bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of Shape Reconfigurable, Highly Stretchable Honeycomb Lattice With Tunable Poisson’s Ratio
Authors: Dong Le , Jiang Chengru , Wang Jinqiang , Wang Dong
Published: May 2021

The mechanical behaviors of lattice structures can be tuned by arranging or adjusting their geometric parameters. Once fabricated, the lattice’s mechanical behavior is generally fixed and cannot adapt to environmental change. In this paper, we developed a shape reconfigurable, highly stretchable lattice structure with tunable Poisson’s ratio. The lattice is built based on a hexagonal honeycomb structure. By replacing the straight beam with curled microstructure, the stretchability of the lattice is significantly improved. The Poisson’s ratio is adjusted using a geometric angle. The lattice is 3D printed using a shape memory polymer. Using its shape memory effect, the lattice demonstrates tunable shape reconfigurability as the ambient temperature changes. To capture its high stretchability, tunable Poisson’s ratio and shape reconfigurability, a phase evolution model for lattice structure is used. In the theoretical model, the effects of temperature on the material’s nonlinearity and geometric nonlinearity due to the lattice structure are assumed to be decoupled. The theoretical shape change agrees well with the Finite element results, while the theoretical model significantly reduces the computational cost. Numerical results show that the geometrical parameters and the ambient temperature can be manipulated to transform the lattice into target shapes with varying Poisson’s ratios. This work provides a design method for the 3D printed lattice structures and has potential applications in flexible electronics, soft robotics, and biomedicine.
Integrating Real-World Evidence in the Regulatory Decision-Making Process: A Systematic Analysis of Experiences in the US, EU, and China Using a Logic Model
Authors: Li Meng , Chen Shengqi , Lai Yunfeng , Liang Zuanji , Wang Jiaqi , Shi Junnan , Lin Haojie , Yao Dongning , Hu Hao , Ung Carolina Oi Lam
Published: May 2021

Real world evidence (RWE) and real-world data (RWD) are drawing ever-increasing attention in the pharmaceutical industry and drug regulatory authorities (DRAs) all over the world due to their paramount role in supporting drug development and regulatory decision making. However, there is little systematic documentary analysis about how RWE was integrated for the use by the DRAs in evaluating new treatment approaches and monitoring post-market safety. This study aimed to analyze and discuss the integration of RWE into regulatory decision-making process from the perspective of DRAs. Different development strategies to develop and adopt RWE by the DRAs in the US, Europe, and China were reviewed and compared, and the challenges encountered were discussed. It was found that different strategies on development of RWE were applied by FDA, EMA, and NMPA. The extent to which RWE was adopted in China was relatively limited compared to that in the US and EU, which was highly related to the national pharmaceutical environment and development stages. A better understanding of the overall goals, inputs, activities, outputs, and outcomes in developing RWE will help inform actions to harness RWD and leverage RWE for better health care decisions.
Theranostic Terbium Radioisotopes: Challenges in Production for Clinical Application
Authors: Naskar Nabanita , Lahiri Susanta
Published: May 2021

Currently, research on terbium has gained a momentum owing to its four short-lived radioisotopes, 149Tb, 152Tb, 155Tb, and 161Tb, all of which can be considered in one or another field of nuclear medicine. The members of this emerging quadruplet family have appealing nuclear characteristics and have the potential to do justice to the proposed theory of theranostics nuclear medicine, which amalgamates therapeutic and diagnostic radioisotopes together. The main challenge for in vivo use of these radioisotopes is to produce them in sufficient quantity. This review discusses that, at present, neither light charged particle nor the heavy ion (HI) activation are suitable for large-scale production of neutron deficient terbium nuclides. Three technological factors like (i) enrichment of stable isotopes to a considerable level, (ii) non-availability of higher energies in commercial cyclotrons, and (iii) non-availability of the isotope separation technique coupled with commercial accelerators limit the large scale production of terbium radionuclides by light charged particle activation. If in future, the technology can overcome these hurdles, then the light charged particle activation of enriched targets would produce a high amount of useful terbium radionuclides. On the other hand, to date, the spallation reaction coupled with an online isotope separator has been found suitable for such a requirement, which has been adopted by the CERN MEDICIS programme. The therapeutic 161Tb radionuclide can be produced in a reactor by neutron bombardment on enriched 160Gd target to produce 161Gd which subsequently decays to 161Tb. The radiochemical separation is mandatory even if the ISOL technique is used to obtain high radioisotopic purity of the desired radioisotope.
Similarities and Differences Between Juvenile and Adult Spondyloarthropathies
Authors: Fisher Corinne , Ciurtin Coziana , Leandro Maria , Sen Debajit , Wedderburn Lucy R.
Published: May 2021

Spondyloarthritis (SpA) encompasses a broad spectrum of conditions occurring from childhood to middle age. Key features of SpA include axial and peripheral arthritis, enthesitis, extra-articular manifestations, and a strong association with HLA-B27. These features are common across the ages but there are important differences between juvenile and adult onset disease. Juvenile SpA predominantly affects the peripheral joints and the incidence of axial arthritis increases with age. Enthesitis is important in early disease. This review article highlights the similarities and differences between juvenile and adult SpA including classification, pathogenesis, clinical features, imaging, therapeutic strategies, and disease outcomes. In addition, the impact of the biological transition from childhood to adulthood is explored including the importance of musculoskeletal and immunological maturation. We discuss how the changes associated with adolescence may be important in explaining age-related differences in the clinical phenotype between juvenile and adult SpA and their implications for the treatment of juvenile SpA.
A Diagnostic Solution for Lupus Anticoagulant Testing in Patients Taking Direct Oral FXa Inhibitors Using DOAC Filter
Authors: Farkh Carine , Ellouze Syrine , Gounelle Louis , Sad Houari Mama , Duchemin Jérôme , Proulle Valérie , Fontenay Michaela , Delavenne Xavier , Jourdi Georges
Published: May 2021

