bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical spectrum, outcome and management of immune thrombocytopenia associated with myelodysplastic syndromes and chronic myelomonocytic leukemia
Authors: Jachiet Vincent , Moulis Guillaume , Hadjadj Jérome , Seguier Julie , Laribi Kamel , Schleinitz Nicolas , Vey Norbert , Sacre Karim , Godeau Bertrand , Beyne-Rauzy Odile , Bouvet Romain , Broner Jonathan , Brun Natacha , Comont Thibault , Gaudin Clément , Lambotte Olivier , Le Clech Lenaïg , Peterlin Pierre , Roy-Peaud Frédérique , Salvado Clémentine , Versini Mathilde , Isnard Françoise , Kahn Jean Emmanuel , Gobert Delphine , Adès Lionel , Fenaux Pierre , Fain Olivier , Mekinian Arsène
Published: February 2021

Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are associated with systemic inflammatory or autoimmune diseases in 10-20 % of cases. Among them, immune thrombocytopenia (ITP) has been reported but large studies assessing this association are missing. Whether such patients have a particular phenotype and require particular management is unclear.

This study analyzes the clinical spectrum, outcome and therapeutic management of patients with ITP associated with MDS or CMML, in comparison (i) to patients with primary ITP without MDS/CMML and (ii) to patients with MDS/CMML without ITP.

Forty-one MDS/CMML-associated ITP patients were included, with chronic ITP in 26 (63%) patients, low-risk myelodysplasia in 30 (73%) patients and CMML in 24 (59%) patients. An associated autoimmune disease was noted in 10 (24%) patients. In comparison to primary ITP patients, MDS/CMML-associated ITP patients had a higher occurrence of severe bleeding despite similar platelet counts at diagnosis. First-line treatment consisted of glucocorticoids (98%) and intravenous immunoglobulin (IVIg) (56%). Response achievement with IVIg was more frequent in primary ITP than in MDS/CMML-associated ITP patients. Response rates to second-line therapies were not statistically different between primary ITP and MDS/CMMLassociated ITP patients. Ten percent (n=4) of patients with MDS/CMML-associated ITP had multirefractory ITP versus none in primary ITP controls. After a median follow-up of 60 months, there was no difference in overall survival between MDS/CMML-associated ITP and primary ITP patients. Leukemia-free-survival was significantly better in MDS/CMMLassociated ITP patients than in MDS/CMML without ITP MDS/CMML-associated ITP have a particular outcome with more severe bleeding and multirefractory profile than primary ITP, similar response profile to primary ITP therapy except for IVIg, and less progression toward acute myeloid leukemia than MDS/CMML without ITP.
INFORMATION CONFLICT BETWEEN A COMMUNICATION SYSTEM AND A SYSTEM OF DESTABILIZING INFLUENCES
Part II
FORMALIZED MAIN ASPECTS DETERMINE
WIN IN THE CONFLICT
Authors: Makarenko S. I.
Published: February 2021

In the paper is presented formalization of the main aspects that determine a win in a multi-stage conflict of a communication system and a system of destabilizing influences. The peculiarity of formalization is that each the stage of the conflict is represented by strictly defined strategies of intelligence, attack and defense, as well as duration of steps for intelligence, attack and defending reaction during the one. It is shown that the final winning score for the multi-stage conflict is determined by summing the particular scores at all stages. At the same time, the particular winning scores at each single stage is determined by the adequacy of choice of attacking and protecting strategies of conflicting parties on this stage.
METHOD FOR MEASURING THE EQUIVALENT PARAMETERS
OF INDUCTORS AS PART OF LOW-PASS FILTERS
Authors: Zinovev A. G. , Shestakov I. A.
Published: February 2021

A method for measuring the self-capacitance, inductance, loss resistance, and Q-factor of inductors as part of an LC low-pass filter at its operating frequency is presented. An example of the practical application of this method for measuring the equivalent pa-rameters of inductors and capacitors as part of a fifth-order Cauer low-pass filter using network analyzer.
STRUCTURE OF V-Mо-SiO2 BRAGG REFLECTOR OBTAINED
BY MAGNETRON SPUTTERING
Authors: Strunin V. I. , Baranova L. V. , Baysova B. T. , Nesov S. N. , Korusenko P. M.
Published: February 2021

The results of the study of the composition and chemical state of the coating of samples of Bragg reflectors based on films of molybdenum (Mo), vanadium (V), silicon dioxide (SiO2) and aluminum (Al) formed by direct current magnetron sput-tering in an argon atmosphere are presented. The effect of sputtering on the surface of silicon oxide films, as well as surface etching, has been studied. The reasons that affect the adhesion and roughness of the surfaces of thin-film layers of the Bragg reflector are determined.
A SELF-ORGANIZING NETWORK WITH AN INFINITE
OF NODES WITH A LIMITED NUMBER OF CHANNELS
IN THE NODES AND A LIMITED QUEUE
Authors: Kozoriz D. A.
Published: February 2021

Self-organizing dynamic networks (SDN) or Ad-hoc networks are widely used in emergency communications systems and combat operations. Based on technology Wi-Fi, Bluetooth SDN are formed in the picocell. However, the analysis of the functioning of such networks is very difficult due to the randomness of their topol-ogy. In this work, we study networks using the previously proposed method of analysis based on the theory of Queuing.
ESTIMATION OF THE ERROR IN PREDICTING
THE MAXIMUM OBSERVED FREQUENCY IN CONDITIONS
OF MINIMAL SOLAR ACTIVITY
Authors: Vertogradov G. G. , Vertogradov V. G.
Published: February 2021

