bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure and Dynamics of the Breast Tissue Microbiomes Under Tumor Influences: An Approach With Neutral, Near-Neutral, and Niche-Neutral Hybrid Models
Authors: Li Lianwei , Ning Ping , Ma Zhanshan (Sam)
Published: July 2021

The structure and dynamics of breast tissue bacteria can have far-reaching influences on women’s health, particularly on breast tumor development. However, there is little understanding on the ecological processes that shape the structure and dynamics of breast tissue bacteria. Here, we fill the gap by applying three metacommunity models for investigating the community assembly and diversity maintenance, including Sloan near neutral model, Harris et al. multisite neutral and Tang & Zhou niche-neutral hybrid models to reanalyze the 16S-rRNA sequencing datasets of 23 healthy, 12 benign tumor, and 33 malignant tumor tissue samples. First, we found that, at the community/metacommunity levels, the mechanisms of bacteria assembly and diversity maintenance of breast tissue bacteria were moderately influenced by stochastic drifts of bacteria demography (division, death, and dispersal of bacterial cells). At species level, on average, approximately 10 and 5% species were above (positively selected) and below (negatively selected) neutral, respectively. Furthermore, malignant tumor may raise the positively selected species up to 17%. Second, malignant tumor appears to inhibit microbial dispersal as evidenced by lowered migration rates, compared with the migration in normal and benign tumor tissues. These theoretic findings can be inspirational for further investigating the relationships between tissue bacteria and breast tumor progression/development.
New Insights From Transcriptomic Data Reveal Differential Effects of CO2 Acidification Stress on Photosynthesis of an Endosymbiotic Dinoflagellate in hospite
Authors: Herrera Marcela , Liew Yi Jin , Venn Alexander , Tambutté Eric , Zoccola Didier , Tambutté Sylvie , Cui Guoxin , Aranda Manuel
Published: July 2021

Ocean acidification (OA) has both detrimental as well as beneficial effects on marine life; it negatively affects calcifiers while enhancing the productivity of photosynthetic organisms. To date, many studies have focused on the impacts of OA on calcification in reef-building corals, a process particularly susceptible to acidification. However, little is known about the effects of OA on their photosynthetic algal partners, with some studies suggesting potential benefits for symbiont productivity. Here, we investigated the transcriptomic response of the endosymbiont Symbiodinium microadriaticum (CCMP2467) in the Red Sea coral Stylophora pistillata subjected to different long-term (2 years) OA treatments (pH 8.0, 7.8, 7.4, 7.2). Transcriptomic analyses revealed that symbionts from corals under lower pH treatments responded to acidification by increasing the expression of genes related to photosynthesis and carbon-concentrating mechanisms. These processes were mostly up-regulated and associated metabolic pathways were significantly enriched, suggesting an overall positive effect of OA on the expression of photosynthesis-related genes. To test this conclusion on a physiological level, we analyzed the symbiont’s photochemical performance across treatments. However, in contrast to the beneficial effects suggested by the observed gene expression changes, we found significant impairment of photosynthesis with increasing pCO2. Collectively, our data suggest that over-expression of photosynthesis-related genes is not a beneficial effect of OA but rather an acclimation response of the holobiont to different water chemistries. Our study highlights the complex effects of ocean acidification on these symbiotic organisms and the role of the host in determining symbiont productivity and performance.
Native AMF Communities in an Italian Vineyard at Two Different Phenological Stages of Vitis vinifera
Authors: Cesaro Patrizia , Massa Nadia , Bona Elisa , Novello Giorgia , Todeschini Valeria , Boatti Lara , Mignone Flavio , Gamalero Elisa , Berta Graziella , Lingua Guido
Published: July 2021

Arbuscular mycorrhizal fungi (AMF) are beneficial soil microorganisms that can establish symbiotic associations withVitis viniferaroots, resulting in positive effects on grapevine performance, both in terms of water use efficiency, nutrient uptake, and replant success. Grapevine is an important perennial crop cultivated worldwide, especially in Mediterranean countries. In Italy, Piedmont is one of the regions with the longest winemaking tradition. In the present study, we characterized the AMF communities of the soil associated or not with the roots ofV. viniferacv. Pinot Noir cultivated in a vineyard subjected to conventional management using 454 Roche sequencing technology. Samplings were performed at two plant phenological stages (flowering and early fruit development). The AMF community was dominated by members of the family Glomeraceae, with a prevalence of the genusGlomusand the speciesRhizophagus intraradicesandRhizophagus irregularis. On the contrary, the genusArchaeosporawas the only one belonging to the family Archaeosporaceae. Since different AMF communities occur in the two considered soils, independently from the plant phenological stage, a probable role ofV. viniferain determining the AMF populations associated to its roots has been highlighted.
Efficacy of Plant Growth-Promoting Bacteria Bacillus cereus YN917 for Biocontrol of Rice Blast
Authors: Zhou Hu , Ren Zuo-hua , Zu Xue , Yu Xi-yue , Zhu Hua-jun , Li Xiao-juan , Zhong Jie , Liu Er-ming
Published: July 2021