Background: Direct oral factor Xa (FXa) inhibitors interfere with lupus anticoagulant (LA) assays challenging antiphospholipid syndrome diagnosis in treated patients. We evaluated a new device, called DOAC Filter, and its usefulness in this setting. It is a single-use filtration cartridge in which FXa inhibitor compounds are trapped by non-covalent binding while plasma is filtered through a solid phase. Patient samples were analyzed before and after filtration: 38 rivaroxaban, 41 apixaban, and 68 none. Anticoagulant plasma concentrations were measured using specific anti-Xa assays and HPLC-MS/MS. LA testing was performed using dilute Russell Viper Venom Time (dRVVT) and Silica Clotting Time (SCT). Baseline median [min–max] concentrations were 64.8 [17.6; 311.4] for rivaroxaban and 92.1 ng/mL [37.1; 390.7] for apixaban (HPLC-MS/MS). They were significantly correlated with anti-Xa assay results (r = 0.98 and r = 0.94, respectively). dRVVT was positive in 92% rivaroxaban and 72% apixaban and SCT in 28 and 41% of samples, respectively. Post-filtration, median % of neutralization was 100% with rivaroxaban and apixaban concentrations of, respectively, <2 [<2–2.4] and <2 ng/mL [<2–9.6] using HPLC-MS/MS. No significant effect of DOAC Filter was observed on LA testing in controls (n = 31) and LA-positive (n = 37) non-anticoagulated samples. dRVVT and SCT remained positive in, respectively, 16 and 8% of rivaroxaban and 41 and 18% of apixaban samples. DOAC Filter would be an easy-to-use device allowing FXa inhibitor removal from plasma samples, limiting their interference with LA testing in treated patients.
Compositional Differences in the Oral Microbiome of E-cigarette Users
Authors: Chopyk Jessica , Bojanowski Christine M. , Shin John , Moshensky Alex , Fuentes Ana Lucia , Bonde Saniya S. , Chuki Dagni , Pride David T. , Crotty Alexander Laura E.
Published: May 2021

Electronic (e)-cigarettes have been advocated as a safer alternative to conventional tobacco cigarettes. However, there is a paucity of data regarding the impact of e-cigarette aerosol deposition on the human oral microbiome, a key component in human health and disease. We aimed to fill this knowledge gap through a comparative analysis of the microbial community profiles from e-cigarette users and healthy controls [non-smokers/non-vapers (NSNV)]. Moreover, we sought to determine whether e-cigarette aerosol exposure from vaping induces persistent changes in the oral microbiome. To accomplish this, salivary and buccal mucosa samples were collected from e-cigarette users and NSNV controls, with additional oral samples collected from e-cigarette users after 2 weeks of decreased use. Total DNA was extracted from all samples and subjected to PCR amplification and sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene. Our analysis revealed several prominent differences associated with vaping, specific to the sample type (i.e., saliva and buccal). In the saliva, e-cigarette users had a significantly higher alpha diversity, observed operational taxonomic units (OTUs) and Faith’s phylogenetic diversity (PD) compared to NSNV controls, which declined with decreased vaping. The buccal mucosa swab samples were marked by a significant shift in beta diversity between e-cigarette users and NSNV controls. There were also significant differences in the relative abundance of several bacterial taxa, with a significant increase in Veillonella and Haemophilus in e-cigarette users. In addition, nasal swabs demonstrated a trend toward higher colonization rates with Staphylococcus aureus in e-cigarette users relative to controls (19 vs. 7.1%; p = n.s.). Overall, these data reveal several notable differences in the oral bacterial community composition and diversity in e-cigarette users as compared to NSNV controls.
Different Modulatory Effects of Cognitive Training and Aerobic Exercise on Resting State Functional Connectivity of Entorhinal Cortex in Community-Dwelling Older Adults
Authors: Gu NanNan , Li Hechun , Cao Xinyi , Li Ting , Jiang Lijuan , Zhang Han , Zhao Binglei , Luo Cheng , Li Chunbo
Published: May 2021

