bluuebunny/crossref_metadata_2025 huggingface dataset:
Database Mining to Unravel the Ecology of the Phylum Chloroflexi in Methanogenic Full Scale Bioreactors
Authors: Bovio-Winkler Patricia , Cabezas Angela , Etchebehere Claudia
Published: January 2021

Although microbial communities of anaerobic bioreactors have been extensively studied using DNA-based tools, there are still several knowledge gaps regarding the microbiology of the process, in particular integration of all generated data is still limited. One understudied core phylum within anaerobic bioreactors is the phylum Chloroflexi, despite being one of the most abundant groups in anaerobic reactors. In order to address the abundance, diversity and phylogeny of this group in full-scale methanogenic reactors globally distributed, a compilation of 16S ribosomal RNA gene sequence data from 62 full-scale methanogenic reactors studied worldwide, fed either with wastewater treatment anaerobic reactors (WTARs) or solid-waste treatment anaerobic reactors (STARs), was performed. One of the barriers to overcome was comparing data generated using different primer sets and different sequencing platforms. The sequence analysis revealed that the average abundance of Chloroflexi in WTARs was higher than in STARs. Four genera belonging to the Anaerolineae class dominated both WTARs and STARs but the core populations were different. According to the phylogenetic analysis, most of the sequences formed clusters with no cultured representatives. The Anaerolineae class was more abundant in reactors with granular biomass than in reactors with disperse biomass supporting the hypothesis that Anaerolineae play an important role in granule formation and structure due to their filamentous morphology. Cross-study comparisons can be fruitfully used to understand the complexity of the anaerobic digestion process. However, more efforts are needed to standardize protocols and report metadata information.
Evidence for Proline Utilization by Oral Bacterial Biofilms Grown in Saliva
Authors: Cleaver Leanne M. , Moazzez Rebecca V. , Carpenter Guy H.
Published: January 2021

Within the mouth bacteria are starved of saccharides as their main nutrient source between meals and it is unclear what drives their metabolism. Previously oralin vitrobiofilms grown in saliva have shown proteolytic degradation of salivary proteins and increased extracellular proline. Although arginine and glucose have been shown before to have an effect on oral biofilm growth and activity, there is limited evidence for proline. Nuclear magnetic resonance (NMR) spectroscopy was used to identify extracellular metabolites produced by bacteria in oral biofilms grown on hydroxyapatite discs. Biofilms were inoculated with stimulated whole mouth saliva and then grown for 7 days using sterilized stimulated whole mouth saliva supplemented with proline, arginine or glucose as a growth-medium. Overall proline had a beneficial effect on biofilm growth—with significantly fewer dead bacteria present by biomass and surface area of the biofilms (p< 0.05). Where arginine and glucose significantly increased and decreased pH, respectively, the pH of proline supplemented biofilms remained neutral at pH 7.3–7.5. SDS-polyacrylamide gel electrophoresis of the spent saliva from proline and arginine supplemented biofilms showed inhibition of salivary protein degradation of immature biofilms. NMR analysis of the spent saliva revealed that proline supplemented biofilms were metabolically similar to unsupplemented biofilms, but these biofilms actively metabolized proline to 5-aminopentanoate, butyrate and propionate, and actively utilized glycine. This study shows that in a nutrient limited environment, proline has a beneficial effect onin vitrooral biofilms grown from a saliva inoculum.
CLEC3B as a Potential Prognostic Biomarker in Hepatocellular Carcinoma
Authors: Xie Xing-Wei , Jiang Shan-Shan , Li Xiang
Published: January 2021

C-Type Lectin Domain Family 3 Member B (CLEC3B) encodes proteins associated with tumor invasion and metastasis. However, the interrelation between CLEC3B gene expression, tumor immunity, and prognosis of patients with hepatocellular carcinoma (HCC) is unclear. This study was conducted to investigate the prognostic potential of CLEC3B and its association with tumor tissue infiltration markers. CLEC3B expression was examined using the TIMER and Oncomine databases, with its prognostic potential assessed using the GEPIA and Kaplan–Meier plotter databases. The relationship between CLEC3B and tumor immune cell infiltration biomarkers was analyzed using TIMER. Here, we revealed that CLEC3B expression was decreased in HCC and was correlated with a poor survival rate in patients with HCC. Additionally, the expression of CLEC3B was negatively correlated with differential immune cell infiltration and various immune biomarkers. These results indicate a potential mechanism by which the expression of CLEC3B might adjust tumor immunity by modulating the infiltration of HCC immune cells. Our study demonstrated that CLEC3B could be a potential prognostic biomarker and might be involved in tumor immune cell infiltration in HCC.
Long-Term Prognosis of Cognitive Function in Patients With Idiopathic Normal Pressure Hydrocephalus After Shunt Surgery
Authors: Kambara Akihiro , Kajimoto Yoshinaga , Yagi Ryokichi , Ikeda Naokado , Furuse Motomasa , Nonoguchi Naosuke , Kawabata Shinji , Kuroiwa Toshihiko , Kuroda Kenji , Tsuji Shohei , Saura Ryuichi , Wanibuchi Masahiko
Published: January 2021

