bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical significance of PD-L1 expression in serum-derived exosomes in NSCLC patients
Authors: Li Chuling , Li Chuwei , Zhi Chunchun , Liang Wenjun , Wang Xuan , Chen Xi , Lv Tangfeng , Shen Qin , Song Yong , Lin Dang , Liu Hongbing
Published: October 2019

Background

Exosomes are 50–150 nm endocytic vesicles secreted by almost all type of cells that carry bioactive molecules from host. These small vesicles are considered to be novel cross-talk circuits established by tumor cells and tumor microenvironment. Previous studies have shown certain biological influence of exosomal programmed cell-death ligand 1 (Exo-PD-L1) on immune suppression and dysfunction. The aim of the current study was to investigate the impact of Exo-PD-L1 and soluble PD-L1 (sPD-L1) on non-small cell lung cancer (NSCLC) and explore the concordance between Exo-PD-L1 and PD-L1 expression in matched tumor tissues in NSCLC patients.

Methods

85 consecutive patients from April 2017 to December 2017 at General Hospital of Eastern Command Theatre who were primarily diagnosed with NSCLC and 27 healthy individuals were enrolled in this study. Two milliliters of whole blood samples were collected from each participant and further centrifuged. Exosomes were derived from serum using the commercial kit (Total Exosome Isolation Kit), which was further identified by Western blotting analysis (CD63/TSG101), transmission electron microscope analysis (TEM) and nanoparticle tracking analysis (NTA). Exosomes were next solubilized for Exo-PD-L1 detection by enzyme-linked immuno-sorbent assay (ELISA). PD-L1 expression in matched tissue were assessed by PD-L1 immunohistochemistry (IHC) (clone 28-8) assay. Tumor proportion score (TPS) ≥ 1% was deemed as “positive” in this study and TPS < 1% was deemed as “negative”. Written informed consent were obtained before acquisition of all data and biological sample. Data were analyzed using SPSS 20.0 and Graphpad Prism 5 software. Chi square test was conducted to estimate the correlation between Exo-PD-L1 levels, sPD-L1 levels, PD-L1 IHC profiles and clinicopathological features. For all analysis, a two-sided p < 0.05 was considered significant statistically.

Results

Exo-PD-L1 levels were higher in NSCLC patients with advanced tumor stage, larger tumor size (> 2.5 cm) (p < 0.001), positive lymph node status (p < 0.05) and distant metastasis (p < 0.05). In contrast, sPD-L1 levels were not different between NSCLC patients and healthy donors, it was not correlated with any clinicopathologic features except for tumor size (> 2.5 cm) (p < 0.05). In addition, Exo-PD-L1 levels showed slight correlation with sPD-L1 levels (Spearman’s correlation at r = 0.3, p = 0.0027) while no correlation with PD-L1 IHC profiles was detected.

Conclusions

In conclusion, Exo-PD-L1, but not sPD-L1, was correlated with NSCLC disease progression, including tumor size, lymph node status, metastasis and TNM stage. However, Exo-PD-L1 was not associated with PD-L1 IHC status.
RapidPlan knowledge based planning: iterative learning process and model ability to steer planning strategies
Authors: Fogliata A. , Cozzi L. , Reggiori G. , Stravato A. , Lobefalo F. , Franzese C. , Franceschini D. , Tomatis S. , Scorsetti M.
Published: October 2019

Purpose

To determine if the performance of a knowledge based RapidPlan (RP) planning model could be improved with an iterative learning process, i.e. if plans generated by an RP model could be used as new input to re-train the model and achieve better performance.

Methods

Clinical VMAT plans from 83 patients presenting with head and neck cancer were selected to train an RP model, CL-1. With this model, new plans on the same patients were generated, and subsequently used as input to train a novel model, CL-2. Both models were validated on a cohort of 20 patients and dosimetric results compared. Another set of 83 plans was realised on the same patients with different planning criteria, by using a simple template with no attempt to manually improve the plan quality. Those plans were employed to train another model, TP-1. The differences between the plans generated by CL-1 and TP-1 for the validation cohort of patients were compared with respect to the differences between the original plans used to build the two models.

Results

The CL-2 model presented an improvement relative to CL-1, with higher R2 values and better regression plots. The mean doses to parallel organs decreased with CL-2, while D1% to serial organs increased (but not significantly). The different models CL-1 and TP-1 were able to yield plans according to each original strategy.

Conclusion

A refined RP model allowed the generation of plans with improved quality, mostly for parallel organs at risk and, possibly, also the intrinsic model quality.
Sequence characterization of RET in 117 Chinese Hirschsprung disease families identifies a large burden of de novo and parental mosaic mutations
Authors: Jiang Qian , Wang Yang , Li Qi , Zhang Zhen , Xiao Ping , Wang Hui , Liu Na , Wu Jian , Zhang Feng , Chakravarti Aravinda , Cai Wei , Li Long
Published: October 2019

Background

Hirschsprung disease (HSCR) is an inherited congenital disorder characterized by the absence of enteric ganglia in the distal part of the gut. RET is the major causative gene and contains > 80% of all known disease-causing mutations.