The entorhinal cortex (EC) plays an essential role in age-related cognitive decline. However, the effect of functional connectivity (FC) changes between EC and other cerebral cortices on cognitive function remains unclear. The aim of this study was to explore the modulation of two interventions (cognitive training and aerobic exercise) on EC-FC in community-dwelling older adults. In total, 94 healthy older adults aged between 65 and 75 years were assigned to either the cognitive training or aerobic exercise group to receive 24 sessions over 12 weeks, or to a control group. Resting-state functional magnetic resonance imaging was performed at both baseline and 12-month follow-up. Compared to the cognitive training group, the aerobic exercise group showed greater EC-FC in the bilateral middle temporal gyrus, right supramarginal gyrus, left angular gyrus, and right postcentral gyrus. Compared to the control group, the cognitive training group had a decreased EC-FC in the right hippocampus, right middle temporal gyrus, left angular gyrus, and right postcentral gyrus and an increased EC-FC in the bilateral pallidum, while the aerobic exercise group showed increased EC-FC between the right medial prefrontal cortex(mPFC), bilateral pallidum, and right precuneus. Baseline EC-FC in the mPFC was positively correlated with the visuospatial/constructional index score of the Repeatable Battery for the Assessment of Neuropsychological Status. In the cognitive training group, EC-FC value changes in the right hippocampus were negatively correlated with changes in the RBANS delayed memory index score, while in the aerobic exercise group, EC-FC value changes in the left angular gyrus were positively correlated with changes in the RBANS attention index score. These findings support the hypothesis that both cognitive training and aerobic exercise can modulate EC-FC in aging populations but through different neural pathways.
Towards a Bio-Inspired Real-Time Neuromorphic Cerebellum
Authors: Bogdan Petruţ A. , Marcinnò Beatrice , Casellato Claudia , Casali Stefano , Rowley Andrew G.D. , Hopkins Michael , Leporati Francesco , D'Angelo Egidio , Rhodes Oliver
Published: May 2021

This work presents the first simulation of a large-scale, bio-physically constrained cerebellum model performed on neuromorphic hardware. A model containing 97,000 neurons and 4.2 million synapses is simulated on the SpiNNaker neuromorphic system. Results are validated against a baseline simulation of the same model executed with NEST, a popular spiking neural network simulator using generic computational resources and double precision floating point arithmetic. Individual cell and network-level spiking activity is validated in terms of average spike rates, relative lead or lag of spike times, and membrane potential dynamics of individual neurons, and SpiNNaker is shown to produce results in agreement with NEST. Once validated, the model is used to investigate how to accelerate the simulation speed of the network on the SpiNNaker system, with the future goal of creating a real-time neuromorphic cerebellum. Through detailed communication profiling, peak network activity is identified as one of the main challenges for simulation speed-up. Propagation of spiking activity through the network is measured, and will inform the future development of accelerated execution strategies for cerebellum models on neuromorphic hardware. The large ratio of granule cells to other cell types in the model results in high levels of activity converging onto few cells, with those cells having relatively larger time costs associated with the processing of communication. Organizing cells on SpiNNaker in accordance with their spatial position is shown to reduce the peak communication load by 41%. It is hoped that these insights, together with alternative parallelization strategies, will pave the way for real-time execution of large-scale, bio-physically constrained cerebellum models on SpiNNaker. This in turn will enable exploration of cerebellum-inspired controllers for neurorobotic applications, and execution of extended duration simulations over timescales that would currently be prohibitive using conventional computational platforms.
Event-Based Sensing and Signal Processing in the Visual, Auditory, and Olfactory Domain: A Review
Authors: Tayarani-Najaran Mohammad-Hassan , Schmuker Michael
Published: May 2021

The nervous systems converts the physical quantities sensed by its primary receptors into trains of events that are then processed in the brain. The unmatched efficiency in information processing has long inspired engineers to seek brain-like approaches to sensing and signal processing. The key principle pursued in neuromorphic sensing is to shed the traditional approach of periodic sampling in favor of an event-driven scheme that mimicks sampling as it occurs in the nervous system, where events are preferably emitted upon the change of the sensed stimulus. In this paper we highlight the advantages and challenges of event-based sensing and signal processing in the visual, auditory and olfactory domains. We also provide a survey of the literature covering neuromorphic sensing and signal processing in all three modalities. Our aim is to facilitate research in event-based sensing and signal processing by providing a comprehensive overview of the research performed previously as well as highlighting conceptual advantages, current progress and future challenges in the field.
Developmental Changes in Pyramidal Cell Morphology in Multiple Visual Cortical Areas Using Cluster Analysis
Authors: Khalil Reem , Farhat Ahmad , Dłotko Paweł
Published: May 2021

Neuronal morphology is characterized by salient features such as complex axonal and dendritic arbors. In the mammalian brain, variations in dendritic morphology among cell classes, brain regions, and animal species are thought to underlie known differences in neuronal function. In this work, we obtained a large dataset from http://neuromorpho.org/ comprising layer III pyramidal cells in different cortical areas of the ventral visual pathway (V1, V2, V4, TEO, and TE) of the macaque monkey at different developmental stages. We performed an in depth quantitative analysis of pyramidal cell morphology throughout development in an effort to determine which aspects mature early in development and which features require a protracted period of maturation. We were also interested in establishing if developmental changes in morphological features occur simultaneously or hierarchically in multiple visual cortical areas. We addressed these questions by performing principal component analysis (PCA) and hierarchical clustering analysis on relevant morphological features. Our analysis indicates that the maturation of pyramidal cell morphology is largely based on early development of topological features in most visual cortical areas. Moreover, the maturation of pyramidal cell morphology in V1, V2, V4, TEO, and TE is characterized by unique developmental trajectories.
The Relationship Between Electrical Energy Delivered by Deep Brain Stimulation and Levodopa-Induced Dyskinesias in Parkinson's Disease: A Retrospective Preliminary Analysis
Authors: Prenassi Marco , Arlotti Mattia , Borellini Linda , Bocci Tommaso , Cogiamanian Filippo , Locatelli Marco , Rampini Paolo , Barbieri Sergio , Priori Alberto , Marceglia Sara
Published: May 2021

Background: Adaptive Deep Brain Stimulation (aDBS) is now considered as a new feasible and effective paradigm to deliver DBS to patients with Parkinson's disease (PD) in such a way that not only stimulation is personalized and finely tuned to the instantaneous patient's state, but also motor improvement is obtained with a lower amount of energy transferred to the tissue. Amplitude-controlled aDBS was shown to significantly decrease the amplitude-driven total electrical energy delivered to the tissue (aTEED), an objective measure of the amount of energy transferred by DBS amplitude to the patient's brain. However, there is no direct evidence of a relationship between aTEED and the occurrence of DBS-related adverse events in humans.