Bacillus cereusYN917, obtained from a rice leaf with remarkable antifungal activity againstMagnaporthe oryzae, was reported in our previous study. The present study deciphered the possible biocontrol properties. YN917 strain exhibits multiple plant growth-promoting and disease prevention traits, including production of indole-3-acetic acid (IAA), ACC deaminase, siderophores, protease, amylase, cellulase, and β-1,3-glucanase, and harboring mineral phosphate decomposition activity. The effects of the strain YN917 on growth promotion and disease prevention were further evaluated under detached leaf and greenhouse conditions. The results revealed thatB. cereusYN917 can promote seed germination and seedling plant growth. The growth status of rice plants was measured from the aspects of rice plumule, radicle lengths, plant height, stem width, root lengths, fresh weights, dry weights, and root activity when YN917 was used as inoculants. YN917 significantly reduced rice blast severity under detached leaf and greenhouse conditions. Genome analysis revealed the presence of gene clusters for biosynthesis of plant promotion and antifungal compounds, such as IAA, tryptophan, siderophores, and phenazine. In summary, YN917 can not only be used as biocontrol agents to minimize the use of chemical substances in rice blast control, but also can be developed as bio-fertilizers to promote the rice plant growth.
Associative Conditioning Is a Robust Systemic Behavior in Unicellular Organisms: An Interspecies Comparison
Authors: Carrasco-Pujante Jose , Bringas Carlos , Malaina Iker , Fedetz Maria , Martínez Luis , Pérez-Yarza Gorka , Dolores Boyano María , Berdieva Mariia , Goodkov Andrew , López José I. , Knafo Shira , De la Fuente Ildefonso M.
Published: July 2021

The capacity to learn new efficient systemic behavior is a fundamental issue of contemporary biology. We have recently observed, in a preliminary analysis, the emergence of conditioned behavior in some individual amoebae cells. In these experiments, cells were able to acquire new migratory patterns and remember them for long periods of their cellular cycle, forgetting them later on. Here, following a similar conceptual framework of Pavlov’s experiments, we have exhaustively studied the migration trajectories of more than 2000 individual cells belonging to three different species: Amoeba proteus, Metamoeba leningradensis, and Amoeba borokensis. Fundamentally, we have analyzed several relevant properties of conditioned cells, such as the intensity of the responses, the directionality persistence, the total distance traveled, the directionality ratio, the average speed, and the persistence times. We have observed that cells belonging to these three species can modify the systemic response to a specific stimulus by associative conditioning. Our main analysis shows that such new behavior is very robust and presents a similar structure of migration patterns in the three species, which was characterized by the presence of conditioning for long periods, remarkable straightness in their trajectories and strong directional persistence. Our experimental and quantitative results, compared with other studies on complex cellular responses in bacteria, protozoa, fungus-like organisms and metazoans that we discus here, allow us to conclude that cellular associative conditioning might be a widespread characteristic of unicellular organisms. This new systemic behavior could be essential to understand some key principles involved in increasing the cellular adaptive fitness to microenvironments.
Durlobactam, a New Diazabicyclooctane β-Lactamase Inhibitor for the Treatment of Acinetobacter Infections in Combination With Sulbactam
Authors: Shapiro Adam B. , Moussa Samir H. , McLeod Sarah M. , Durand-Réville Thomas , Miller Alita A.
Published: July 2021

Durlobactam is a new member of the diazabicyclooctane class of β-lactamase inhibitors with broad spectrum activity against Ambler class A, C, and D serine β-lactamases. Sulbactam is a first generation β-lactamase inhibitor with activity limited to a subset of class A enzymes that also has direct-acting antibacterial activity against Acinetobacter spp. The latter feature is due to sulbactam’s ability to inhibit certain penicillin-binding proteins, essential enzymes involved in bacterial cell wall synthesis in this pathogen. Because sulbactam is also susceptible to cleavage by numerous β-lactamases, its clinical utility for the treatment of contemporary Acinetobacter infections is quite limited. However, when combined with durlobactam, the activity of sulbactam is effectively restored against these notoriously multidrug-resistant strains. This sulbactam-durlobactam combination is currently in late-stage development for the treatment of Acinectobacter infections, including those caused by carbapenem-resistant isolates, for which there is a high unmet medical need. The following mini-review summarizes the molecular drivers of efficacy of this combination against this troublesome pathogen, with an emphasis on the biochemical features of each partner.
Expression and Gene Regulation Network of Adenosine Receptor A2B in Lung Adenocarcinoma: A Potential Diagnostic and Prognostic Biomarker
Authors: Sui Yutong , Liu Jiayin , Zhang Jing , Zheng Zena , Wang Ziwei , Jia Zhenghu , Meng Ziyu
Published: July 2021

Adenosinereceptor A2B (ADORA2B) encodes a protein belonging to the G protein–coupled receptor superfamily. Abnormal expression of ADORA2B may play a pathophysiological role in some human cancers. We investigated whether ADORA2B is a potential diagnostic and prognostic biomarker for lung adenocarcinoma (LUAD). The expression, various mutations, copy number variations, mRNA expression levels, and related network signaling pathways of ADORA2B were analyzed using bioinformatics-related websites, including Oncomine, UALCAN, cBioPortal, GeneMANIA, LinkedOmics, KM Plotter, and TIMER. We found that ADORA2B was overexpressed and amplified in LUAD, and a high ADORA2B expression predicted a poor prognosis for LUAD patients. Pathway analyses of ADORA2B in LUAD revealed ADORA2B-correlated signaling pathways, and the expression level of ADORA2B was associated with immune cell infiltration. Furthermore, ADORA2B mRNA and protein levels were significantly higher in human LUAD cell lines (A549 cells and NCl-H1299 cells) than in normal human bronchial epithelial (HBE) cells, and the transcript levels of genes positively or negatively correlated with ADORA2B were consistent and statistically significant. siRNA transfection experiments and functional experiments further confirmed these results. In vitro results were also consistent with those of bioinformatics analysis. Our findings provide a foundation for studying the role of ADORA2B in tumorigenesis and support the development of new drug targets for LUAD.
BGM-Net: Boundary-Guided Multiscale Network for Breast Lesion Segmentation in Ultrasound
Authors: Wu Yunzhu , Zhang Ruoxin , Zhu Lei , Wang Weiming , Wang Shengwen , Xie Haoran , Cheng Gary , Wang Fu Lee , He Xingxiang , Zhang Hai
Published: July 2021

