bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteome-Wide Analysis of Lysine 2-Hydroxyisobutyrylated Proteins in Fusarium oxysporum
Authors: Qian Hengwei , Wang Lulu , Ma Xianliang , Yi Xingling , Wang Baoshan , Liang Wenxing
Published: February 2021

Protein lysine 2-hydroxyisobutyrylation (Khib), a new type of post-translational modification, occurs in histones and non-histone proteins and plays an important role in almost all aspects of both eukaryotic and prokaryotic living cells. Fusarium oxysporum, a soil-borne fungal pathogen, can cause disease in more than 150 plants. However, little is currently known about the functions of Khib in this plant pathogenic fungus. Here, we report a systematic analysis of 2-hydroxyisobutyrylated proteins in F. oxysporum. In this study, 3782 Khib sites in 1299 proteins were identified in F. oxysporum. The bioinformatics analysis showed that 2-hydroxyisobutyrylated proteins are involved in different biological processes and functions and are located in diverse subcellular localizations. The enrichment analysis revealed that Khib participates in a variety of pathways, including the ribosome, oxidative phosphorylation, and proteasome pathways. The protein interaction network analysis showed that 2-hydroxyisobutyrylated protein complexes are involved in diverse interactions. Notably, several 2-hydroxyisobutyrylated proteins, including three kinds of protein kinases, were involved in the virulence or conidiation of F. oxysporum, suggesting that Khib plays regulatory roles in pathogenesis. Moreover, our study shows that there are different Khib levels of F. oxysporum in conidial and mycelial stages. These findings provide evidence of Khib in F. oxysporum, an important filamentous plant pathogenic fungus, and serve as a resource for further exploration of the potential functions of Khib in Fusarium species and other filamentous pathogenic fungi.
Toward an Integrated Genome-Based Surveillance of Salmonella enterica in Germany
Authors: Uelze Laura , Becker Natalie , Borowiak Maria , Busch Ulrich , Dangel Alexandra , Deneke Carlus , Fischer Jennie , Flieger Antje , Hepner Sabrina , Huber Ingrid , Methner Ulrich , Linde Jörg , Pietsch Michael , Simon Sandra , Sing Andreas , Tausch Simon H. , Szabo Istvan , Malorny Burkhard
Published: February 2021

Despite extensive monitoring programs and preventative measures, Salmonella spp. continue to cause tens of thousands human infections per year, as well as many regional and international food-borne outbreaks, that are of great importance for public health and cause significant socio-economic costs. In Germany, salmonellosis is the second most common cause of bacterial diarrhea in humans and is associated with high hospitalization rates. Whole-genome sequencing (WGS) combined with data analysis is a high throughput technology with an unprecedented discriminatory power, which is particularly well suited for targeted pathogen monitoring, rapid cluster detection and assignment of possible infection sources. However, an effective implementation of WGS methods for large-scale microbial pathogen detection and surveillance has been hampered by the lack of standardized methods, uniform quality criteria and strategies for data sharing, all of which are essential for a successful interpretation of sequencing data from different sources. To overcome these challenges, the national GenoSalmSurv project aims to establish a working model for an integrated genome-based surveillance system of Salmonella spp. in Germany, based on a decentralized data analysis. Backbone of the model is the harmonization of laboratory procedures and sequencing protocols, the implementation of open-source bioinformatics tools for data analysis at each institution and the establishment of routine practices for cross-sectoral data sharing for a uniform result interpretation. With this model, we present a working solution for cross-sector interpretation of sequencing data from different sources (such as human, veterinarian, food, feed and environmental) and outline how a decentralized data analysis can contribute to a uniform cluster detection and facilitate outbreak investigations.
Association Between Gamma-Glutamyl Transferase and Mild Cognitive Impairment in Chinese Women
Authors: Tang Zhaoyang , Chen Xueyu , Zhang Wenran , Sun Xiangfu , Hou Qingzhi , Li Yuejin , Feng Xia , Chen Yanru , Lv Jian , Ji Long , Ding Guoyong , Li Dong
Published: February 2021

Background: Dementia, as a global public health problem, is becoming increasingly serious. As a precursor of dementia, mild cognitive impairment (MCI) plays an important role in the diagnosis and prevention of dementia. Recent studies have found a correlation between gamma-glutamyl transferase (GGT) levels and cognitive function in men. The relationship between GGT levels and cognitive function in women remains unclear because GGT activity and expression differ between the sexes.

Method: We recruited a total of 2,943 Chinese women from Jidong and Taian in 2019. We grouped the participants according to GGT levels, diagnosed MCI using the Montreal Cognitive Assessment (MOCA) scale, and modeled the study outcomes using logistic regression to explore the relationship between GGT level and MCI. We also analyzed the interaction of obesity, sleep duration, and hyperuricemia with GGT in the development of MCI.

Results: The prevalence of MCI increased with increasing GGT level, from the lowest quartile to the highest quartile of GGT: 8.4% (66/786), 14.2% (119/840), 17.6% (108/613), and 21.4% (151/704), respectively. At the same time, as GGT levels increased, so did the risk of MCI. In the fully adjusted model, compared with those for participants in the lowest GGT quartiles, the odds ratios (ORs), and 95% confidence intervals (CIs) for MCI for participants in the second, third, and fourth GGT quartiles were 1.49 (1.04–2.12), 1.53(1.06–2.21), and 1.88 (1.33–2.65), respectively. The risk of developing MCI was further increased in people with high GGT levels who were obese (OR = 1.96, 95% CI: 1.39–2.76, P < 0.001), slept less (OR = 1.91, 95% CI: 1.35–2.71, P < 0.001), had high levels of uric acid (OR = 1.55, 95% CI: 1.03–2.32, P < 0.001), or after menopause (OR = 2.92, 95% CI: 2.07–4.12, P < 0.001).