Objective: In this work, we investigated the correlation of aTEED with the occurrence of levodopa-induced dyskinesias pooling all the data available from our previous experiments using aDBS and cDBS.

Methods: We retrospectively analyzed data coming from 19 patients with PD undergoing surgery for STN-DBS electrode positioning and participating to experiments involving cDBS and aDBS delivery. Patients were all studied some days after the surgery (acute setting). The aTEED and dyskinesia assessments (Rush Dyskinesia Rating Scale, RDRS) considered in the Med ON-Stim ON condition.

Results: We confirmed both that aTEED values and RDRS were significantly lower in the aDBS than in cDBS sessions (aTEED mean value, cDBS: 0.0278 ± 0.0011 j, vs. aDBS: 0.0071 ± 0.0003 j, p < 0.0001 Wilcoxon's rank sum; normalized RDRS mean score, cDBS: 0.66 ± 0.017 vs. aDBS: 0.45 ± 0.01, p = 0.025, Wilcoxon's rank sum test). In addition, we found a direct significant correlation between aTEED and RDRS (ρ = 0.44, p = 0.0032, Spearman's correlation).

Conclusions: Our results provide a first piece of evidence that aTEED is correlated to the amount of levodopa-induced dyskinesias in patients with PD undergoing STN-DBS, thus supporting the role of aDBS as feasible and safe alternative to cDBS.
C-reactive Protein for Stroke Detection in the Emergency Department in Patients With Dizziness Without Neurological Deficits
Authors: Hong Seok-In , Kim June-Sung , Bae Hong Jun , Kim Won Young
Published: May 2021

Background: Stroke diagnosis can be challenging in patients with dizziness without neurologic deficits. The aim of this study was to evaluate the predictive value of C-reactive protein (CRP) for identifying acute stroke in such patients.

Methods: Data from adult patients (>18 years) admitted to the emergency department from August 2019 to February 2020 were evaluated. The study subjects were 1,188 patients presenting with dizziness without neurological deficits whose serum CRP level was measured within 2 h of arriving at the emergency department and who underwent brain magnetic resonance imaging. The relationship between CRP and acute stroke was analyzed using univariable and multivariable models.

Results: Acute stroke was detected in 53 (4.4%) patients (40 with brain infarction, 10 with vertebrobasilar insufficiency, 2 with intracerebral hemorrhage, and 1 with subarachnoid hemorrhage). The CRP levels did not differ significantly between the acute stroke and non-stroke groups [0.10 (0.10–0.31) vs. 0.10 (0.10–0.16), P = 0.074]. The area under receiver operating characteristic curve of CRP for acute stroke was not statistically significant (0.567, P = 0.101). On multivariable analysis, the following variables were associated with acute stroke: age (odds ratio [OR], 1.041; 95% confidence interval [CI], 1.011–1.071), history of cerebrovascular accidents (OR, 1.823; 95% CI, 1.068–3.110), white blood cell count (OR, 1.126; 95% CI, 1.017–1.248), and hemoglobin (OR, 1.316; 95% CI, 1.056–1.640). However, CRP (P = 0.183) was not associated with acute stroke.

Conclusion: Serum CRP levels do not have significant discriminative value for identifying acute stroke in patients with dizziness without definite neurologic deficits.
Cervical Artery Dissection and Sports
Authors: Engelter Stefan T. , Traenka Christopher , Grond-Ginsbach Caspar , Brandt Tobias , Hakimi Maani , Worrall Bradford B. , Debette Stephanie , Pezzini Alessandro , Leys Didier , Tatlisumak Turgut , Nolte Christian H. , Lyrer Philippe
Published: May 2021

Cervical artery dissection (CeAD) occurring in the context of sports is a matter of concern for CeAD patients. They seek advice on the role of sports in CeAD and on the safety of resuming sports after CeAD. The scarcity of studies and guidelines addressing these issues poses a challenge. We aimed at summarizing the current knowledge about CeAD and sports in order to provide an informed, comprehensive opinion for counseling CeAD patients. We took into account pathophysiological considerations, observations of cases reports, series, and registries, and conclusions by analogy from aortic dissection or inherited connective tissue syndromes. In summary, practicing active sports as the cause of CeAD seems uncommon. It seems recommendable to refrain from any kind of sports activities for at least 1 month, which can be extended in case of an unfavorable clinical or neurovascular course. We recommend starting with sport activities at low intensity—preferably with types of endurance sports—and to gradually increase the pace in an individually tailored manner, taking into circumstances of the occurrences of the CeAD in the individual patient (particularly in relation to sports), the meaning of sports activities for the individual well-being, the presence or absence of comorbidities and of neurological sequela, neurovascular findings, and whether there are signs of an underlying connective tissue alteration. Major limitations and several forms of bias are acknowledged. Still, in the absence of any better data, the summarized observations and considerations might help clinicians in advising and counseling patients with CeAD in clinical practice.
Flow Diversion for Intracranial Aneurysms Beyond the Circle of Willis
Authors: Yu Jinlu , Lv Xianli
Published: May 2021

Background: Few reports have shown the therapeutic outcomes of flow diversion (FD) for intracranial aneurysms beyond the circle of Willis, and the efficacy of this technique remains unclear.