The long-term prognosis of cognitive function in patients with idiopathic normal pressure hydrocephalus (iNPH) remains unclear. This study aimed to determine the long-term prognosis of cognitive function in patients with iNPH, as well as the factors related to it. It included 48 patients with iNPH who were treated with cerebrospinal fluid shunting between January 2015 and December 2017 at Osaka Medical College Hospital, with follow-up evaluation of their cognitive function for >2 years. Cognitive function was measured using the Mini-Mental State Examination (MMSE) preoperatively and at 3 months, 1 and 2 years post-operatively. The mean MMSE score (22.4 ± 5.4 preoperatively) improved at 3 months [23.8 ± 5.0 (p = 0.0002)] and 1 year [23.7 ± 4.8 (p = 0.004)] post-operatively. At 2 years post-operatively, they were able to maintain their preoperative level (22.6 ± 5.3). The patients were classified in to the cognitive decline group [11 (23%) patients; a decrease in the MMSE score by ≥ 2 points 2 years after surgery] and the maintenance/improvement group [37 (77%) patients]. Univariate and receiver operating characteristic analyses were performed for the two groups to identify factors associated with cognitive prognosis. In both groups, the patients who were younger (p = 0.009) or had milder symptoms (p = 0.035) had a better long-term prognosis of cognitive function. The cutoffs for age and disease severity (idiopathic normal-pressure hydrocephalus grading scale; INPHGS) were 78 years (area under the curve = 0.77) and 5 points (area under the curve = 0.71), respectively. In conclusion, most patients (77%) were able to improve and maintain cognitive function for at least 2 years after surgery. The fact that disease severity and age are associated with cognitive prognosis suggests that early iNPH intervention is desirable to improve cognitive prognosis.
The Contribution of Physical Exercise to Brain Resilience
Authors: Arida Ricardo Mario , Teixeira-Machado Lavinia
Published: January 2021

Increasing attention has been given to understanding resilience to brain diseases, often described as brain or cognitive reserve. Among the protective factors for the development of resilience, physical activity/exercise has been considered to play an important role. Exercise is known to induce many positive effects on the brain. As such, exercise represents an important tool to influence neurodevelopment and shape the adult brain to react to life's challenges. Among many beneficial effects, exercise intervention has been associated with cognitive improvement and stress resilience in humans and animal models. Thus, a growing number of studies have demonstrated that exercise not only recovers or minimizes cognitive deficits by inducing better neuroplasticity and cognitive reserve but also counteracts brain pathology. This is evidenced before disease onset or after it has been established. In this review, we aimed to present encouraging data from current clinical and pre-clinical neuroscience research and discuss the possible biological mechanisms underlying the beneficial effects of physical exercise on resilience. We consider the implication of physical exercise for resilience from brain development to aging and for some neurological diseases. Overall, the literature indicates that brain/cognitive reserve built up by regular exercise in several stages of life, prepares the brain to be more resilient to cognitive impairment and consequently to brain pathology.
Examinations of Bilateral Epileptiform Activities in Hippocampal Slices Obtained From Young Mice
Authors: Liu Haiyu , Carlen Peter L. , Zhang Liang
Published: January 2021

Bilateral interconnections through the hippocampal commissure play important roles in synchronizing or spreading hippocampal seizure activities. Intact hippocampi or bilateral hippocampal slices have been isolated from neonatal or immature rats (6–7 or 12–21 days old, respectively) and the mechanisms underlying the bilateral synchrony of hippocampal epileptiform activities have been investigated. However, the feasibility of examining bilateral epileptiform activities of more developed hippocampal circuitryin vitroremains to be explored. For this, we prepared bilateral hippocampal slices from C57 black mice, a strain commonly used in neuroscience and for genetic/molecular modifications. Young mice (21–24-day-old) were used in most experiments. A 600-μm-thick slice was obtained from each mouse by horizontal vibratome sectioning. Bilateral dorsal hippocampal and connecting dorsal hippocampal commissure (DHC) tissues were preserved in the slice and extrahippocampal tissues were removed. Slices were recorded in a submerged chamber mainly at a room temperature (21–22°C). Bilateral CA3 areas were monitored by extracellular recordings, and unilateral electrical stimulation was used to elicit CA3 synaptic field potentials. The unilateral stimulation could elicit population spikes in the contralateral CA3 area. These contralateral spikes were attenuated by inhibiting synaptic transmission with cobalt-containing medium and were abolished when a cut was made at the DHC. Self-sustained and bilaterally correlated epileptiform potentials were observed following application of 4-aminopyradine and became independent after the DHC cut. Bilateral hippocampal activities were detectable in some slices of adult mice and/or at 35–36°C, but with smaller amplitudes and variable waveforms compared to those observed from slices of young mice and at the room temperature. Together, these observations suggested that examining bilateral epileptiform activities in hippocampal slices of young mice is feasible. The weaknesses and limitations of this preparation and our experimentation are discussed.
Use of Chinese Herbal Medicines Is Related to a Reduction in Depression Risk Among Patients With Insomnia: A Matched Cohort Study
Authors: Chiao Yun-Wen , Livneh Hanoch , Guo How-Ran , Chen Wei-Jen , Lu Ming-Chi , Lin Miao-Chiu , Yeh Chia-Chou , Tsai Tzung-Yi
Published: January 2021

Objective: Subjects with insomnia have a higher risk of depression, thus possibly making them live with serious health conditions. To date, information regarding the effect of Chinese herbal medicines (CHMs), a commonly used complementary and alternative medicine, on depression risk among people with insomnia is still unknown. This study aimed to investigate the effect of CHMs on the risk of depression among individuals with insomnia.

Methods: This cohort study used a national health insurance database to identify 68,573 subjects newly diagnosed with insomnia, aged 20–70 years, who received treatment between 1998 and 2010. Using propensity score matching, we randomly selected 26,743 CHMs users and 26,743 non-CHMs users from this sample. All enrollees were followed to the end of 2012 to identify any treatment for depression as the end point. Cox proportional hazards regression was used to compute the adjusted hazard ratio of depression associated with CHMs use.