Conclusion: We found that MCI is more common in women with elevated GGT levels, so GGT could be a potential diagnostic marker for MCI. Meanwhile, our findings indicated that women with high GGT levels had an increased risk of MCI when they were obese, sleep deprived, had high serum uric acid (SUA) levels or underwent menopause.
Interleukin-1β Modulates Synaptic Transmission and Synaptic Plasticity During the Acute Phase of Sepsis in the Senescence-Accelerated Mouse Hippocampus
Authors: Hoshino Koji , Uchinami Yuka , Uchida Yosuke , Saito Hitoshi , Morimoto Yuji
Published: February 2021

Background

Aging and pre-existing cognitive impairment are considered to be independent risk factors for sepsis-associated encephalopathy. This study aimed to investigate the manner in which aging and pre-existing cognitive dysfunction modified neuroinflammation, synaptic plasticity, and basal synaptic transmission during the acute phase of sepsis using Senescence-Accelerated Mice Prone 8 (SAMP8) and Senescence-Accelerated Resistant Mice 1 (SAMR1).

Methods

We used 6-month-old SAMP8 and SAMR1. Sepsis was induced using cecal ligation and puncture (CLP). The animal’s hippocampi and blood were collected for subsequent investigations 24 h after surgery.

Results

Long-term potentiation (LTP) was impaired in the Shaffer-collateral (SC)-CA1 pathway of the hippocampus in SAMP8 without surgery compared to the age-matched SAMR1, which was reflective of cognitive dysfunction in SAMP8. CLP impaired the SC-CA1 LTP in SAMR1 compared to the sham-operated controls, but not in SAMP8. Moreover, CLP decreased the input-output curve and increased the paired-pulse ratio in SAMP8, suggesting the reduced probability of basal synaptic transmission due to sepsis. Immunohistochemical analysis revealed that CLP elevated IL-1β levels, especially in the hippocampi of SAMP8 with microglial activation. In vivo peripheral IL-1 receptor antagonist (IL-1ra) administration in the septic SAMP8 revealed that the neuroinflammation was not correlated with the peripheral elevation of IL-1β. Ex vivo IL-1ra administration to the hippocampus ameliorated LTP impairment in SAMR1 and the reduction in basal transmission in SAMP8 after sepsis.

Conclusions

The mechanism of the modulation of synaptic transmission and synaptic plasticity by the acute stage of sepsis differed between SAMR1 and SAMP8. These changes were related to centrally derived IL-1 receptor-mediated signaling and were accompanied by microglial activation, especially in SAMP8.
Engine Failure in Axo-Myelinic Signaling: A Potential Key Player in the Pathogenesis of Multiple Sclerosis
Authors: Bergaglio Talia , Luchicchi Antonio , Schenk Geert J.
Published: February 2021

Multiple Sclerosis (MS) is a complex and chronic disease of the central nervous system (CNS), characterized by both degenerative and inflammatory processes leading to axonal damage, demyelination, and neuronal loss. In the last decade, the traditionaloutside-instandpoint on MS pathogenesis, which identifies a primary autoimmune inflammatory etiology, has been challenged by a complementaryinside-outtheory. By focusing on the degenerative processes of MS, the axo-myelinic system may reveal new insights into the disease triggering mechanisms. Oxidative stress (OS) has been widely described as one of the means driving tissue injury in neurodegenerative disorders, including MS. Axonal mitochondria constitute the main energy source for electrically active axons and neurons and are largely vulnerable to oxidative injury. Consequently, axonal mitochondrial dysfunction might impair efficient axo-glial communication, which could, in turn, affect axonal integrity and the maintenance of axonal, neuronal, and synaptic signaling. In this review article, we argue that OS-derived mitochondrial impairment may underline the dysfunctional relationship between axons and their supportive glia cells, specifically oligodendrocytes and that this mechanism is implicated in the development of a primary cytodegeneration and a secondary pro-inflammatory response (inside-out), which in turn, together with a variably primed host’s immune system, may lead to the onset of MS and its different subtypes.
Glypicans and Heparan Sulfate in Synaptic Development, Neural Plasticity, and Neurological Disorders
Authors: Kamimura Keisuke , Maeda Nobuaki
Published: February 2021

