bluuebunny/crossref_metadata_2025 huggingface dataset:
Precision radiotherapy for non-small cell lung cancer
Authors: Yang Wen-Chi , Hsu Feng-Ming , Yang Pan-Chyr
Published: July 2020

Precision medicine is becoming the standard of care in anti-cancer treatment. The personalized precision management of cancer patients highly relies on the improvement of new technology in next generation sequencing and high-throughput big data processing for biological and radiographic information.

Systemic precision cancer therapy has been developed for years. However, the role of precision medicine in radiotherapy has not yet been fully implemented. Emerging evidence has shown that precision radiotherapy for cancer patients is possible with recent advances in new radiotherapy technologies, panomics, radiomics and dosiomics.

This review focused on the role of precision radiotherapy in non-small cell lung cancer and demonstrated the current landscape.
Continuously available ratio of SpO2/FiO2 serves as a noninvasive prognostic marker for intensive care patients with COVID-19
Authors: Lu Xiaofan , Jiang Liyun , Chen Taige , Wang Yang , Zhang Bing , Hong Yizhou , Wang Jun , Yan Fangrong
Published: July 2020

Rationale

Oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) has been described as potential predictor of poor outcome for COVID-19, without considering its time-varying behavior though.

Methods

Prognostic value of SpO2/FiO2 was evaluated by jointly modeling the longitudinal responses of SpO2/FiO2 and time-to-event data retrieved from 280 severe and critically ill (intensive care) patients with COVID-19.

Results

A sharply decrease of SpO2/FiO2 from the first to second measurement for non-survivors was observed, and a strong association between square root SpO2/FiO2 and mortality risk was demonstrated, with a unit decrease in the marker corresponding to 1.82-fold increase in mortality risk (95% CI: 1.56–2.13).

Conclusions

The current study suggested that SpO2/FiO2 could serve as a non-invasive prognostic marker to facilitate early adjustment for treatment, thus improving overall survival.
Quantifying flight aptitude variation in wild Anopheles gambiae in order to identify long-distance migrants
Authors: Faiman Roy , Yaro Alpha S. , Diallo Moussa , Dao Adama , Djibril Samake , Sanogo Zana L. , Sullivan Margery , Krishna Asha , Krajacich Benjamin J. , Lehmann Tovi
Published: July 2020

Background

In the West African Sahel, mosquito reproduction is halted during the 5–7 month-long dry season, due to the absence of surface waters required for larval development. However, recent studies have suggested that bothAnopheles gambiaesensu stricto (s.s.) andAnopheles arabiensisrepopulate this region via migration from distant locations where larval sites are perennial.Anopheles coluzziiengages in more regional migration, presumably within the Sahel, following shifting resources correlating with the ever-changing patterns of Sahelian rainfall. Understanding mosquito migration is key to controlling malaria—a disease that continues to claim more than 400,000 lives annually, especially those of African children. Using tethered flight data of wild mosquitoes, the distribution of flight parameters were evaluated as indicators of long-range migrantsversusappetitive flyers, and the species specific seasonal differences and gonotrophic states compared between two flight activity modalities. Morphometrical differences were evaluated in the wings of mosquitoes exhibiting high flight activity (HFA) vs. low flight activity (LFA).

Methods

A novel tethered-flight assay was used to characterize flight in the three primary malaria vectors-An. arabiensis, An. coluzziiandAn. gambiae s.s. The flights of tethered wild mosquitoes were audio-recorded from 21:00 h to 05:00 h in the following morning and three flight aptitude indices were examined: total flight duration, longest flight bout, and the number of flight bouts during the assay.

Results

The distributions of all flight indices were strongly skewed to the right, indicating that the population consisted of a majority of low-flight activity (LFA) mosquitoes and a minority of high-flight activity (HFA) mosquitoes. The median total flight was 586 s and the maximum value was 16,110 s (~ 4.5 h). In accordance with recent results, flight aptitude peaked in the wet season, and was higher in gravid females than in non-blood-fed females. Flight aptitude was also found to be higher inAn. coluzziicompared toAn. arabiensis, with intermediate values inAn. gambiae s.s., but displaying no statistical difference. Evaluating differences in wing size and shape between LFA individuals and HFA ones, the wing size of HFAAn. coluzziiwas larger than that of LFAs during the wet season—its length was wider than predicted by allometry alone, indicating a change in wing shape. No statistically significant differences were found in the wing size/shape ofAn. gambiae s.s.orAn. arabiensis.

Conclusions

The partial agreement between the tethered flight results and recent results based on aerial sampling of these species suggest a degree of discrimination between appetitive flyers and long-distance migrants although identifying HFAs as long-distance migrants is not recommended without further investigation.
Reduced neurobehavioral functioning in agricultural workers and rural inhabitants exposed to pesticides in northern Chile and its association with blood biomarkers inhibition
Authors: Ramírez-Santana Muriel , Zúñiga-Venegas Liliana , Corral Sebastián , Roeleveld Nel , Groenewoud Hans , Van der Velden Koos , Scheepers Paul T. J. , Pancetti Floria
Published: July 2020

Background

Previous biomonitoring studies have shown that people in the rural population of Coquimbo, the major agricultural area in northern Chile are being occupationally and environmentally exposed to organophosphate/carbamate (OP/CB) pesticides. Given their harmful effects, this study had two aims; first, to evaluate the effect of cumulative or chronic exposure to OP/CB pesticides on the neurobehavioral performance of agricultural workers and rural inhabitants; second, to determine if changes in the neurobehavioral performance are associated to changes in blood biomarkers of OP/CB pesticides during the spray season, when exposure is higher.