The results of experimental studies of variations in the maximum observed fre-quency in 2016–2019 are presented on the mid-latitude route Cyprus – Rostov-on-Don. The accuracy of forecasting the maximum usable frequency when setting the state of the ionosphere using the IRI-2016 model is estimated. It is shown that in calm geophysical conditions, the typical values of the root-mean-square deviations of the maximum usable frequency from the maximum observed frequency reach 2,6 MHz.
THE INFLUENCE OF THE IONOSPHERE ON THE VERTICAL
FORCE EXCITED BY A HORIZONTAL ELECTRIC DIPOLE
Authors: Tereshchenko P. E.
Published: February 2021

An analytical expression for the vertical component of the magnetic field has been obtained, with the help of which calculations have been made showing the effect of the ionosphere on the low-frequency field in the Earth-ionosphere waveguide. At distances from the source that are less than the doubled waveguide height, in ELF, and a lower frequency range, noticeable changes in the field strength caused by the state of the ionosphere are found.
METHOD FOR INCREASING TRANSFER RATE
IN HF RADIO SYSTEMS AND ITS IMPLEMENTATION
(part 1)
Authors: Shadrin B. G. , Dvoryanchikov V. A. , Bogankov B. S.
Published: February 2021

A method for increasing the transfer rate in HF radio communication systems is proposed, which, in comparison with existing methods, allows it to be doubled without expanding the frequency band occupied by the communication channel. The block diagram of one of the variants of the HF radio communication system that implements the proposed method is presented. The analysis of the operation of the communication system in the absence of external interference and the influence of interference concentrated over the spectrum is carried out.
INFLATABLE SPHERICAL SPIRAL ANTENNA OF DECAMETER RANGE FOR USE IN POP-UP INFORMATION (EMERGENCY-INFORMATION) DEVICES OF NAVY
Authors: Tipikin A. A. , Belkov S. V.
Published: February 2021

The drawbacks of the existing antenna-feeder devices of decameter range used in pop-up information (emergency information) devices are analyzed. A variant of the solution in the form of an inflatable spherical spiral antenna is proposed. The characteristics of the antenna have been calculated, and approximate data have been obtained for the gas injection system and the withstanding wind load.
Use of Metabolomic Approaches in Analysis of Medicinal Plants and Phytopreparations (Review)
Authors: Orlova A. A. , Strugar Jo. , Shtark O. Yu. , Zhukov V. A. , Luzhanin V. G. , Povydysh M. N.
Published: February 2021

Introduction. The purpose of the analytical review is to summarize the data of modern scientific literature on the directions and possibilities of using the approaches of metabolomics in the analysis of medicinal plants, plant raw materials and herbal drugs.

Text. Analysis of literature data showed that metabolomic approaches have great potential in the field of quality control of multicomponent phytopreparations and biologically active additives, detection of falsifications of rare and expensive plant materials, chemosystematics of medicinal plants, study of the mechanisms of action and toxicity of medicinal plants, etc.

Conclusion. Metabolic analysis can become an effective analytical platform both for phytochemical research of plant raw materials and for regular activities to control the quality of plant material and phytopreparations.
Diferentes concentrações de fungo micorrízico em mudas de três cultivares de maracujá
Authors: Andrade João Carlos Santos de , Sousa Geslanny Oliveira , Damascena Jossimara Ferreira , Pereira Juliana Andrade
Published: February 2021

A utilização da micorriza é considerada uma alternativa para a redução do uso de insumos na agricultura, devido aos seus efeitos benéficos no desenvolvimento de plantas de interesse agronômico, florestal, hortícola e pastoril. O trabalho tem como objetivo avaliar a produção de mudas de três cultivares de maracujá submetidas a diferentes concentrações de fungo micorrízico da espécie Gigaspora candida. Para isto, conduziu-se um experimento em delineamento de blocos casualizados em esquema fatorial de 3 x 4, com três cultivares de maracujá e quatro concentrações de fungo, com três repetições em cada tratamento. Foi usado as seguintes cultivares de maracujá: Gigante Amarelo; Rubi do Cerrado e Sol do Cerrado, cada cultivar foi inoculada com quatro densidades de FMA (0, 100, 200 e 300 esporos.planta-1) da espécie Gigaspora candida. A altura da planta nas mudas no tratamento com concentração 0 esporos.planta-1 apresentou maiores valores comparado a 100 esporos.planta-1 e tendem a aumentar a partir da concentração de 200 esporos.planta-1 com o fungo Gigaspora candida. Para o número de folhas, as cultivares Gigante amarelo e Sol do Cerrado mostram tendência em aumentar a quantidade em todas as densidades de FMA testadas. A cv. Rubi do Cerrado apresentou o menor número de folhas em todas as doses testadas.
Rare causes of respiratory insufficiency in newborns
Authors: Brucknerová J , Babala J , Ujházy E , Mach M , Juránek I , Brucknerová I
Published: February 2021