Automatic and accurate segmentation of breast lesion regions from ultrasonography is an essential step for ultrasound-guided diagnosis and treatment. However, developing a desirable segmentation method is very difficult due to strong imaging artifacts e.g., speckle noise, low contrast and intensity inhomogeneity, in breast ultrasound images. To solve this problem, this paper proposes a novel boundary-guided multiscale network (BGM-Net) to boost the performance of breast lesion segmentation from ultrasound images based on the feature pyramid network (FPN). First, we develop a boundary-guided feature enhancement (BGFE) module to enhance the feature map for each FPN layer by learning a boundary map of breast lesion regions. The BGFE module improves the boundary detection capability of the FPN framework so that weak boundaries in ambiguous regions can be correctly identified. Second, we design a multiscale scheme to leverage the information from different image scales in order to tackle ultrasound artifacts. Specifically, we downsample each testing image into a coarse counterpart, and both the testing image and its coarse counterpart are input into BGM-Net to predict a fine and a coarse segmentation maps, respectively. The segmentation result is then produced by fusing the fine and the coarse segmentation maps so that breast lesion regions are accurately segmented from ultrasound images and false detections are effectively removed attributing to boundary feature enhancement and multiscale image information. We validate the performance of the proposed approach on two challenging breast ultrasound datasets, and experimental results demonstrate that our approach outperforms state-of-the-art methods.
Language Disorder in Progressive Supranuclear Palsy and Corticobasal Syndrome: Neural Correlates and Detection by the MLSE Screening Tool
Authors: Peterson Katie A. , Jones P. Simon , Patel Nikil , Tsvetanov Kamen A. , Ingram Ruth , Cappa Stefano F. , Lambon Ralph Matthew A. , Patterson Karalyn , Garrard Peter , Rowe James B.
Published: July 2021

Background: Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) affect speech and language as well as motor functions. Clinical and neuropathological data indicate a close relationship between these two disorders and the non-fluent variant of primary progressive aphasia (nfvPPA). We use the recently developed Mini Linguistic State Examination tool (MLSE) to study speech and language disorders in patients with PSP, CBS, and nfvPPA, in combination with structural magnetic resonance imaging (MRI).

Methods: Fifty-one patients (PSP N = 13, CBS N = 19, nfvPPA N = 19) and 30 age-matched controls completed the MLSE, the short form of the Boston Diagnostic Aphasia Examination (BDAE), and the Addenbrooke’s Cognitive Examination III. Thirty-eight patients and all controls underwent structural MRI at 3 Tesla, with T1 and T2-weighted images processed by surface-based and subcortical segmentation within FreeSurfer 6.0.0 to extract cortical thickness and subcortical volumes. Morphometric differences were compared between groups and correlated with the severity of speech and language impairment.

Results: CBS and PSP patients showed impaired MLSE performance, compared to controls, with a similar language profile to nfvPPA, albeit less severe. All patient groups showed reduced cortical thickness in bilateral frontal regions and striatal volume. PSP and nfvPPA patients also showed reduced superior temporal cortical thickness, with additional thalamic and amygdalo-hippocampal volume reductions in nfvPPA. Multivariate analysis of brain-wide cortical thickness and subcortical volumes with MLSE domain scores revealed associations between performance on multiple speech and language domains with atrophy of left-lateralised fronto-temporal cortex, amygdala, hippocampus, putamen, and caudate.

Conclusions: The effect of PSP and CBS on speech and language overlaps with nfvPPA. These three disorders cause a common anatomical pattern of atrophy in the left frontotemporal language network and striatum. The MLSE is a short clinical screening tool that can identify the language disorder of PSP and CBS, facilitating clinical management and patient access to future clinical trials.
The Influence of Demographics and Vascular Risk Factors on Glymphatic Function Measured by Diffusion Along Perivascular Space
Authors: Zhang Yao , Zhang Ruiting , Ye Yongquan , Wang Shuyue , Jiaerken Yeerfan , Hong Hui , Li Kaicheng , Zeng Qingze , Luo Xiao , Xu Xiaopei , Yu Xinfeng , Wu Xiao , Yu Wenke , Zhang Minming , Huang Peiyu
Published: July 2021

