latin America and the broader Global South.
The Interplay Between Presence and Learning
Authors: Ochs Carli , Sonderegger Andreas
Published: February 2022

The highly immersive Virtual reality (VR) headset is gaining popularity in multiple application domains. In the context of learning, it has been proposed to be beneficial by increasing presence and attention in noisy and distracting environments, both factors that are considered important for learning. Despite intensified research efforts in recent years, empirical knowledge of experimental research addressing the link between presence and learning in specific environmental contexts is still rather scarce. In this study following an experimental mixed-method approach, the link between presence and memorization as a particular form of learning is addressed by comparing memorization with a highly immersive VR headset to a less immersive system (desktop screen) in noisy and calm learning environments. Using a 2 (learning location) x 2 (learning device) between-subjects design, 63 participants interacted with one of the two devices in either of the two environments. As expected, VR headset users reported higher presence levels. While participants subjectively evaluated the VR headset as a better device for learning, the memorization test scores were higher for desktop screen users in both calm and noisy environments. Learning location did not show significant effects. Attention distraction and context-dependent learning are discussed with regard to the unexpected results, while implications for practice and future research are discussed.
Capturing Regional Differences in Flood Vulnerability Improves Flood Loss Estimation
Authors: Sairam Nivedita , Schröter Kai , Steinhausen Max , Kreibich Heidi
Published: February 2022

Flood vulnerability is quantified by loss models which are developed using either empirical or synthetic approaches. In reality, processes influencing flood risk are stochastic and loss predictions bear significant uncertainty, especially due to differences in vulnerability across exposed objects and regions. However, many state-of-the-art flood loss models are deterministic, i.e., they do not account for data and model uncertainty. The Bayesian Data-Driven Synthetic (BDDS) model was one of the first approaches that used empirical data to reduce the prediction errors at object-level and enhance the reliability of synthetic flood loss models. However, the BDDS model does not account for regional differences in vulnerability which may result in over-/under-estimation of losses in some regions. In order to overcome this limitation, this study introduces a hierarchical parameterization of the BDDS model which enhances synthetic flood loss model predictions by quantifying regional differences in vulnerability. The hierarchical parameterization makes optimal use of the process information contained in the overall data set for the various regional applications, so that it is particularly suitable for cases in which only a small amount of empirical data is available. The implementation and performance of the hierarchical parametrization is demonstrated with the Multi-Colored Manual (MCM) loss functions and empirical damage dataset from the UK consisting of residential buildings from the regions Appleby, Carlisle, Kendal and Cockermouth that suffered losses during the 2015 flood event. The developed model improves prediction accuracy of flood loss compared to MCM by reducing the absolute error and bias by at least 23 and 90%, respectively. The model reliability in terms of hit rate (i.e., the probability that the observed value lies in the 90% high density interval of predictions) is 88% for residential buildings from the same regions used for calibration and 73% for residential buildings from new regions. The approach is of high practical relevance for all regions where only limited amounts of empirical flood loss data is available.