Materials and methods: A retrospective study was performed on 22 consecutive patients, diagnosed with intracranial aneurysms beyond the circle of Willis, and treated with pipeline embolization device (PED) (Medtronic, Irvine, California, USA) between January 2015 and December 2019.

Result: The 22 patients were between 16 and 66 years old (mean 44.5 ± 12.7 years), and six patients were male (27.3%, 6/22). Twenty-two patients had 23 aneurysms. The 23 aneurysms were 3–25 mm in diameter (12.2 ± 7.1 mm on average). The diameter of the parent artery was 1.3–3.0 mm (2.0 ± 0.6 mm on average). The 23 aneurysms were located as follows: 17 (73.9%, 17/23) were in the anterior circulation, and 6 (26.1%, 6/23) were in the posterior circulation. PED deployment was technically successful in all cases. Two overlapping PEDs were used to cover the aneurysm neck in 3 cases. One PED was used to overlap the two tandem P1 and P2 aneurysms. Other cases were treated with single PED. Coil assistance was used to treat 7 aneurysms, including 4 recurrent aneurysms and 3 new cases requiring coiling assistance during PED deployment. There were no cases of complications during PED deployment. All patients were available at the follow-up (mean, 10.9 ± 11.4 months). All patients presented with a modified Rankin Score (mRS) of 0. During angiographic follow-up, complete embolization was observed in 22 aneurysms in 21 patients, and one patient had subtotal embolization with the prolongation of stasis in the arterial phase.

Conclusion: PED deployment for intracranial aneurysms beyond the circle of Willis is feasible and effective, with high rates of aneurysm occlusion.
Is the Middle Meningeal Artery the Optimal Path for Dural Arteriovenous Fistula Embolization?
Authors: Su Han , Xu Kan , Wang Yiheng , Yu Jinlu
Published: May 2021

Background: The middle meningeal artery (MMA) is the optimal arterial path for endovascular treatment (EVT) of dural arteriovenous fistulas (DAVFs). However, the details are not completely understood.

Materials and Methods: We performed a retrospective study of patients who were admitted to the First Hospital of Jilin University with a diagnosis of cranial DAVF with involvement of the MMA as a feeding artery. On the basis of the arterial path chosen and the role of the MMA in the first EVT procedure, EVT was divided into three types (I–III), each of which was further divided into two subclasses (a and b). The degree of embolization was analyzed.

Result: The 104 included patients ranged in age from 13 to 80 years (mean, 53.6 ± 11.8 years). There were 48 cases of hemorrhage (46.2%, 48/104). Complete embolization was achieved in the first procedure in 64.4% of cases, and success was eventually achieved using EVT (the first attempt or a subsequent attempt) in 74.1% of cases. EVT caused complications in 6.7% of cases. A modified Rankin scale score of 0 or 1 was achieved in 78.8% of patients. Statistical analyses revealed that type Ia and IIb EVTs had the lowest complete embolization rates, but no difference was found between type Ia and IIb EVTs. Types IIa and III EVT had the highest complete embolization rates. Most cases had a good prognosis.

Conclusion: These findings elucidate the features of the different EVT classes defined by the first EVT procedure and the role of the MMA. The delivery of treatment via slim and tortuous MMA branches increased the failure rate of EVT. A thick, straight MMA branch is the optimal path for treatment.
Voice Analysis to Differentiate the Dopaminergic Response in People With Parkinson's Disease
Authors: Jain Anubhav , Abedinpour Kian , Polat Ozgur , Çalışkan Mine Melodi , Asaei Afsaneh , Pfister Franz M. J. , Fietzek Urban M. , Cernak Milos
Published: May 2021

Humans' voice offers the widest variety of motor phenomena of any human activity. However, its clinical evaluation in people with movement disorders such as Parkinson's disease (PD) lags behind current knowledge on advanced analytical automatic speech processing methodology. Here, we use deep learning-based speech processing to differentially analyze voice recordings in 14 people with PD before and after dopaminergic medication using personalized Convolutional Recurrent Neural Networks (p-CRNN) and Phone Attribute Codebooks (PAC). p-CRNN yields an accuracy of 82.35% in the binary classification of ON and OFF motor states at a sensitivity/specificity of 0.86/0.78. The PAC-based approach's accuracy was slightly lower with 73.08% at a sensitivity/specificity of 0.69/0.77, but this method offers easier interpretation and understanding of the computational biomarkers. Both p-CRNN and PAC provide a differentiated view and novel insights into the distinctive components of the speech of persons with PD. Both methods detect voice qualities that are amenable to dopaminergic treatment, including active phonetic and prosodic features. Our findings may pave the way for quantitative measurements of speech in persons with PD.
Visual Neuropsychology in Development: Anatomo-Functional Brain Mechanisms of Action/Perception Binding in Health and Disease
Authors: Ionta Silvio
Published: May 2021