Assessing glymphatic function using in-vivo imaging method is of great value for understanding its contribution to major brain diseases. In the present study, we aim to validate the association between a variety of risk factors and a potential index of glymphatic function—Diffusion Tensor Image Analysis Along the Perivascular Space (ALPS index). We enrolled 142 subjects from communities and performed multi-modality magnetic resonance imaging scans. The ALPS index was calculated from diffusion tensor imaging data, and its associations with demographic factors, vascular factors were investigated using regression analyses. We found that the ALPS index was negatively associated with age (β = −0.284,p< 0.001). Compared to males, females had significantly higher ALPS index (β = −0.243,p= 0.001). Hypertensive subjects had significantly lower ALPS index compared to non-hypertensive subjects (β = −0.189,p= 0.013). Furthermore, venous disruption could decrease ALPS index (β = −0.215,p= 0.003). In general, our results are in consistent with previous conceptions and results from animal studies about the pathophysiology of glymphatic dysfunction. Future studies utilizing this method should consider introducing the above-mentioned factors as important covariates.
High-Definition Transcranial Direct Current Stimulation Over the Right Lateral Prefrontal Cortex Increases Maximization Tendencies
Authors: Wang Haixia , Zhang Hanqi
Published: July 2021

People seek the best in every aspect of life. However, little is known about the neurobiological mechanisms supporting this process of maximization. In this study, maximization tendencies were increased by using high-definition transcranial direct current stimulation (HD-tDCS) over the right dorsolateral prefrontal cortex (DLPFC). Participants (n= 64) received 2 mA anodal 4 × 1 HD-tDCS or sham stimulation over the right DLPFC in two sessions and subsequently completed an N-back working memory task and a maximization scale (MS). We observed that maximization tendency scores increased during anodal stimulation. Furthermore, the results indicate that this increase in maximization tendency was driven by motivational changes. On the MS, alternative search subscale scores were significantly increased, demonstrating an increase in motivation to evaluate more alternatives; however, the results did not indicate that the increase in maximization tendencies was due to working memory improvement. These results demonstrated that maximization tendencies can be strengthened through noninvasive interventions and that the right DLPFC has a causal relationship with maximization tendencies.
Automatic Intra-/Extra-Dimensional Attentional Set-Shifting Task in Adolescent Mice
Authors: Ciampoli Mariasole , Scheggia Diego , Papaleo Francesco
Published: July 2021

Adolescence is a developmental period crucial for the maturation of higher-order cognitive functions. Indeed, adolescence deficits in executive functions are strong predictors of increased vulnerability to several mental disabilities later in life. Here, we tested adolescent mice in a fully-automated attentional set-shifting task equivalent to the humans’ Wisconsin Card Sorting Test (WCST) and the Cambridge Neuropsychological Test Automated Battery Intra-/Extra-Dimensional set-shift task (ID/ED). Compared to an adult, adolescent mice required more time to complete the task (≈16 days), and a higher percentage failed to finish the entire task. Nevertheless, adolescent mice completing this demanding task showed an increased effort in solving the extradimensional shift stage (EDS) compared to previous stages. Moreover, we found that this paradigm can be used to detect early cognitive dysfunctions in adolescent genetically modified mice. Thus, this automatic paradigm provides a further tool to assess attentional control in adolescent mice, and the development of dysfunctional executive functions from adolescence to adulthood.
Safety and Efficacy of Direct Angioplasty in Acute Basilar Artery Occlusion Due to Atherosclerosis
Authors: Ma Gaoting , Sun Xuan , Tong Xu , Jia Baixue , Huo Xiaochuan , Luo Gang , Wang Bo , Deng Yiming , Gao Feng , Song Ligang , Ma Ning , Miao Zhongrong , Mo Dapeng
Published: July 2021

Background and Purpose: Endovascular treatment (EVT) is one of the promising treatment options in patients with intracranial atherosclerotic disease (ICAD)-related basilar artery occlusion (BAO). In this study, we compared the safety and efficacy of direct angioplasty (DA) with stent-retriever thrombectomy (SRT) with or without rescue treatment in ICAD-related BAO.

Methods: We retrospectively evaluated 187 patients who underwent EVT for BAO from January 2012 to July 2018. We identified patients who underwent EVT due to ICAD-related BAO. Patients who accepted SRT with or without rescue treatment were classified into the SRT group. Patients treated with DA with or without stent placement were classified into DA group. Clinical and laboratory findings and outcomes were compared between groups.

Results: A total of 108 patients were enrolled, among them 77 underwent SRT and 31 underwent DA; 61 (79.2%) SRT group patients underwent angioplasty with or without stent placement. Compared with patients in the SRT group, those in the DA group experienced a significantly shorter procedure time [60 min (60–120 min) vs. 120 min (60–120 min); p = 0.038] and a lower number of device passes [2 passes (1–2 passes) vs. 3 passes (2–4 passes); p < 0.001]. No significant differences in balloon angioplasty (35.5 vs. 22.1%; p = 0.150), emergent stent placement (64.5 vs. 57.1%; p = 0.481), successful recanalization (93.5 vs. 85.7%; p = 0.340), embolization in distal or new territory (3.2 vs. 9.1%, p = 0.314), and reocclusion (22.6 vs. 9.1%; p = 0.109) among DA and SRT groups were found. Additionally, no differences in symptomatic intracranial hemorrhage incidence [adjusted odds ratio (OR), 0.74; 95% CI, 0.06–9.44; p = 0.815], functional independence (adjusted OR, 1.44; 95% CI, 0.50–4.16; p = 0.497), and mortality rate (adjusted OR, 0.36; 95% CI, 0.06–2.04; p = 0.247) were noted among groups.