Heparan sulfate proteoglycans (HSPGs) are components of the cell surface and extracellular matrix, which bear long polysaccharides called heparan sulfate (HS) attached to the core proteins. HSPGs interact with a variety of ligand proteins through the HS chains, and mutations in HSPG-related genes influence many biological processes and cause various diseases. In particular, recent findings from vertebrate and invertebrate studies have raised the importance of glycosylphosphatidylinositol-anchored HSPGs, glypicans, as central players in the development and functions of synapses. Glypicans are important components of the synapse-organizing protein complexes and serve as ligands for leucine-rich repeat transmembrane neuronal proteins (LRRTMs), leukocyte common antigen-related (LAR) family receptor protein tyrosine phosphatases (RPTPs), and G-protein-coupled receptor 158 (GPR158), regulating synapse formation. Many of these interactions are mediated by the HS chains of glypicans. Neurexins (Nrxs) are also synthesized as HSPGs and bind to some ligands in common with glypicans through HS chains. Therefore, glypicans and Nrxs may act competitively at the synapses. Furthermore, glypicans regulate the postsynaptic expression levels of ionotropic glutamate receptors, controlling the electrophysiological properties and non-canonical BMP signaling of synapses. Dysfunctions of glypicans lead to failures in neuronal network formation, malfunction of synapses, and abnormal behaviors that are characteristic of neurodevelopmental disorders. Recent human genetics revealed that glypicans and HS are associated with autism spectrum disorder, neuroticism, and schizophrenia. In this review, we introduce the studies showing the roles of glypicans and HS in synapse formation, neural plasticity, and neurological disorders, especially focusing on the mouse andDrosophilaas potential models for human diseases.
Association of SNCA Parkinson's Disease Risk Polymorphisms With Disease Progression in Newly Diagnosed Patients
Authors: Szwedo Aleksandra A. , Pedersen Camilla Christina , Ushakova Anastasia , Forsgren Lars , Tysnes Ole-Bjørn , Counsell Carl E. , Alves Guido , Lange Johannes , Macleod Angus D. , Maple-Grødem Jodi
Published: February 2021

Objectives: To evaluate the impact of SNCA polymorphisms originally identified as risk factors for Parkinson's disease (PD) on the clinical presentation and progression of the disease in a large cohort of population-based patients with incident PD.

Methods: Four hundred thirty-three patients and 417 controls from three longitudinal cohorts were included in the study. Disease progression was recorded annually for up to 9 years using the Unified Parkinson's Disease Rating Scale (UPDRS) or Mini-Mental State Examination. Genotypes for five variants within the SNCA locus (rs2870004, rs356182, rs5019538, rs356219, and rs763443) were determined. We studied the association between each variant and disease progression using linear mixed-effects regression models.

Results: The clinical profile of the patients with PD at the point of diagnosis was highly uniform between genotype groups. The rs356219-GG genotype was associated with a higher UPDRS II score than A-allele carriers (β = 1.52; 95% confidence interval 0.10–2.95; p = 0.036), but no differences were observed in the rate of progression of the UPDRS II scores. rs356219-GG was also associated with a faster annual change in Mini-Mental State Examination score compared with A-carriers (β = 0.03; 95% confidence interval 0.00–0.06; p = 0.043).

Conclusions: We show that the known PD-risk variant rs356219 has a minor effect on modifying disease progression, whereas no differences were associated with rs2870004, rs356182, rs5019538, and rs763443. These findings suggest that SNCA variants associated with PD risk may not be major driving factors to the clinical heterogeneity observed for PD.
Physiological Ripples Associated With Sleep Spindles Can Be Identified in Patients With Refractory Epilepsy Beyond Mesio-Temporal Structures
Authors: Bruder Jonas C. , Schmelzeisen Christoph , Lachner-Piza Daniel , Reinacher Peter , Schulze-Bonhage Andreas , Jacobs Julia
Published: February 2021

Introduction: High frequency oscillations (HFO) are promising biomarkers of epileptic tissue. While group analysis suggested a correlation between surgical removal of HFO generating tissue and seizure free outcome, HFO could not predict seizure outcome on an individual patient level. One possible explanation is the lack of differentiation between physiological and epileptic HFO. In the mesio-temporal lobe, a proportion of physiological ripples can be identified by their association with scalp sleep spindles. Spike associated ripples in contrast can be considered epileptic. This study investigated whether categorizing ripples by the co-occurrence with sleep spindles or spikes improves outcome prediction after surgery. Additionally, it aimed to investigate whether spindle-ripple association is limited to the mesio-temporal lobe structures or visible across the whole brain.

Methods: We retrospectively analyzed EEG of 31 patients with chronic intracranial EEG. Sleep spindles in scalp EEG and ripples and epileptic spikes in iEEG were automatically detected. Three ripple subtypes were obtained: SpindleR, Non-SpindleR, and SpikeR. Rate ratios between removed and non-removed brain areas were calculated. We compared the distinct ripple subtypes and their rates in different brain regions, inside and outside seizure onset areas and between patients with good and poor seizure outcome.

Results: SpindleR were found across all brain regions. SpikeR had significantly higher rates in the SOZ than in Non-SOZ channels. A significant positive correlation between removal of ripple-events and good outcome was found for the mixed ripple group (rs = 0.43, p = 0.017) and for ripples not associated with spindles (rs=0.40, p = 0.044). Also, a significantly high proportion of spikes associated with ripples were removed in seizure free patients (p = 0.036).

Discussion: SpindleR are found in mesio-temporal and neocortical structures, indicating that ripple-spindle-coupling might have functional importance beyond mesio-temporal structures. Overall, the proportion of SpindleR was low and separating spindle and spike associated ripples did not improve outcome prediction in our patient group. SpindleR analysis therefore can be a tool to identify physiological events but needs to be used in combination with other methods to have clinical relevance.
Education, Training, and Practices of Neurorehabilitation in India During the COVID-19 Pandemic
Authors: Surya Nirmal , Srivastava Abhishek , Nagda Taral , Palande Deepak , Someshwar Hitav
Published: February 2021

Background: Corona virus disease (COVID-19) was declared a pandemic by the World Health Organization in March 2020. This has affected service delivery among all medical disciplines in India including neurorehabilitation services.

Aims and Objectives: The aims and objectives of the study were to assess the effect of COVID-19 pandemic on neurorehabilitation services across India.