Congenital lung masses (CLM) the rare group of causes of acute respiratory insufficiency (RI) in newborns include congenital airway pulmonary malformation (CAPM), congenital overinflation, bronchopulmonary sequestration, and bronchial atresia. The presenting group consists of 13 newborns who were admitted to the Neonatal Department of Intensive Medicine (NDIM) during January 1st 2015-December 31st 2019 (8 males, 5 females, 2 premature/11 term newborns, spontaneous delivery: 2, caesarean section: 11) with positive prenatal diagnosis of CAPM in all cases. In 2 cases prenatal intervention was performed (drainage of the amniotic fluid, attempt of thoracentesis). Signs of acute RI immediately after delivery were seen in 5 newborns. Postnatal echocardiographic investigation confirmed the presence of increased pulmonary pressure in 8 patients, no patient had congenital heart abnormality. A thorax x-ray was positive also in asymptomatic patients. Computed tomography in patients brought detailed information about the position, size and character of CAPM. Six patients underwent surgery. In 15.4 % right lungs were affected by cystic malformation and in 23 % left lungs were affected. A final diagnosis of CAPM was confirmed in 5 patients using histopathologic examination. Multidisciplinary cooperation during prenatal as well as postnatal period is necessary.
Extracellular Vesicles Derived From Adult and Fetal Bone Marrow Mesenchymal Stromal Cells Differentially Promote ex vivo Expansion of Hematopoietic Stem and Progenitor Cells
Authors: Ghebes Corina A. , Morhayim Jess , Kleijer Marion , Koroglu Merve , Erkeland Stefan J. , Hoogenboezem Remco , Bindels Eric , van Alphen Floris P. J. , van den Biggelaar Maartje , Nolte Martijn A. , van der Eerden Bram C. J. , Braakman Eric , Voermans Carlijn , van de Peppel Jeroen
Published: February 2021

Recently, we and others have illustrated that extracellular vesicles (EVs) have the potential to support hematopoietic stem and progenitor cell (HSPC) expansion; however, the mechanism and processes responsible for the intercellular communication by EVs are still unknown. In the current study, we investigate whether primary human bone marrow derived mesenchymal stromal cells (BMSC) EVs isolated from two different origins, fetal (fEV) and adult (aEV) tissue, can increase the relative low number of HSPCs found in umbilical cord blood (UCB) and which EV-derived components are responsible for ex vivo HSPC expansion. Interestingly, aEVs and to a lesser extent fEVs, showed supportive ex vivo expansion capacity of UCB-HSPCs. Taking advantage of the two BMSC sources with different supportive effects, we analyzed the EV cargo and investigated how gene expression is modulated in HSPCs after incubation with aEVs and fEVs. Proteomics analyses of the protein cargo composition of the supportive aEV vs. the less-supportive fEV identified 90% of the Top100 exosome proteins present in the ExoCarta database. Gene Ontology (GO) analyses illustrated that the proteins overrepresented in aEVs were annotated to oxidation-reduction process, mitochondrial ATP synthesis coupled proton transport, or protein folding. In contrast, the proteins overrepresented in fEVs were annotated to extracellular matrix organization positive regulation of cell migration or transforming growth factor beta receptor (TGFBR) signaling pathway. Small RNA sequencing identified different molecular signatures between aEVs and fEVs. Interestingly, the microRNA cluster miR-99b/let-7e/miR-125a, previously identified to increase the number of HSPCs by targeting multiple pro-apoptotic genes, was highly and significantly enriched in aEVs. Although we identified significant differences in the supportive effects of aEVs and fEVs, RNAseq analyses of the 24 h treated HSPCs indicated that a limited set of genes was differentially regulated when compared to cells that were treated with cytokines only. Together, our study provides novel insights into the complex biological role of EVs and illustrates that aEVs and fEVs differentially support ex vivo expansion capacity of UCB-HSPCs. Together opening new means for the application of EVs in the discovery of therapeutics for more efficient ex vivo HSPC expansion.
Dr. Jekyll and Mr. Hyde? Physiology and Pathology of Neuronal Stress Granules
Authors: Jeon Pureum , Lee Jin A.
Published: February 2021

Stress granules (SGs) are membraneless cytosolic granules containing dense aggregations of RNA-binding proteins and RNAs. They appear in the cytosol under stress conditions and inhibit the initiation of mRNA translation. SGs are dynamically assembled under stressful conditions and rapidly disassembled after stress removal. They are heterogeneous in their RNA and protein content and are cell type- and stress-specific. In post-mitotic neurons, which do not divide, the dynamics of neuronal SGs are tightly regulated, implying that their dysregulation leads to neurodegeneration. Mutations in RNA-binding proteins are associated with SGs. SG components accumulate in cytosolic inclusions in many neurodegenerative diseases, such as frontotemporal dementia and amyotrophic lateral sclerosis. Although SGs primarily mediate a pro-survival adaptive response to cellular stress, abnormal persistent SGs might develop into aggregates and link to the pathogenesis of diseases. In this review, we present recent advances in the study of neuronal SGs in physiology and pathology, and discuss potential therapeutic approaches to remove abnormal, persistent SGs associated with neurodegeneration.
Clinical Significance of a Novel Tumor Progression-Associated Immune Signature in Colorectal Adenocarcinoma
Authors: Mao Rui , Yang Fan , Wang Zheng , Xu Chenxin , Liu Qian , Liu Yanjun , Zhang Tongtong
Published: February 2021

Background

Some colorectal adenocarcinoma (CRC) patients are susceptible to recurrence, and they rapidly progress to advanced cancer stages and have a poor prognosis. There is an urgent need for efficient screening criteria to identify patients who tend to relapse in order to treat them earlier and more systematically.

Methods

We identified two groups of patients with significantly different outcomes by unsupervised cluster analysis of GSE39582 based on 101 significantly differentially expressed immune genes. To develop an accurate and specific signature based on immune-related genes to predict the recurrence of CRC, a multivariate Cox risk regression model was constructed with a training cohort composed of 519 CRC samples. The model was then validated using 129, 292, and 446 samples in the real-time quantitative reverse transcription PCR (qRT-PCR), test, and validation cohorts, respectively.