Methods

For the first aim, a cross sectional study of neurobehavioral performance in adult volunteers (men and women, 18–50 years-old, right-handed) was carried out in the pre-spray season. Sampling was done by convenience and a questionnaire was used to categorize participants depending on their level of chronic exposure, as either: occupationally exposed (OE, n = 87), environmentally exposed (EE, n = 81), or non-exposed controls or reference group (RG, n = 100). A neurobehavioral test battery consisting of 21 tests to measure cognitive, motor and emotional state was applied. For the second aim, neurobehavioral measures were taken a second time from EE and OE groups during the spray season, and their exposure corroborated by blood-based biomarker inhibition.

Results

Lower neurobehavioral performance was observed in the pre-spray evaluation of EE and OE groups compared to the non-exposed, OE being the worst performing group. Seasonal exposure impaired performance in both exposure groups on all tests except those on attention and mood. Data modeling of the basal (pre-spray) measurements showed that the level of exposure was the best predictor of performance. During spraying, inhibition of BChE activity in the EE group was the best predictor of low performance in tests measuring logical, auditory and visual memory, inhibitory control of cognitive interference, constructional and planning abilities, executive functions, and motor speed and coordination.

Conclusion

Long-term occupational or environmental exposure to pesticides caused impairment in neurobehavioral functioning, which worsened during the spraying season, mainly in EE. BChE inhibition was the best predictor for seasonal neurobehavioral changes in EE.
Opioid agonist therapy uptake among people who inject drugs: the findings of two consecutive bio-behavioral surveillance surveys in Iran
Authors: Nakhaeizadeh Mehran , Abdolahinia Zahra , Sharifi Hamid , Mirzazadeh Ali , Haghdoost Ali Akbar , Shokoohi Mostafa , Baral Stefan , Karamouzian Mohammad , Shahesmaeili Armita
Published: July 2020

Background

Opioid agonist therapy (OAT) uptake has been associated with multiple positive health outcomes among people who inject drugs (PWID). This study evaluated the pattern of OAT uptake among PWID in two consecutive national bio-behavioral surveillance surveys (2010 and 2014) in Iran.

Methods

Data were obtained from two national bio-behavioral surveillance surveys (N2010 = 1783 and N2014 = 2166) implemented using convenience sampling at the harm reduction facilities and street venues in 10 geographically diverse urban centers across Iran. Multivariable logistic regression models were built to determine the correlates of OAT uptake for the 2014 survey, and adjusted odds ratios (AORs) along with 95% confidence intervals (CI) were reported.

Results

The prevalence of OAT uptake decreased from 49.2% in 2010 to 45.8% in 2014 (P value = 0.033). OAT uptake varied across the studied cities ranging from 0.0 to 69.3% in the 2010 survey and 3.2 to 75.5% in the 2014 survey. Ever being married (AOR = 1.40; 95% CI 1.12, 1.75), having a history of incarceration (AOR = 1.56; 95% CI 1.16, 2.09), and human immunodeficiency virus (HIV) sero-positivity (AOR = 1.63; 95% CI 1.08, 2.50) were associated with OAT uptake. Conversely, PWID who reported using only non-opioid drugs (AOR = 0.43; 95% CI 0.26, 0.71) and those who reported concurrent use of opioid and non-opioid drugs (AOR = 0.66; 95% CI 0.51, 0.86) were less likely to uptake OAT.

Conclusions

Although OAT uptake among PWID in Iran is above the 40% threshold defined by the World Health Organization, there remain significant disparities across urban settings in Iran. Importantly, the OAT services appear to be serving high-risk PWID including those living with HIV and those with a history of incarceration. Evaluating service integration including mental health, HIV and hepatitis C virus care, and other harm reduction services may support the optimization of health outcomes associated with OAT across Iran.
Histamine 2/3 receptor agonists alleviate perioperative neurocognitive disorders by inhibiting microglia activation through the PI3K/AKT/FoxO1 pathway in aged rats
Authors: Chen Yi-Nan , Sha Huan-Huan , Wang Yi-Wei , Zhou Qin , Bhuiyan Piplu , Li Na-Na , Qian Yan-Ning , Dong Hong-Quan
Published: July 2020

Background

Microglia, the principal sentinel immune cells of the central nervous system (CNS), play an extensively vital role in neuroinflammation and perioperative neurocognitive disorders (PND). Histamine, a potent mediator of inflammation, can both promote and prevent microglia-related neuroinflammation by activating different histamine receptors. Rat microglia express four histamine receptors (H1R, H2R, H3R, and H4R), among which the histamine 1 and 4 receptors can promote microglia activation, whereas the role and cellular mechanism of the histamine 2 and 3 receptors have not been elucidated. Therefore, we evaluated the effects and potential cellular mechanisms of histamine 2/3 receptors in microglia-mediated inflammation and PND.

Methods

This study investigated the role of histamine 2/3 receptors in microglia-induced inflammation and PND both in vivo and in vitro. In the in vivo experiments, rats were injected with histamine 2/3 receptor agonists in the right lateral ventricle and were then subjected to exploratory laparotomy. In the in vitro experiments, primary microglia were pretreated with histamine 2/3 receptor agonists before stimulation with lipopolysaccharide (LPS). Cognitive function, microglia activation, proinflammatory cytokine production, NF-κb expression, M1/M2 phenotypes, cell migration, and Toll-like receptor-4 (TLR4) expression were assessed.

Results

In our study, the histamine 2/3 receptor agonists inhibited exploratory laparotomy- or LPS-induced cognitive decline, microglia activation, proinflammatory cytokine production, NF-κb expression, M1/M2 phenotype transformation, cell migration, and TLR4 expression through the PI3K/AKT/FoxO1 pathway.