Results

To determine the incidence of RET pathogenic variants, be they Mendelian inherited, mosaic in parents or true de novo variants (DNVs) in 117 Chinese families, we used high-coverage NGS and droplet digital polymerase chain reaction (ddPCR) to identify 15 (12.8%) unique RET coding variants (7 are novel); one was inherited from a heterozygous unaffected mother, 11 were DNVs (73.3%), and 3 full heterozygotes were inherited from parental mosaicism (2 paternal, 1 maternal): two clinically unaffected parents were identified by NGS and confirmed by ddPCR, with mutant allele frequency (13–27%) that was the highest in hair, lowest in urine and similar in blood and saliva. An extremely low-level paternal mosaicism (0.03%) was detected by ddPCR in blood. Six positive-controls were examined to compare the mosaicism detection limit and sensitivity of NGS, amplicon-based deep sequencing and ddPCR.

Conclusion

Our findings expand the clinical and molecular spectrum of RET variants in HSCR and reveal a high frequency of RET DNVs in the Chinese population.
Correlation between end-tidal carbon dioxide and the degree of compression of heart cavities measured by transthoracic echocardiography during cardiopulmonary resuscitation for out-of-hospital cardiac arrest
Authors: Skulec Roman , Vojtisek Petr , Cerny Vladimir
Published: October 2019

Background

The concept of personalized cardiopulmonary resuscitation (CPR) requires a parameter that reflects its hemodynamic efficiency. While intra-arrest ultrasound is increasingly implemented into the advanced life support, we realized a pre-hospital clinical study to evaluate whether the degree of compression of the right ventricle (RV) and left ventricle (LV) induced by chest compressions during CPR for out-of-hospital cardiac arrest (OHCA) and measured by transthoracic echocardiography correlates with the levels of end-tidal carbon dioxide (EtCO2) measured at the time of echocardiographic investigation.

Methods

Thirty consecutive patients resuscitated for OHCA were included in the study. Transthoracic echocardiography was performed from a subcostal view during ongoing chest compressions in all of them. This was repeated three times during CPR in each patient, and EtCO2 levels were registered. From each investigation, a video loop was recorded. Afterwards, maximal and minimal diameters of LV and RV were obtained from the recorded loops and the compression index of LV (LVCI) and RV (RVCI) was calculated as (maximal − minimal/maximal diameter) × 100. Maximal compression index (CImax) defined as the value of LVCI or RVCI, whichever was greater was also assessed. Correlations between EtCO2 and LVCI, RVCI, and CImax were expressed as Spearman’s correlation coefficient (r).

Results

Evaluable echocardiographic records were found in 18 patients, and a total of 52 measurements of all parameters were obtained. Chest compressions induced significant compressions of all observed cardiac cavities (LVCI = 20.6 ± 13.8%, RVCI = 34.5 ± 21.6%, CImax = 37.4 ± 20.2%). We identified positive correlation of EtCO2 with LVCI (r = 0.672, p < 0.001) and RVCI (r = 0.778, p < 0.001). The strongest correlation was between EtCO2 and CImax (r = 0.859, p < 0.001). We identified that a CImax cut-off level of 17.35% predicted to reach an EtCO2 level > 20 mmHg with 100% sensitivity and specificity.

Conclusions

Evaluable echocardiographic records were reached in most of the patients. EtCO2 positively correlated with all parameters under consideration, while the strongest correlation was found between CImax and EtCO2. Therefore, CImax is a candidate parameter for the guidance of hemodynamic-directed CPR.

Trial registration

ClinicalTrial.gov, NCT03852225. Registered 21 February 2019 - Retrospectively registered.
Preparing intensive care for the next pandemic influenza
Authors: Kain Taylor , Fowler Robert
Published: October 2019

Few viruses have shaped the course of human history more than influenza viruses. A century since the 1918–1919 Spanish influenza pandemic—the largest and deadliest influenza pandemic in recorded history—we have learned much about pandemic influenza and the origins of antigenic drift among influenza A viruses. Despite this knowledge, we remain largely underprepared for when the next major pandemic occurs.

While emergency departments are likely to care for the first cases of pandemic influenza, intensive care units (ICUs) will certainly see the sickest and will likely have the most complex issues regarding resource allocation. Intensivists must therefore be prepared for the next pandemic influenza virus. Preparation requires multiple steps, including careful surveillance for new pandemics, a scalable response system to respond to surge capacity, vaccine production mechanisms, coordinated communication strategies, and stream-lined research plans for timely initiation during a pandemic. Conservative models of a large-scale influenza pandemic predict more than 170% utilization of ICU-level resources. When faced with pandemic influenza, ICUs must have a strategy for resource allocation as strain increases on the system.

There are several current threats, including avian influenza A(H5N1) and A(H7N9) viruses. As humans continue to live in closer proximity to each other, travel more extensively, and interact with greater numbers of birds and livestock, the risk of emergence of the next pandemic influenza virus mounts. Now is the time to prepare and coordinate local, national, and global efforts.
Fingerprinting cities: differentiating subway microbiome functionality
Authors: Zhu Chengsheng , Miller Maximilian , Lusskin Nick , Mahlich Yannick , Wang Yanran , Zeng Zishuo , Bromberg Yana
Published: October 2019

Background

Accumulating evidence suggests that the human microbiome impacts individual and public health. City subway systems are human-dense environments, where passengers often exchange microbes. The MetaSUB project participants collected samples from subway surfaces in different cities and performed metagenomic sequencing. Previous studies focused on taxonomic composition of these microbiomes and no explicit functional analysis had been done till now.