Methodology: A prospective nationwide survey study was undertaken by the Indian Federation of Neurorehabilitation during the pandemic. A questionnaire was prepared using Google forms software consisting of four sections: demography, neurorehabilitation practice before COVID-19 pandemic, neurorehabilitation practice during COVID-19 pandemic, and continuing medical education during COVID-19 pandemic.

Results: Responses (872) were received from neurorehabilitation professionals across the country out of which 2.2% professionals did not give consent for participating in the survey. Participants (36.6%) were practicing traditional or independent referral basis rehabilitation, while 63.4% participants were practicing multidisciplinary rehabilitation. On an average, respective units were conducting 500–750 therapy sessions per month. Majority of the rehabilitation units in India lacked a physiatrist, rehabilitation nurse, music therapist, cognitive therapist, and urologist. Approximately 80% of the rehabilitation units have the basic rehabilitation modalities and advance technology was present in only 20% of the rehabilitation units. During COVID-19 pandemic, 19.5% centers were providing elective services, 50.3% emergency services, 15.6% new outpatient services, and 22.7% were providing follow-up outpatient services. Centers (51.5%) were providing telerehabilitation services for neurological conditions during the times of COVID-19 pandemic. Professionals (61.1%) providing telerehabilitation were working from home. Among the patients who needed neurorehabilitation, 28% were doing their exercises independently, 31% were supervised by caregivers, 17% were supervised by therapists, and 24% were not receiving any therapy. Participants (95.5%) wanted to receive more training in the field of neurorehabilitation. The participants utilized webinars (71%), online courses (22%), case discussion forums (19%), panel discussions (13%), and literature search (8%) during COVID-19 pandemic to continue education.

Conclusion: The study reflects the situation of neurorehabilitation service delivery in India during the pandemic as the respondents were from all parts of the country and included most components of the neurorehabilitation team. Neurorehabilitation services were severely affected across India during the COVID-19 pandemic. Tele-neurorehabilitation has emerged as a new service delivery model during the pandemic. Online means of education has emerged as the primary source of continuing medical education during the pandemic.
Perspectives on (A)symmetry of Arcuate Fasciculus. A Short Review About Anatomy, Tractography and TMS for Arcuate Fasciculus Reconstruction in Planning Surgery for Gliomas in Language Areas
Authors: Di Cristofori Andrea , Basso Gianpaolo , de Laurentis Camilla , Mauri Ilaria , Sirtori Martina Andrea , Ferrarese Carlo , Isella Valeria , Giussani Carlo
Published: February 2021

Gliomas are brain tumors that are treated with surgical resection. Prognosis is influenced by the extent of resection and postoperative neurological status. As consequence, given the extreme interindividual and interhemispheric variability of subcortical white matter (WM) surgical planning requires to be patient's tailored. According to the “connectionist model,” there is a huge variability among both cortical areas and subcortical WM in all human beings, and it is known that brain is able to reorganize itself and to adapt to WM lesions. Brain magnetic resonance imaging diffusion tensor imaging (DTI) tractography allows visualization of WM bundles. Nowadays DTI tractography is widely available in the clinical setting for presurgical planning. Arcuate fasciculus (AF) is a long WM bundle that connects the Broca's and Wernicke's regions with a complex anatomical architecture and important role in language functions. Thus, its preservation is important for the postoperative outcome, and DTI tractography is usually performed for planning surgery within the language-dominant hemisphere. High variability among individuals and an asymmetrical pattern has been reported for this WM bundle. However, the functional relevance of AF in the contralateral non-dominant hemisphere in case of tumoral or surgical lesion of the language-dominant AF is unclear. This review focuses on AF anatomy with special attention to its asymmetry in both normal and pathological conditions and how it may be explored with preoperative tools for planning surgery on gliomas in language areas. Based on the findings available in literature, we finally speculate about the potential role of preoperative evaluation of the WM contralateral to the surgical site.
Precision Medicine for Intracranial Atherosclerotic Disease
Authors: Liebeskind David S.
Published: February 2021

Diagnostic and therapeutic strategies for intracranial atherosclerotic disease (ICAD) have vastly expanded within the last several years. Challenges and concrete initiatives have emerged in the implementation of precision medicine for ICAD, focusing personalized treatment for the prevention of stroke and cognitive impairment around pathophysiology. Theranostics for ICAD incorporates an integrated diagnostic and therapeutic approach tailored to a specific individual. The ICAS 2019 meeting provided a roadmap for accelerating global innovation, underscoring the epidemiology, prior scientific evidence from trials, diagnostic tools or imaging, novel biomarkers, management approaches, and a broad range of treatments including many new medications, endovascular, and surgical strategies. This thematic overview provides perspective on current definitions for arterial stenosis, symptomatic lesions and outcomes or endpoints in clinical trials. Imaging correlates are reviewed, from routine multimodal CT or MRI to advanced angiographic techniques. The temporal features of ICAD and longitudinal observation are considered with respect to management and risk factor modification. The evolving science of multivariable interactions in ICAD and use of big data are explored, followed by an overview of recently launched clinical trials.
The Impact of Vigorous Cycling Exercise on Visual Attention: A Study With the BR8 Wireless Dry EEG System
Authors: Lin Chin-Teng , King Jung-Tai , John Alka Rachel , Huang Kuan-Chih , Cao Zehong , Wang Yu-Kai
Published: February 2021