Conclusion

Based on our findings, we conclude that histamine 2/3 receptors ameliorate PND by inhibiting microglia activation through the PI3K/AKT/FoxO1 pathway. Our results highlight histamine 2/3 receptors as potential therapeutic targets to treat neurological conditions associated with PND.
Muramyl dipeptide-mediated immunomodulation on monocyte subsets exerts therapeutic effects in a mouse model of Alzheimer’s disease
Authors: Fani Maleki Adham , Cisbani Giulia , Plante Marie-Michèle , Préfontaine Paul , Laflamme Nataly , Gosselin Jean , Rivest Serge
Published: July 2020

Background

Muramyl dipeptide (MDP) is a component derived from minimal peptidoglycan motif from bacteria, and it is a ligand for the NOD2 receptor. Peripheral administration of MDP converts Ly6Chigh into Ly6Clow monocytes. Previously, we have shown that Ly6Clow monocytes play crucial roles in the pathology of a mouse model of Alzheimer’s disease (AD). However, medications with mild immunomodulatory effects that solely target specific monocyte subsets, without triggering microglial activation, are rare.

Methods

Three months old APPswe/PS1 transgenic male mice and age-matched C57BL/6 J mice were used for high frequency (2 times/week) over 6 months and low frequency (once a week) over 3 months of intraperitoneally MDP (10 mg/kg) administrations. Flow cytometry analysis of monocyte subsets in blood, and behavioral and postmortem analyses were performed.

Results

Memory tests showed mild to a strong improvement in memory function, increased expression levels of postsynaptic density protein 95 (PSD95), and low-density lipoprotein receptor-related protein 1 (LRP1), which are involved in synaptic plasticity and amyloid-beta (Aβ) elimination, respectively. In addition, we found monocyte chemoattractant protein-1(MCP-1) levels significantly increased, whereas intercellular adhesion molecule-1(ICAM-1) significantly decreased, and microglial marker (Iba1) did not change in the treatment group compared to the control. In parallel, we discovered elevated cyclooxygenase-2 (COX2) expression levels in the treated group, which might be a positive factor for synaptic activity.

Conclusions

Our results demonstrate that MDP is beneficial in both the early phase and, to some extent, later phases of the pathology in the mouse model of AD. These data open the way for potential MDP-based medications for AD.
Differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human
Authors: Zhang Wandong , Liu Qing Yan , Haqqani Arsalan S. , Leclerc Sonia , Liu Ziying , Fauteux François , Baumann Ewa , Delaney Christie E. , Ly Dao , Star Alexandra T. , Brunette Eric , Sodja Caroline , Hewitt Melissa , Sandhu Jagdeep K. , Stanimirovic Danica B.
Published: July 2020

Receptor-mediated transcytosis (RMT) is a principal pathway for transport of macromolecules essential for brain function across the blood–brain barrier (BBB). Antibodies or peptide ligands which bind RMT receptors are often co-opted for brain delivery of biotherapeutics. Constitutively recycling transferrin receptor (TfR) is a prototype receptor utilized to shuttle therapeutic cargos across the BBB. Several other BBB-expressed receptors have been shown to mediate transcytosis of antibodies or protein ligands including insulin receptor (INSR) and insulin-like growth factor-1 receptor (IGF1R), lipid transporters LRP1, LDLR, LRP8 and TMEM30A, solute carrier family transporter SLC3A2/CD98hc and leptin receptor (LEPR). In this study, we analyzed expression patterns of genes encoding RMT receptors in isolated brain microvessels, brain parenchyma and peripheral organs of the mouse and the human using RNA-seq approach. IGF1R, INSR and LRP8 were highly enriched in mouse brain microvessels compared to peripheral tissues. In human brain microvessels only INSR was enriched compared to either the brain or the lung. The expression levels of SLC2A1, LRP1, IGF1R, LRP8 and TFRC were significantly higher in the mouse compared to human brain microvessels. The protein expression of these receptors analyzed by Western blot and immunofluorescent staining of the brain microvessels correlated with their transcript abundance. This study provides a molecular transcriptomics map of key RMT receptors in mouse and human brain microvessels and peripheral tissues, important to translational studies of biodistribution, efficacy and safety of antibodies developed against these receptors.
Temperature and flow rate limit the optimal ex-vivo perfusion of the heart - an experimental study
Authors: Quader Mohammed , Torrado Juan Francisco , Mangino Martin J. , Toldo Stefano
Published: July 2020

Background

Ex-vivo heart perfusion can be utilized to study a variety of physiologic and molecular pathways in a controlled system outside of the body. It can also be used in clinical settings such as for organ preservation before transplantation. Myocardial oxygen consumption (MVO2) correlates with energy production in the myocardium and can also be used to determine the balance between the oxygen supply and demand of the perfused heart. This study sought to determine an ex-vivo perfusion rate that matches the metabolic demands of the heart according to different temperatures and solution compositions (with and without the addition of erythrocytes), a flow below which the supply of oxygen is not sufficient to maintain an aerobic state of the perfused heart (“DCRIT”).

Methods

Under general anesthesia, rat hearts were procured and preserved by perfusing with the University of Wisconsin Belzer machine perfusion system (UW Belzer MPS) solution saturated with 100% O2. The key elements of this solution include supraphysiological potassium (to stop the heartbeat and reduce the cellular metabolic demand), starch, gluconate and mannitol (to maintain cell wall integrity), glucose (to sustain basal metabolism), and glutathione (to scavenge free radicals). Three groups of rat hearts (n = 7) were randomly allocated to be perfused at 15 °C, 22 °C or 37 °C, at a varying flow index (FI) starting from a minimum of 380 mL/min/100 g to less than 50 mL/min/100 g, decreasing by 50 mL/min/100 g at 10 min intervals while measuring the MVO2 at each FI. Lactate was measured from coronary sinus samples to determine the onset of tissue hypoxia/anaerobic state.