Results

As a part of the 2018 CAMDA challenge, we functionally profiled the available ~ 400 subway metagenomes and built predictor for city origin. In cross-validation, our model reached 81% accuracy when only the top-ranked city assignment was considered and 95% accuracy if the second city was taken into account as well. Notably, this performance was only achievable if the similarity of distribution of cities in the training and testing sets was similar. To assure that our methods are applicable without such biased assumptions we balanced our training data to account for all represented cities equally well. After balancing, the performance of our method was slightly lower (76/94%, respectively, for one or two top ranked cities), but still consistently high. Here we attained an added benefit of independence of training set city representation. In testing, our unbalanced model thus reached (an over-estimated) performance of 90/97%, while our balanced model was at a more reliable 63/90% accuracy. While, by definition of our model, we were not able to predict the microbiome origins previously unseen, our balanced model correctly judged them to be NOT-from-training-cities over 80% of the time.

Our function-based outlook on microbiomes also allowed us to note similarities between both regionally close and far-away cities. Curiously, we identified the depletion in mycobacterial functions as a signature of cities in New Zealand, while photosynthesis related functions fingerprinted New York, Porto and Tokyo.

Conclusions

We demonstrated the power of our high-speed function annotation method, mi-faser, by analysing ~ 400 shotgun metagenomes in 2 days, with the results recapitulating functional signals of different city subway microbiomes. We also showed the importance of balanced data in avoiding over-estimated performance. Our results revealed similarities between both geographically close (Ofa and Ilorin) and distant (Boston and Porto, Lisbon and New York) city subway microbiomes. The photosynthesis related functional signatures of NYC were previously unseen in taxonomy studies, highlighting the strength of functional analysis.
Simultaneous production of DHA and squalene from Aurantiochytrium sp. grown on forest biomass hydrolysates
Authors: Patel Alok , Rova Ulrika , Christakopoulos Paul , Matsakas Leonidas
Published: October 2019

Background

Recent evidence points to the nutritional importance of docosahexaenoic acid (DHA) in the human diet. Thraustochytrids are heterotrophic marine oleaginous microorganisms capable of synthesizing high amounts of DHA, as well as other nutraceutical compounds such as squalene, in their cellular compartment. Squalene is a natural triterpene and an important biosynthetic precursor to all human steroids. It has a wide range of applications in the cosmetic and pharmaceutical industries, with benefits that include boosting immunity and antioxidant activity. Apart from its nutritional quality, it can also be utilized for high-grade bio-jet fuel by catalytic conversion.

Results

In the present study, the potential of thraustochytrid strain Aurantiochytrium sp. T66 to produce DHA and squalene was evaluated. When the strain was cultivated on organosolv-pretreated birch hydrolysate (30 g/L glucose) in flask, it resulted in 10.39 g/L of cell dry weight and 4.98 g/L of total lipids, of which 25.98% was DHA. In contrast, when the strain was grown in a bioreactor, cell dry weight, total lipid, and DHA increased to 11.24 g/L, 5.90 g/L, and 35.76%, respectively. The maximum squalene yield was 69.31 mg/gCDW (0.72 g/L) when the strain was cultivated in flask, but it increased to 88.47 mg/gCDW (1.0 g/L), when cultivation shifted to a bioreactor.

Conclusions

This is the first report demonstrating the utilization of low cost non-edible lignocellulosic feedstock to cultivate the marine oleaginous microorganism Aurantiochytrium sp. for the production of nutraceutical vital compounds. Owing to the simultaneous generation of DHA and squalene, the strain is suitable for industrial-scale production of nutraceuticals.
The Geshiyaro Project: a study protocol for developing a scalable model of interventions for moving towards the interruption of the transmission of soil-transmitted helminths and schistosome infections in the Wolaita zone of Ethiopia
Authors: Mekete Kalkidan , Ower Alison , Dunn Julia , Sime Heven , Tadesse Gemechu , Abate Ebba , Nigussu Nebiyu , Seife Fikreselasie , McNaughton Emily , Anderson Roy Malcolm , Phillips Anna Elizabeth
Published: October 2019

Background

National deworming programmes rely almost exclusively on mass drug administration (MDA) to children to control morbidity caused by these parasitic infections. The provision of other interventions, consisting of preventive chemotherapy at high population level coverage together with water, sanitation and hygiene (WaSH) and changes in risk behaviour, should enable sustainable control of soil-transmitted helminths (STH) and schistosomiasis and ultimately interrupt transmission.

Methods/Design

Two interventions will be implemented by the project: (i) community-wide biannual albendazole and annual praziquantel treatment with a target of 80–90% treatment coverage (“expanded MDA”); and (ii) provision of WaSH with behaviour change communication (BCC), within the Wolaita zone, Ethiopia. The project has three study arms: (i) expanded community-wide MDA, WaSH and BCC; (ii) expanded community-wide MDA only; and (iii) annual school-based MDA (the current National STH/schistosomiasis Control Programme). The impact of these interventions will be evaluated through prevalence mapping at baseline and endline (after four rounds of MDA), combined with annual longitudinal parasitological surveillance in defined cohorts of people to monitor trends in prevalence and reinfection throughout the project. Treatment coverage and individual compliance to treatment will be monitored by employing fingerprint biometric technology and barcoded identification cards at treatment. WaSH utilisation will be evaluated through school and household level observations and annual WaSH assessment survey. Complementary qualitative surveys will explore practices, cultural and social drivers of risk behaviours, uptake of WaSH and treatment, and assessing the impact of the BCC.