Conclusions: In certain patients with ICAD-related BAO, DA may shorten procedure time and reduce required device passes compared to SRT. In this study, DA was retrospectively found to be of similar safety and efficacy as SRT.
Association Between Diabetes Medications and the Risk of Parkinson's Disease: A Systematic Review and Meta-Analysis
Authors: Qin Xiaocui , Zhang Xia , Li Pinyu , Wang Min , Yan Li , Bao Zeqing , Liu Qili
Published: July 2021

Background: Diabetes mellitus (DM) increases the risk of Parkinson's disease (PD). However, whether DM medications play a part on that increased PD risk is unclear. We designed this meta-analysis to assess the influence of different oral DM medications on the PD risk in patients with DM.

Methods: We searched PubMed, Embase, and CENTRAL databases for relevant studies up until January 2021. We pooled adjusted outcomes to assess the PD risk in patients using different DM medications including sulfonylurea, metformin, glitazones (GTZ), dipeptidyl peptidase-4 inhibitors (DPP4i), and glucagon-like peptide-1 agonists (GLP1a).

Results: We included 10 studies in our analysis. Our results indicate a lack of significant association between the PD risk and the use of sulfonylureas (three studies; HR, 1.26; 95% CI, 0.95 to 1.66; I2, 70%; p = 0.11), DPP4i (three studies; HR, 0.69; 95% CI, 0.35 to 1.38; I2, 88%; p = 0.30), metformin (five studies; HR, 1.23; 95% CI, 0.98 to 1.78; I2, 84%; p = 0.13), and GTZ (six studies; HR, 0.88; 95% CI, 0.66 to 1.16; I2, 92%; p = 0.35). After exclusion of a single study in the GTZ analysis, our results indicate a significantly reduced PD risk with GTZ use (HR, 0.78; 95% CI, 0.65 to 0.93; I2, 59%; p = 0.06). Similarly, after the exclusion of a single study, our results indicate a significantly increased PD risk with the use of metformin (HR, 1.50; 95% CI, 1.11 to 2.02; I2, 80%; p = 0.008). We also found a significantly reduced PD risk with the use of GLP1a (two studies; HR, 0.41; 95% CI, 0.19 to 0.87; I2, 0%; p = 0.02).

Conclusion: The role of different DM medications on the PD risk remains unclear, and the quality of studies is low. While our analysis suggests a lack of association between the use of metformin, GTZ, DPP4i, and sulfonylureas and the PD risk, metformin (to a higher degree) and GTZ may still increase the risk. Limited data suggest a protective effect of GLP1a on the PD risk.
Outcomes of a Multicenter Safety and Efficacy Study of the SuitX Phoenix Powered Exoskeleton for Ambulation by Patients With Spinal Cord Injury
Authors: Koljonen Paul Aarne , Virk Anna Sternin , Jeong Yoon , McKinley Michael , Latorre Juan , Caballero Amaya , Hu Yong , Wong Yat Wa , Cheung Kenneth , Kazerooni Homayoon
Published: July 2021

Objective: To examine the safety and efficacy of ambulation utilizing a semi-passive and lightweight powered exoskeleton by spinal cord injury (SCI) patients.

Methods: This is a multi-center, open-label, prospective cohort study across three facilities. A cohort of 40 individuals with SCI from T4-L5 was recruited into a 20-session training and assessment protocol, utilizing the SuitX Phoenix. All patients were tested using a 10-m-walk test (10 MWT), 6-min-walk test (6 MWT), and Timed up & Go test (TUG). Patient satisfaction, pain, exertion, changes in affect, as well as overall comfort and confidence were reported using a satisfaction survey, Rated Perceived Exertion (RPE) scale, and Positive and Negative Affect Schedule (PANAS). Safety outcomes, adverse events, and device malfunctions were reported.

Results: Forty participants completed the study. There were no serious adverse events. All participants reported moderate to high levels of comfort and confidence using the device. All patients were able to achieve FIM of >4 on transitional movements and walking. The neurological level of injury had a statistically significant association with walking speed, WISCI-II, and FIM. Participants with an incomplete spinal cord injury had a higher FIM, faster speed, and higher WISCI-II in all outcome measures.

Conclusion: This is the first study to examine the safety and efficacy of SuitX Phoenix for ambulation by SCI patients. We have shown that Phoenix is efficacious in allowing adults with SCI T4 to L5 perform walking and transitional movements. This study also reports the safety-profile of the device, user satisfaction, and psychological trends during training.
Electroclinical Features of Epilepsy in Mucopolysaccharidosis III: Outcome Description in a Cohort of 15 Italian Patients
Authors: Barone Rita , Fiumara Agata , Gulisano Mariangela , Cirnigliaro Lara , Cocuzza Maria Donatella , Guida Claudia , Pettinato Fabio , Greco Filippo , Elia Maurizio , Rizzo Renata
Published: July 2021