Many studies have reported that exercise can influence cognitive performance. But advancing our understanding of the interrelations between psychology and physiology in sports neuroscience requires the study of real-time brain dynamics during exercise in the field. Electroencephalography (EEG) is one of the most powerful brain imaging technologies. However, the limited portability and long preparation time of traditional wet-sensor systems largely limits their use to laboratory settings. Wireless dry-sensor systems are emerging with much greater potential for practical application in sports. Hence, in this paper, we use the BR8 wireless dry-sensor EEG system to measure P300 brain dynamics while cycling at various intensities. The preparation time was mostly less than 2 min as BR8 system’s dry sensors were able to attain the required skin-sensor interface impedance, enabling its operation without any skin preparation or application of conductive gel. Ten participants performed four sessions of a 3 min rapid serial visual presentation (RSVP) task while resting and while cycling. These four sessions were pre-CE (RSVP only), low-CE (RSVP in 40–50% of max heart rate), vigorous-CE (RSVP in 71–85% of max heart rate) and post-CE (RSVP only). The recorded brain signals demonstrate that the P300 amplitudes, observed at the Pz channel, for the target and non-target responses were significantly different in all four sessions. The results also show decreased reaction times to the visual attention task during vigorous exercise, enriching our understanding of the ways in which exercise can enhance cognitive performance. Even though only a single channel was evaluated in this study, the quality and reliability of the measurement using these dry sensor-based EEG systems is clearly demonstrated by our results. Further, the smooth implementation of the experiment with a dry system and the success of the data analysis demonstrate that wireless dry EEG devices can open avenues for real-time measurement of cognitive functions in athletes outside the laboratory.
Learning Without Feedback: Fixed Random Learning Signals Allow for Feedforward Training of Deep Neural Networks
Authors: Frenkel Charlotte , Lefebvre Martin , Bol David
Published: February 2021

While the backpropagation of error algorithm enables deep neural network training, it implies (i) bidirectional synaptic weight transport and (ii) update locking until the forward and backward passes are completed. Not only do these constraints preclude biological plausibility, but they also hinder the development of low-cost adaptive smart sensors at the edge, as they severely constrain memory accesses and entail buffering overhead. In this work, we show that the one-hot-encoded labels provided in supervised classification problems, denoted as targets, can be viewed as a proxy for the error sign. Therefore, their fixed random projections enable a layerwise feedforward training of the hidden layers, thus solving the weight transport and update locking problems while relaxing the computational and memory requirements. Based on these observations, we propose the direct random target projection (DRTP) algorithm and demonstrate that it provides a tradeoff between accuracy and computational cost that is suitable for adaptive edge computing devices.
Dynamics of Structured Networks of Winfree Oscillators
Authors: Laing Carlo R. , Bläsche Christian , Means Shawn
Published: February 2021

Winfree oscillators are phase oscillator models of neurons, characterized by their phase response curve and pulsatile interaction function. We use the Ott/Antonsen ansatz to study large heterogeneous networks of Winfree oscillators, deriving low-dimensional differential equations which describe the evolution of the expected state of networks of oscillators. We consider the effects of correlations between an oscillator's in-degree and out-degree, and between the in- and out-degrees of an “upstream” and a “downstream” oscillator (degree assortativity). We also consider correlated heterogeneity, where some property of an oscillator is correlated with a structural property such as degree. We finally consider networks with parameter assortativity, coupling oscillators according to their intrinsic frequencies. The results show how different types of network structure influence its overall dynamics.
The Prognostic and Predictive Significance of circRNA CDR1as in Tumor Progression
Authors: Jian Fang , Yangyang Ren , Wei Xu , Jiadan Xu , Na Li , Peng Yang , Maohong Bian , Guoping Niu , Zhaoji Pan
Published: February 2021

Cerebellar degeneration-related protein 1 antisense (CDR1as) is an important member of the circRNAs family, also known as cirs-7. Its main function in vivo is to act as a mir-7 sponge. Accumulated studies show that CDR1as is closely related to various diseases, especially cancer. Our analysis show that CDR1as expression in human cancer is significantly associated with poor overall survival (hazard ratio [HR] = 2.50, 95% confidence interval [CI] = 2.06–3.04; p < 0.00001) and that high CDR1as expression is associated with the tumor node metastasis stage (odds ratio [OR] = 2.13, 95% CI = 1.63–2.78; p < 0.00001), and distant metastasis (OR = 3.50, 95% CI = 1.90–6.64; p < 0.00001). Furthermore, the results reveal the prognostic significance of CDR1as in neoplasms of the digestive system (HR = 1.69, 95% CI = 2.14–2.71; p < 0.001), colorectal cancer (HR = 1.34, 95% CI = 1.96–2.85; p < 0.001), and non-small cell lung cancer (HR = 2.40, 95% CI = 3.42–4.83; p = 0.008). In this study, we summarize in detail the latest research findings and demonstrate the function and regulatory mechanism of CDR1as in various cancer processes, and its potential as a biomarker for cancer prevention and prognosis.
Serum Chemokine CXCL7 as a Potential Novel Biomarker for Obstructive Colorectal Cancer
Authors: Li Longhai , Zhang Lihua , Zhang Ting , Qi Xiaowei , Cheng Gang , Xia Lingxia
Published: February 2021