Results

The DCRIT at 15 °C was 99.9 ± 4.9 mL/min/100 g; however, at 22 °C and 37 °C we could not reach a DCRIT. The myocardial oxygen demand could not be met at 22 °C and 37 °C with the maximum FI above 380 mL/min/100 g even when erythrocytes (10% V/V) were added to the solution. At 15 °C, the production of lactate was evident only below the DCRIT, while at 22 °C lactate production was present at all flow indices.

Conclusions

Determining the DCRIT for optimal ex-vivo perfusion of the heart is necessary to ensure adequate tissue oxygenation and limit anaerobic state. Temperatures employed above 15 °C limit the efficient ex-vivo perfusion preservation of heart with the UW Belzer MPS solution.
Bovine Leukemia virus (BLV) and risk of breast cancer: a systematic review and meta-analysis of case-control studies
Authors: Khatami Alireza , Pormohammad Ali , Farzi Rana , Saadati Hassan , Mehrabi Maryam , Kiani Seyed Jalal , Ghorbani Saied
Published: July 2020

Background

Breast cancer is reported as one of the most common cancers among females worldwide. Infectious agents especially viruses have been considered as role players in the development of breast cancer. Although some investigations suggest an association between bovine leukemia virus (BLV) and breast cancer, the involvement of this virus as a risk factor remains controversial. The present study aimed to find out any possible association between BLV and breast cancer through conducting a systematic review and meta-analysis.

Methods

Systematic literature search was performed by finding related case-control articles from the PubMed, Google Scholar, Web of Science, Scopus, and EMBASE databases. The heterogeneity and the multivariable-adjusted OR and corresponding 95% CI were applied by meta-analysis and forest plot across studies. All statistical analyses were performed using Stata 14.1.

Result

Based on a comprehensive literature search, 9 case-control studies were included for meta-analysis. The combination of all included studies showed that BLV infection is associated with an increased risk of breast cancer [summary OR (95% CI) 2.57 (1.45, 4.56)].

Conclusion

This is the first meta-analysis to analyze a potential association between BLV infection and the risk of breast cancer. Control of the infection in cattle herds and screening of the milk and dairy products may help to reduce the transmission of the virus to humans.
First molecular subtyping and phylogeny of Blastocystis sp. isolated from domestic and synanthropic animals (dogs, cats and brown rats) in southern Iran
Authors: Mohammadpour Iraj , Bozorg-Ghalati Farzaneh , Gazzonis Alessia Libera , Manfredi Maria Teresa , Motazedian Mohammad Hossein , Mohammadpour Niloofar
Published: July 2020

Background

Blastocystis sp. is a common intestinal protist that infects humans and many animals globally. Thus far, 22 subtypes (STs) have been identified in mammalian and avian hosts. Since various STs are common to humans and animals, it was suggested that some human infections might arise from zoonotic transmission. Therefore, the aim of this study was to assess the presence of Blastocystis sp. in domestic (dogs and cats) and synanthropic animals (rats) of Fars Province, Iran, and to genetically characterize the samples.

Methods

A total of 400 fresh faecal samples from 154 dogs, 119 cats, and 127 rats were inspected by direct microscopy, Wheatley’s trichrome staining, in vitro culture, and 18S rRNA gene nested-PCR. Finally, sequencing and phylogenetic analyses were performed.

Results

Out of 400 samples, 47 (11.8%) and 61 (15.3%) samples were detected as positive by direct wet mount and culture, respectively. Molecular analysis detected a larger number of positive samples (n = 70, 17.5%): nested-PCR showed that 29 (18.8%) dogs, 21 (17.7%) cats, and 20 (15.8%) rats were infected by Blastocystis sp. Sequence analysis of positive samples indicated the presence of zoonotic STs in all investigated host species. Specifically, ST2 (allele 9), ST3 (allele 34), ST4 (allele 94), ST7 (allele 99), ST8 (allele 21), and ST10 (allele 152) were detected in dogs; ST1 (allele 2), ST3 (allele 34), ST4 (allele 94), ST10 (allele 152), and ST14 (allele 159) were detected in cats; and ST1 (allele 2), ST3 (allele 34), and ST4 (allele 92) were detected in rats.

Conclusions

Our data suggest that domestic dogs and cats can serve as possible reservoirs for in-contact humans, especially those who handle shelter-resident and client-owned animals. Moreover, rats as synanthropic animals can function as a potential source of human infections. Conversely, humans can act as a source of infections to animals. These results should be reinforced in future molecular epidemiological studies.
The role of the Acanthamoeba castellanii Sir2-like protein in the growth and encystation of Acanthamoeba
Authors: Joo So-Young , Aung Ja Moon , Shin Minsang , Moon Eun-Kyung , Kong Hyun-Hee , Goo Youn-Kyoung , Chung Dong-Il , Hong Yeonchul
Published: July 2020

Background

The encystation of Acanthamoeba leads to the development of resilient cysts from vegetative trophozoites. This process is essential for the survival of parasites under unfavorable conditions. Previous studies have reported that, during the encystation of A. castellanii, the expression levels of encystation-related factors are upregulated. However, the regulatory mechanisms for their expression during the encystation process remains unknown. Proteins in the sirtuin family, which consists of nicotinamide adenine dinucleotide-dependent deacetylases, are known to play an important role in various cellular functions. In the present study, we identified the Acanthamoeba silent-information regulator 2-like protein (AcSir2) and examined its role in the growth and encystation of Acanthamoeba.