Results

This classification system can also be used to predict the prognosis in clinical subgroups and patients with different mutation states. Four independent datasets, including qRT-PCR and The Cancer Genome Atlas (TCGA), demonstrated that they can also be used to accurately predict the overall survival of CRC patients. Further analysis suggested that high-risk patients were characterized by worse effects of chemotherapy and immunotherapy, as well as lower immune scores. Ultimately, the signature was identified as an independent prognostic factor.

Conclusion

The signature can accurately predict recurrence and overall survival in patients with CRC and may serve as a powerful prognostic tool to further optimize cancer immunotherapy.
Rv3722c Promotes Mycobacterium tuberculosis Survival in Macrophages by Interacting With TRAF3
Authors: Lei Yingying , Cao Xiaojian , Xu Weize , Yang Bing , Xu Yangyang , Zhou Wei , Dong Shuang , Wu Qijun , Rahman Khaista , Tyagi Rohit , Zhao Shuhong , Chen Xi , Cao Gang
Published: February 2021

Mycobacterium tuberculosis (M.tb) secretes numerous proteins to interfere with host immune response for its long-term survival. As one of the top abundant M.tb secreted proteins, Rv3722c was found to be essential for bacilli growth. However, it remains elusive how this protein interferes with the host immune response and regulates M.tb survival. Here, we confirmed that Rv3722c interacted with host TRAF3 to promote M.tb replication in macrophages. Knock-down of TRAF3 attenuated the effect of Rv3722c on the intracellular M.tb survival. The interaction between Rv3722c and TRAF3 hampered MAPK and NF-κB pathways, resulting in a significant increase of IFN-β expression and decrease of IL-1β, IL-6, IL-12p40, and TNF-α expression. Our study revealed that Rv3722c interacted with TRAF3 and interrupted its downstream pathways to promote M.tb survival in macrophages. These findings facilitate further understanding of the mechanism of M.tb secreted proteins in regulating the host cell immune response and promoting its intracellular survival.
Genome-Wide Scans for Ghanaian Plasmodium falciparum Genes Under Selection From Local and Chinese Host Populations
Authors: Shi Shan-Mei , Shi Tian-Qi , Chen Shen-Bo , Cui Yan-Bing , Kassegne Kokouvi , Okpeku Moses , Chen Jun-Hu , Shen Hai-Mo
Published: February 2021

Initial malarial infection mostly causes symptomatic illness in humans. Infection that is not fatal induces complete protection from severe illness and death, and thus complete protection from severe illness or death is granted with sufficient exposure. However, malaria parasite immunity necessitates constant exposure. Therefore, it is important to evaluate lowered immunity and recurrent susceptibility to symptomatic disease in lower transmission areas. We aimed to investigate selection pressure based on transmission levels, antimalarial drug use, and environmental factors. We whole genome sequenced (WGS) P. falciparum clinical samples from Chinese hosts working in Ghana and compared the results with the WGS data of isolates from native Ghanaians downloaded from pf3k. The P. falciparum samples were generally clustered according to their geographic origin, and Chinese imported samples showed a clear African origin with a slightly different distribution from the native Ghanaian samples. Moreover, samples collected from two host populations showed evidence of differences in the intensity of selection. Compared with native Ghanaian samples, the China-imported isolates exhibited a higher proportion of monoclonal infections, and many genes associated with RBC invasion and immune evasion were found to be under less selection pressure. There was no significant difference in the selection of drug-resistance genes due to a similar artemisinin-based combination therapy medication profile. Local selection of malarial parasites is considered to be a result of differences in the host immunity or disparity in the transmission opportunities of the host. In China, most P. falciparum infections were imported from Africa, and under these circumstances, distinct local selective pressures may be caused by varying acquired immunity and transmission intensity. This study revealed the impact of host switching on the immune system, and it may provide a better understanding of the mechanisms that enable clinical immunity to malaria.
Development of a Rapid and Fully Automated Multiplex Real-Time PCR Assay for Identification and Differentiation of Vibrio cholerae and Vibrio parahaemolyticus on the BD MAX Platform
Authors: Li Zhenpeng , Guan Hongxia , Wang Wei , Gao He , Feng Weihong , Li Jie , Diao Baowei , Zhao Hongqun , Kan Biao , Zhang Jingyun
Published: February 2021

Vibrio cholerae and Vibrio parahaemolyticus are common diarrheal pathogens of great public health concern. A multiplex TaqMan-based real-time PCR assay was developed on the BD MAX platform; this assay can simultaneously detect and differentiate V. cholerae and V. parahaemolyticus directly from human fecal specimens. The assay includes two reactions. One reaction, BDM-VC, targets the gene ompW, the cholera toxin (CT) coding gene ctxA, the O1 serogroup specific gene rfbN, and the O139 serogroup specific gene wbfR of V. cholerae. The other, BDM-VP, targets the gene toxR and the toxin coding genes tdh and trh of V. parahaemolyticus. In addition, each reaction contains a sample process control. When evaluated with spiked stool samples, the detection limit of the BD MAX assay was 195–780 CFU/ml for V. cholerae and 46–184 CFU/ml for V. parahaemolyticus, and the amplification efficiency of all genes was between 95 and 115%. The assay showed 100% analytical specificity, using 63 isolates. The BD MAX assay was evaluated for its performance compared with conventional real-time PCR after automated DNA extraction steps, using 164 retrospective stool samples. The overall percent agreement between the BD MAX assay and real-time PCR was ≥ 98.8%; the positive percent agreement was 85.7% for ompW, 100% for toxR/tdh, and lower (66.7%) for trh because of a false negative. This is the first report to evaluate the usage of the BD MAX open system in detection and differentiation of V. cholerae and V. parahaemolyticus directly from human samples.
Case Report: Isolated and Focal Non-necrotizing Granulomatous Inflammation of Mitral Valves: A Report of Two Cases
Authors: Pichler Sekulic Simona , Sekulic Miroslav
Published: February 2021