Discussion

The study has the potential to define an ‘End Game’ for STH and schistosomiasis programmes through provision of multiple interventions. Interrupting transmission of these infections would eliminate the need for long-term repeated MDA, lead to sustained health improvements in children and adults, thereby allowing health systems to focus on other disease control priorities.
Regional biogeography of microbiota composition in the Chagas disease vector Rhodnius pallescens
Authors: Kieran Troy J. , Arnold Kaylee M. H. , Thomas Jesse C. , Varian Christina P. , Saldaña Azael , Calzada Jose E. , Glenn Travis C. , Gottdenker Nicole L.
Published: October 2019

Background

Triatomine bugs are vectors of the protozoan parasite Trypanosoma cruzi, which causes Chagas disease. Rhodnius pallescens is a major vector of Chagas disease in Panama. Understanding the microbial ecology of disease vectors is important in the development of vector management strategies that target vector survival and fitness. In this study we examined the whole-body microbial composition of R. pallescens from three locations in Panama.

Methods

We collected 89 R. pallescens specimens using Noireau traps in Attalea butyracea palms. We then extracted total DNA from whole-bodies of specimens and amplified bacterial microbiota using 16S rRNA metabarcoding PCR. The 16S libraries were sequenced on an Illumina MiSeq and analyzed using QIIME2 software.

Results

We found Proteobacteria, Actinobacteria, Bacteroidetes and Firmicutes to be the most abundant bacterial phyla across all samples. Geographical location showed the largest difference in microbial composition with northern Veraguas Province having the most diversity and Panama Oeste Province localities being most similar to each other. Wolbachia was detected in high abundance (48–72%) at Panama Oeste area localities with a complete absence of detection in Veraguas Province. No significant differences in microbial composition were detected between triatomine age class, primary blood meal source, or T. cruzi infection status.

Conclusions

We found biogeographical regions differ in microbial composition among R. pallescens populations in Panama. While overall the microbiota has bacterial taxa consistent with previous studies in triatomine microbial ecology, locality differences are an important observation for future studies. Geographical heterogeneity in microbiomes of vectors is an important consideration for future developments that leverage microbiomes for disease control.
A 9-year longitudinal study on trajectories of aggressive and depressive symptoms in male and female children with overweight
Authors: Cerniglia Luca , Cimino Silvia , Erriu Michela , Jezek Stanislav , Almenara Carlos A. , Tambelli Renata
Published: October 2019

Objectives

The aim of this four waves 9-year longitudinal study was to examine aggressive/depressive symptoms trajectories in a sample of N = 90 children with overweight and a matched group of children with normal weight (subjects balanced by sex and sociodemographic characteristics). Weight and height were measured by pediatricians to calculate body mass index (BMI). Aggressive/depressive symptoms were measured through the Child Behavior Check-List filled out by children’s parents. Multilevel modeling was used to obtain the best fitting curves describing the change over time in aggression and depression scores. These analyses were performed by sex and group.

Results

Children with overweight showed a general increase of aggressive symptoms over time, with a peak at 8 years of age in males, whereas scores of the control group decreased over time both in males and in females. Female children with overweight showed increasing levels of depressive symptoms, with a peak at 8 years of age; children with normal weight, instead, showed low scores at all assessment points. The results highlight the importance of considering the developmental trajectories of aggression and depression in children of different weight status.
Liver enzyme elevation in patients taking HAART compared with treatment naïve controls at Debre Berhan Referral Hospital: a comparative cross-sectional study, Northeast Ethiopia
Authors: Tesfa Endalamaw , Siefu Daniel , Belayneh Yididya , Mekonnen Zewdie
Published: October 2019

Objective

HAART had significantly improved the quality of life of HIV patients. However, it results different adverse effects such as: hepatotoxicity, nephrotoxicity, lipodystrophy, anemia, diarrhea, psychiatric disorder and others. Therefore, this comparative cross sectional study was designed to investigate liver enzyme elevation in patients taking HAART compared with treatment naïve controls at Debre Berhan Referral Hospital.

Result

A total of 152 individuals (76 cases and 76 controls) were included in this study. The mean ages of treatment and control groups were 37.37 and 36.38 respectively. The mean values of liver enzymes (ALT, AST and ALP), total bilirubin and direct bilirubin were significantly higher (p < 0.05) while, total protein and creatinine were significantly lower in patients taking HAART compared with treatment naïve controls. In this study, about 19 (25%) of clients in HAART treated groups and 7 (9.2%) of treatment naïve controls had showed liver enzyme changes. Moreover, 23.7% and 1.3% of the HAART treated groups developed mild and moderate liver enzyme elevation or hepatotoxicity, respectively. In this study, significant difference was observed in liver enzyme elevation between ART and pre-ART patients. As a result, regular clinical and laboratory monitoring of liver function will be necessary to prevent severe form of liver injury.
Measurement of serum tenascin-X in patients with congenital adrenal hyperplasia at risk for Ehlers–Danlos contiguous gene deletion syndrome CAH-X
Authors: Kolli Vipula , Kim Hannah , Rao Hamsini , Lao Qizong , Gaynor Alison , Milner Joshua D. , Merke Deborah P.
Published: October 2019

