bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengaruh Edukasi Stimulasi Tumbuh Kembang terhadap Kemampuan Deteksi Dini Tumbuh Kembang Anak Usia 0-5 Tahun oleh Orangtua
Authors: Nurul Abidah Siska , Novianti Hinda
Published: December 2020

Stimulasi merupakan salah satu faktor yang mempengaruhi perkembangan anak. Hal ini seringkali oleh sebagian orangtua mengabaikannya akibat ketidaktahuan orangtua tentang cara dan pentingnya memberikan stimulasi anak sejak usia dini. Tujuan penelitian untuk mengetahui pengaruh edukasi stimulasi tumbuh kembang terhadap kemampuan deteksi dini tumbuh kembang anak usia 0-5 tahun oleh orangtua. Penelitian ini merupakan penelitian kuantitatif dengan desain Quasy Eksperiment Desaign dengan rancangan one group pretest postest desaign. Variabel independen adalah edukasi stimulasi tumbuh kembang dan variabel dependen adalah kemampuan orangtua dalam deteksi dini tumbuh kembang anak usia 0-5 tahun. Populasi ibu yang mempunyai anak usia 0-5 tahun. Sampel berjumlah 80 orang dengan cara simple random sampling. Penelitian dilakukan selama 3 bulan yaitu Mei-Juli 2020 di RW 01 dan RW 02 Kelurahan Wonokromo Surabaya. Pengumpulan data berupa kuesioner yang mengacu pada KPSP (Kuesioner Pra Skrining Perkembangan), Uji statistik menggunakan wilcoxon-test. Hasil uji statistik menggunakan uji wilcoxon-test diperoleh hasil nilai signifikan 0,000 (p-value < 0.05) artinya terdapat pengaruh edukasi stimulasi tumbuh kembang terhadap kemampuan deteksi dini tumbuh kembang anak usia 0-5 tahun oleh orangtua. Pemberian edukasi stimulasi tumbuh kembang anak oleh orangtua dapat meningkatkan kemampuan orangtua dalam memberikan stimulasi tumbuh kembang sejak dini yang akan berdampak positif seperti meningkatkan perkembangan bahasa dan memori anak, kesiapan anak dalam sekolah dan membantu anak untuk memaksimalkan potensi dalam hidup mereka.
Status Gizi Baduta dan Grafik Pertumbuhan Anak Usia 0-23 Bulan di Wilayah Kerja Puskesmas Pantoloan
Authors: Kusumawati Dwi Erma , Latipa Latipa , Hafid Fahmi
Published: December 2020

Anak usia di bawah dua tahun (Baduta) sehat jika mereka tumbuh dan berkembang secara memadai. Pertumbuhan anak baduta adalah proses yang dinamis dimana dibutuhkan kurva pertumbuhan sebagai alat pembanding untuk mengetahui pertumbuhannya sesuai usia. Tujuan penelitian untuk mengetahui status gizi dan grafik pertumbuhan anak usia 0-23 bulan di wilayah kerja Puskesmas Pantoloan. Penelitian deskriptif ini menggunakan data sekunder laporan rutin Puskesmas Pantoloan pada bulan Februari 2020. Sampel adalah seluruh anak baduta usia 0-24 bulan di wilayah kerja Puskesmas Pantoloan sebanyak 319 anak baduta. Status gizi ditentukan dengan indikator berat badan menurut usia (BB/U) serta tinggi badan menurut usia (TB/U) yang dibandingkan dengan standar WHO 2005. Hasil penelitian menunjukkan bahwa status gizi menurut indeks Berat badan menurut usia (BB/U) sebagian besar normal (84,6%), Panjang badan menurut usia (PB/U) sebagian besar normal (83,7%), dan berat badan menurut panjang bandan (BB/PB) sebagian besar gizi baik (87,1%). Grafik median berat badan dan panjang badan anak baduta menunjukkan kurva pertumbuhan berada di bawah kurva median standar WHO-Antro mulai usia 9 bulan dan tampak jelas ketika anak masuk usia 20-21 bulan. Kesimpulan pada umumnya status gizi normal dan baik, grafik kurva median anak baduta berada di bawah kurva median standar WHO Antro. Disarankan agar pemantauan pertumbuhan dilakukan untuk mengetahui status gizi anak baduta secara teratur.
CSF Levels of Elongation Factor Tu Is Associated With Increased Mortality in Malawian Adults With Streptococcus pneumoniae Meningitis
Authors: Wall Emma C. , Brownridge Philip , Laing Gavin , Terra Vanessa S. , Mlozowa Veronica , Denis Brigitte , Nyirenda Mulinda , Allain Theresa , Ramos-Sevillano Elisa , Carrol Enitan , Collins Andrea , Gordon Stephen B. , Lalloo David G. , Wren Brendan , Beynon Robert , Heyderman Robert S. , Brown Jeremy S.
Published: December 2020

Background

Mortality from bacterial meningitis, predominately caused by Streptococcus pneumoniae, exceeds 50% in sub-Saharan African countries with high HIV prevalence. Underlying causes of high mortality are poorly understood. We examined the host and pathogen proteome in the CSF of adults with proven pneumococcal meningitis (PM), testing if there was an association between differentially expressed proteins and outcome.

Materials/Methods

CSF proteomes were analyzed by quantitative Mass-Spectrometry. Spectra were identified using the Swissprot human and TIGR4 pneumococcal protein libraries. Proteins were quantitated and analyzed against mortality. Unique proteins in PM were identified against published normal CSF proteome. Random-Forest models were used to test for protein signatures discriminating outcome. Proteins of interest were tested for their effects on growth and neutrophil opsonophagocytic killing of S. pneumoniae.