Results: After utilizing the propensity score matching, we randomly selected 26,743 CHMs users and 26,743 non-CHMs users from this sample. During follow up, 3,328 CHMs users and 6,988 non-CHMs users developed depression at incidence rates of 17.24 and 37.97 per 1,000 person-years, respectively. CHMs users had a lower depression risk than the non-CHMs users (adjusted hazard ratio = 0.44; 95% Confidence Interval, 0.42–0.46). The greatest effect was observed for those taking CHMs for more than 2 years. Gegen, Huangqin, Dan-Shen, Beimu, Dahuang, Shegan, Shu-jing-huo-xue-tang, Ge-gen-tang, Shao-yao-gan-cao-tang and Píng wèi sǎn were significantly associated with a lower risk of depression.

Conclusions: Findings from this study demonstrated that adding CHMs to conventional treatment significantly reduces depression risk among patients with insomnia.
Adaptive Working Memory Training Can Improve Executive Functioning and Visuo-Spatial Skills in Children With Pre-term Spastic Diplegia
Authors: Di Lieto Maria Chiara , Pecini Chiara , Brovedani Paola , Sgandurra Giuseppina , Dell'Omo Marta , Chilosi Anna Maria , Guzzetta Andrea , Perazza Silvia , Sicola Elisa , Cioni Giovanni
Published: January 2021

Pre-term spastic diplegia (pSD) due to periventricular leukomalacia is a form of cerebral palsy in which weaknesses in executive functions are reported beyond the core visuo-spatial deficits. The study aimed at improving executive functioning and visuo-spatial skills with an evidence-based training focused on working memory in children with pSD. The intervention study followed a stepped wedge design. 19 children with pSD (11 female and 8 male; age range: 4;1–13;1 years), mild to moderate upper limb impairment and Verbal Intelligence Quotient (VIQ) >80 participated to the study. The children were trained with a home-based adaptive working memory training (CogMed®) over a 5-week period. The primary outcome measure was the CogMed Improvement index; pre- and post-test explorative neuropsychological assessment was conducted with a subset of tests from the NEPSY-II battery. Working memory training in children with pSD significantly improved trained working memory abilities (CogMed indices) as well as non-trained skills, such as visuo-spatial skills, inhibition of automatic responses and phonological processing. The results suggest that standard rehabilitation schedules for children with pSD should be integrated with trainings on executive functions.
Angiographic Evaluation and Endovascular Treatment Considerations of Brain Arteriovenous Malformations With a Transdural Blood Supply: A Single-Center Experience
Authors: Hou Kun , Xu Kan , Qu Lai , Li Guichen , Guo Yunbao , Yu Jinlu
Published: January 2021

Background: In rare circumstances, brain arteriovenous malformations (BAVMs) can recruit a transdural blood supply (TBS). The clinical and radiologic characteristics of BAVMs with a TBS are poorly understood.

Methods: A retrospective review of the medical records was conducted for adult patients who were admitted for BAVMs from Jan 2013 to Dec 2019. TBSs for BAVMs were divided into 3 types: (1) unilateral TBSs from the external carotid artery (ECA) and/or meningeal branch of the vertebral artery (VA); (2) bilateral TBSs from the ECA and/or meningeal branch of the VA; and (3) meningohypophyseal trunk TBSs of the internal carotid artery.

Results: Four hundred and twenty-eight patients were diagnosed with BAVMs during the study period, of whom 30 (7.0%, 30/428) were identified as having a TBS. Type 1, type 2, and type 3 TBSs were identified in 21 (70%, 21/30), 7 (23.3%, 7/30), and 2 (6.7%, 2/30) patients, respectively. Six (20%, 6/30) patients were conservatively managed. Twelve (40%, 12/30) patients underwent endovascular treatment (EVT) of the BAVM through non-TBS feeders. Eight (26.8%, 8/30) patients underwent EVT of the BAVM both through the TBS and non-TBS feeders. The modified Rankin Scale scores at the 3-month follow-up were 0, 1, 2, 4, and 5 in 24 (80%, 24/30), 2 (6.7%, 2/30), 2 (6.7%, 2/30), 1 (3.3%, 1/30), and 1 (3.3%, 1/30) patients, respectively. Good short-term recovery was achieved in 86.7% (26/30) of the patients. The size of the BAVMs with a TBS was larger than that of BAVMs without a TBS. Patients with higher Spetzler-Martin grades tended to have a TBS. No statistical difference was noted between the patients with and without a TBS with regard to age, sex, location, or concurrent aneurysms.

Conclusions: This study showed that a TBS was likely to develop in patients with larger BAVMs and that a TBS was likely to be located in the temporal lobe in patients BAVMs with higher SM grades. Weak structures were the primary targets of management. In addition, a BAVM could be embolized via the TBS.
Effectiveness of Lomustine Combined With Bevacizumab in Glioblastoma: A Meta-Analysis
Authors: Ren Xing , Ai Di , Li Tong , Xia Lei , Sun Lingzhi
Published: January 2021

Introduction: Despite surgical and chemotherapeutical treatment options, the prognosis for glioblastoma (GBM) remains poor. Some studies have found that using lomustine plus bevacizumab to treat GBM can prolong overall survival (OS) and progression-free survival (PFS). The aim of this study was to explore the efficacy of the two drugs in combination treatment of GBM using a meta-analysis of the existing literature to help settle the ongoing debate.

Materials and Methods: PubMed, EMBASE, and the Cochrane Library were searched for the effectiveness of lomustine plus bevacizumab in GBM literature, updated on June 6, 2020. The main outcomes analyzed included PFS and OS; the effects of this drug combination on the 6-month PFS, which represents the percentage of patients who had PFS for 6 months, were also analyzed. All the data were pooled: OS and PFS with the mean difference (MD) and 6-month PFS with the risk ratio (RR). Because there were different control groups and dose groups, two subgroup analyses were run to ensure they were comparable. All statistical analyses were performed using the Review Manager Version 5.3 software.