Cardiac valve inflammation is seen in the setting of autoimmune or infectious processes, and rarely is valvulitis characterized by granulomatous inflammation. We present two patients who underwent surgical repair of prolapsing/regurgitating mitral valves. Excised valve tissue in both cases revealed commonly encountered nodular fibrosis and calcification, however each also revealed an isolated focus of non-necrotizing granulomatous inflammation. Typical implicating etiologies for non-necrotizing granulomatous inflammation were not present for either patient based on clinical history, or radiologic and laboratory data. In a review of 1048 cardiac valves excised at our institution, the finding of non-necrotizing granulomatous inflammation was seen in only the two described cases (prevalence of 0.19%). The description of non-necrotizing granulomatous inflammation within cardiac valves is limited in the literature, and the significance of the detailed isolated and incidental finding is unclear and requiring further investigation.
Experimental Approaches for Characterizing the Endocrine-Disrupting Effects of Environmental Chemicals in Fish
Authors: Celino-Brady Fritzie T. , Lerner Darren T. , Seale Andre P.
Published: February 2021

Increasing industrial and agricultural activities have led to a disturbing increase of pollutant discharges into the environment. Most of these pollutants can induce short-term, sustained or delayed impacts on developmental, physiological, and behavioral processes that are often regulated by the endocrine system in vertebrates, including fish, thus they are termed endocrine-disrupting chemicals (EDCs). Physiological impacts resulting from the exposure of these vertebrates to EDCs include abnormalities in growth and reproductive development, as many of the prevalent chemicals are capable of binding the receptors to sex steroid hormones. The approaches employed to investigate the action and impact of EDCs is largely dependent on the specific life history and habitat of each species, and the type of chemical that organisms are exposed to. Aquatic vertebrates, such as fish, are among the first organisms to be affected by waterborne EDCs, an attribute that has justified their wide-spread use as sentinel species. Many fish species are exposed to these chemicals in the wild, for either short or prolonged periods as larvae, adults, or both, thus, studies are typically designed to focus on either acute or chronic exposure at distinct developmental stages. The aim of this review is to provide an overview of the approaches and experimental methods commonly used to characterize the effects of some of the environmentally prevalent and emerging EDCs, including 17 α-ethinylestradiol, nonylphenol, BPA, phthalates, and arsenic; and the pervasive and potential carriers of EDCs, microplastics, on reproduction and growth. In vivo and in vitro studies are designed and employed to elucidate the direct effects of EDCs at the organismal and cellular levels, respectively. In silico approaches, on the other hand, comprise computational methods that have been more recently applied with the potential to replace extensive in vitro screening of EDCs. These approaches are discussed in light of model species, age and duration of EDC exposure.
Baseline Volumetric T2 Relaxation Time Histogram Analysis: Can It Be Used to Predict the Response to Intravenous Methylprednisolone Therapy in Patients With Thyroid-Associated Ophthalmopathy?
Authors: Liu Ping , Luo Ban , Chen Lang , Wang Qiu-Xia , Yuan Gang , Jiang Gui-hua , Zhang Jing
Published: February 2021

Objective

Prediction of therapy response to intravenous methylprednisolone pulses (ivMP) is crucial for thyroid-associated ophthalmopathy (TAO). Image histograms may offer sensitive imaging biomarkers for therapy effect prediction. This study aimed to investigate whether pretherapeutic, multiparametric T2 relaxation time(T2RT) histogram features of extraocular muscles (EOMs) can be used to predict therapy response.

Materials and Methods

Forty-five active and moderate-severe TAO patients, who were treated with standard ivMP and underwent orbital MRI before therapy, were retrospectively included in this study. The patients were divided into responsive (n = 24, 48 eyes) and unresponsive group(n = 21, 42 eyes) according to clinical evaluation. Baseline clinical features of patients and histogram-derived T2RT parameters of the EOMs were analyzed and compared. Logistic regression model was conducted to determine independent predictors, and a histogram features nomogram was formulated for personalized prediction.

Results

Responsive group displayed lower values for 5th, 10th percentiles (P < 0.050, respectively), and higher values for 75th, 90th, and 95th percentiles, skewness, entropy, and inhomogeneity (P < 0.050, respectively) than unresponsive group. Multivariate logistic regression analysis showed that 95th percentile of >88.1 [odds ratio (OR) = 12.078; 95% confidence interval (CI) = 3.98–36.655, p < 0.001], skewness of >0.31 (OR = 3.935; 95% CI = 2.28–6.788, p < 0.001) and entropy of >3.41 (OR = 4.375; 95% CI = 2.604–7.351, p < 0.001) were independent predictors for favorable response. The nomogram integration of three independent predictors demonstrated optimal predictive efficiency, with a C-index of 0.792.