Results

CSF proteomes were available for 57 Adults with PM (median age 32 years, 60% male, 70% HIV-1 co-infected, mortality 63%). Three hundred sixty individual human and 23 pneumococcal proteins were identified. Of the human protein hits, 30% were not expressed in normal CSF, and these were strongly associated with inflammation and primarily related to neutrophil activity. No human protein signature predicted outcome. However, expression of the essential S. pneumoniae protein Elongation Factor Tu (EF-Tu) was significantly increased in CSF of non-survivors [False Discovery Rate (q) <0.001]. Expression of EF-Tu was negatively co-correlated against expression of Neutrophil defensin (r 0.4 p p < 0.002), but not against complement proteins C3 or Factor H. In vitro, addition of EF-Tu protein impaired S. pneumoniae neutrophil killing in CSF.

Conclusions

Excessive S. pneumoniae EF-Tu protein in CSF was associated with reduced survival in meningitis in a high HIV prevalence population. We show EF-Tu may inhibit neutrophil mediated killing of S. pneumoniae in CSF. Further mechanistic work is required to better understand how S. pneumoniae avoids essential innate immune responses during PM through production of excess EF-Tu.
Combining Models of Environment, Behavior, and Physiology to Predict Tissue Hydrogen and Oxygen Isotope Variance Among Individual Terrestrial Animals
Authors: Magozzi Sarah , Vander Zanden Hannah B. , Wunder Michael B. , Trueman Clive N. , Pinney Kailee , Peers Dori , Dennison Philip E. , Horns Joshua J. , Şekercioğlu Çağan H. , Bowen Gabriel J.
Published: December 2020

Variations in stable hydrogen and oxygen isotope ratios in terrestrial animal tissues are used to reconstruct origin and movement. An underlying assumption of these applications is that tissues grown at the same site share a similar isotopic signal, representative of the location of their origin. However, large variations in tissue isotopic compositions often exist even among conspecific individuals within local populations, which complicates origin and migration inferences. Field-data and correlation analyses have provided hints about the underlying mechanisms of within-site among-individual isotopic variance, but a theory explaining the causes and magnitude of such variance has not been established. Here we develop a mechanistic modeling framework that provides explicit predictions of the magnitude, patterns, and drivers of isotopic variation among individuals living in a common but environmentally heterogeneous habitat. The model toolbox includes isoscape models of environmental isotopic variability, an agent-based model of behavior and movement, and a physiology-biochemistry model of isotopic incorporation into tissues. We compare model predictions against observed variation in hatch-year individuals of the songbird Spotted Towhee (Pipilo maculatus) in Red Butte Canyon, Utah, and evaluate the ability of the model to reproduce this variation under different sets of assumptions. Only models that account for environmental isotopic variability predict a similar magnitude of isotopic variation as observed. Within the modeling framework, behavioral rules and properties govern how animals nesting in different locations acquire resources from different habitats, and birds nesting in or near riparian habitat preferentially access isotopically lighter resources than those associated with the meadow and slope habitats, which results in more negative body water and tissue isotope values. Riparian nesters also have faster body water turnover and acquire more water from drinking (vs. from food), which exerts a secondary influence on their isotope ratios. Thus, the model predicts that local among-individual isotopic variance is linked first to isotopic heterogeneity in the local habitat, and second to how animals sample this habitat during foraging. Model predictions provide insight into the fundamental mechanisms of small-scale isotopic variance and can be used to predict the utility of isotope-based methods for specific groups or environments in ecological and forensic research.
Conditional Generative Adversarial Networks for Individualized Treatment Effect Estimation and Treatment Selection
Authors: Ge Qiyang , Huang Xuelin , Fang Shenying , Guo Shicheng , Liu Yuanyuan , Lin Wei , Xiong Momiao
Published: December 2020

Treatment response is heterogeneous. However, the classical methods treat the treatment response as homogeneous and estimate the average treatment effects. The traditional methods are difficult to apply to precision oncology. Artificial intelligence (AI) is a powerful tool for precision oncology. It can accurately estimate the individualized treatment effects and learn optimal treatment choices. Therefore, the AI approach can substantially improve progress and treatment outcomes of patients. One AI approach, conditional generative adversarial nets for inference of individualized treatment effects (GANITE) has been developed. However, GANITE can only deal with binary treatment and does not provide a tool for optimal treatment selection. To overcome these limitations, we modify conditional generative adversarial networks (MCGANs) to allow estimation of individualized effects of any types of treatments including binary, categorical and continuous treatments. We propose to use sparse techniques for selection of biomarkers that predict the best treatment for each patient. Simulations show that MCGANs outperform seven other state-of-the-art methods: linear regression (LR), Bayesian linear ridge regression (BLR), k-Nearest Neighbor (KNN), random forest classification [RF (C)], random forest regression [RF (R)], logistic regression (LogR), and support vector machine (SVM). To illustrate their applications, the proposed MCGANs were applied to 256 patients with newly diagnosed acute myeloid leukemia (AML) who were treated with high dose ara-C (HDAC), Idarubicin (IDA) and both of these two treatments (HDAC+IDA) at M. D. Anderson Cancer Center. Our results showed that MCGAN can more accurately and robustly estimate the individualized treatment effects than other state-of-the art methods. Several biomarkers such as GSK3, BILIRUBIN, SMAC are identified and a total of 30 biomarkers can explain 36.8% of treatment effect variation.
Identification of circRNAs in the Liver of Whitespotted Bamboo Shark (Chiloscyllium plagiosum)
Authors: Zhang Wenjie , Qin Ping , Gong Xiaoxia , Huang Lei , Wang Chan , Chen Guiqian , Chen Jianqing , Wang Lei , Lv Zhengbing
Published: December 2020