Methods

We obtained the full-length sequence for AcSir2 using reverse-transcription polymerase chain reaction. In Acanthamoeba transfectants that constitutively overexpress AcSir2 protein, SIRT deacetylase activity was measured, and the intracellular localization of AcSir2 and the effects on the growth and encystation of trophozoites were examined. In addition, the sirtuin inhibitor salermide was used to determine whether these effects were caused by AcSir2 overexpression

Results

AcSir2 was classified as a class-IV sirtuin. AcSir2 exhibited functional SIRT deacetylase activity, localized mainly in the nucleus, and its transcription was upregulated during encystation. In trophozoites, AcSir2 overexpression led to greater cell growth, and this growth was inhibited by treatment with salermide, a sirtuin inhibitor. When AcSir2 was overexpressed in the cysts, the encystation rate was significantly higher; this was also reversed with salermide treatment. In AcSir2-overexpressing encysting cells, the transcription of cellulose synthase was highly upregulated compared with that of control cells, and this upregulation was abolished with salermide treatment. Transmission electron microscope-based ultrastructural analysis of salermide-treated encysting cells showed that the structure of the exocyst wall and intercyst space was impaired and that the endocyst wall had not formed.

Conclusions

These results indicate that AcSir2 is a SIRT deacetylase that plays an essential role as a regulator of a variety of cellular processes and that the regulation of AcSir2 expression is important for the growth and encystation of A. castellanii.
Identification and antigenicity of the Babesia caballi spherical body protein 4 (SBP4)
Authors: Mahmoud Mona S. , Kandil Omnia M. , Abu El-Ezz Nadia T. , Hendawy Seham H. M. , Elsawy Bassma S. M. , Knowles Donald P. , Bastos Reginaldo G. , Kappmeyer Lowell S. , Laughery Jacob M. , Alzan Heba F. , Suarez Carlos E.
Published: July 2020

Background

The tick-borne intra-erythrocytic apicomplexan Babesia caballi is one of the etiological agents of equine babesiosis, an economically important disease of equids in most tropical and subtropical areas of the world. Discovering candidate antigens for improved diagnostic tools and vaccines remains needed for controlling equine babesiosis. This study describes the B. caballi sbp4 (Bcsbp4) gene and protein (BcSBP4) and analyzes its antigenicity in infected equids.

Methods

BLAST searches of an uncurated B. caballi assembly genome using the B. bovis SBP4 as a query were carried out, followed by PCR amplification and sequencing of a newly identified BcSBP4. Characterization of this novel gene and protein was performed by bioinformatics analysis, western blots, immunofluorescence (IFA) and an in vitro neutralization test using anti SBP4 peptide antibodies. Antigenicity of recombinant BcSBP4 (rBcSBP4) was tested with sera from field animals (n = 18) using an indirect ELISA (iELISA).

Results

Babesia caballi genome searches using B. bovis SBP4 as a query allowed identification of a novel gene termed Bcsbp4. The Bcsbp4 gene encodes for a protein of 30.58 kDa, which is fully conserved among B. caballi isolates from USA and Egypt. Bioinformatics analysis indicates that BcSBP4 contains a signal peptide and lacks additional transmembrane domains. Expression of BcSBP4 in blood stages of B. caballi was confirmed by western blot and IFA using antibodies against synthetic peptides representing putative B-cell epitopes of BcSBP4 predicted by in silico analysis. In vitro neutralization tests using anti-BcSBP4 peptide antibodies showed a marginal, but statistically significant inhibitory effect on the infectivity of B. caballi merozoites in horse red blood cells. Sera from eight B. caballi-infected equids, but none out of ten negative equid control sera, gave a positive signal in an rBcSBP4 based iELISA.

Conclusions

The Bcsbp4 gene is expressed in B. caballi blood stages. The BcSBP4 protein is a potential candidate for developing a novel serological test that could detect B. caballi infection in equids in tropical and subtropical countries worldwide.
Elevated serum levels of checkpoint molecules in patients with adult Still’s disease
Authors: Fujita Yuya , Asano Tomoyuki , Matsumoto Haruki , Matsuoka Naoki , Temmoku Jumpei , Sato Shuzo , Furuya Makiko Yashiro , Suzuki Eiji , Watanabe Hiroshi , Koga Tomohiro , Kawakami Atsushi , Migita Kiyoshi
Published: July 2020

Background

The interaction between galectin-9 (Gal-9) and its ligand, T cell immunoglobulin, and mucin-containing-molecule-3 (TIM-3), one of the coinhibitory receptors, transduce the inhibitory signaling to regulate immune responses. The dysregulated expression of checkpoint molecules has been reported under various inflammatory or autoimmune conditions. The aim of this study is to investigate the levels of these checkpoint molecules and their associations between proinflammatory markers in patients with adult Still’s disease (ASD).

Methods

Serum samples were collected from 47 patients with active ASD, 116 patients with rheumatoid arthritis (RA), and 37 healthy controls (HCs). Serum levels of Gal-9, soluble TIM-3 (sTIM-3), and IL-18 were determined using enzyme-linked immunosorbent assay (ELISA). Results were compared with the clinical features of ASD.