Due to the lack of typical symptoms and signs and sensitive indicators for early diagnosis of obstructive colorectal cancer (OCRC), it is critically needed to find new novel biomarkers to ameliorate the management of OCRC patients. In this study, 472 blood samples were collected and measured by enzyme-linked immunosorbent assay (ELISA) to investigate the value of serum chemokine ligand 7 (CXCL7) in diagnosis and prognosis for OCRC patients. The median concentrations of CXCL7 in non-OCRC and OCRC were both higher than that in controls (both P < 0.05). Importantly, the median serum concentration of CXCL7 in OCRC was also higher than that in non-OCRC (P < 0.001). In all OCRC patients, the area under the curve (AUC) of CXCL7 was 0.918 with a sensitivity of 86.54% and a specificity of 81.87%. Similarly, the AUC of CXCL7 was 0.684 when the diagnostic test was performed between OCRC and CRC patients. CXCL7 had a higher AUC than other markers. The concentration of CXCL7 in 40 postoperative OCRC patients was higher than normal people and lower than preoperative patients. The median survival time was 62.00 months and the 5-year overall survival (OS) rate of the patients was 51.80% in all 155 OCRC patients. Multivariate Cox proportional hazard regression model analysis showed that high CXCL7 in serum was independent factors associated with poor OS of OCRC patients (HR = 2.216, P = 0.032). These results demonstrate that serum CXCL7 may be a potential biomarker both in diagnosis and prognosis for OCRC patients.
Management of Malaria in Children Younger Than 5 Years Old During Coronavirus Disease 2019 Pandemic in Sierra Leone: A Lesson Learned?
Authors: Buonsenso Danilo , Iodice Francesco , Cinicola Bianca , Raffaelli Francesca , Sowa Solia , Ricciardi Walter
Published: February 2021

Growing evidences are showing the potential indirect effects of the Coronavirus Disease 2019 (COVID-19) on the health systems of low-resource settings, where diseases such as Tuberculosis, Human Immunodeficiency Virus (HIV) and Malaria represent major killers. Therefore, we performed a retrospective study aimed to evaluate the impact of COVID-19 on Malaria programs in a peripheral region of Sierra Leone, previously involved by the Ebola outbreak in 2015, when malaria care have been impaired since local health systems were overwhelmed by Ebola cases. During COVID-19 in Sierra Leone, we did not notice a significant drop in malaria diagnosis in children, suggesting that a proactive approach in the management of malaria in endemic countries during COVID-19 may have had a positive impact. A comprehensive approach that include also educational activities to sensitize the local population, was useful to guarantee successful malaria diagnosis and treatment, and prevents excess of malaria deaths due to potential disruption of the local health systems related to the SARS-CoV-2 pandemic.
Case Report: A Case Report and Literature Review of 3p Deletion Syndrome
Authors: Fu Junxian , Wang Ting , Fu Zhuo , Li Tianxia , Zhang Xiaomeng , Zhao Jingjing , Yang Guanglu
Published: February 2021

Objective: The aim of the present study is to explore the clinical and genetic characteristics of 3p deletion syndrome to improve clinicians' understanding of the disease.

Methods: The clinical manifestations, process of diagnosis and treatment, and genetic characteristics of an individual case of 3p deletion syndrome were analyzed. CNKI, Wanfang Data, and the Biomedical Literature Database (PubMed) were searched. The search time limit, using “3p deletion syndrome” and “BRPF1” as keywords, was from the creation of the database up to June 2020. Related data were reviewed.

Results: The proband was a male child with general developmental and intellectual disabilities, special facial features and congenital heart disease. The child was the parents' first pregnancy and first born. Gene microarray analysis showed a 10.095 Mb deletion in the 3p26.3-p25.3 region, resulting in a heterozygous mutation of the BRPF1 gene; thus, the patient was diagnosed with 3p deletion syndrome. At the time of diagnosis, the child was 1 year of age and was responding to comprehensive rehabilitation training. A total of 29 well-documented cases were found in the literature, of which 19 cases had an onset within 1 year of birth, and mainly manifested with mental and motor development disabilities and abnormal facial features, with different gene deletions, depending on the size and location of the 3p deletion.

Conclusion: The genetic test results of the child in this study indicated a heterozygous deletion of the BRPF1 gene on the short arm of chromosome 3, which was a unique feature of this study, since it was rarely mentioned in other reports of 3p deletion syndrome. The clinical phenotype of this syndrome is complex as it can include intellectual and motor development backwardness, low muscle tone, certain abnormal facial features (low hairline, bilateral ptosis, widely spaced eyes, a forward nose, left ear auricle deformity, a high-arched palate, a small jaw), and the deformation of systems such as the gastrointestinal tract and the urinary tract malformation or symptoms of epilepsy. As clinical manifestations can be relatively mild, the syndrome is easy to miss or misdiagnose. Clinical workers need to be aware of this disease when they find that children have special features, such as stunted growth, low muscle tone or ptosis, and it needs to be diagnosed through genetic testing. Most children are able to develop certain social skills after rehabilitation treatment.
Case Report: Insulin-Dependent Diabetes Mellitus and Diabetic Keto-Acidosis in a Child With COVID-19
Authors: Nielsen-Saines Karin , Li Erica , Olivera Adriana Martinez , Martin-Blais Rachel , Bulut Yonca
Published: February 2021

During the COVID pandemic, a surge in pediatric Type 1 Diabetes Mellitus (T1DM) cases appears to be occurring, potentially due to the presence of autoantibody-induced immune dysregulation triggered by COVID-19. We describe one such case in a previously healthy 7-year-old with asymptomatic COVID-19 presenting with a high nasopharyngeal SARS CoV-2 virus load, detectable COVID-19 IgG antibodies, diabetic keto-acidosis and islet cell autoantibodies. COVID-19 is not a trivial disease in children and adolescents and can lead to lifelong sequelae such as T1DM. Raising awareness about a possible association between COVID-19 and T1DM in children is critical.
Bazedoxifene Regulates Th17 Immune Response to Ameliorate Experimental Autoimmune myocarditis via Inhibition of STAT3 Activation
Authors: Wang Jing , Liu Tianshu , Chen Xiongwen , Jin Qiaofeng , Chen Yihan , Zhang Li , Han Zhengyang , Chen Dandan , Li Yuman , Lv Qing , Xie Mingxing
Published: February 2021