Whitespotted bamboo shark (Chiloscyllium plagiosum), a member of the cartilaginous fish family, has an extremely large liver and demonstrates a strong regeneration ability and immune regulation. Circular RNAs (circRNAs) is an important class of non-coding RNAs. Increasing evidences suggest that circRNAs are a kind of potential regulators. Recently, researchers have isolated and identified different circRNAs from various species, while few reports were on the circRNAs of C. plagiosum. In this study, we have identified a total of 4,558 circRNAs in the liver of C. plagiosum. This finding suggests that circRNAs are not evenly distributed in the chromosomes and follow the GT-AG rule during cyclization. Alternative back-splicing might exist in shark circRNAs as shown by the authenticity identification of predicted circRNAs. The binding strength of circRNAs (<2,000 bp) and the detected miRNAs in shark liver were simultaneously analyzed to construct an mRNA–miRNA–circRNA network for the Glutathione S-transferase P1 gene, and the circRNA authenticity was simultaneously verified. Our data provide not only novel insights into the rich existence of circRNAs in marine animals, but also a basis for characterizing functions of identified circRNAs in the liver homeostasis of C. plagiosum.
Multi-Omics Analysis of Diabetic Nephropathy Reveals Potential New Mechanisms and Drug Targets
Authors: Sha Qian , Lyu Jinxiu , Zhao Meng , Li Haijuan , Guo Mengzhe , Sun Qiang
Published: December 2020

Diabetic nephropathy (DN) is one of the most common diabetic complications, which is the major course of end-stage renal disease (ESRD). However, the systematical molecular characterizations during DN pathogenesis and progression has not been not well understood. To identify the fundamental mediators of the pathogenesis and progression of DN. we performed a combination RNASeq, proteomics, and metabolomics analyses of both patients’ derived kidney biopsy samples and kidneys from in vivo DN model. As a result, molecular changes of DN contain extracellular matrix accumulation, abnormal activated inflamed microenvironment, and metabolism disorders, bringing about glomerular sclerosis and tubular interstitial fibrosis. Specificity, Further integration analyses have identified that the linoleic acid metabolism and fatty-acids β-oxidation are significantly inhibited during DN pathogenesis and progression, the transporter protein ABCD3, the fatty acyl-CoA activated enzymes ACOX1, ACOX2, and ACOX3, and some corresponding metabolites such as 13′-HODE, stearidonic acid, docosahexaenoic acid, (±)10(11)-EpDPA were also significantly reduced. Our study thus provides potential molecular mechanisms for DN progression and suggests that targeting the key enzymes or supplying some lipids may be a promising avenue in the treatment of DN, especially advanced-stage DN.
SARS-CoV-2: Immune Response Elicited by Infection and Development of Vaccines and Treatments
Authors: Canedo-Marroquín Gisela , Saavedra Farides , Andrade Catalina A. , Berrios Roslye V. , Rodríguez-Guilarte Linmar , Opazo María C. , Riedel Claudia A. , Kalergis Alexis M.
Published: December 2020

The World Health Organization (WHO) announced in March a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This new infectious disease was named Coronavirus Disease 19 (COVID-19), and at October 2020, more than 39,000,000 cases of SARS-CoV-2 have been detected worldwide leading to near 1,100,000 deaths. Clinically, COVID-19 is characterized by clinical manifestations, such as fever, dry cough, headache, and in more severe cases, respiratory distress. Moreover, neurological-, cardiac-, and renal-related symptoms have also been described. Clinical evidence suggests that migration of immune cells to the affected organs can produce an exacerbated release of proinflammatory mediators that contribute to disease and render the immune response as a major player during the development of the COVID-19 disease. Due to the current sanitary situation, the development of vaccines is imperative. Up to the date, 42 prototypes are being tested in humans in different clinical stages, with 10 vaccine candidates undergoing evaluation in phase III clinical trials. In the same way, the search for an effective treatment to approach the most severe cases is also in constant advancement. Several potential therapies have been tested since COVID-19 was described, including antivirals, antiparasitic and immune modulators. Recently, clinical trials with hydroxychloroquine—a promising drug in the beginning—were suspended. In addition, the Food and Drug Administration (FDA) approved convalescent serum administration as a treatment for SARS-CoV-2 patients. Moreover, monoclonal antibody therapy is also under development to neutralize the virus and prevent infection. In this article, we describe the clinical manifestations and the immunological information available about COVID-19 disease. Furthermore, we discuss current therapies under study and the development of vaccines to prevent this disease.
Pharmacokinetics and Immunological Effects of Romidepsin in Rhesus Macaques
Authors: Kleinman Adam J. , Xu Cuiling , Cottrell Mackenzie L. , Sivanandham Ranjit , Brocca-Cofano Egidio , Dunsmore Tammy , Kashuba Angela , Pandrea Ivona , Apetrei Cristian
Published: December 2020