Vision is the main entrance for environmental input to the human brain. Even if vision is our most used sensory modality, its importance is not limited to environmental exploration. Rather it has strong links to motor competences, further extending to cognitive and social aspects of human life. These multifaceted relationships are particularly important in developmental age and become dramatically evident in presence of complex deficits originating from visual aberrancies. The present review summarizes the available neuropsychological evidence on the development of visual competences, with a particular focus on the associated visuo-motor integration skills in health and disease. With the aim of supporting future research and interventional settings, the goal of the present review is to constitute a solid base to help the translation of neuropsychological hypotheses into straightforward empirical investigations and rehabilitation/training protocols. This approach will further increase the impact, ameliorate the acceptance, and ease the use and implementation of lab-derived intervention protocols in real-life situations.
Substantia Nigra Radiomics Feature Extraction of Parkinson’s Disease Based on Magnitude Images of Susceptibility-Weighted Imaging
Authors: Ren Qingguo , Wang Yihua , Leng Shanshan , Nan Xiaomin , Zhang Bin , Shuai Xinyan , Zhang Jianyuan , Xia Xiaona , Li Ye , Ge Yaqiong , Meng Xiangshui , Zhao Cuiping
Published: May 2021

Background

It is reported that radiomic features extracted from quantitative susceptibility mapping (QSM) had promising clinical value for the diagnosis of Parkinson’s disease (PD). We aimed to explore the usefulness of radiomics features based on magnitude images to distinguish PD from non-PD controls.

Methods

We retrospectively recruited PD patients and controls who underwent brain 3.0T MR including susceptibility-weighted imaging (SWI). A total of 396 radiomics features were extracted from the SN of 95 PD patients and 95 non-PD controls based on SWI. Intra-/inter-observer correlation coefficients (ICCs) were applied to measure the observer agreement for the radiomic feature extraction. Then the patients were randomly grouped into training and validation sets in a ratio of 7:3. In the training set, the maximum correlation minimum redundancy algorithm (mRMR) and the least absolute shrinkage and selection operator (LASSO) were conducted to filter and choose the optimized subset of features, and a radiomics signature was constructed. Moreover, radiomics signatures were constructed by different machine learning models. Area under the ROC curves (AUCs) were applied to evaluate the predictive performance of the models. Then correlation analysis was performed to evaluate the correlation between the optimized features and clinical factors.

Results

The intro-observer CC ranged from 0.82 to 1.0, and the inter-observer CC ranged from 0.77 to 0.99. The LASSO logistic regression model showed good prediction efficacy in the training set [AUC = 0.82, 95% confidence interval (CI, 0.74–0.88)] and the validation set [AUC = 0.81, 95% CI (0.68–0.91)]. One radiomic feature showed a moderate negative correlation with Hoehn-Yahr stage (r = −0.49, P = 0.012).

Conclusion

Radiomic predictive features based on SWI magnitude images could reflect the Hoehn-Yahr stage of PD to some extent.
Understanding the Role of Sensorimotor Beta Oscillations
Authors: Barone Jacopo , Rossiter Holly E.
Published: May 2021

Beta oscillations have been predominantly observed in sensorimotor cortices and basal ganglia structures and they are thought to be involved in somatosensory processing and motor control. Although beta activity is a distinct feature of healthy and pathological sensorimotor processing, the role of this rhythm is still under debate. Here we review recent findings about the role of beta oscillations during experimental manipulations (i.e., drugs and brain stimulation) and their alteration in aging and pathology. We show how beta changes when learning new motor skills and its potential to integrate sensory input with prior contextual knowledge. We conclude by discussing a novel methodological approach analyzing beta oscillations as a series of transient bursting events.
Designing and Development of FRET-Based Nanosensor for Real Time Analysis of N-Acetyl-5-Neuraminic Acid in Living Cells
Authors: Naz Ruphi , Okla Mohammad K. , Fatima Urooj , Mohsin Mohd. , Soufan Walid H. , Alaraidh Ibrahim A. , Abdel-Maksoud Mostafa A. , Ahmad Altaf
Published: May 2021

N-acetyl-5-neuraminic acid (NeuAc) plays crucial role in improving the growth, brain development, brain health maintenance, and immunity enhancement of infants. Commercially, it is used in the production of antiviral drugs, infant milk formulas, cosmetics, dietary supplements, and pharmaceutical products. Because of the rapidly increasing demand, metabolic engineering approach has attracted increasing attention for NeuAc biosynthesis. However, knowledge of metabolite flux in biosynthetic pathways is one of the major challenges in the practice of metabolic engineering. So, an understanding of the flux of NeuAc is needed to determine its cellular level at real time. The analysis of the flux can only be performed using a tool that has the capacity to measure metabolite level in cells without affecting other metabolic processes. A Fluorescence Resonance Energy Transfer (FRET)-based genetically-encoded nanosensor has been generated in this study to monitor the level of NeuAc in prokaryotic and eukaryotic cells. Sialic acid periplasmic binding protein (SiaP) from Haemophilus influenzae was exploited as a sensory element for the generation of nanosensor. The enhanced cyan fluorescent protein (ECFP) and Venus were used as Fluroscence Resonance Energy Transfer (FRET) pair. The nanosensor, which was termed fluorescent indicator protein for sialic acid (FLIP-SA), was successfully transformed into, and expressed in Escherichia coli BL21 (DE3) cells. The expressed protein of the nanosensor was isolated and purified. The purified nanosensor protein was characterized to assess the affinity, specificity, and stability in the pH range. The developed nanosensor exhibited FRET change after addition to NeuAc. The developed nanosensor was highly specific, exhibited pH stability, and detected NeuAc levels in the nanomolar to milimolar range. FLIP-SA was successfully introduced in bacterial and yeast cells and reported the real-time intracellular levels of NeuAc non-invasively. The FLIP-SA is an excellent tool for the metabolic flux analysis of the NeuAc biosynthetic pathway and, thus, may help unravel the regulatory mechanism of the metabolic pathway of NeuAc. Furthermore, FLIP-SA can be used for the high-throughput screening of E. coli mutant libraries for varied NeuAc production levels.
Effect of a Probiotic Combination in an Experimental Mouse Model and Clinical Patients With Chronic Kidney Disease: A Pilot Study
Authors: Wang I-Kuan , Yen Tzung-Hai , Hsieh Pei-Shan , Ho Hsieh-Hsun , Kuo Yi-Wei , Huang Yen-Yu , Kuo Yu-Lun , Li Chi-Yuan , Lin Hung-Chih , Wang Jiu-Yao
Published: May 2021