Conclusions

Pre-treatment volumetric T2RT histogram features of EOMs could function to predict the response to ivMP in patients with TAO. The nomogram based on histogram features facilitates the selection of patients who will derive maximal benefit from ivMP.
Differential Effect of Metabolic Health and Obesity on Incident Heart Failure: A Nationwide Population-Based Cohort Study
Authors: Kim Hwi Seung , Lee Jiwoo , Cho Yun Kyung , Park Joong-Yeol , Lee Woo Je , Kim Ye-Jee , Jung Chang Hee
Published: February 2021

Background

Metabolically healthy obese (MHO) individuals and their association with cardiometabolic diseases have remained controversial. We aimed to explore the risk of incident heart failure (HF) based on the baseline metabolic health and obesity status as well as their transition over 2 years.

Methods

The Korean National Health Insurance Service-National Health Screening Cohort data of 514,886 participants were analyzed. Obesity was defined as BMI ≥25 kg/m2 according to the Korean Centers for Disease Control and Prevention. The metabolic health and obesity status were evaluated at baseline and after two years. Study participants were followed to either the date of newly diagnosed HF or the last follow-up visit, whichever occurred first.

Results

The MHO group comprised 9.1% of the entire population and presented a better baseline metabolic profile than the metabolically unhealthy non-obese (MUNO) and metabolicavlly unhealthy obese (MUO) groups. During the median 71.3 months of follow-up, HF developed in 5,406 (1.5%) participants. The adjusted hazard ratios [HRs (95% CI)] of HF at baseline compared with the metabolically healthy non-obese (MHNO) group were 1.29 [1.20–1.39], 1.37 [1.22–1.53], and 1.63 [1.50–1.76] for MUNO, MHO, and MUO groups, respectively. With the stable MHNO group as reference, transition into metabolically unhealthy status (MUNO and MUO) increased the risk of HF, regardless of the baseline status. Subjects who were obese at both baseline and follow-up showed an increased risk of HF, regardless of their metabolic health status.

Conclusions

Metabolic health and obesity status and their transition can predict the risk of incident HF. Losing metabolic health in baseline non-obese and obese individuals and remaining obese in baseline obese individuals showed a significantly increased risk of incident HF. Maintaining good metabolic health and a lean body may prevent the development of HF.
Al2O3 Thin Films on Magnesium: Assessing the Impact of an Artificial Solid Electrolyte Interphase
Authors: Sahadeo Emily , Rubloff Gary , Lee Sang Bok , Lin Chuan-Fu
Published: February 2021

Among the many emerging technologies under investigation as alternatives to the successful Lithium-ion battery, the magnesium battery is promising due to the wide availability of magnesium, its high volumetric capacity, and the possibility for safety improvements. One of the largest challenges facing rechargeable magnesium batteries is the formation of a passivation layer at the Mg metal anode interface when reactive species in the electrolyte are reduced at the electrode-electrolyte interface. To control the solid electrolyte interphase in Lithium batteries, protective layers called artificial solid electrolyte interphase (ASEI) layers have been successful in improving Li metal anode performance. The approach of protecting Mg metal anodes from electrolyte degradation has been demonstrated by fewer studies in the literature than Li systems. In this work, we discuss the properties of Al2O3 thin films deposited using atomic layer deposition as an artificial solid electrolyte interphase at the Mg anode. Our results demonstrate that Al2O3 does prevent electrolyte degradation due to the reductive nature of Mg. However, undesirable properties such as defects and layer breakdown lead to Mg growth that causes soft-shorting. The soft-shorting occurs with and without the protection layer, indicating the ALD layer does not prevent it and hinders Al2O3 from being an ideal candidate for a protection layer. Crucial effects of this layer on Mg electrochemistry at the interface were observed, including growth of Mg deposits leading to soft-shorting of the cell whose morphology showed a dependence on the Al2O3 layer. These results may provide guidelines for the future design and development of protective ASEI layers for Mg anodes.
Maternal Care-Providing Cichlid Neolamprologus furcifer Selectively Focuses on High-Threat Carnivorous Intruders, Limiting Attention to Other Threats
Authors: Satoh Shun , Hotta Takashi , Kohda Masanori
Published: February 2021

Animals adjust their behaviors based on information from multiple sources; however, the brain can effectively process limited amounts of information. Therefore, attention is restricted to a small portion of environmental stimuli. When animals process multiple information inputs, focusing on information that is deemed important improves detection probability. However, selective focus limits attention to other stimuli and associated behavioral responses. In this study, we examined how Tanganyikan cichlid, Neolamprologus furcifer, mothers selectively attack intruder fishes depending on the threat level and presence or absence of offspring. Species composition is complicated in Lake Tanganyika, and fish density is exceedingly high. Thus, parents must focus on high-threat-level intruders according to their parental care stage. Compared to females without offspring, mothers preferentially attacked carnivorous fishes farther from the nest over closer scale-eating fishes. Moreover, the percentage of females with injuries from scale-eating fish was significantly higher in those caring for offspring than those without offspring, demonstrating the cost of limited attention. Our results show that females focus on the early detection of carnivorous fishes because these predators dart in from long distances to forage eggs, fry, and juveniles, but this selective focus limits the attention placed on low-level threats. This study is the first to document the cost of limited attention in parents guarding offspring.
“Saving Lives, Protecting Livelihoods, and Safeguarding Nature”: Risk-Based Wildlife Trade Policy for Sustainable Development Outcomes Post-COVID-19
Authors: Booth Hollie , Arias Melissa , Brittain Stephanie , Challender Daniel W. S. , Khanyari Munib , Kuiper Timothy , Li Yuhan , Olmedo Alegria , Oyanedel Rodrigo , Pienkowski Thomas , Milner-Gulland E. J.
Published: February 2021