HIV/SIV persistence in latent reservoirs requires lifelong antiretroviral treatment and calls for effective cure strategies. Romidepsin (RMD), a histone deacetylase inhibitor, was reported to reactivate HIV/SIV from reservoirs in virus-suppressed individuals. We characterized in detail the pharmacokinetics and safety profile of RMD in three SIV-naïve rhesus macaques which received two rounds of treatment. In plasma, RMD mean terminal half-life was 15.3 h. In comparison, RMD mean terminal half-life was much longer in tissues: 110 h in the lymph nodes (LNs) and 28 h in gastrointestinal tract. RMD administration was accompanied by transient liver and systemic toxicity. Isoflurane anesthesia induced near-immediate transient lymphopenia, which was further exacerbated and extended with the extensive immune modifications by RMD. The effect of RMD on circulating immune cells was complex: (i) slight increase in lymphocyte death rates; (ii) transient, robust increase in neutrophils; (iii) massive downregulation of lymphocyte surface markers; (iv) important migration of CD3+ T cells to the gut and LNs; and (v) hindrance to CD8+ T cell functionality, yet without reaching significance. Our results show that, in contrast to transient plasma concentrations, RMD has a long-term presence in tissues, with multiple immunomodulatory effects and minimal to moderate kidney, liver, and lymphocyte toxicities. As such, we concluded that RMD can be used for “shock and kill” approaches, preferentially in combination with other latency reversal agents or cytotoxic T lymphocyte boosting strategies with consideration taken for adverse effects.
Tolerance to Bone Marrow Transplantation: Do Mesenchymal Stromal Cells Still Have a Future for Acute or Chronic GvHD?
Authors: Introna Martino , Golay Josée
Published: December 2020

Mesenchymal Stromal Cells (MSCs) are fibroblast-like cells of mesodermal origin present in many tissues and which have the potential to differentiate to osteoblasts, adipocytes and chondroblasts. They also have a clear immunosuppressive and tissue regeneration potential. Indeed, the initial classification of MSCs as pluripotent stem cells, has turned into their identification as stromal progenitors. Due to the relatively simple procedures available to expand in vitro large numbers of GMP grade MSCs from a variety of different tissues, many clinical trials have tested their therapeutic potential in vivo. One pathological condition where MSCs have been quite extensively tested is steroid resistant (SR) graft versus host disease (GvHD), a devastating condition that may occur in acute or chronic form following allogeneic hematopoietic stem cell transplantation. The clinical and experimental results obtained have outlined a possible efficacy of MSCs, but unfortunately statistical significance in clinical studies has only rarely been reached and effects have been relatively limited in most cases. Nonetheless, the extremely complex pathogenetic mechanisms at the basis of GvHD, the fact that studies have been conducted often in patients who had been previously treated with multiple lines of therapy, the variable MSC doses and schedules administered in different trials, the lack of validated potency assays and clear biomarkers, the difference in MSC sources and production methods may have been major factors for this lack of clear efficacy in vivo. The heterogeneity of MSCs and their different stromal differentiation potential and biological activity may be better understood through more refined single cell sequencing and proteomic studies, where either an “anti-inflammatory” or a more “immunosuppressive” profile can be identified. We summarize the pathogenic mechanisms of acute and chronic GvHD and the role for MSCs. We suggest that systematic controlled clinical trials still need to be conducted in the most promising clinical settings, using better characterized cells and measuring efficacy with specific biomarkers, before strong conclusions can be drawn about the therapeutic potential of these cells in this context. The same analysis should be applied to other inflammatory, immune or degenerative diseases where MSCs may have a therapeutic potential.
Streamlining Data and Service Centers for Easier Access to Data and Analytical Services: The Strategy of ODATIS as the Gateway to French Marine Data
Authors: Schmidt Sabine , Maudire Gilbert , Nys Cécile , Sudre Joël , Harscoat Valérie , Dibarboure Gérald , Huynh Frédéric
Published: December 2020

The past few decades have seen a marked acceleration in the amount of marine observation data derived using both in situ and remote sensing measurements. For example, high-frequency monitoring of key physical-chemical parameters has become an essential tool for assessing natural and human-induced changes in coastal waters as well as their consequences on society. The number and variety of data acquisition techniques require efficient methods of improving data availability. The challenge is to make ocean data available via interoperable portals, which facilitate data sharing according to Findable, Accessible, Interoperable, and Reusable (FAIR) principles for producers and users. Ocean DAta Information and Services (ODATIS) aims to become a unique gateway to all French marine data, regardless of the discipline (e.g., physics, chemistry, biogeochemistry, biology, sedimentology). ODATIS is the ocean cluster of the Data Terra research infrastructure for Earth data, which relies on a network of data and service centers (DSC) supported by the major French oceanic research organizations (CNRS, CNES, Ifremer, IRD, SHOM; Marine Universities). ODATIS, through its components, is involved in European and international initiatives such as Copernicus, SeaDataCloud, and EMODnet. The first challenge of ODATIS is to catalog all open ocean and coastal data and facilitate data collection and access (discovery, visualization, extraction) through its web portal. A specific task is to develop tools for handling large amounts of data and generate products for policymakers, practitioners, and academics. This study presents the strategy used by ODATIS to implement the FAIR and CoreTrustSeal requirements in each of its DSCs and promote adherence within the scientific community (the main data producer) regarding the upload and/or use of data and suggestion of new products. A second challenge is to cover the end-user needs ranging from proximity to the producer to cross-analysis of data from all Earth compartments. This involves defining and organizing a classification of DSCs in the network, which will be developed within the framework of the French Data Terra research infrastructure, the only framework capable of providing the necessary IT and human resources.
Humidified Warmed CO2 Treatment Therapy Strategies Can Save Lives With Mitigation and Suppression of SARS-CoV-2 Infection: An Evidence Review
Authors: El-Betany Alaa M. M. , Behiry Enas M. , Gumbleton Mark , Harding Keith G.
Published: December 2020