Mucopolysaccharidosis III (Sanfilippo syndromes) types A–D are rare lysosomal storage disorders characterized by heparan sulfate accumulation and neurodegeneration. Patients with MPS III present with developmental stagnation and/or regression, sleep disturbance, and behavioral abnormalities usually in the first years of life. Epilepsy may occur in a proportion of patients during the disease course. However, the progression of epilepsy and EEG changes in MPS III have not been systematically investigated. We report electroclinical features in a cohort of patients with MPS III over a follow-up period ranging from 6.5 to 22 years. Participants include 15 patients (11 females; aged 7–31 years) with MPS III A (n = 7, 47%), MPS III B (n = 5, 34%), MPS III C (n = 2, 13%), and MPS III D (n = 1, 6%). At the time of this study, 8 out of 15 patients (53%) had epilepsy. Epilepsy occurred in patients with advanced disease even in the first decade of life (mean age at onset: 12.1 ± 6.7 years). However, seizure onset may also be associated with abrupt worsening of the neurobehavioral phenotype. The main epilepsy types observed were generalized (four out of eight, 50%), followed by focal (three out of eight, 37%) and combined (two out of eight, 25%) epilepsy and status epilepticus (one out of eight, 12.5%). Seizures were generally controlled by one antiepileptic drug (AED) and most patients (seven out of eight, 87%) were still on therapy after a median follow-up period of 5 years (range: 1–9 years). A total of 66 EEGs were analyzed with a median EEG follow-up duration of 7 years (range: 6 months−14 years). Slowing of the background activity occurred in 7 (46%) patients aged 4–19 years. Epileptiform EEG abnormalities were observed in 10 patients at a mean age of 9.6 ± 2.9 years. EEG epileptiform discharges were not unavoidably linked to epilepsy. Early recognition and careful monitoring of electroclinical features in MPS III is necessary for appropriate care and for the detection of disease progression.
Diffusional Kurtosis Imaging in the Diffusion Imaging in Python Project
Authors: Henriques Rafael Neto , Correia Marta M. , Marrale Maurizio , Huber Elizabeth , Kruper John , Koudoro Serge , Yeatman Jason D. , Garyfallidis Eleftherios , Rokem Ariel
Published: July 2021

Diffusion-weighted magnetic resonance imaging (dMRI) measurements and models provide information about brain connectivity and are sensitive to the physical properties of tissue microstructure. Diffusional Kurtosis Imaging (DKI) quantifies the degree of non-Gaussian diffusion in biological tissue from dMRI. These estimates are of interest because they were shown to be more sensitive to microstructural alterations in health and diseases than measures based on the total anisotropy of diffusion which are highly confounded by tissue dispersion and fiber crossings. In this work, we implemented DKI in the Diffusion in Python (DIPY) project—a large collaborative open-source project which aims to provide well-tested, well-documented and comprehensive implementation of different dMRI techniques. We demonstrate the functionality of our methods in numerical simulations with known ground truth parameters and in openly available datasets. A particular strength of our DKI implementations is that it pursues several extensions of the model that connect it explicitly with microstructural models and the reconstruction of 3D white matter fiber bundles (tractography). For instance, our implementations include DKI-based microstructural models that allow the estimation of biophysical parameters, such as axonal water fraction. Moreover, we illustrate how DKI provides more general characterization of non-Gaussian diffusion compatible with complex white matter fiber architectures and gray matter, and we include a novel mean kurtosis index that is invariant to the confounding effects due to tissue dispersion. In summary, DKI in DIPY provides a well-tested, well-documented and comprehensive reference implementation for DKI. It provides a platform for wider use of DKI in research on brain disorders and in cognitive neuroscience.
Neural Hierarchy of Color Categorization: From Prototype Encoding to Boundary Encoding
Authors: Sun Mengdan , Hu Luming , Xin Xiaoyang , Zhang Xuemin
Published: July 2021

A long-standing debate exists on how our brain assigns the fine-grained perceptual representation of color into discrete color categories. Recent functional magnetic resonance imaging (fMRI) studies have identified several regions as the candidate loci of color categorization, including the visual cortex, language-related areas, and non-language-related frontal regions, but the evidence is mixed. Distinct from most studies that emphasized the representational differences between color categories, the current study focused on the variability among members within a category (e.g., category prototypes and boundaries) to reveal category encoding in the brain. We compared and modeled brain activities evoked by color stimuli with varying distances from the category boundary in an active categorization task. The frontal areas, including the inferior and middle frontal gyri, medial superior frontal cortices, and insular cortices, showed larger responses for colors near the category boundary than those far from the boundary. In addition, the visual cortex encodes both within-category variability and cross-category differences. The left V1 in the calcarine showed greater responses to colors at the category center than to those far from the boundary, and the bilateral V4 showed enhanced responses for colors at the category center as well as colors around the boundary. The additional representational similarity analyses (RSA) revealed that the bilateral insulae and V4a carried information about cross-category differences, as cross-category colors exhibited larger dissimilarities in brain patterns than within-category colors. Our study suggested a hierarchically organized network in the human brain during active color categorization, with frontal (both lateral and medial) areas supporting domain-general decisional processes and the visual cortex encoding category structure and differences, likely due to top-down modulation.
Surface-Based Falff: A Potential Novel Biomarker for Prediction of Radiation Encephalopathy in Patients With Nasopharyngeal Carcinoma
Authors: Zhang You-ming , Kang Ya-fei , Zeng Jun-jie , Li Li , Gao Jian-ming , Liu Li-zhi , Shi Liang-rong , Liao Wei-hua
Published: July 2021