Myocarditis is a type of inflammatory cardiomyopathy that has no specific treatment. Accumulating evidence suggests that Th17 cells play a prominent role in the pathogenesis of myocarditis. Interleukin-(IL)-6-mediated signal transducer and activation of transcription 3 (STAT3) signaling is essential for Th17 cell differentiation and secretion of inflammatory cytokines. Bazedoxifene inhibits IL-6/STAT3 signaling in cancer cells, but its effect on the Th17 immune response induced by myocarditis remains unknown. Here we explore the effect of Bazedoxifene on Th17 immune response and cardiac inflammation in a mouse model of experimental autoimmune myocarditis, which has been used to mimic human inflammatory heart disease. After eliciting an immune response, we found Bazedoxifene ameliorated cardiac inflammatory injury and dysfunction. Th17 cells and related inflammatory factors in splenic CD4+ T cells at day 14 and in the heart at day 21 were increased, which were reduced by Bazedoxifene. Furthermore, Bazedoxifene could regulate autophagy induction in polarized Th17 cells. In conclusion, Bazedoxifene affected STAT3 signaling and prevented cardiac inflammation deterioration, so may provide a promising therapeutic strategy for the treatment of experimental autoimmune myocarditis (EAM).
Multiple Biological Activities of Rhododendron przewalskii Maxim. Extracts and UPLC-ESI-Q-TOF/MS Characterization of Their Phytochemical Composition
Authors: Dai Lixia , He Jian , Miao Xiaolou , Guo Xiao , Shang Xiaofei , Wang Weiwei , Li Bing , Wang Yu , Pan Hu , Zhang Jiyu
Published: February 2021

Backgroud:Rhododendron przewalskii Maxim. is an evergreen shrub that is used as a traditional medicine in China. However, the modern pharmacology and the chemical components of this plant has not been studied. In this paper, we aimed to investigate the antifungal, anti-inflammatory and antioxidant activities and underlying mechanism of its aqueous and ethanol extracts, and analyze their chemical composition and active compounds of R. przewalskii.

Methods: The antifungal activity was determined in vitro, and anti-inflammatory and antioxidant activities and underlying mechanism of its aqueous and ethanol extracts were evaluated in vitro and in RAW 264.7 cells. The chemical composition were analyzed using UPLC-ESI-Q-TOF/MS, and the contents of six compounds were determined via HPLC.

Results: Both extracts of R. przewalskii showed promising anti-inflammatory activity in vitro; decreased the production of four inflammatory cytokines, namely, nitric oxide, IL-1β, IL-6 and TNF-ɑ, in RAW 264.7 cells induced by lipopolysaccharide; and exhibited weak cytotoxicity. The extracts significantly scavenged DPPH radicals, superoxide radicals and hydroxyl radicals to exert antioxidant effects in vitro. The two extracts also exhibited cellular antioxidant activity by increasing superoxide dismutase and CAT activities and decreasing malondialdehyde content in RAW 264.7 cells induced by LPS. However, the antifungal activity of the two extracts was weak. Nine flavonoids were identified by UPLC-ESI-Q-TOF/MS. Of these, six compounds were analyzed quantitatively, including avicularin, quercetin, azaleatin, astragalin and kaempferol, and five compounds (myricetin 3-O-galactoside, paeoniflorin, astragalin, azaleatin and kaempferol) were found in this species for the first time. These compounds demonstrated antioxidant activities that were similar to those of the R. przewalskii extracts and were thought to be the active compounds in the extracts.

Conclusion:R. przewalskii extracts presented promising anti-inflammatory and antioxidant activities. The extracts contained amounts of valuable flavonoids (8.98 mg/g fresh material) that were likely the active compounds in the extract contributing to the potential antioxidant activity. These results highlight the potential of R. przewalskii as a source of natural antioxidant and anti-inflammatory agents for the pharmaceutical industry.
Negative Impact of Sigma-1 Receptor Agonist Treatment on Tissue Integrity and Motor Function Following Spinal Cord Injury
Authors: Lattard Alise , Poulen Gaëtan , Bartolami Sylvain , Gerber Yannick N. , Perrin Florence E.
Published: February 2021

In traumatic spinal cord injury, the initial trauma is followed by a cascade of impairments, including excitotoxicity and calcium overload, which ultimately induces secondary damages. The sigma-1 receptor is widely expressed in the central nervous system and is acknowledged to play a key role in calcium homeostasis. Treatments with agonists of the sigma-1 receptor induce beneficial effects in several animal models of neurological diseases. In traumatic injury the use of an antagonist of the sigma-1 receptor reversed several symptoms of central neuropathic pain. Here, we investigated whether sigma-1 receptor activation with PRE-084 is beneficial or detrimental following SCI in mice. First, we report that PRE-084 treatment after injury does not improve motor function recovery. Second, using ex vivo diffusion weighted magnetic resonance imaging completed by histological analysis, we highlight that σ1R agonist treatment after SCI does not limit lesion size. Finally, PRE-084 treatment following SCI decreases NeuN expression and increases astrocytic reactivity. Our findings suggest that activation of sigma-1 receptor after traumatic spinal cord injury is detrimental on tissue preservation and motor function recovery in mice.
Anti-PTSD Effects of Hypidone Hydrochloride (YL-0919): A Novel Combined Selective 5-HT Reuptake Inhibitor/5-HT1A Receptor Partial Agonist/5-HT6 Receptor Full Agonist
Authors: Liu Wen-Gang , Zhang Li-Ming , Yao Jun-Qi , Yin Yong-Yu , Zhang Xiao-Ying , Li Yun-Feng , Cao Jiang-Bei
Published: February 2021