The coronavirus disease (COVID-19) outbreak has presented enormous challenges for healthcare, societal, and economic systems worldwide. There is an urgent global need for a universal vaccine to cover all SARS-CoV-2 mutant strains to stop the current COVID-19 pandemic and the threat of an inevitable second wave of coronavirus. Carbon dioxide is safe and superior antimicrobial, which suggests it should be effective against coronaviruses and mutants thereof. Depending on the therapeutic regime, CO2could also ameliorate other COVID-19 symptoms as it has also been reported to have antioxidant, anti-inflammation, anti-cytokine effects, and to stimulate the human immune system. Moreover, CO2has beneficial effects on respiratory physiology, cardiovascular health, and human nervous systems. This article reviews the rationale of early treatment by inhaling safe doses of warmed humidified CO2gas, either alone or as a carrier gas to deliver other inhaled drugs may help save lives by suppressing SARS-CoV-2 infections and excessive inflammatory responses. We suggest testing this somewhat counter-intuitive, but low tech and safe intervention for its suitability as a preventive measure and treatment against COVID-19. Overall, development and evaluation of this therapy now may provide a safe and economical tool for use not only during the current pandemic but also for any future outbreaks of respiratory diseases and related conditions.
Application of Artificial Intelligence in the Analysis of Features Affecting Cataract Surgery Complications in a Teaching Hospital
Authors: Lanza Michele , Koprowski Robert , Boccia Rosa , Krysik Katarzyna , Sbordone Sandro , Tartaglione Antonio , Ruggiero Adriano , Simonelli Francesca
Published: December 2020

Aims: To evaluate the ocular and systemic factors involved in cataract surgery complications in a teaching hospital using artificial intelligence.

Methods: One eye of 1,229 patients with a mean age of 70.2 ± 10.3 years old that underwent cataract surgery was selected for this study. Ocular and systemic details of the patients were recorded and then analyzed by means of artificial intelligence. A total of 1.25 billion simulations of artificial intelligence learning and testing were conducted on several variables and a customized model of analysis was developed.

Results: A total of 73 complications were recorded in this study. According to the analysis performed, the main factors involved in cataract surgery complications were: a surgeon in training, axial length and intraocular lens power. The model predicted how long surgery would last with an error of <6 min compared to the effective time needed.

Conclusions: According to the data here obtained, artificial intelligence could be an interesting option to build customized models able to prevent complications and to predict actual surgery time. The customized algorithm option allows the development of better models adaptable to different units as well as the possibility to be calibrated for the same unit along time.
MR Imaging of Peripheral Nerves Using Targeted Application of Contrast Agents: An Experimental Proof-of-Concept Study
Authors: Tereshenko Vlad , Pashkunova-Martic Irena , Manzano-Szalai Krisztina , Friske Joachim , Bergmeister Konstantin D. , Festin Christopher , Aman Martin , Hruby Laura A. , Klepetko Johanna , Theiner Sarah , Klose Matthias H. M. , Keppler Bernhard , Helbich Thomas H. , Aszmann Oskar C.
Published: December 2020

Introduction: Current imaging modalities for peripheral nerves display the nerve's structure but not its function. Based on a nerve's capacity for axonal transport, it may be visualized by targeted application of a contrast agent and assessing the distribution through radiological imaging, thus revealing a nerve's continuity. This concept has not been explored, however, may potentially guide the treatment of peripheral nerve injuries. In this experimental proof-of-concept study, we tested imaging through MRI after administering gadolinium-based contrast agents which were then retrogradely transported.

Methods: We synthesized MRI contrast agents consisting of paramagnetic agents and various axonal transport facilitators (HSA-DTPA-Gd, chitosan-DTPA-Gd or PLA/HSA-DTPA-Gd). First, we measured their relaxivity values in vitro to assess their radiological suitability. Subsequently, the sciatic nerve of 24 rats was cut and labeled with one of the contrast agents to achieve retrograde distribution along the nerve. One week after surgery, the spinal cords and sciatic nerves were harvested to visualize the distribution of the respective contrast agent using 7T MRI. In vivo MRI measurements were performed using 9.4 T MRI on the 1st, 3rd, and the 7th day after surgery. Following radiological imaging, the concentration of gadolinium in the harvested samples was analyzed using inductively coupled mass spectrometry (ICP-MS).

Results: All contrast agents demonstrated high relaxivity values, varying between 12.1 and 116.0 mM−1s−1. HSA-DTPA-Gd and PLA/HSA-DTPA-Gd application resulted in signal enhancement in the vertebral canal and in the sciatic nerve in ex vivo MRI. In vivo measurements revealed significant signal enhancement in the sciatic nerve on the 3rd and 7th day after HSA-DTPA-Gd and chitosan-DTPA-Gd (p < 0.05) application. Chemical evaluation showed high gadolinium concentration in the sciatic nerve for HSA-DTPA-Gd (5.218 ± 0.860 ng/mg) and chitosan-DTPA-Gd (4.291 ± 1.290 ng/mg).