Objective

Approximately 10% of patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency carry a mutation that disruptsCYP21A2and the flankingTNXBgene resulting in CAH-X, a contiguous gene deletion syndrome.TNXBencodes tenascin-X (TNX), an extracellular matrix glycoprotein that plays an important role in collagen organization.TNXBimpairment is associated with Ehlers–Danlos syndrome. Symptoms include joint hypermobility, hernias and cardiac defects. We measured serum TNX using an antibody targeting the amino-terminal of the TNX protein in 161 subjects, including extensively genotyped and phenotyped CAH patients, their relatives, and healthy controls.

Results

We evaluated the potential of serum TNX as a screening tool for CAH-X. CAH-X patients, especially haploinsufficient patients carrying theTNXA-TNXBchimeric gene CAH-X-CH-1 showed reduced TNX levels compared to controls (P < 0.05). TNX levels were similar in all subjects carrying aTNXBmutation. However, CAH patients who did not harbor aTNXBmutation also had reduced TNX compared to controls (P < 0.001). Thus, measuring serum TNX is not an effective screen for CAH-X amongst patients with CAH.TNXBgenotyping is recommended for CAH patients who have symptoms of a connective tissue disorder. Epigenetic factors that influence TNX expression require further study.
Practice towards pesticide handling, storage and its associated factors among farmers working in irrigations in Gondar town, Ethiopia, 2019
Authors: Mequanint Chalie , Getachew Betelihem , Mindaye Yonas , Amare Dagnachew Eyachew , Guadu Tadesse , Dagne Henok
Published: October 2019

Objectives

The main objective of this study was to assess pesticide handling and storage practice, and its associated factors among farmers engaged in irrigation in Gondar town, Ethiopia, 2019. Community-based cross-sectional study was used to assess pesticide handling and storage practice, and its associated factors among farmers. Simple random sampling technique was used to select study subjects. Semi-structured questionnaires were used to collect data. Data were entered using Epi Info 7.0 and exported to SPSS 20. Descriptive statistics were used for some variables. Univariate and multivariable binary logistic regression was used to test the factors associated with the outcome. Adjusted odd ratio (AOR) and 95% confidence interval (CI) with P value less than 0.05 were used to report association.

Results

About 409 study subjects completed the semi-structured questionnaires. Among the studies subjects, 261 (63.8%) of them had poor pesticide handling and storage practice. Knowledge [AOR = 3.23 (95% CI 1.91, 5.46)], attitude [AOR = 1.77 (95% CI 1.11, 2.81) and educational status (informal education [AOR = 3.05 (95% CI 1.72, 5.42)], elementary education [AOR = 5.38 (95% CI 2.62, 11.06)], secondary education [AOR = 9.51 (95% CI 4.24, 21.32)] and certificate and above [AOR = 6.00 (95% CI 1.58, 22.78)]) were factors significantly associated with pesticide handling and storage practice. To improve the pesticide handling and storage practice, it is imperative to enhance the level of the farmer’s knowledge through training, and information dissemination in workshops.
Plasma cytokine profiles associated with rhodesiense sleeping sickness and falciparum malaria co-infection in North Eastern Uganda
Authors: Nsubuga Julius , Kato Charles Drago , Nanteza Ann , Matovu Enock , Alibu Vincent Pius
Published: October 2019

Background

Immunological Human African Trypanosomiasis (HAT) studies often exclude malaria, although both infections overlap in specific endemic areas. During this co-infection, it is not known whether this parasitic interaction induces synergistic or antagonistic cytokine response among humans. This study determined prevalence of Plasmodium falciparum malaria among Trypanosoma brucei rhodesiense HAT and plasma cytokine profile levels associated with HAT and/or malaria infections.

Methods

Participants were recruited at Lwala hospital in north eastern Uganda: healthy controls (30), malaria (28), HAT (17), HAT and malaria (15) diagnosed by microscopy and PCR was carried out for parasite species identification. Plasma cytokine levels of Interferon-gamma (IFN-γ), Tumour Necrosis Factor-alpha (TNF-α), Interleukin (IL)-6, IL-10 and Transforming Growth Factor-beta (TGF-β) were measured by sandwich Enzyme-Linked Immuno Sorbent Assay and data statistically analysed using Graphpad Prism 6.0.

Results

The prevalence of P. falciparum malaria among T. rhodesiense HAT cases was high (46.8%). Malaria and/or HAT cases presented significant higher plasma cytokine levels of IFN-γ, TNF-α, IL-6, IL-10 and TGF-β than healthy controls (P < 0.05). Levels of IFN-γ, IL-6 and IL-10 were significantly elevated in HAT over malaria (P < 0.05) but no significant difference in TNF-α and TGF-β between HAT and malaria (P > 0.05). Co-infection expressed significantly higher plasma IFN-γ, IL-6, and IL-10 levels than malaria (P < 0.05) but no significant difference with HAT mono-infection (P > 0.05). The TNF-α level was significantly elevated in co-infection over HAT or malaria mono-infections (P < 0.05) unlike TGF-β level. Significant positive correlations were identified between IFN-γ verses TNF-α and IL-6 verses IL-10 in co-infection (Spearman’s P < 0.05).