The COVID-19 pandemic has caused huge loss of life, and immense social and economic harm. Wildlife trade has become central to discourse on COVID-19, zoonotic pandemics, and related policy responses, which must focus on “saving lives, protecting livelihoods, and safeguarding nature.” Proposed policy responses have included extreme measures such as banning all use and trade of wildlife, or blanket measures for entire Classes. However, different trades pose varying degrees of risk for zoonotic pandemics, while some trades also play critical roles in delivering other key aspects of sustainable development, particularly related to poverty and hunger alleviation, decent work, responsible consumption and production, and life on land and below water. Here we describe how wildlife trade contributes to the UN Sustainable Development Goals (SDGs) in diverse ways, with synergies and trade-offs within and between the SDGs. In doing so, we show that prohibitions could result in severe trade-offs against some SDGs, with limited benefits for public health via pandemic prevention. This complexity necessitates context-specific policies, with multi-sector decision-making that goes beyond simple top-down solutions. We encourage decision-makers to adopt a risk-based approach to wildlife trade policy post-COVID-19, with policies formulated via participatory, evidence-based approaches, which explicitly acknowledge uncertainty, complexity, and conflicting values across different components of the SDGs. This should help to ensure that future use and trade of wildlife is safe, environmentally sustainable and socially just.
Epigenetic Regulation of the N-Terminal Truncated Isoform of Matrix Metalloproteinase-2 (NTT-MMP-2) and Its Presence in Renal and Cardiac Diseases
Authors: Cruz Juliana de Oliveira , Silva Alessandra O. , Ribeiro Jessyca M. , Luizon Marcelo R. , Ceron Carla S.
Published: February 2021

Several clinical and experimental studies have documented a compelling and critical role for the full-length matrix metalloproteinase-2 (FL-MMP-2) in ischemic renal injury, progressive renal fibrosis, and diabetic nephropathy. A novel N-terminal truncated isoform of MMP-2 (NTT-MMP-2) was recently discovered, which is induced by hypoxia and oxidative stress by the activation of a latent promoter located in the first intron of the MMP2 gene. This NTT-MMP-2 isoform is enzymatically active but remains intracellular in or near the mitochondria. In this perspective article, we first present the findings about the discovery of the NTT-MMP-2 isoform, and its functional and structural differences as compared with the FL-MMP-2 isoform. Based on publicly available epigenomics data from the Encyclopedia of DNA Elements (ENCODE) project, we provide insights into the epigenetic regulation of the latent promoter located in the first intron of the MMP2 gene, which support the activation of the NTT-MMP-2 isoform. We then focus on its functional assessment by covering the alterations found in the kidney of transgenic mice expressing the NTT-MMP-2 isoform. Next, we highlight recent findings regarding the presence of the NTT-MMP-2 isoform in renal dysfunction, in kidney and cardiac diseases, including damage observed in aging, acute ischemia-reperfusion injury (IRI), chronic kidney disease, diabetic nephropathy, and human renal transplants with delayed graft function. Finally, we briefly discuss how our insights may guide further experimental and clinical studies that are needed to elucidate the underlying mechanisms and the role of the NTT-MMP-2 isoform in renal dysfunction, which may help to establish it as a potential therapeutic target in kidney diseases.
Case Report: Reversible Neurotoxicity and a Clinical Response Induced by BCMA-Directed Chimeric Antigen Receptor T Cells Against Multiple Myeloma With Central Nervous System Involvement
Authors: Zhang Ying , Zhang Changfeng , Zhou Jin , Zhang Jingren , Chen Xiaochen , Chen Jia , Wang Pu , Sun Xiuli , Lou Xiaoyan , Qi Wei , Kang Liqing , Yu Lei , Wu Depei , Li Caixia
Published: February 2021

Isolated central nervous system involvement in multiple myeloma (CNS-MM) is rare and carries extremely poor prognosis. Chimeric antigen receptor T cell therapy (CART) targeting B-cell maturation antigen (BCMA) is demonstrated as a promising strategy in MM treatment, but the clinical safety and efficacy of BCMA-CART against isolated CNS-MM remain elusive. Here we report on a 56-year-old male with refractory isolated CNS-MM who received autologous BCMA-CART therapy and developed grade 4 neurological complications. Cerebrospinal fluid (CSF) analyses showed significant expansion of CART cells and a substantially elevated interleukin-6 (IL-6) level. Intravenous methylprednisolone was administered and the symptoms resolved gradually. Unexpectedly, the level of IL-6 in the CSF was maintained for another 3 days even after the relief of the neurological symptoms. A partial response was achieved and sustained for 5.5 months. This is the first report describing a patient with isolated CNS-MM treated using BCMA-CART therapy. The results demonstrated that BCMA-CART cells administered intravenously trafficked into the CSF, eradicated tumor cells, and induced severe but reversible neurological adverse events. This single-patient report suggests that BCMA-CART therapy can be considered as an alternative option for isolated CNS-MM.