Results: Six clinical trials were identified which included 1,095 patients (treatment group: 516; control group: 579). The group treated with lomustine and bevacizumab showed an improvement in OS (MD =1.37; 95% CI, 0.49–2.25; p = 0.002), PFS (MD = 0.23; 95% CI, 0.13–0.34; p < 0.00001), and 6-month PFS (RR = 2.29; 95% CI, 1.43–3.65; p = 0.0005). Two subgroup analyses of the main outcome, OS, show that the results of Control group A (p = 0.01) and Dose group 2 (p = 0.003) are significantly different from those of the other control or dose groups.

Conclusion: This study shows that lomustine and bevacizumab can effectively increase OS, PFS, and 6-month PFS in patients with GBM. The encouraging results of the lomustine and bevacizumab combination therapy for GBM should be studied in more clinical trials in the future.
Neuromechanics of Dynamic Balance Tasks in the Presence of Perturbations
Authors: Munoz-Martel Victor , Santuz Alessandro , Bohm Sebastian , Arampatzis Adamantios
Published: January 2021

Understanding the neuromechanical responses to perturbations in humans may help to explain the reported improvements in stability performance and muscle strength after perturbation-based training. In this study, we investigated the effects of perturbations, induced by unstable surfaces, on the mechanical loading and the modular organization of motor control in the lower limb muscles during lunging forward and backward. Fifteen healthy adults performed 50 forward and 50 backward lunges on stable and unstable ground. Ground reaction forces, joint kinematics, and the electromyogram (EMG) of 13 lower limb muscles were recorded. We calculated the resultant joint moments and extracted muscle synergies from the stepping limb. We found sparse alterations in the resultant joint moments and EMG activity, indicating a little if any effect of perturbations on muscle mechanical loading. The time-dependent structure of the muscle synergy responsible for the stabilization of the body was modified in the perturbed lunges by a shift in the center of activity (later in the forward and earlier in the backward lunge) and a widening (in the backward lunge). Moreover, in the perturbed backward lunge, the synergy related to the body weight acceptance was not present. The found modulation of the modular organization of motor control in the unstable condition and related minor alteration in joint kinetics indicates increased control robustness that allowed the participants to maintain functionality in postural challenging settings. Triggering specific modulations in motor control to regulate robustness in the presence of perturbations may be associated with the reported benefits of perturbation-based training.
Two-Level Domain Adaptation Neural Network for EEG-Based Emotion Recognition
Authors: Bao Guangcheng , Zhuang Ning , Tong Li , Yan Bin , Shu Jun , Wang Linyuan , Zeng Ying , Shen Zhichong
Published: January 2021

Emotion recognition plays an important part in human-computer interaction (HCI). Currently, the main challenge in electroencephalogram (EEG)-based emotion recognition is the non-stationarity of EEG signals, which causes performance of the trained model decreasing over time. In this paper, we propose a two-level domain adaptation neural network (TDANN) to construct a transfer model for EEG-based emotion recognition. Specifically, deep features from the topological graph, which preserve topological information from EEG signals, are extracted using a deep neural network. These features are then passed through TDANN for two-level domain confusion. The first level uses the maximum mean discrepancy (MMD) to reduce the distribution discrepancy of deep features between source domain and target domain, and the second uses the domain adversarial neural network (DANN) to force the deep features closer to their corresponding class centers. We evaluated the domain-transfer performance of the model on both our self-built data set and the public data set SEED. In the cross-day transfer experiment, the ability to accurately discriminate joy from other emotions was high: sadness (84%), anger (87.04%), and fear (85.32%) on the self-built data set. The accuracy reached 74.93% on the SEED data set. In the cross-subject transfer experiment, the ability to accurately discriminate joy from other emotions was equally high: sadness (83.79%), anger (84.13%), and fear (81.72%) on the self-built data set. The average accuracy reached 87.9% on the SEED data set, which was higher than WGAN-DA. The experimental results demonstrate that the proposed TDANN can effectively handle the domain transfer problem in EEG-based emotion recognition.
Modulation of Functional Connectivity and Low-Frequency Fluctuations After Brain-Computer Interface-Guided Robot Hand Training in Chronic Stroke: A 6-Month Follow-Up Study
Authors: Lau Cathy C. Y. , Yuan Kai , Wong Patrick C. M. , Chu Winnie C. W. , Leung Thomas W. , Wong Wan-wa , Tong Raymond K. Y.
Published: January 2021

Hand function improvement in stroke survivors in the chronic stage usually plateaus by 6 months. Brain-computer interface (BCI)-guided robot-assisted training has been shown to be effective for facilitating upper-limb motor function recovery in chronic stroke. However, the underlying neuroplasticity change is not well understood. This study aimed to investigate the whole-brain neuroplasticity changes after 20-session BCI-guided robot hand training, and whether the changes could be maintained at the 6-month follow-up. Therefore, the clinical improvement and the neurological changes before, immediately after, and 6 months after training were explored in 14 chronic stroke subjects. The upper-limb motor function was assessed by Action Research Arm Test (ARAT) and Fugl-Meyer Assessment for Upper-Limb (FMA), and the neurological changes were assessed using resting-state functional magnetic resonance imaging. Repeated-measure ANOVAs indicated that long-term motor improvement was found by both FMA (F[2,26]= 6.367,p= 0.006) and ARAT (F[2,26]= 7.230,p= 0.003). Seed-based functional connectivity analysis exhibited that significantly modulated FC was observed between ipsilesional motor regions (primary motor cortex and supplementary motor area) and contralesional areas (supplementary motor area, premotor cortex, and superior parietal lobule), and the effects were sustained after 6 months. The fALFF analysis showed that local neuronal activities significantly increased in central, frontal and parietal regions, and the effects were also sustained after 6 months. Consistent results in FC and fALFF analyses demonstrated the increase of neural activities in sensorimotor and fronto-parietal regions, which were highly involved in the BCI-guided training.