Discussion: In this study a novel imaging approach for the evaluation of a peripheral nerve's integrity was implemented. The findings provide radiological and chemical evidence of successful contrast agent uptake along the sciatic nerve and its distribution within the spinal canal in rats. This novel concept may assist in the diagnostic process of peripheral nerve injuries in the future.
A Cross-Protective Vaccine Against 4b and 1/2b Listeria monocytogenes
Authors: Meng Fanzeng , Zhu Tengfei , Yao Hao , Ling Zhiting , Feng Youwei , Li Guo , Li Jing , Sun Xinyu , Chen Jiaqi , Meng Chuang , Jiao Xin’an , Yin Yuelan
Published: December 2020

Listeria monocytogenes(Lm) is a foodborne zoonotic pathogen that causes listeriosis with a mortality rate of 20–30%. Serovar 4b and 1/2b isolates account for most of listeriosis outbreaks, however, no listeriosis vaccine is available for either prophylactic or therapeutic use. Here, we developed a triple-virulence-genes deletion vaccine strain, and evaluated its safety, immunogenicity, and cross-protective efficiency. The virulence of NTSNΔactA/plcB/orfXwas reduced 794-folds compared with the parental strain. Additionally, it was completely eliminated in mice at day 7 post infection and no obvious pathological changes were observed in the organs of mice after prime-boost immunization for 23 days. These results proved that the safety of theLmvaccine strain remarkably increased. More importantly, the NTSNΔactA/plcB/orfXstrain stimulated higher anti-Listeriolysin O (LLO) antibodies, induced significantly higher expression of IFN-γ, TNF-α, IL-17, and IL-6 than the control group, and afforded 100% protection against serovar 4b and 1/2b challenges. Taken together, our research demonstrates that the triple-genes-deletion vaccine has high safety, can elicit strong Th1 type immune response, and affords efficient cross-protection against two serovarLmstrains. It is a promising vaccine for prevention of listeriosis.
Olfactory Dysfunction and Its Association With Neuropathologic Proteins in Cerebrospinal Fluid From Patients With Parkinson Disease
Authors: Guo Peng , Wang Rui-dan , Lian Teng-hong , Ding Du-yu , Zhang Ya-nan , Zhang Wei-Jiao , Li Dan-ning , Li Li-xia , Li Jing-hui , Guan Hui-ying , Yu Shu-yang , Liu Li , Hu Yang , Zuo Li-jun , Yu Qiu-jin , Wang Xiao-min , Zhang Wei
Published: December 2020

Background and Purpose: Olfactory dysfunction (OD) is a common non-motor symptom of Parkinson disease (PD). However, the relationship between OD and neuropathologic proteins in cerebrospinal fluid (CSF) from PD patients remains unclear.

Methods: 166 PD patients were included in the study. Overall olfactory function was assessed by summing up the scores of olfactory threshold, discrimination, and identification by a Sniffin' Sticks test, based on which, patients were divided into PD with OD (PD-OD) and PD with no OD (PD-NOD) groups. CSF samples were obtained from 76 PD patients. The levels of neuropathologic proteins, including α-Synuclein, Aβ1-42, total tau (T-tau), and multiple forms of phosphorylated tau (P-tau) in CSF were measured by an enzyme-linked immunosorbent assay.

Results: out of the 166 PD patients, 103 cases (62.0%) had OD. The scores of overall olfactory functions, and olfactory threshold, discrimination, and identification in the PD-OD group were all significantly lower than that in the PD-NOD group (P < 0.001). α-Synuclein level in CSF was significantly higher in the PD-OD group than the PD-NOD group (P < 0.05), and was significantly and negatively correlated with the scores of overall olfactory function, and olfactory discrimination and identification (P < 0.05). Aβ1-42 level in CSF was higher in the PD-OD group than the PD-NOD group, and was significantly and negatively correlated with the olfactory identification score (P < 0.05). T-tau level in CSF was significantly lower in the PD-OD group than the PD-NOD group (P < 0.05), and was significantly and positively correlated with the olfactory discrimination score (P < 0.05). There was no significant difference in P-tau level in CSF between the PD-OD and PD-NOD groups and no correlation between OD score and P-tau level in CSF.

Conclusions: PD-OD includes the impairments of olfactory threshold, discrimination, and identification, and is associated with the significant elevation of α-Synuclein and the decrease of the T-tau level in CSF.
Central Nervous System Demyelination Associated With Immune Checkpoint Inhibitors: Review of the Literature
Authors: Oliveira Marcos C. B. , de Brito Marcelo H. , Simabukuro Mateus M.
Published: December 2020

Immune checkpoint inhibitors (ICI) are a novel class of antineoplastic treatment that enhances immunity against tumors. They are associated with immune adverse events, and several neurological syndromes have been described, including multiple sclerosis and atypical demyelination. We performed a systematic literature review of case reports with neurological immune adverse events that presented with central nervous system demyelination, up to December 2019. We found 23 cases: seven with myelitis, four isolated optic neuritis, one neuromyelitis optica spectrum disorder, five multiple sclerosis, and six with atypical demyelination. Ipilimumab was the most frequently used ICI (11/23). The median time to develop symptoms from the onset of ICI was 6.5 weeks [range 1.0–43.0], and from last ICI dose was 14 days [range 0–161]. Anatomopathological examination was performed in four cases, with the finding of a T-cell mediated immune response. Outcomes were generally favorable after immunosuppression: 18 patients had improvement or a full recovery, three patients did not respond to treatment, three patients died, and in one, treatment was not reported. We describe the patients' clinical presentation, treatment administered, and outcomes. We further speculate on possible pathophysiological mechanisms and discuss potential treatments that may be worth investigating.
Semi-automatic Extraction of Functional Dynamic Networks Describing Patient's Epileptic Seizures
Authors: Frusque Gaëtan , Borgnat Pierre , Gonçalves Paulo , Jung Julien
Published: December 2020