Clinical Trial Registration

ClinicalTrials.gov, identifier NCT03196414.
Down-Regulation of LOC645166 in T Cells of Ankylosing Spondylitis Patients Promotes the NF-κB Signaling via Decreasingly Blocking Recruitment of the IKK Complex to K63-Linked Polyubiquitin Chains
Authors: Yu Hui-Chun , Huang Kuang-Yung , Lu Ming-Chi , Huang Tseng Hsien-Yu , Liu Su-Qin , Lai Ning-Sheng , Huang Hsien-Bin
Published: February 2021

Ankylosing spondylitis (AS) is a chronic inflammatory disease that mainly affects the spine. AS is highly associated with the expression of HLA-B27. Up to 95% AS patients are HLA-B27-positive. However, only 1%–2% of the HLA-B27-positive carriers suffer from AS, implying that other factors may also govern the development of AS. Long non-coding RNAs (lncRNAs) can regulate the immune response via their binding proteins. In the present study, we have identified that the levels of lncRNA, LOC645166, in T cells of AS patients were reduced. Overexpression of LOC645166 in Jurkat cells down-regulated the IL-23p19 expression and suppressed the JAK2/STAT3 signaling in response to stimulation by phorbol 12-myristate 13-acetate. Suppression of STAT3 activation by LOC645166 was also observed when Jurkat cells or T cells of AS patient were treated with anti-CD3/CD28 antibodies. In order to explore the role of LOC645166 in the pathogenesis of AS, RNA pull-down assay plus proteomic approach and western blotting were performed and identified that LOC645166 prefers binding the K63-linked polyubiquitin chains. LOC645166 can suppress recruitment of the IKK complex to K63-linked polyubiquitin chains and diminish IKK2 activation, leading to down-regulation of NF-κB activation. Down-regulation of LOC645166 expression in T cells of AS patients up-regulates NF-kB activation via decreasingly impeding recruitment of the IKK complex to K63-linked polyubiquitin chains, allowing AS patients to exhibit more sensitivity to stimulation by the proinflammatory cytokines or by TLR ligands.
In Nasal Mucosal Secretions, Distinct IFN and IgA Responses Are Found in Severe and Mild SARS-CoV-2 Infection
Authors: Santos Juliana de Melo Batista dos , Soares Camila Pereira , Monteiro Fernanda Rodrigues , Mello Ralyria , Amaral Jonatas Bussador do , Aguiar Andressa Simões , Soledade Mariana Pereira , Sucupira Carolina , De Paulis Milena , Andrade Juliana Bannwart , Almeida Flavia Jaqueline , Sáfadi Marco Aurélio Palazzi , Mau Luciana Becker , Brasil Jamile Menezes , Ramalho Theresa , Loures Flávio V. , Vieira Rodolfo Paula , Durigon Edison Luiz , de Oliveira Danielle Bruna Leal , Bachi André Luis Lacerda
Published: February 2021

Likely as in other viral respiratory diseases, SARS-CoV-2 elicit a local immune response, which includes production and releasing of both cytokines and secretory immunoglobulin (SIgA). Therefore, in this study, we investigated the levels of specific-SIgA for SARS-CoV-2 and cytokines in the airways mucosa 37 patients who were suspected of COVID-19. According to the RT-PCR results, the patients were separated into three groups: negative for COVID-19 and other viruses (NEGS,n= 5); negative for COVID-19 but positive for the presence of other viruses (OTHERS,n= 5); and the positive for COVID-19 (COVID-19,n= 27). Higher specific-SIgA for SARS-CoV-2, IFN-β, and IFN-γ were found in the COVID-19 group than in the other groups. Increased IL-12p70 levels were observed in OTHERS group as compared to COVID-19 group. When the COVID-19 group was sub stratified according to the illness severity, significant differences and correlations were found for the same parameters described above comparing severe COVID-19 to the mild COVID-19 group and other non-COVID-19 groups. For the first time, significant differences are shown in the airway's mucosa immune responses in different groups of patients with or without respiratory SARS-CoV-2 infection.
Mucosal Nanoemulsion Allergy Vaccine Suppresses Alarmin Expression and Induces Bystander Suppression of Reactivity to Multiple Food Allergens
Authors: Farazuddin Mohammad , Landers Jeffrey J. , Janczak Katarzyna W. , Lindsey Hayley K. , Finkelman Fred D. , Baker James R. , O’Konek Jessica J.
Published: February 2021

We have demonstrated that intranasal immunotherapy with allergens formulated in a nanoemulsion (NE) mucosal adjuvant suppresses Th2/IgE-mediated allergic responses and protects from allergen challenge in murine food allergy models. Protection conferred by this therapy is associated with strong suppression of allergen specific Th2 cellular immunity and increased Th1 cytokines. Here we extend these studies to examine the effect of NE-allergen immunization in mice sensitized to multiple foods. Mice were sensitized to both egg and peanut and then received NE vaccine formulated with either one or both of these allergens. The animals were then subjected to oral challenges with either egg or peanut to assess reactivity. Immunization with NE formulations containing both egg and peanut markedly reduced reactivity after oral allergen challenge with either allergen. Interestingly, mice that received the vaccine containing only peanut also had reduced reactivity to challenge with egg. Protection from oral allergen challenge was achieved despite the persistence of allergen-specific IgE and was associated with strong suppression of both Th2-polarized immune responses, alarmins and type 2 innate lymphoid cells (ILC2). NE-induced bystander suppression of reactivity required IFN-γ and the presence of an allergen in the NE vaccine. These results demonstrate that anaphylactic reactions to food allergens can be suppressed using allergen-specific immunotherapy without having to eliminate allergen-specific IgE and suggests that modulation of Th2 immunity towards one allergen may induce bystander effects that suppress reactivity to other allergens through the induction of IFN-γ and suppression of alarmins in the intestine. In addition, these data suggest that a NE vaccine for a single food allergen may lead to a global suppression of allergic responses to multiple foods.