Clinical Trial Registration:This study has been registered atClinicalTrials.govwith clinical trial registration number NCT02323061.
Global Trends and Performances of Magnetic Resonance Imaging Studies on Acupuncture: A Bibliometric Analysis
Authors: Zhang Jinhuan , Zhang Yangxin , Hu Liyu , Huang Xingxian , Liu Yongfeng , Li Jiaying , Hu Qingmao , Xu Jinping , Yu Haibo
Published: January 2021

Objectives: To summarize development processes and research hotspots of MRI research on acupuncture and to provide new insights for researchers in future studies.

Methods: Publications regarding MRI on acupuncture from inception to 2020 were downloaded from the Web of Science Core Collection. VOSviewer 1.6.15 and CiteSpace V software were used for bibliometric analyses. The main analyses include collaboration analyses between countries/institutions/authors, co-occurrence analysis between keywords, as well as analyses on keyword bursts, citation references, and clusters of references.

Results: A total of 829 papers were obtained with a continually increased trend over time. The most productive country and institution in this field were the People's Republic of China (475) and KyungHee University (70), respectively. Evidence-based Complementary and Alternative Medicine (83) was the most productive journal, and Neuroimage (454) was the most co-cited journal. Dhond's et al. (2008) article (co-citation counts: 58) and Napadow's et al. (2005) article (centrality: 0.21) were the most representative and symbolic references, with the highest co-citation number and centrality, respectively. Jie Tian had the highest number of publications (35) and Kathleen K S Hui was the most influential author (280 co-citations). The four hot topics in MRI on acupuncture were acupuncture, fMRI, pain, and stimulation. The three frontier topics were connectivity, modulation, and fMRI. Based on the clustering of co-cited documents, chronic low back pain, sham electro-acupuncture treatment, and clinical research were the main research directions.

Conclusion: This study provides an in-depth perspective for MRI research on acupuncture and provides researchers with valuable information to determine the current status, hot spots, and frontier trends of MRI research on acupuncture.
Reduced Sleep Duration and Sleep Efficiency Were Independently Associated With Frequent Nightmares in Chinese Frontline Medical Workers During the Coronavirus Disease 2019 Outbreak
Authors: Lin Yi-Qi , Lin Ze-Xin , Wu Yong-Xi , Wang Lin , Zeng Zhao-Nan , Chen Qiu-Yang , Wang Ling , Xie Xiao-Liang , Wei Shi-Chao
Published: January 2021

Objectives

Nightmares were related to emotion and behavioral problems and also emerged as one of the core features of post-traumatic stress disorder (PTSD). Our study aimed to investigate the associations of frequent nightmares with sleep duration and sleep efficiency among frontline medical workers in Wuhan during the coronavirus disease 2019 (COVID-19) outbreak.

Methods

A total of 528 health-care workers from the province of Fujian providing medical aid in Wuhan completed the online questionnaires. There were 114 doctors and 414 nurses. The age, sex, marital status, and work situation were recorded. A battery of scales including the Pittsburgh Sleep Quality Index (PSQI) and the 12-item General Health Questionnaire (GHQ-12) were used to evaluate subjects’ sleep and general mental health. Frequent nightmares were defined as the response of at least once a week in the item of “nightmare” of PSQI.

Results

Frequent nightmares were found in 27.3% of subjects. The frequent nightmare group had a higher score of PSQI-sleep duration and PSQI-habitual sleep efficiency (frequent nightmares vs. non-frequent nightmares: PSQI-sleep duration, 1.08 ± 0.97 vs. 0.74 ± 0.85, P < 0.001; PSQI-habitual sleep efficiency, 1.08 ± 1.10 vs. 0.62 ± 0.88, P < 0.001). Reduced sleep duration and reduced sleep efficiency were independently associated with frequent nightmares after adjustment for age, sex, poor mental health, and regular sleeping medication use (reduced sleep duration: OR = 1.96, 95% CI = 1.07–3.58, P = 0.029; reduced sleep efficiency: OR = 2.17, 95% CI = 1.09–4.32, P = 0.027). Subjects with both reduced sleep duration and sleep efficiency were also associated with frequent nightmares (OR = 2.70, 95% CI = 1.57–4.65, P < 0.001).

Conclusion

The present study found that sleep duration and sleep efficiency were both independently associated with frequent nightmares among frontline medical workers in Wuhan during the COVID-19 pandemic. We should pay attention to nightmares and even the ensuing PTSD symptoms among subjects with reduced sleep duration or sleep efficiency facing potential traumatic exposure.
Scale-Free Dynamics in Animal Groups and Brain Networks
Authors: Ribeiro Tiago L. , Chialvo Dante R. , Plenz Dietmar
Published: January 2021