Intracranial electroencephalography (EEG) studies using stereotactic EEG (SEEG) have shown that during seizures, epileptic activity spreads across several anatomical regions from the seizure onset zone toward remote brain areas. A full and objective characterization of this patient-specific time-varying network is crucial for optimal surgical treatment. Functional connectivity (FC) analysis of SEEG signals recorded during seizures enables to describe the statistical relations between all pairs of recorded signals. However, extracting meaningful information from those large datasets is time consuming and requires high expertise. In the present study, we first propose a novel method named Brain-wide Time-varying Network Decomposition (BTND) to characterize the dynamic epileptogenic networks activated during seizures in individual patients recorded with SEEG electrodes. The method provides a number of pathological FC subgraphs with their temporal course of activation. The method can be applied to several seizures of the patient to extract reproducible subgraphs. Second, we compare the activated subgraphs obtained by the BTND method with visual interpretation of SEEG signals recorded in 27 seizures from nine different patients. As a whole, we found that activated subgraphs corresponded to brain regions involved during the course of the seizures and their time course was highly consistent with classical visual interpretation. We believe that the proposed method can complement the visual analysis of SEEG signals recorded during seizures by highlighting and characterizing the most significant parts of epileptic networks with their activation dynamics.
Insights Into the Proteomic Profiling of Extracellular Vesicles for the Identification of Early Biomarkers of Neurodegeneration
Authors: Quiroz-Baez Ricardo , Hernández-Ortega Karina , Martínez-Martínez Eduardo
Published: December 2020

Extracellular vesicles (EVs) are involved in the development and progression of neurodegenerative diseases, including Alzheimer's and Parkinson's disease. Moreover, EVs have the capacity to modify the physiology of neuronal circuits by transferring proteins, RNA, lipids, and metabolites. The proteomic characterization of EVs (exosomes and microvesicles) from preclinical models and patient samples has the potential to reveal new proteins and molecular networks that affect the normal physiology prior to the appearance of traditional biomarkers of neurodegeneration. Noteworthy, many of the genetic risks associated to the development of Alzheimer's and Parkinson's disease affect the crosstalk between mitochondria, endosomes, and lysosomes. Recent research has focused on determining the role of endolysosomal trafficking in the onset of neurodegenerative diseases. Proteomic studies indicate an alteration of biogenesis and molecular content of EVs as a result of endolysosomal and autophagic dysfunction. In this review, we discuss the status of EV proteomic characterization and their usefulness in discovering new biomarkers for the differential diagnosis of neurodegenerative diseases. Despite the challenges related to the failure to follow a standard isolation protocol and their implementation for a clinical setting, the analysis of EV proteomes has revealed the presence of key proteins with post-translational modifications that can be measured in peripheral fluids.
Abnormal Whole Brain Functional Connectivity Pattern Homogeneity and Couplings in Migraine Without Aura
Authors: Zhang Yingxia , Chen Hong , Zeng Min , He Junwei , Qi Guiqiang , Zhang Shaojin , Liu Rongbo
Published: December 2020

Previous studies have reported abnormal amplitude of low-frequency fluctuation and regional homogeneity in patients with migraine without aura using resting-state functional magnetic resonance imaging. However, how whole brain functional connectivity pattern homogeneity and its corresponding functional connectivity changes in patients with migraine without aura is unknown. In the current study, we employed a recently developed whole brain functional connectivity homogeneity (FcHo) method to identify the voxel-wise changes of functional connectivity patterns in 21 patients with migraine without aura and 21 gender and age matched healthy controls. Moreover, resting-state functional connectivity analysis was used to reveal the changes of corresponding functional connectivities. FcHo analyses identified significantly decreased FcHo values in the posterior cingulate cortex (PCC), thalamus (THA), and left anterior insula (AI) in patients with migraine without aura compared to healthy controls. Functional connectivity analyses further found decreased functional connectivities between PCC and medial prefrontal cortex (MPFC), between AI and anterior cingulate cortex, and between THA and left precentral gyrus (PCG). The functional connectivities between THA and PCG were negatively correlated with pain intensity. Our findings indicated that whole brain FcHo and connectivity abnormalities of these regions may be associated with functional impairments in pain processing in patients with migraine without aura.
Comparison of the Bifidogenic Effects of Goat and Cow Milk-Based Infant Formulas to Human Breast Milk in an in vitro Gut Model for 3-Month-Old Infants
Authors: Gallier Sophie , Van den Abbeele Pieter , Prosser Colin
Published: December 2020