Posttraumatic stress disorder (PTSD) is a debilitating trauma and stressor-related disorder that has become a major neuropsychiatric problem, leading to substantial disruptions in individual health and societal costs. Our previous studies have demonstrated that hypidone hydrochloride (YL-0919), a novel combined selective 5-HT reuptake inhibitor/5-HT1A receptor partial agonist/5-HT6 receptor full agonist, exerts notable antidepressant- and anxiolytic-like as well as procognitive effects. However, whether YL-0919 exerts anti-PTSD effects and its underlying mechanisms are still unclear. In the present study, we showed that repeated treatment with YL-0919 caused significant suppression of contextual fear, enhanced anxiety and cognitive dysfunction induced by the time-dependent sensitization (TDS) procedure in rats and by inescapable electric foot-shock in a mouse model of PTSD. Furthermore, we found that repeated treatment with YL-0919 significantly reversed the accompanying decreased expression of the brain-derived neurotrophic factor (BDNF) and the synaptic proteins (synapsin1 and GluA1), and ameliorated the neuroplasticity disruption in the prefrontal cortex (PFC), including the dendritic complexity and spine density of pyramidal neurons. Taken together, the current study indicated that YL-0919 exerts clear anti-PTSD effects, which might be partially mediated by ameliorating the structural neuroplasticity by increasing the expression of BDNF and the formation of synaptic proteins in the PFC.
Quantum Control for Nanoscale Spectroscopy With Diamond Nitrogen-Vacancy Centers: A Short Review
Authors: Hernández-Gómez Santiago , Fabbri Nicole
Published: February 2021

Diamond quantum technologies based on color centers have rapidly emerged in the most recent years. The nitrogen-vacancy (NV) color center has attracted a particular interest, thanks to its outstanding spin properties and optical addressability. The NV center has been used to realize innovative multimode quantum-enhanced sensors that offer an unprecedented combination of high sensitivity and spatial resolution at room temperature. The technological progress and the widening of potential sensing applications have induced an increasing demand for performance advances of NV quantum sensors. Quantum control plays a key role in responding to this demand. This short review affords an overview on recent advances in quantum control-assisted quantum sensing and spectroscopy of magnetic fields.
Robust Physiological Metrics From Sparsely Sampled Networks
Authors: Cohen Alan A. , Leblanc Sebastien , Roucou Xavier
Published: February 2021

Physiological and biochemical networks are highly complex, involving thousands of nodes as well as a hierarchical structure. True network structure is also rarely known. This presents major challenges for applying classical network theory to these networks. However, complex systems generally share the property of having a diffuse or distributed signal. Accordingly, we should predict that system state can be robustly estimated with sparse sampling, and with limited knowledge of true network structure. In this review, we summarize recent findings from several methodologies to estimate system state via a limited sample of biomarkers, notably Mahalanobis distance, principal components analysis, and cluster analysis. While statistically simple, these methods allow novel characterizations of system state when applied judiciously. Broadly, system state can often be estimated even from random samples of biomarkers. Furthermore, appropriate methods can detect emergent underlying physiological structure from this sparse data. We propose that approaches such as these are a powerful tool to understand physiology, and could lead to a new understanding and mapping of the functional implications of biological variation.
Regulation of a Trehalose-Specific Facilitated Transporter (TRET) by Insulin and Adipokinetic Hormone in Rhodnius prolixus, a Vector of Chagas Disease
Authors: Leyria Jimena , El-Mawed Hanine , Orchard Ian , Lange Angela B.
Published: February 2021

Using the blood-sucking kissing bug, Rhodnius prolixus as an experimental model, we have studied the involvement of insulin-like peptides (ILPs) and adipokinetic hormone (AKH) signaling in carbohydrate metabolism, focusing on the regulation of the trehalose-specific facilitated transporter (Rhopr-TRET), particularly in the ovaries. We find that trehalose stores in ovaries increase after feeding, synchronously with the beginning of vitellogenesis, but that the transcript expression of enzymes involved in trehalose synthesis show no changes between unfed and blood-fed animals. However, an eightfold increase in Rhopr-TRET transcript expression is observed in the ovaries post-blood meal. In vivo and ex vivo assays using exogenous insulins and Rhopr-AKH, reveal that Rhopr-TRET is up-regulated in ovaries by both peptide families. In accordance with these results, when ILP and AKH signaling cascades are impaired using RNA interference, Rhopr-TRET transcript is down-regulated. In addition, trehalose injection induces an up-regulation of Rhopr-TRET transcript expression and suggests an activation of insulin signaling. Overall, the results support the hypothesis of a direct trehalose uptake by ovaries from the hemolymph through Rhopr-TRET, regulated by ILP and/or AKH. We also show that Rhopr-TRET may work cooperatively with AKH signaling to support the release of trehalose from the ovaries into the hemolymph during the unfed (starved) condition. In conclusion, the results indicate that in females of R. prolixus, trehalose metabolism and its hormonal regulation by ILP and AKH play critical roles in adapting to different nutritional conditions and physiological states.