Collective phenomena fascinate by the emergence of order in systems composed of a myriad of small entities. They are ubiquitous in nature and can be found over a vast range of scales in physical and biological systems. Their key feature is the seemingly effortless emergence of adaptive collective behavior that cannot be trivially explained by the properties of the system's individual components. This perspective focuses on recent insights into the similarities of correlations for two apparently disparate phenomena: flocking in animal groups and neuronal ensemble activity in the brain. We first will summarize findings on the spontaneous organization in bird flocks and macro-scale human brain activity utilizing correlation functions and insights from critical dynamics. We then will discuss recent experimental findings that apply these approaches to the collective response of neurons to visual and motor processing, i.e., to local perturbations of neuronal networks at the meso- and microscale. We show how scale-free correlation functions capture the collective organization of neuronal avalanches in evoked neuronal populations in nonhuman primates and between neurons during visual processing in rodents. These experimental findings suggest that the coherent collective neural activity observed at scales much larger than the length of the direct neuronal interactions is demonstrative of a phase transition and we discuss the experimental support for either discontinuous or continuous phase transitions. We conclude that at or near a phase-transition neuronal information can propagate in the brain with similar efficiency as proposed to occur in the collective adaptive response observed in some animal groups.
Exogenous Ketones Lower Post-exercise Acyl-Ghrelin and GLP-1 but Do Not Impact Ad libitum Energy Intake
Authors: Okada Tetsuro E. , Quan Tony , Bomhof Marc R.
Published: January 2021

Ketosis and exercise are both associated with alterations in perceived appetite and modification of appetite-regulating hormones. This study utilized a ketone ester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE) to examine the impact of elevated ketone body D-β-hydroxybutyrate (βHB) during and after a bout of exercise on appetite-related hormones, appetite perception, and ad libitum energy intake over a 2 h post-exercise period. In a randomized crossover trial, 13 healthy males and females (age: 23.6 ± 2.4 years; body mass index: 25.7 ± 3.2 kg·m−2) completed an exercise session @ 70% VO2peak for 60 min on a cycling ergometer and consumed either: (1) Ketone monoester (KET) (0.5 g·kg−1 pre-exercise + 0.25 g·kg−1 post-exercise); or (2) isocaloric dextrose control (DEX). Transient ketonaemia was achieved with βHB concentrations reaching 5.0 mM (range 4.1–6.1 mM) during the post-exercise period. Relative to the dextrose condition, acyl-ghrelin (P = 0.002) and glucagon-like peptide-1 (P = 0.038) were both reduced by acute ketosis immediately following exercise. AUC for acyl-ghrelin was lower in KET compared to DEX (P = 0.001), however there were no differences in AUC for GLP-1 (P = 0.221) or PYY (P = 0.654). Perceived appetite (hunger, P = 0.388; satisfaction, P = 0.082; prospective food consumption, P = 0.254; fullness, P = 0.282) and 2 h post-exercise ad libitum energy intake (P = 0.488) were not altered by exogenous ketosis. Although KE modifies homeostatic regulators of appetite, it does not appear that KE acutely alters energy intake during the post-exercise period in healthy adults.
Presence of Human Papillomavirus and Epstein–Barr Virus, but Absence of Merkel Cell Polyomavirus, in Head and Neck Cancer of Non-Smokers and Non-Drinkers
Authors: Mulder Frans J. , Klufah Faisal , Janssen Famke M. E. , Farshadpour Farzaneh , Willems Stefan M. , de Bree Remco , zur Hausen Axel , van den Hout Mari F. C. M. , Kremer Bernd , Speel Ernst-Jan M.
Published: January 2021

Objective

Determine the presence and prognostic value of human papillomavirus (HPV), Epstein-Barr virus (EBV), Merkel cell polyomavirus (MCPyV), and cell cycle proteins in head and neck squamous cell carcinoma (HNSCC) of non-smokers and non-drinkers (NSND).

Methods

Clinical characteristics and tumors of 119 NSND with HNSCC were retrospectively collected and analyzed on tissue microarrays. RNAscope in situ hybridization (ISH) was used to screen for the presence of HPV and MCPyV mRNA. Immunohistochemistry was performed for expression of p16 as surrogate marker for HPV, Large T-antigen for MCPyV, and cell cycle proteins p53 and pRb. Positive virus results were confirmed with polymerase chain reaction. For EBV, EBV encoded RNA ISH was performed. Differences in 5-year survival between virus positive and negative tumors were determined by log rank analysis.

Results

All oropharyngeal tumors (OPSCC) (n = 10) were HPV-positive, in addition to one oral (OSCC) and one nasopharyngeal tumor (NPSCC). The other three NPSCC were EBV-positive. MCPyV was not detected. Patients with HPV or EBV positive tumors did not have a significantly better 5-year disease free or overall survival. Over 70% of virus negative OSCC showed mutant-type p53 expression.

Conclusion

In this cohort, all OPSCC and NPSCC showed HPV or EBV presence. Besides one OSCC, all other oral (n = 94), hypopharyngeal (n = 1), and laryngeal (n = 9) tumors were HPV, EBV, and MCPyV negative. This argues against a central role of these viruses in the ethiopathogenesis of tumors outside the oro- and nasopharynx in NSND. So, for the majority of NSND with virus negative OSCC, more research is needed to understand the carcinogenic mechanisms in order to consider targeted therapeutic options.
Rhophilin-2 Upregulates Glutamine Synthetase by Stabilizing c-Myc Protein and Confers Resistance to Glutamine Deprivation in Lung Cancer
Authors: Xiao Dakai , He Jiaxi , Guo Zhihua , He Huiming , Yang Shengli , Huang Liyan , Pan Hui , He Jianxing
Published: January 2021

Introduction

RHPN2, a member of rhophilin family of rho-binding proteins, regulates actin cytoskeleton and vesicular trafficking, and promotes mesenchymal transformation in cancer. We have found that RHPN2 was significantly mutated in lung adenocarcinoma (LUAD). However, the role of RHPN2 in lung cancer is not fully understood.