Results

Serum Gal-9 levels in patients with ASD (median: 21.57 ng/ml, interquartile range IQR [11.41–39.72]) were significantly higher compared to those in patients with RA (7.58 ng/ml, IQR [5.57–10.20] p < 0.001) as well as those in HCs (4.51 ng/ml, [IQR; 3.58–5.45], p < 0.001). Similarly, serum sTIM-3 levels in patients with ASD were significantly higher than those in patients with RA and HCs. Serum levels of Gal-9 or sTIM-3 showed positive correlations with IL-18 levels (Gal-9; r = 0.90, p < 0.001, sTIM-3; r = 0.78, p < 0.001) in patients with ASD. Serum levels of Gal-9 or sTIM-3 correlated with serum ferritin (Gal-9; r = 0.77, p < 0.001, sTIM-3; r = 0.71, p < 0.001) and ASD disease activity score (Pouchot’s score, Gal-9; r = 0.66, p < 0.001, sTIM-3; r = 0.59, p < 0.001), whereas there was no significant correlation between serum Gal-9 or sTIM-3 and CRP. ASD patients with chronic arthritis phenotype had a significantly higher Gal-9/ferritin and sTIM-3/ferritin ratio than those without this phenotype. After immunosuppressive treatment, Gal-9 and sTIM-3 levels showed a significant decline in parallel to the disease activity scores.

Conclusions

Serum levels of the coinhibitory checkpoint molecules were elevated and correlated with disease activity in patients with ASD. These coinhibitory checkpoint molecules may be implicated in the autoinflammatory process seen in ASD.
Comparison of complete renal response and mortality in early- and late-onset lupus nephritis: a multicenter retrospective study of a Japanese cohort
Authors: Ichinose Kunihiro , Kitamura Mineaki , Sato Shuntaro , Fujikawa Keita , Horai Yoshiro , Matsuoka Naoki , Tsuboi Masahiko , Nonaka Fumiaki , Shimizu Toshimasa , Sumiyoshi Remi , Koga Tomohiro , Kawashiri Shin-ya , Iwamoto Naoki , Igawa Takashi , Tamai Mami , Nakamura Hideki , Origuchi Tomoki , Nishino Tomoya , Kawakami Atsushi
Published: July 2020

Background

Most patients with systemic lupus erythematosus (SLE) progress to lupus nephritis (LN) within 5 years of their SLE diagnosis, although it is not uncommon for LN to develop at later time points. Here we evaluated the clinical features of early- and late-onset LN.

Patients and methods

We retrospectively analyzed the cases of 184 of the 201 patients who underwent a renal biopsy at Nagasaki University Hospital and associated community hospitals between 1990 and 2016 and were diagnosed as having LN. Early onset was defined as the development of LN within the first 5 years after the patient’s SLE diagnosis, and late onset was defined as LN development > 5 years post-diagnosis. We analyzed the complete renal response (CR) at 6 and 12 months after induction therapy, the classification of renal pathology, and the mortality of the early- and late-onset LN groups.

Results

The mean follow-up duration after the renal biopsy was 123 ± 85 months. There were 113 (61.4%) early-onset patients and 71 (38.6%) late-onset patients. A multivariate analysis revealed that the following factors were predictive of CR: at 6 months: female sex (odds ratio [OR] 3.93, 95% confidence interval [CI] 1.31–11.77, p = 0.010), proteinuria (OR 0.83, 95% CI 0.71–0.97, p = 0.009), index of activity (0–24) (OR 0.83, 95% CI 0.70–0.99, p = 0.030), and early-onset LN (OR 2.39, 95% CI 1.15–4.98, p = 0.018); at 12 months: female sex (OR 3.60, 95% CI 1.32–9.83, p = 0.013), mixed LN (OR 0.18, 95% CI 0.04–0.80, p = 0.024), index of activity (0–24) (OR 0.80, 95% CI 0.68–0.94, p = 0.007), and early-onset LN (OR 2.10, 95% CI 1.05–4.23, p = 0.035). In a Cox proportional hazards and Fine-Gray regression model, the early-onset LN group had a significantly better mortality rate than the late-onset LN group (p = 0.038 and p = 0.043, respectively).

Conclusions

In our cohort, early-onset LN was a better predictor of CR at 6 and 12 months than late-onset LN. Our results suggest that early-onset LN patients had lower mortality than late-onset LN patients.
The role of CA-125, GLS and FASN in predicting cytoreduction for epithelial ovarian cancers
Authors: Winarno G. N. A. , Hidayat Y. M. , Soetopo S. , Krisnadi S. R. , Tobing M. D. L. , Rauf S.
Published: July 2020

Objective

Cytoreduction has an important role in improving the survival rate of epithelial ovarian cancer (EOC) patients. This study aimed to assess the ability of preoperative serum CA125, FASN and GLS as predictors of cytoreductive surgery for epithelial ovarian cancer (EOC).

Results

The average values of serum CA-125, FASN, and GLS in the suboptimal cytoreduction group were higher than those in optimal cytoreduction group. The cut off point (COP) was 248.55 (p = 0.0001) with 73.2% sensitivity and 73.6% specificity for CA-125, 0.445 (p = 0.017) with 62.5% sensitivity and 60.4% specificity for FASN, and 22.895 (p = 0.0001) with 73.2% sensitivity and 75.5% specificity for GLS. The COP of CA-125 and GLS combined was 29.16 (p = 0.0001) with sensitivity 82.1% and specificity 73.6%, while the COP of CA-125, GLS, and FASN combined was 0.83 (p = 0.0001) with 87.5% sensitivity and 73.6% specificity.
Adaptive control realization for canonic Caputo fractional-order systems with actuator nonlinearity: application to mechatronic devices
Authors: Aghababa Mohammad Pourmahmood , Saif Mehrdad
Published: July 2020