Conclusions

The T. b. rhodesiense significantly induced the cytokine response more than P. falciparum infections. Co-infection led to synergistic stimulation of pro-inflammatory (IFN-γ, TNF-α), and anti-inflammatory (IL-6, and IL-10) cytokine responses relative to malaria mono-infection. Level of TNF-α partially indicates the effect induced by T. b. rhodesiense and P. falciparum mono-infections or a synergistic interaction of co-infections which may have adverse effects on pathogenesis, prognosis and resolution of the infections.

Trial registration VCD-IRC/021, 26/08/2011; HS 1089, 16/01/2012
Diverse cell junctions with unique molecular composition in tissues of a sponge (Porifera)
Authors: Mitchell Jennyfer M. , Nichols Scott A.
Published: October 2019

The integrity and organization of animal tissues depend upon specialized protein complexes that mediate adhesion between cells with each other (cadherin-based adherens junctions), and with the extracellular matrix (integrin-based focal adhesions). Reconstructing how and when these cell junctions evolved is central to understanding early tissue evolution in animals. We examined focal adhesion protein homologs in tissues of the freshwater sponge,Ephydatia muelleri(phylum Porifera; class Demospongiae). Our principal findings are that (1) sponge focal adhesion homologs (integrin, talin, focal adhesion kinase, etc.) co-precipitate as a complex, separate from adherens junction proteins; (2) that actin-based structures resembling focal adhesions form at the cell–substrate interface, and their abundance is dynamically regulated in response to fluid shear; (3) focal adhesion proteins localize to both cell–cell and cell–extracellular matrix adhesions, and; (4) the adherens junction protein β-catenin is co-distributed with focal adhesion proteins at cell–cell junctions everywhere except the choanoderm, and at novel junctions between cells with spicules, and between cells with environmental bacteria. These results clarify the diversity, distribution and molecular composition of cell junctions in tissues ofE. muelleri, but raise new questions about their functional properties and ancestry.
Clinical, pathological, and laboratory diagnoses of diseases of harbour porpoises (Phocoena phocoena), live stranded on the Dutch and adjacent coasts from 2003 to 2016
Authors: van Elk Cornelis E. , van de Bildt Marco W. G. , van Run Peter R. W. A. , Bunskoek Paulien , Meerbeek Jolanda , Foster Geoffrey , Osterhaus Albert D. M. E. , Kuiken Thijs
Published: October 2019

Harbour porpoises (Phocoena phocoena) in the North Sea live in an environment heavily impacted by humans, the consequences of which are a concern for their health. Autopsies carried out on stranded harbour porpoises provide an opportunity to assess health problems in this species. We performed 61 autopsies on live-stranded harbour porpoises, which died following admission to a rehabilitation centre between 2003 and 2016. The animals had stranded on the Dutch (n = 52) and adjacent coasts of Belgium (n = 2) and Germany (n = 7). We assigned probable causes for stranding based on clinical and pathological criteria. Cause of stranding was associated in the majority of cases with pathologies in multiple organs (n = 29) compared to animals with pathologies in a single organ (n = 18). Our results show that the three most probable causes of stranding were pneumonia (n = 35), separation of calves from their mother (n = 10), and aspergillosis (n = 9). Pneumonia as a consequence of pulmonary nematode infection occurred in 19 animals. Pneumonia was significantly associated with infection with Pseudalius inflexus, Halocercus sp., and Torynurus convolutus but not with Stenurus minor infection. Half of the bacterial pneumonias (6/12) could not be associated with nematode infection. Conclusions from this study are that aspergillosis is an important probable cause for stranding, while parasitic infection is not a necessary prerequisite for bacterial pneumonia, and approximately half of the animals (29/61) probably stranded due to multiple causes. An important implication of the observed high prevalence of aspergillosis is that these harbour porpoises suffered from reduced immunocompetence.
Investigation of MiSeq reproducibility on biomarker identification
Authors: Jo Hyejun , Hong Jiwan , Unno Tatsuya
Published: October 2019

MiSeq-derived artificial sequences appeared to be of good quality, thus bioinformatics tools failed to remove MiSeq artefacts. Even after removing singleton sequences or operational taxonomic units (OTUs), it is not clear how many sequence artefacts remained. Here, 16S rRNA genes were amplified from soil, human feces, pig feces, and groundwater. These were sequenced with five separate runs of MiSeq. Subsequently, each run of MiSeq was compared through alpha and beta-diversity analyses. We found more than half the OTUs were not in consensus through the multiple MiSeq runs, resulting in varying group-specific biomarker OTUs in each MiSeq run. Thus, differential abundance test should be interpreted with caution, and we suggest that results also should be verified further with other quantification methods such as qPCR.
Antimelanogenic activities of piperlongumine derived from Piper longum on murine B16F10 melanoma cells in vitro and zebrafish embryos in vivo: its molecular mode of depigmenting action
Authors: Jeon Hwang-Ju , Kim Kyeongnam , Kim Yong-Deuk , Lee Sung-Eun
Published: October 2019