Methods

In the present study, we investigated the expression of RHPN2 in 125 patients with LUAD by qRT-PCR and correlated its expression with clinical characteristics. The effects of RHPN2 on the proliferation and invasion of lung cancer cells were determined by CCK-8 and in vitro transwell assays, clonogenic assay, and xenograft mouse model. The RhoA pull down assay and Western blotting were performed to elucidate the mechanism of RNPN2 in tumorigenesis of lung cancer.

Results

RHPN2 was overexpressed in tumors from LUAD, and high levels of RHPN2 were associated with poor prognosis of LUAD patients. RHPN2 was required for proliferation and invasion of lung cancer cells. Intriguingly, overexpression of RHPN2 conferred the resistance to glutamine depletion in lung cancer cells. Mechanistic studies revealed that ectopic overexpression of RHPN2 promoted the stability of c-Myc protein via phosphorylation at Ser62 and increased c-Myc target glutamine synthetase (GS). Analysis of GS expression in clinical sample showed that the expression of GS was elevated in tumor cells. Kaplan-Meier analysis revealed that high levels of GS were significantly associated with worse overall survival time of the patients with LUAD.

Conclusions

Taken together, this study suggested that RHPN2 was involved in tumorigenesis of lung cancer via modulating c-Myc stability and the expression of its target GS in lung adenocarcinoma, which links RHPN2 and glutamine metabolism.
Turmeric Is Therapeutic in Vivo on Patient-Derived Colorectal Cancer Xenografts: Inhibition of Growth, Metastasis, and Tumor Recurrence
Authors: Li Mingyue , Yue Grace Gar-Lee , Luo Lianxiang , Tsui Stephen Kwok-Wing , Fung Kwok-Pui , Ng Simon Siu-Man , Lau Clara Bik-San
Published: January 2021

Colorectal cancer is the third most frequently diagnosed cancer worldwide. Clinically, chemotherapeutic agents such as FOLFOX are the mainstay of colorectal cancer treatment. However, the side effects including toxicity of FOLFOX stimulated the enthusiasm for developing adjuvants, which exhibit better safety profile. Turmeric extract (TE), which has been previously shown to suppress the growth of human and murine colon xenografts, was further demonstrated here for its inhibitory effects on colon cancer patient-derived xenografts (PDX). PDX models were successfully established from tissues of colon cancer patients and the PDX preserved the heterogeneous architecture through passages. NOD/SCID mice bearing PDX were treated either with TE or FOLFOX and differential responses toward these treatments were observed. The growth of PDX, metastasis and tumor recurrence in PDX-bearing mice were suppressed after TE treatments with 60% anti-tumor response rate and 83.3% anti-metastasis rate. Mechanistic studies showed that TE reduced tumor cell proliferation, induced cell apoptosis, inhibited metastasis via modulating multiple targets, such as molecules involved in Wnt and Src pathways, EMT and EGFR-related pathways. Nevertheless, FOLFOX treatments inhibited the PDX growth with sharp decreases of mice body weight and only mild anti-metastasis activities were observed. Furthermore, in order to have a better understanding of the underlying mechanisms, network pharmacology was utilized to predict potential targets and mechanism. In conclusion, the present study demonstrated for the first time that oral TE treatment was effective to suppress the growth of colon PDX and the recurrence of colon tumors in mice. The findings obtained from this clinically relevant PDX model would certainly provide valuable information for the potential clinical use of TE in colorectal cancer patients. The application of PDX model was well illustrated here as a good platform to verify the efficacy of multi-targeted herbal extracts.
SurvNet: A Novel Deep Neural Network for Lung Cancer Survival Analysis With Missing Values
Authors: Wang Jianyong , Chen Nan , Guo Jixiang , Xu Xiuyuan , Liu Lunxu , Yi Zhang
Published: January 2021

Survival analysis is important for guiding further treatment and improving lung cancer prognosis. It is a challenging task because of the poor distinguishability of features and the missing values in practice. A novel multi-task based neural network, SurvNet, is proposed in this paper. The proposed SurvNet model is trained in a multi-task learning framework to jointly learn across three related tasks: input reconstruction, survival classification, and Cox regression. It uses an input reconstruction mechanism cooperating with incomplete-aware reconstruction loss for latent feature learning of incomplete data with missing values. Besides, the SurvNet model introduces a context gating mechanism to bridge the gap between survival classification and Cox regression. A new real-world dataset of 1,137 patients with IB-IIA stage non-small cell lung cancer is collected to evaluate the performance of the SurvNet model. The proposed SurvNet achieves a higher concordance index than the traditional Cox model and Cox-Net. The difference between high-risk and low-risk groups obtained by SurvNet is more significant than that of high-risk and low-risk groups obtained by the other models. Moreover, the SurvNet outperforms the other models even though the input data is randomly cropped and it achieves better generalization performance on the Surveillance, Epidemiology, and End Results Program (SEER) dataset.
circ_NOTCH3 Functions as a Protooncogene Competing With miR-205-5p, Modulating KLF12 Expression and Promoting the Development and Progression of Basal-Like Breast Carcinoma
Authors: Guan Bing , Li Qing , Zhang Hui-Zhen , Yang Hai-Sheng
Published: January 2021