The aim of the present study was to evaluate whether probiotic administration could slow declining renal function. C57BL/6 mice (6–8 weeks of age, male) were fed a diet supplemented with adenine to induce chronic kidney disease (CKD). The experimental groups were additionally supplemented with 109 colony-forming units (CFU)/day (high-dose) and 107 CFU/day (low-dose) probiotics containing Lactobacillus acidophilus (TYCA06), Bifidobacterium longum subspecies infantis (BLI-02), and B. bifidum (VDD088). Renal function and histology were examined. Patients with stage 3–5 CKD and not on dialysis were recruited from July 2017 to January 2019. Two capsules of probiotics containing 2.5 × 109 CFU with the same composition were administered twice daily for 6 months. The decline in the estimated glomerular filtration rate (eGFR) was measured before and after the intervention. In addition, changes in the serum endotoxin and cytokine levels, gastrointestinal symptom scores, and the stool microbiota were measured. Probiotics could attenuate renal fibrosis and improve renal function in CKD mice. Thirty-eight patients completed the 6-month study. The mean baseline eGFR was 30.16 ± 16.52 ml/min/1.73 m2. The rate of decline in the eGFR was significantly slower, from −0.54 (−0.18, −0.91) to 0.00 (0.48, −0.36) ml/min/1.73 m2/month (P = 0.001) after 6 months of treatment. The serum levels of TNF-α, IL-6, IL-18, and endotoxin were significantly decreased after probiotic administration. Borborygmus and flatulence scores, as well as stool formation improved significantly. The abundance of B. bifidum and B. breve in the stool microbiota increased significantly. In conclusion, a combination of probiotics might attenuate renal function deterioration in CKD mice and human patients.
Exploration of the Tumor-Suppressive Immune Microenvironment by Integrated Analysis in EGFR-Mutant Lung Adenocarcinoma
Authors: Li Teng , Pang Xiaocong , Wang Junyun , Wang Shouzheng , Guo Yiying , He Ning , Xing Puyuan , Li Junling
Published: May 2021

Background

Clinical evidence has shown that few non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations can benefit from immunotherapy. The tumor immune microenvironment (TIME) is a significant factor affecting the efficacy of immunotherapy. However, the TIME transformational process in EGFR-mutation patients is unknown.

Methods

The mRNA expression and mutation data and lung adenocarcinoma (LUAD) clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Profiles describing the immune landscape of patients with EGFR mutations were characterized by differences in tumor mutation burden (TMB), ESTIMATE, CIBERSORT, and microenvironment cell populations-counter (MCP-counter).

Results

In total, the TCGA data for 585 patients were analyzed. Among these patients, 98 had EGFR mutations. The TMB was lower in the EGFR group (3.94 mut/Mb) than in the KRAS mutation group (6.09 mut/Mb, P < 0.001) and the entire LUAD (6.58 mut/Mb, P < 0.001). The EGFR group had a lower population of activated immune cells and an even higher score of immunosuppressive cells. A further inter-group comparison showed that differences in the TMB and tumor-infiltrating lymphocytes were only found between patients with oncogenic mutations and unknown mutation. Meanwhile, there were more myeloid dendritic cells (DCs) in EGFR 19del than in L858R-mutation patients and in common mutation patents than in uncommon mutation patients (P < 0.05). Additionally, we established a D score, where D = MCP-counter score for cytotoxic T lymphocytes (CTLs)/MCP-counter score for myeloid DCs. Further analysis revealed that lower D scores indicated immune suppression and were negatively related to several immunotherapy biomarkers.

Conclusions

The TIME of EGFR mutant NSCLC was immunosuppressive. Myeloid DCs gradually increased in EGFR 19del, L858R, and uncommon mutations. The potential role of CTLs and DCs in the TIME of patients requires further investigation.
The Novel Tumor Suppressor Gene ZNF24 Induces THCA Cells Senescence by Regulating Wnt Signaling Pathway, Resulting in Inhibition of THCA Tumorigenesis and Invasion
Authors: Xiong Juan , Jiang Panpan , Zhong Li , Wang Youling
Published: May 2021

Object

Clinically, the effective treatment options available to thyroid cancer (THCA) patients are very limited. Elucidating the features of tumor suppressor genes (TSGs) and the corresponding signal transduction cascade may provide clues for the development of new strategies for targeted therapy of THCA. Therefore, this paper aims to explore the mechanism of ZNF24 underlying promoting THCA cell senescence at molecular level.

Methods

We performed RT-PCR and Western Blotting for evaluating associated RNA and protein expression. CCK8, colony forming, wound healing and Transwell chamber assays were conducted to examine THCA cell proliferation, invasion and migration. β-galactosidase staining assay was performed to detect THCA cells senescence. The size and volume of xenotransplanted tumors in nude mice are calculated to asses ZNF24 effect in vivo.