In this study, the antimelanogenic activity of piperlongumine in murine B16F10 melanoma cells and zebrafish was investigated, and its mode of antimelanogenic action was elucidated using quantitative reverse transcription-polymerase chain reaction. A melanocyte-stimulating hormone (α-MSH, 200 nM) was used to induce melanin production in B16F10 melanoma cells, and kojic acid (200 μM) was used as a positive control. Piperlongumine had no inhibitory effects on cell growth at the treated concentrations (3 and 6 μM), and it significantly reduced total melanin production. Piperlongumine decreased the expression of Mitf, Tyr, Trp-1, and Trp-2 and tyrosinase activity was also dramatically reduced by the piper amide addition under α-MSH treatment. With these findings, zebrafish embryos were used to confirm antimelanogenic activity of piperlongumine, and it showed the potent antimelanogenic activity at the concentration of 1 μM. Altogether, piperlongumine has potent antimelanogenic activity, and these results support it as a candidate for natural depigmentation agent in a cosmetic and pharmaceutical industries.
Superior mesenteric artery dissection with prolonged abdominal angina treated by laparotomy, endarterectomy, patch angioplasty, and retrograde open mesenteric stenting: a case report
Authors: Tanaka Shinichi , Fukuda Atsushi , Kawakubo Eisuke , Matsumoto Takuya
Published: October 2019

Background

Most patients with isolated superior mesenteric artery (SMA) dissection are successfully managed conservatively. However, some patients require more invasive treatment.

Case presentation

We herein describe a 45-year-old man with isolated SMA dissection. He initially underwent conservative treatment. However, because of persistent abdominal angina, we considered the need for surgical revascularization. He was successfully treated by endarterectomy, patch angioplasty, and retrograde open mesenteric stenting. The abdominal angina was stabilized thereafter.

Conclusions

The combination of endarterectomy, patch angioplasty, and retrograde open mesenteric stenting is useful for isolated SMA dissection, and long patency can be expected for some patients.
Responsiveness of PROMIS® to change in chronic obstructive pulmonary disease
Authors: Yount Susan E. , Atwood Charles , Donohue James , Hays Ron D. , Irwin Debra , Leidy Nancy Kline , Liu Honghu , Spritzer Karen L. , DeWalt Darren A.
Published: October 2019

Background

Chronic obstructive pulmonary disease (COPD) is a progressive chronic disease characterized by airflow obstruction that leads to shortness of breath and substantial negative impacts on health-related quality of life (HRQL). The course of COPD includes periodic acute exacerbations that require changes in treatment and/or hospitalizations. This study was designed to examine the responsiveness of Patient-Reported Outcomes Measurement Information System® (PROMIS®) measures to changes associated with COPD exacerbation recovery.

Methods

A longitudinal analysis using mixed-effects models was conducted of people who were enrolled while stable (n = 100) and those who experienced an acute exacerbation (n = 85). PROMIS (physical function, pain interference, pain behavior, fatigue, anxiety, depression, anger, social roles, discretionary social activities, Global Health, dyspnea severity and dyspnea functional limitations) and COPD-targeted HRQL measures were completed at baseline and at 12 weeks.

Results

We administered PROMIS measures using computer adaptive testing (CAT), followed by administration of any remaining short form (SF) items that had not yet been administered by CAT. Examination of the difference between group differences from baseline to 12 weeks in the stable and exacerbation groups revealed that the exacerbation group changed (improved) significantly more than the stable group in anxiety (p < .001 to p < .01; f2 effect size [ES] = 0.023/0.021), fatigue (p < .0001; ES = 0.036/0.047) and social roles (p < .001 to p < .05; ES = 0.035/0.024). All effect sizes were small in magnitude and smaller than hypothesized. Depression was also statistically significant (p < .05, SF only) but the ES was trivial. For all other PROMIS domains, the differences were not significant and ES were trivial.

Conclusions

This longitudinal study provides some support for the validity of the PROMIS fatigue, anxiety, and social roles domains in COPD, but further evaluation of responsiveness is warranted.
Confederation debt management since 1970
Authors: Guggenheim Basil , Meichle Mario , Nellen Thomas
Published: October 2019

This paper analyzes the Confederation’s debt management. The Confederation actively manages roll over and interest rate risk by increasing bond maturity with increasing marketable debt-to-GDP levels. It further engages in active but asymmetric, one-sided interest rate positioning; i.e., it uses mostly bonds to affect debt maturity and does so only when the interest rate environment is favorable to lock-in interest rates by issuing longer-term bonds. Debt management is mainly driven by marketable debt rather than total debt. Issuing behavior became more regular and demand-oriented during the early 1990s when marketable and total debt increased in tandem.
A review of the applications of fuel cells in microgrids: opportunities and challenges
Authors: Li Zhongliang , Zheng Zhixue , Xu Liangfei , Lu Xiaonan
Published: October 2019