Nonlinearities, such as dead-zone, backlash, hysteresis, and saturation, are common in the mechanical and mechatronic systems’ components and actuators. Hence, an effective control strategy should take into account such nonlinearities which, if unaccounted for, may cause serious response problems and might even result in system failure. Input saturation is one of the most common nonlinearities in practical control systems. So, this article introduces a novel adaptive variable structure control strategy for nonlinear Caputo fractional-order systems despite the saturating inputs. Owing to the complex nature of the fractional-order systems and lack of proper identification strategies for such systems, this research focuses on the canonic systems with complete unknown dynamics and even those with model uncertainties and external noise. Using mathematical stability theory and adaptive control strategy, a simple stable integral sliding mode control is proposed. The controller will be shown to be effective against actuator saturation as well as unknown characteristics and system uncertainties. Finally, two case studies, including a mechatronic device, are considered to illustrate the effectiveness and practicality of the proposed controller in the applications.
A mathematical model of COVID-19 using fractional derivative: outbreak in India with dynamics of transmission and control
Authors: Shaikh Amjad Salim , Shaikh Iqbal Najiroddin , Nisar Kottakkaran Sooppy
Published: July 2020

Since the first case of 2019 novel coronavirus disease (COVID-19) detected on 30 January, 2020, in India, the number of cases rapidly increased to 3819 cases including 106 deaths as of 5 April, 2020. Taking this into account, in the present work, we have analysed a Bats–Hosts–Reservoir–People transmission fractional-order COVID-19 model for simulating the potential transmission with the thought of individual response and control measures by the government. The real data available about number of infected cases from 14 March, 2000 to 26 March, 2020 is analysed and, accordingly, various parameters of the model are estimated or fitted. The Picard successive approximation technique and Banach’s fixed point theory have been used for verification of the existence and stability criteria of the model. Further, we conduct stability analysis for both disease-free and endemic equilibrium states. On the basis of sensitivity analysis and dynamics of the threshold parameter, we estimate the effectiveness of preventive measures, predicting future outbreaks and potential control strategies of the disease using the proposed model. Numerical computations are carried out utilising the iterative Laplace transform method and comparative study of different fractional differential operators is done. The impacts of various biological parameters on transmission dynamics of COVID-19 is investigated. Finally, we illustrate the obtained results graphically.
Some modifications in conformable fractional integral inequalities
Authors: Baleanu Dumitru , Mohammed Pshtiwan Othman , Vivas-Cortez Miguel , Rangel-Oliveros Yenny
Published: July 2020

The prevalence of the use of integral inequalities has dramatically influenced the evolution of mathematical analysis. The use of these useful tools leads to faster advances in the presentation of fractional calculus. This article investigates the Hermite–Hadamard integral inequalities via the notion of Ϝ-convexity. After that, we introduce the notion of $\digamma _{\mu}$

Ϝ
μ

-convexity in the context of conformable operators. In view of this, we establish some Hermite–Hadamard integral inequalities (both trapezoidal and midpoint types) and some special case of those inequalities as well. Finally, we present some examples on special means of real numbers. Furthermore, we offer three plot illustrations to clarify the results.
Laplace decomposition for solving nonlinear system of fractional order partial differential equations
Authors: Khan Hassan , Shah Rasool , Kumam Poom , Baleanu Dumitru , Arif Muhammad
Published: July 2020

In the present article a modified decomposition method is implemented to solve systems of partial differential equations of fractional-order derivatives. The derivatives of fractional-order are expressed in terms of Caputo operator. The validity of the proposed method is analyzed through illustrative examples. The solution graphs have shown a close contact between the exact and LADM solutions. It is observed that the solutions of fractional-order problems converge towards the solution of an integer-order problem, which confirmed the reliability of the suggested technique. Due to better accuracy and straightforward implementation, the extension of the present method can be made to solve other fractional-order problems.
Comparative efficacy of hospital disinfectants against nosocomial infection pathogens
Authors: Amini Tapouk Fahim , Nabizadeh Ramin , Mirzaei Nezam , Hosseini Jazani Nima , Yousefi Mahmood , Valizade Hasanloei Mohamad Amin
Published: July 2020

Background

Due to the increasing rate of hospital-acquired infections, it is essential to select appropriate disinfectant agents. In this study, the efficacy of hospital disinfectants against nosocomial infection pathogens was compared.

Methods

High level disinfectants (Steranios 2%, Deconex HLDPA, and Microzed Quatenol) were tested for their antibacterial effects by determining their minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) againstEnterococcus faecalisATCC 29212 andBurkholderia cepaciaATCC 10673.

Results

E. faecalis, as gram-positive bacterium, was more susceptible to high level disinfectants compared to gram-negativeB.cepacia.The MIC = MBC values of 2% Steranios, Deconex HLDPA and Microzed Quatenol againstE. faecalisandB.cepaciawere 0.31, 9.77, 2.2 mg/L and 9.8, 78.13, 70.31 mg/L, respectively.

Conclusions

According to the findings of this study, the most effective disinfectants against bothE. faecalisandB.cepaciawere Steranios 2%, Microzed Quatenol, and Deconex HLDPA in order. Considering the importance of these bacterial strains in healthcare-associated infections, the use of these effective disinfectants is recommended in the hospitals.
Family-related non-abuse adverse life experiences occurring for adults diagnosed with eating disorders: a systematic review
Authors: Grogan Katie , MacGarry Diarmuid , Bramham Jessica , Scriven Mary , Maher Caroline , Fitzgerald Amanda
Published: July 2020

Background

Although previous reviews suggest a strong association between abuse and eating disorders, less is known about non-abuse adverse life experiences, such as parental mental illness or family discord, which occur frequently for this population. The aim of the current study was to identify family-related non-abuse adverse life experiences occurring for adults with eating disorders, and to establish whether they occur for people with anorexia nervosa, bulimia nervosa or binge-eating disorder more than the general population and other psychiatric populations.