Human milk contains prebiotic components, such as human milk oligosaccharides (HMOs), which stimulate the growth of specific members of the infant gut microbiota (e.g.,Bifidobacteria). Plant-based or synthetic oligosaccharides are often added to infant formulas to simulate the bifidogenic effect of HMOs. Cow milk, the most common source of protein in infant formula, and goat milk, used increasingly in the manufacture of infant formula, contain naturally-occurring prebiotics. This study compared the upper gastrointestinal digestion and subsequent colonic fermentation of human milk vs. goat and cow milk-based infant formulas (goat IF and cow IF, respectively), without additional oligosaccharides using anin vitromodel for 3-month-old infants based on the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®). First, a dialysis approach using 3.5 kDa membranes was demonstrated to simulate small intestinal absorption of carbohydrates in conditions similar to thosein vivo. During thein vitrodigestion experiment, oligosaccharides were detected in human milk and goat IF but barely detected in the cow IF. Further, all three milk matrices decreased colonic pH by boosting acetate, lactate, and propionate production, which related to increased abundances of acetate/lactate-producingBifidobacteriaceaefor human milk (+25.7%) and especially goat IF (33.8%) and cow IF (37.7%). Only cow IF stimulated butyrate production which correlated with an increase inLachnospiraceaeandClostridiaceae. Finally,EnterobacteriaceaeandAcidaminococcaceaealso increased with all three milk matrices, while production of proteolytic metabolites (branched-chain fatty acids) was only detected for the cow IF. Overall, goat and cow milk-based formulas without added oligosaccharides impacted gut microbial activity and composition similarly to human milk. This suggests that even without supplementation of formula with oligosaccharides, whole goat milk, whole cow milk and cow milk ingredients already supply compounds in formulas that exert beneficial bifidogenic effects. Further clinical research is warranted to elucidate the effect of whole goat milk-based formulas on the infant gut microbiome.
CircRNA_ACAP2 Suppresses EMT in Head and Neck Squamous Cell Carcinoma by Targeting the miR-21-5p/STAT3 Signaling Axis
Authors: Ma Chuan , Shi Tingting , Qu Zhuli , Zhang Aobo , Wu Zuping , Zhao Huaqiang , Zhao Haoming , Chen Hongyu
Published: December 2020

Circular RNAs (circRNAs) contain microRNA (miRNA)-specific binding sites and can function as miRNA sponges to regulate gene expression by suppressing the inhibitory effect of miRNAs on their target genes. MiR-21-5p has been reported to be involved in the development of head and neck squamous cell carcinoma (HNSCC) and plays an important role in the activation of epithelial-mesenchymal transition (EMT). However, the upstream regulatory mechanism and downstream targets of miR-21-5p in tumor cells remain unknown. CircRNA_ACAP2 inhibits the function of miR-21-5p by binding to its specific binding sites in HNSCC cells. Overexpression of CircRNA_ACAP2 inhibits the proliferation and migration of HNSCC cells, while downregulation of CircRNA_ACAP2 has the opposite effect. STAT3 is a direct target gene of miR-21-5p and a transcription factor of ZEB1. We demonstrate that CircRNA_ACAP2 functions as a tumor suppressor gene in HNSCC and that its function is regulated via the miR-21-5p/STAT3 signaling axis.
Magnesium in Combinatorial With Valproic Acid Suppressed the Proliferation and Migration of Human Bladder Cancer Cells
Authors: Li Tianye , Yu Yang , Shi Hang , Cao Yuhua , Liu Xiangfu , Hao Zhenzhen , Ren Yuping , Qin Gaowu , Huang Yongye , Wang Bing
Published: December 2020

Magnesium, the second most predominant intracellular cation, plays a crucial role in many physiological functions; magnesium-based biomaterials have been widely used in clinical application. In a variety of cancer types, the high intracellular concentration of magnesium contributes to cancer initiation and progression. Therefore, we initiated this study to investigate the likelihood of confounding magnesium with cancer therapy. In this study, the anti-tumor activity of magnesium and underlying mechanisms were assessed in bladder cancer both in vitro and in vivo. The results indicated that the proliferation of bladder cancer cells was inhibited by treatment with a high concentration of MgCl2 or MgSO4. The apoptosis, G0/G1 cell cycle arrest, autophagy, and ER stress were promoted following treatment with MgCl2. However, the migratory ability of MgCl2 treated cells was similar to that of control cells, as revealed by the trans-well assay. Besides, no significant difference was observed in the proportion of CD44 or CD133 positive cells between the control and MgCl2 treated cells. Thus, to improve the therapeutic effect of magnesium, VPA was used to treat cancer cells in combination with MgCl2. As expected, combination treatment with MgCl2 and VPA could markedly reduce proliferation, migration, and in vivo tumorigenicity of UC3 cells. Moreover, the Wnt signaling was down-regulated, and ERK signaling was activated in the cells treated with combination treatment. In conclusion, the accurate utilization of MgCl2 in targeting autophagy might be beneficial in cancer therapy. Although further studies are warranted, the combination treatment of MgCl2 with VPA is an effective strategy to improve the outcome of chemotherapy.
Use of Mineral Weathering Bacteria to Enhance Nutrient Availability in Crops: A Review
Authors: Ribeiro Igor Daniel Alves , Volpiano Camila Gazolla , Vargas Luciano Kayser , Granada Camille Eichelberger , Lisboa Bruno Brito , Passaglia Luciane Maria Pereira
Published: December 2020

Rock powders are low-cost potential sources of most of the nutrients required by higher plants for growth and development. However, slow dissolution rates of minerals represent an obstacle to the widespread use of rock powders in agriculture. Rhizosphere processes and biological weathering may further enhance mineral dissolution since the interaction between minerals, plants, and bacteria results in the release of macro- and micronutrients into the soil solution. Plants are important agents in this process acting directly in the mineral dissolution or sustaining a wide diversity of weathering microorganisms in the root environment. Meanwhile, root microorganisms promote mineral dissolution by producing complexing ligands (siderophores and organic acids), affecting the pH (via organic or inorganic acid production), or performing redox reactions. Besides that, a wide variety of rhizosphere bacteria and fungi could also promote plant development directly, synergistically contributing to the weathering activity performed by plants. The inoculation of weathering bacteria in soil or plants, especially combined with the use of crushed rocks, can increase soil fertility and improve crop production. This approach is more sustainable than conventional fertilization practices, which may contribute to reducing climate change linked to agricultural activity. Besides, it could decrease the dependency of developing countries on imported fertilizers, thus improving local development.