Breast cancer is the most common type of cancer diagnosed among women, and basal-like breast carcinoma (BLBC) has been associated with a more aggressive histology, poorer prognosis, and non-responsiveness to hormone therapy. In the present study, the role and molecular mechanism of circular (circ)_NOTCH3 in the development and progression for BLBC was identified. circ_RNAs array was used to screen the ectopic expression of hsa_circ_0109177 (circ_NOTCH3) in BLBC. RT-qPCR was conducted to evaluate the circ_NOTCH3 expression in BLBC tissues and paired normal tissues, as well as related cell lines. Cell function changes were analyzed following circ_NOTCH3 or micro (mi)RNA overexpression or co-expression. Bioinformatics analysis and dual-luciferase reporter assay were performed to predict and verify the binding sites between circ_NOTCH3 and miRNAs. Gene expression changes were assessed using western blotting. circ_NOTCH3 had a significantly higher expression in BLBC tissues and cell lines. The upregulation of circ_NOTCH3 promoted the proliferation, migration, invasion and inhibited the apoptosis for BLBC cells. The opposite results were observed following miR-205-5p overexpression. However, the co-expression of circ_NOTCH3 and miR-205-5p resulted in those restoration. circ_NOTCH3 is capable of binding to miR-205-5p, and upregulating its target gene KLF12, which can be downregulated by miR-205-5p overexpression and restored by the co-expression of circ_NOTCH3 and miR205-5p. circ_NOTCH3, being an protooncogene and a powerful biomarker, can function as a sponge, compete with miR-205-5p, modulate KLF12 expression, and promote the development and progression of BLBC.
Platelet Counts and Patent Ductus Arteriosus in Preterm Infants: An Updated Systematic Review and Meta-Analysis
Authors: González-Luis Gema , Ghirardello Stefano , Bas-Suárez Pilar , Cavallaro Giacomo , Mosca Fabio , Clyman Ronald I , Villamor Eduardo
Published: January 2021

Background: A meta-analysis published in 2015 showed a significant association between low platelet counts in the first day(s) of life and risk of patent ductus arteriosus (PDA). The meta-analysis pooled data from 11 studies cohorts (3,479 preterm infants).

Objective: To update the meta-analysis by adding new studies on the topic and including other platelet parameters different from platelet counts.

Methods: PubMed/Medline and Embase databases were searched. Random-effects risk ratios (RR) and differences in means (DM) and 95% confidence intervals (CI) were calculated.

Results: We included 31 studies (7,638 infants). Meta-analysis showed that the risk of developing any PDA was significantly associated with platelet counts<150 × 109/L (11 studies, RR 1.58, 95% CI 1.28 to 1.95), and <100 x 109/L (7 studies, RR 1.61, 95% CI 1.14 to 2.28), but not <50 x 109/L (4 studies, RR 1.34, 95% CI 0.77 to 2.32). Risk of developing hemodynamically significant PDA (hsPDA) was significantly associated with platelet counts<150 x 109/L (12 studies, RR 1.33, 95% CI 1.09 to 1.63), and <100 x 109/L (7 studies, RR 1.39, 95% CI 1.06 to 1.82), but not <50 x 109/L (6 studies, RR 1.24, 95% CI 0.86 to 1.79). Infants with hsPDA had significantly lower mean platelet counts (19 studies, DM 22.0 x 109, 95% CI 14.9 to 29.1) and platelet mass (11 studies, DM 214.4, 95% CI 131.2 to 297.5) and significantly higher platelet distribution width (PDW, 9 studies, DM −0.53, 95% CI −1.01 to −0.05) than infants without hsPDA. Meta-analysis could not demonstrate significant differences in mean platelet volume (MPV).

Conclusion: Compared to the previous analysis, this updated meta-analysis included 21 additional studies that provide stronger evidence of the association between low platelet counts and PDA/hsPDA. Other platelet parameters such as platelet mass and PDW are also associated with hsPDA risk. However, the low number of platelets may be an epiphenomenon associated with the maturity and clinical stability of preterm infants rather than a contributing factor in the pathogenesis of PDA.
Cellular Uptake of Psychostimulants – Are High- and Low-Affinity Organic Cation Transporters Drug Traffickers?
Authors: Jensen Ole , Rafehi Muhammad , Gebauer Lukas , Brockmöller Jürgen
Published: January 2021

Psychostimulants are used therapeutically and for illegal recreational purposes. Many of these are inhibitors of the presynaptic noradrenaline, dopamine, and serotonin transporters (NET, DAT, and SERT). According to their physicochemical properties, some might also be substrates of polyspecific organic cation transporters (OCTs) that mediate uptake in liver and kidneys for metabolism and excretion. OCT1 is genetically highly polymorphic, with strong effects on transporter activity and expression. To study potential interindividual differences in their pharmacokinetics, 18 psychostimulants and hallucinogens were assessedin vitrofor transport by different OCTs as well as by the high-affinity monoamine transporters NET, DAT, and SERT. The hallucinogenic natural compound mescaline was found to be strongly transported by wild-type OCT1 with aKmof 24.3 µM and avmaxof 642 pmol × mg protein−1× min−1. Transport was modestly reduced in variants *2 and *7, more strongly reduced in *3 and *4, and lowest in *5 and *6, while *8 showed a moderately increased transport capacity. The other phenylethylamine derivatives methamphetamine,para-methoxymethamphetamine, (-)-ephedrine, and cathine ((+)-norpseudoephedrine), as well as dimethyltryptamine, were substrates of OCT2 withKmvalues in the range of 7.9–46.0 µM andvmaxvalues between 70.7 and 570 pmol × mg protein−1× min−1. Affinities were similar or modestly reduced and the transport capacities were reduced down to half in the naturally occurring variant A270S. Cathine was found to be a substrate for NET and DAT, with the Kmbeing 21-fold and thevmax10-fold higher for DAT but still significantly lower compared to OCT2. This study has shown that several psychostimulants and hallucinogens are substrates for OCTs. Given the extensive cellular uptake of mescaline by the genetically highly polymorphic OCT1, strong interindividual variation in the pharmacokinetics of mescaline might be possible, which could be a reason for highly variable adverse reactions. The involvement of the polymorphic OCT2 in the renal excretion of several psychostimulants could be one reason for individual differences in toxicity.