Method

A systematic review of studies focusing on family-related non-abuse adverse life experiences and eating disorders was conducted in accordance with PRISMA guidelines. The search string was applied to four electronic databases including Psycinfo, PubMed/Medline, CINAHL Plus and EMBASE.

Results

Of the 26 studies selected for inclusion, six types of family-related non-abuse adverse life experiences were identified: adverse parenting style; family disharmony; loss of a family member, relative or close person; familial mental health issues; family comments about eating, or shape, weight and appearance; and family disruptions. Findings provided tentative evidence for eating disorder specific (i.e. parental demands and criticism) and non-specific (i.e. familial loss and family disruptions) non-abuse adversities, with findings also suggesting that those with bulimia nervosa and binge-eating disorder were more impacted by loss, family separations and negative parent-child interactions compared to those with anorexia nervosa.

Conclusions

This review provides a clear synthesis of previous findings relating to family-related non-abuse adverse life experiences and eating disorders in adults. Implications for trauma-informed care in clinical practice were discussed (e.g. considering the impact of past life events, understanding the function of ED behaviours, reducing the risk of potential re-traumatisation).
Psoralen alleviates high glucose-induced HK-2 cell injury by inhibition of Smad 2 signaling via upregulation of microRNA 874
Authors: Lin Yongtao , Zhong Lili , Li Hailun , Xu Yong , Li Xiang , Zheng Donghui
Published: July 2020

Background

Diabetic nephropathy (DN) causes the vast proportion of excess mortality for patients with diabetes. Novel therapeutic approaches slowing down its incidence is still lacking. Psoralen is the major active ingredient ofPsoralea corylifolia Linn.(PCL), which was used to treat a number of diseases. In this study, we aimed to investigate whether psoralen could alleviate DN using in vitro model.

Methods

Cell viability assay and immunofluorescence were used to evaluate the effect of psoralen on high glucose (HG)-stimulated human kidney HK-2 cells (48 h). RT-qPCR was used to detect the expressions of miRNA in cells. Cell transfection, apoptosis assay, inflammatory cytokines detection and Western blot were further performed to explore the underlying molecular mechanisms.

Results

HG-induced toxicity of HK-2 cells was alleviated by psoralen. Meanwhile, the secretion of inflammatory cytokines and extracellular matrix (ECM) accumulation induced by HG in HK-2 cells were also decreased by psoralen. In addition, the expression of miR-874 in HK-2 cells was significantly upregulated by psoralen. Western blot assays indicated that psoralen could reverse HG-induced increase of TLR-4/NF-κB and Smad2 via upregulation of miR-874.

Conclusion

This study demonstrated that psoralen could significantly alleviate HG-induced HK-2 cell injury via upregulation of miR-874. In addition, HG-induced increase of TLR-4/NF-κB and Smad2 was revered by psoralen. Therefore, psoralen might serve as an agent for the treatment of DN.
Analysis of liquid-type proof mass under oscillating conditions
Authors: Won Dong-Joon , Lee Sangmin , Kim Joonwon
Published: July 2020

In this study, the spring constant of an accelerometer with a liquid-type proof mass was analyzed. Unlike a general solid-type microelectromechanical system accelerometer, the Laplace pressure is considered a restoring force in the analyzed accelerometer. Using a base excitation mathematical model, the sensor output could be estimated for a specific spring constant. Although the estimated sensor output data fit well with the experimental results, the spring constant of the device could also be determined dynamically (for oscillations below 5 Hz). Moreover, the damping constants could be inferred depending on whether sandblasting treatment was performed. Finally, the effects of the oscillation, surface condition, and volume of liquid metal droplets on the spring constant were analyzed.
The association between low pH value and unfavorable neurological outcome among the out-of-hospital cardiac arrest patient treated by extra-corporeal CPR: sensitivity analysis
Authors: Okada Yohei , Kiguchi Takeyuki , Kitamura Tetsuhisa , Iwami Taku
Published: July 2020

This is the response to the comment from Dr. Romain Jouffroy and his colleague, on the manuscript “Association between low pH and unfavorable neurological outcome among out-of-hospital cardiac arrest patients treated by extracorporeal CPR: a prospective observational cohort study in Japan”. We performed sensitivity analysis based on the comment from them. It indicated that the results of primary analysis were robust even in considering their criticism.
Monte Carlo-based scatter correction for the SMARTZOOM collimator
Authors: Dietze Martijn M. A. , Kunnen Britt , Stella Martina , de Jong Hugo W. A. M.
Published: July 2020

Background

Myocardial perfusion imaging is a commonly performed SPECT protocol and hence it would be beneficial if its scan duration could be shortened. For traditional gamma cameras, two developments have separately shown to allow for a shortened scan duration: (i) reconstructing with Monte Carlo-based scatter correction instead of dual-energy window scatter correction and (ii) acquiring projections with the SMARTZOOM collimator instead of a parallel-hole collimator. This study investigates which reduction in scan duration can be achieved when both methods are combined in a single system.

Results

The SMARTZOOM collimator was implemented in a Monte Carlo-based reconstruction package and the implementation was validated through image quality phantom experiments. The potential for scan duration reduction was evaluated with a phantom configuration that is realistic for myocardial perfusion imaging. The original reconstruction quality was achieved in 76 ± 8% of the original scan duration when switching from dual-energy window scatter correction to Monte Carlo-based scatter correction. The original reconstruction quality was achieved in 56 ± 13% of the original scan duration when switching from the parallel-hole to the SMARTZOOM collimator. After combining both methods in a single system, the original reconstruction quality was achieved in 34 ± 7% of the original scan duration.

Conclusions

Monte Carlo-based scatter correction combined with the SMARTZOOM collimator can further decrease the scan duration in myocardial perfusion imaging.