Since the last two decades, microgrid, as one typical structure in smart grid framework, has been receiving increasing attention in the world. Meanwhile, fuel cell (FC), as one promising power source, has redrawn the attention of both academia and industry since the beginning of 21th century. Some encouraging achievements in FC technology have been realized thanks to the efforts taken in the last years. Due to this, it is seen that FC, as a clean and efficient energy source, is penetrating into different fields. Among the applications, integrating FCs into microgrids has shown interesting advantages on improving the performance of microgrids and promoting the use of the hydrogen energy. Some ongoing projects have shown that FCs of different power scales can be integrated into microgrids smartly and in different manners. Along with the advantages carried by the combination of the two technologies, many challenges lying on multiple domains are faced in the process. The challenges can be from the FC, the microgrid, and the integration of these two technologies. In this review paper, the advantages of integrating FCs into microgrids are summarized after recalling the knowledge background of FC. The challenges and ongoing researches on FCs and FCs based microgrids are then reviewed. Based on the analysis, the research directions are then extracted in view of the challenges.
Age-dependent changes of p53 and p63 immunoreactivities in the mouse hippocampus
Authors: Lee Tae-Kyeong , Park Young Eun , Park Cheol Woo , Kim Bora , Lee Jae-Chul , Park Joon Ha , Lee Hyang-Ah , Won Moo-Ho , Ahn Ji Hyeon
Published: October 2019

P53 and its family member p63 play important roles in cellular senescence and organismal aging. In this study, p53 and p63 immunoreactivity were examined in the hippocampus of young, adult and aged mice by using immunohistochemistry. In addition, neuronal distribution and degeneration was examined by NeuN immunohistochemistry and fluoro-Jade B fluorescence staining. Strong p53 immunoreactivity was mainly expressed in pyramidal and granule cells of the hippocampus in young mice. p53 immunoreactivity in the pyramidal and granule cells was significantly reduced in the adult mice. In the aged mice, p53 immunoreactivity in the pyramidal and granule cells was more significantly decreased. p63 immunoreactivity was strong in the pyramidal and granule cells in the young mice. p63 immunoreactivity in these cells was apparently and gradually decreased with age, showing that p63 immunoreactivity in the aged granule cells was hardly shown. However, numbers of pyramidal neurons and granule cells were not significantly decreased in the aged mice with normal aging. Taken together, this study indicates that there are no degenerative neurons in the hippocampus during normal aging, showing that p53 and p63 immunoreactivity in hippocampal neurons was progressively reduced during normal aging, which might be closely related to the normal aging processes.
Adverse childhood experiences research: commonalities with similar, arguably identical, literatures and the need for integration
Authors: Siddaway Andy P.
Published: October 2019

Adverse childhood experiences (ACEs) and their impact cannot be clearly distinguished from other distressing life experiences. Much can be therefore be learned by integrating ACEs research with similar, well-established literatures. Future research needs to explain individual differences in relationships between ACEs and particular variables and locate reliable and strong risk factors for ACEs themselves.
Struggles for Freedom within and against the Legal Order at the Borders of Europe
Authors: Rigo Enrica
Published: October 2019

The rescue of migrants at sea has recently been tackled by authoritative acts that have led to an increasing criminalization of solidarity between and toward migrants. By drawing on the case of the Mediterranea platform of activists, this article argues that the notion of arbitrariness defined as a departure from the rule of law fails to capture the ongoing conflict at the borders of Europe. By highlighting its ambivalent meaning, arbitrariness appears instead either as an authoritative attempt to impose a different order on society or as a means to contrast unorderable acts of resistance to border regimes. The article advocates the importance of reframing the demand for open borders as a call for freedom of those who challenge the pragmatic order of borders.
A luminal EF-hand mutation in STIM1 in mice causes the clinical hallmarks of tubular aggregate myopathy
Authors: Cordero-Sanchez Celia , Riva Beatrice , Reano Simone , Clemente Nausicaa , Zaggia Ivan , Ruffinatti Federico A. , Potenzieri Alberto , Pirali Tracey , Raffa Salvatore , Sangaletti Sabina , Colombo Mario P. , Bertoni Alessandra , Garibaldi Matteo , Filigheddu Nicoletta , Genazzani Armando A.
Published: October 2019

STIM and ORAI proteins play a fundamental role in calcium signaling, allowing for calcium influx through the plasma membrane upon depletion of intracellular stores, in a process known as store-operated Ca2+ entry. Point mutations that lead to gain-of-function activity of either STIM1 or ORAI1 are responsible for a cluster of ultra-rare syndromes characterized by motor disturbances and platelet dysfunction. The prevalence of these disorders is at present unknown. In this study, we describe the generation and characterization of a knock-in mouse model (KI-STIM1I115F) that bears a clinically relevant mutation located in one of the two calcium-sensing EF-hand motifs of STIM1. The mouse colony is viable and fertile. Myotubes from these mice show an increased store-operated Ca2+ entry, as predicted. This most likely causes the dystrophic muscle phenotype observed, which worsens with age. Such histological features are not accompanied by a significant increase in creatine kinase. However, animals have significantly worse performance in rotarod and treadmill tests, showing increased susceptibility to fatigue, in analogy to the human disease. The mice also show increased bleeding time and thrombocytopenia, as well as an unexpected defect in the myeloid lineage and in natural killer cells. The present model, together with recently described models bearing the R304W mutation (located on the coiled-coil domain in the cytosolic side of STIM1), represents an ideal platform to characterize the disorder and test therapeutic strategies for patients with STIM1 mutations, currently without therapeutic solutions.

This article has an associated First Person interview with Celia Cordero-Sanchez, co-first author of the paper.