Radiation encephalopathy (RE) is an important potential complication in patients with nasopharyngeal carcinoma (NPC) who undergo radiotherapy (RT) that can affect the quality of life. However, a functional imaging biomarker of pre-symptomatic RE has not yet been established. This study aimed to assess radiation-induced gray matter functional alterations and explore fractional amplitude of low-frequency fluctuation (fALFF) as an imaging biomarker for predicting or diagnosing RE in patients with NPC. A total of 60 patients with NPC were examined, 21 in the pre-RT cohort and 39 in the post-RT cohort. Patients in the post-RT cohort were further divided into two subgroups according to the occurrence of RE in follow-up: post-RT non−RE (n = 21) and post-RT REprovedinfollow−up (n = 18). Surface-based and volume-based fALFF were used to detect radiation-induced functional alterations. Functional derived features were then adopted to construct a predictive model for the diagnosis of RE. We observed that surface-based fALFF could sensitively detect radiation-induced functional alterations in the intratemporal brain regions (such as the hippocampus and superior temporal gyrus), as well as the extratemporal regions (such as the insula and prefrontal lobe); however, no significant intergroup differences were observed using volume-based fALFF. No significant correlation between fALFF and radiation dose to the ipsilateral temporal lobe was observed. Support vector machine (SVM) analysis revealed that surface-based fALFF in the bilateral superior temporal gyri and left insula exhibited impressive performance (accuracy = 80.49%) in identifying patients likely to develop RE. We conclude that surface-based fALFF may serve as a sensitive imaging biomarker in the prediction of RE.
Altered Fecal Metabolites and Colonic Glycerophospholipids Were Associated With Abnormal Composition of Gut Microbiota in a Depression Model of Mice
Authors: Gong Xue , Huang Cheng , Yang Xun , Chen Jianjun , Pu Juncai , He Yong , Xie Peng
Published: July 2021

The microbiota–gut–brain axis has been considered to play an important role in the development of depression, but the underlying mechanism remains unclear. The gastrointestinal tract is home to trillions of microbiota and the colon is considered an important site for the interaction between microbiota and host, but few studies have been conducted to evaluate the alterations in the colon. Accordingly, in this study, we established a chronic social defeated stress (CSDS) mice model of depression. We applied 16S rRNA gene sequencing to assess the gut microbial composition and gas and liquid chromatography–mass spectroscopy to identify fecal metabolites and colonic lipids, respectively. Meanwhile, we used Spearman’s correlation analysis method to evaluate the associations between the gut microbiota, fecal metabolites, colonic lipids, and behavioral index. In total, there were 20 bacterial taxa and 18 bacterial taxa significantly increased and decreased, respectively, in the CSDS mice. Further, microbial functional prediction demonstrated a disturbance of lipid, carbohydrate, and amino acid metabolism in the CSDS mice. We also found 20 differential fecal metabolites and 36 differential colonic lipids (in the category of glycerolipids, glycerophospholipids, and sphingolipids) in the CSDS mice. Moreover, correlation analysis showed that fecal metabolomic signature was associated with the alterations in the gut microbiota composition and colonic lipidomic profile. Of note, three lipids [PC(16:0/20:4), PG(22:6/22:6), and PI(18:0/20:3), all in the category of glycerophospholipids] were significantly associated with anxiety- and depression-like phenotypes in mice. Taken together, our results indicated that the gut microbiota might be involved in the pathogenesis of depression via influencing fecal metabolites and colonic glycerophospholipid metabolism.
Expression Analysis of Ermin and Listerin E3 Ubiquitin Protein Ligase 1 Genes in Autistic Patients
Authors: Shiva Shadi , Gharesouran Jalal , Sabaie Hani , Asadi Mohammad Reza , Arsang-Jang Shahram , Taheri Mohammad , Rezazadeh Maryam
Published: July 2021

Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder that involves social interaction defects, impairment of non-verbal and verbal interactions, and limited interests along with stereotypic activities. Its incidence has been increasing rapidly in recent decades. Despite numerous attempts to understand the pathophysiology of ASD, its exact etiology is still unclear. Recent data shows the role of accurate myelination and translational regulation in ASD’s pathogenesis. In this study, we assessed Ermin (ERMN) and Listerin E3 Ubiquitin Protein Ligase 1 (LTN1) genes expression in Iranian ASD patients and age- and gender-matched healthy subjects’ peripheral blood using quantitative real-time PCR to recognize any probable dysregulation in the expression of these genes and propose this disorder’s mechanisms. Analysis of the expression demonstrated a significantERMNdownregulation in total ASD patients compared to the healthy individuals (posterior beta = −0.794, adjustedP-value = 0.025).LTN1expression was suggestively higher in ASD patients in comparison with the corresponding control individuals. Considering the gender of study participants, the analysis showed that the mentioned genes’ different expression levels were significant only in male subjects. Besides, a significant correlation was found between expression of the mentioned genes (r= −0.49,P< 0.0001). The present study provides further supports for the contribution ofERMNandLTN1in ASD’s pathogenesis.
From Junk to Function: LncRNAs in CNS Health and Disease
Authors: Policarpo Rafaela , Sierksma Annerieke , De Strooper Bart , d’Ydewalle Constantin
Published: July 2021