Results

Ectopic expression of ZNF24 significantly inhibited the cell viability, colony forming, migration and invasion abilities of THCA cell lines (K1/GLAG-66i and BCPAPi) (P < 0.05). ZNF24 induced BCPAPi cells senescence through regulating Wnt signaling pathway. ZNF24 inhibited Wnt signaling pathway activition by competitively binding β-catenin from LEF1/TCF1-β-catenin complex. In nude mice, both Ectopic expression of ZNF24 and 2,4-Da (the strong β-catenin/Tcf-4 inhibitor) treatment significantly decreased both the size and weight of xenotransplanted tumors when compared with control mice (P < 0.05).

Conclusion

Results obtained in vivo and in vitro reveal the role of ZNF24 in significantly suppressing THCA tumorigenesis and invasion by regulating Wnt signaling pathway.
Retinoic Acid Downregulates HSPB8 Gene Expression in Human Breast Cancer Cells MCF-7
Authors: Piccolella Margherita , Cristofani Riccardo , Tedesco Barbara , Chierichetti Marta , Ferrari Veronica , Casarotto Elena , Cozzi Marta , Crippa Valeria , Rusmini Paola , Galbiati Mariarita , Poletti Angelo , Messi Elio
Published: May 2021

Breast cancer (BC) is a serious and widespread disease for which different treatments have been developed. In addition to the classic therapies, the treatment with retinoic acid (RA) is still being clinically investigated. RA reduces cancer cells proliferation and migration, but its molecular mechanism of action is not clear. In tumor development, autophagy promotes cancer cell survival and prevents apoptosis. Small heat shock protein B8 (HSPB8) acts together with its co-chaperone BCL-2 associated athanogene 3 (BAG3) stimulating BC proliferation and migration. We analyzed whether direct correlations exist between RA and HSPB8 or BAG3 and how this may play a role in BC. We measured HSPB8 and BAG3 gene expression in MCF-7 BC cells and we analyzed the potential correlation between the antiproliferative and antimigratory effect of RA with the expression level of HSPB8. We found that in MCF-7 cells RA reduces both HSPB8 and BAG3 gene expression and it alters the mitotic spindle organization. Notably, the effects of RA on HSPB8 levels are exerted at both transcriptional and translational levels. RA effects are possibly mediated by miR-574-5p that targets the HSPB8 transcript. Our results suggest that therapeutic doses of RA can efficiently counteract the adverse effects of HSPB8 in BC progression.
MV CBCT-Based Synthetic CT Generation Using a Deep Learning Method for Rectal Cancer Adaptive Radiotherapy
Authors: Zhao Jun , Chen Zhi , Wang Jiazhou , Xia Fan , Peng Jiayuan , Hu Yiwen , Hu Weigang , Zhang Zhen
Published: May 2021

Due to image quality limitations, online Megavoltage cone beam CT (MV CBCT), which represents real online patient anatomy, cannot be used to perform adaptive radiotherapy (ART). In this study, we used a deep learning method, the cycle-consistent adversarial network (CycleGAN), to improve the MV CBCT image quality and Hounsfield-unit (HU) accuracy for rectal cancer patients to make the generated synthetic CT (sCT) eligible for ART. Forty rectal cancer patients treated with the intensity modulated radiotherapy (IMRT) were involved in this study. The CT and MV CBCT images of 30 patients were used for model training, and the images of the remaining 10 patients were used for evaluation. Image quality, autosegmentation capability and dose calculation capability using the autoplanning technique of the generated sCT were evaluated. The mean absolute error (MAE) was reduced from 135.84 ± 41.59 HU for the CT and CBCT comparison to 52.99 ± 12.09 HU for the CT and sCT comparison. The structural similarity (SSIM) index for the CT and sCT comparison was 0.81 ± 0.03, which is a great improvement over the 0.44 ± 0.07 for the CT and CBCT comparison. The autosegmentation model performance on sCT for femoral heads was accurate and required almost no manual modification. For the CTV and bladder, although modification was needed for autocontouring, the Dice similarity coefficient (DSC) indices were high, at 0.93 and 0.94 for the CTV and bladder, respectively. For dose evaluation, the sCT-based plan has a much smaller dose deviation from the CT-based plan than that of the CBCT-based plan. The proposed method solved a key problem for rectal cancer ART realization based on MV CBCT. The generated sCT enables ART based on the actual patient anatomy at the treatment position.
False-Positive Radioiodine Uptake in Simple Ovarian Cyst in a DTC Patient: A Case Report
Authors: Wu Tao , Zhao Xuefeng , Xu Huiqin
Published: May 2021

Abnormal radioildine uptake can be caused by various pelvic lesions in differentiated thyroid cancer patient. Here we presented an abnormal uptake in the left side of the pelvic cavity on postablative I-131 scintigraphy in a 51-year-old woman with history of stage T1aN1M0 papillary thyroid cancer. The SPECT/CT fused imaging revealed the lesion in the left ovary. Laparoscopic bilateral adnexectomy showed a left ovarian mass (5 cm) and pathologic finding showed a simple ovarian cyst. The nonstimulated Tg immediately decreased to 143 ng/ml after bilateral adnexectomy 3 days later and to 0.109 ng/ml after 4-month follow-up. Timely intervention measures are very necessary for patients with ovarian cyst with abnormally elevated Tg level.