Recent advances in RNA sequencing technologies helped to uncover the existence of tens of thousands of long non-coding RNAs (lncRNAs) that arise from the dark matter of the genome. These lncRNAs were originally thought to be transcriptional noise but an increasing number of studies demonstrate that these transcripts can modulate protein-coding gene expression by a wide variety of transcriptional and post-transcriptional mechanisms. The spatiotemporal regulation of lncRNA expression is particularly evident in the central nervous system, suggesting that they may directly contribute to specific brain processes, including neurogenesis and cellular homeostasis. Not surprisingly, lncRNAs are therefore gaining attention as putative novel therapeutic targets for disorders of the brain. In this review, we summarize the recent insights into the functions of lncRNAs in the brain, their role in neuronal maintenance, and their potential contribution to disease. We conclude this review by postulating how these RNA molecules can be targeted for the treatment of yet incurable neurological disorders.
Shifts in Estimated Preferred Directions During Simulated BMI Experiments With No Adaptation
Authors: Benyamini Miri , Zacksenhouse Miriam
Published: July 2021

Experiments with brain-machine interfaces (BMIs) reveal that the estimated preferred direction (EPD) of cortical motor units may shift following the transition to brain control. However, the cause of those shifts, and in particular, whether they imply neural adaptation, is an open issue. Here we address this question in simulations and theoretical analysis. Simulations are based on the assumption that the brain implements optimal state estimation and feedback control and that cortical motor neurons encode the estimated state and control vector. Our simulations successfully reproduce apparent shifts in EPDs observed in BMI experiments with different BMI filters, including linear, Kalman and re-calibrated Kalman filters, even with no neural adaptation. Theoretical analysis identifies the conditions for reducing those shifts. We demonstrate that simulations that better satisfy those conditions result in smaller shifts in EPDs. We conclude that the observed shifts in EPDs may result from experimental conditions, and in particular correlated velocities or tuning weights, even with no adaptation. Under the above assumptions, we show that if neurons are tuned differently to the estimated velocity, estimated position and control signal, the EPD with respect to actual velocity may not capture the real PD in which the neuron encodes the estimated velocity. Our investigation provides theoretical and simulation tools for better understanding shifts in EPD and BMI experiments.
Myrcene—What Are the Potential Health Benefits of This Flavouring and Aroma Agent?
Authors: Surendran Shelini , Qassadi Fatimah , Surendran Geyan , Lilley Dash , Heinrich Michael
Published: July 2021

Myrcene (β-myrcene) is an abundant monoterpene which occurs as a major constituent in many plant species, including hops and cannabis. It is a popular flavouring and aroma agent (food additive) used in the manufacture of food and beverages. This review aims to report on the occurrence, biological and toxicological profile of β-myrcene. The main reported biological properties of β-myrcene—anxiolytic, antioxidant, anti-ageing, anti-inflammatory, analgesic properties—are discussed, with the mechanisms of activity. Here we also discuss recent data regarding the safety of β-myrcene. Overall, β-myrcene has shown promising health benefits in many animal studies. However, studies conducted in humans is lacking. In the future, there is potential for the formulation and production of non-alcoholic beers, functional foods and drinks, and cannabis extracts (low in THC) rich in β-myrcene.
Development and External Validation of a Nomogram for Predicting Cancer-Specific Survival of Non-Small Cell Lung Cancer Patients With Ipsilateral Pleural Dissemination
Authors: Wang Zhenfan , Li Hao , Liu Taorui , Sun Zewen , Yang Fan , Jiang Guanchao
Published: July 2021

Background

Non-small-cell lung cancer (NSCLC) patients with ipsilateral pleural dissemination are defined as M1a in the eighth of American Joint Committee on Cancer (AJCC) TNM staging. We aimed to build a nomogram to predict lung cancer specific survival (LCSS) of NSCLC patients with ipsilateral pleural dissemination and to compare the impact of primary tumor resection (PTR) on LCSS among patients with different features.

Methods

A total of 3,918 NSCLC patients with ipsilateral pleural dissemination were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We selected and integrated significant prognostic factors based on competing risk regression to build a nomogram. The model was subjected to internal validation within SEER cohort and external validation with the cohort of 97 patients from Peking University People’s Hospital.

Results

Age (P < 0.001), gender (P = 0.037), T stage (P = 0.002), N stage (P < 0.001), metastasis pattern (P = 0.005), chemotherapy (P < 0.001), and PTR (P < 0.001) were independent prognostic factors. The calibration curves presented a good consistency and the Harrell’s C-index of nomogram were 0.682 (95%CI: 0.673–0.691), 0.687 (95%CI: 0.670–0.704) and 0.667 (95%CI: 0.584–0.750) in training, internal, and external validation cohort, respectively. Interaction tests suggested a greater LCSS difference caused by PTR in patients without chemotherapy (P < 0.001).

Conclusions

We developed a nomogram based on competing risk regression to reliably predict prognosis of NSCLC patients with ipsilateral pleural dissemination and validated this nomogram in an external Chinese cohort. This novel nomogram might be a practical tool for clinicians to anticipate the 1-, 3- and 5-year LCSS for NSCLC patients with pleural dissemination. Subgroup analysis indicated that patients without chemotherapy could get more benefit from PTR. In order to assess the role of PTR in the management of M1a patients more accurately, further prospective study would be urgently required.
PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer
Authors: Zhu Li , Zhang Yan-Jun , Wang Bin , Yang Li , Zheng Yi-Qiong , Sun Lin-De , Tian Lin , Chen Tao , Wang Jian-Dong
Published: July 2021

Breast cancer is one of the most common life-threatening cancers, mainly because of its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood. Here, we demonstrated that lncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion, as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decreased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified that MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer. Overall, the results demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK/NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggesting that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer.