Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Monday, November 2, 2020

Flow signal change in polyps after anti-vascular endothelial growth factor therapy

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journal.pone.0241230.g005&size=inline

by Chia-Jui Chang, Yi-Ming Huang, Ming-Hung Hsieh, An-Fei Li, Shih-Jen Chen

Optical coherence tomography angiography (OCTA) is a novel, non-invasive imaging tool used to detect vascular flow. The absence of a flow signal in OCTA in polyps revealed by indocyanine green angiography (ICGA) in patients with polypoidal choroidal vasculopathy (PCV) may indicate slow or compromised filling of blood flow from choroidal vessels. Naïve patients with PCV treated with intravitreal injections of aflibercept (IVI-A) were enrolled in this study to validate the hypothesis that baseline flow may affect the outcome of polyp regression in ICGA. The flow signal of polyps in OCTA was detected by manual segmentation in the corresponding location by ICGA. Polyps were defined as high-flow if both OCTA and ICGA showed positive findings, and low-flow if OCTA showed a negative flow signal in 3 consecutive horizontal scans at the polyp area shown in ICGA. A total of 24 polyps were identified in 13 PCV patients at baseline. Of these 24 polyps, 22 (91.7%) were high-flow and 2 (8.3%) wer e low-flow. After 3 monthly IVI-A, all low-flow polyps had complete regression in ICGA. Among 17 (77%) high-flow polyps at baseline that had regression after treatment, 10 (58.8%) became low-flow, while 5 (22.7%) persistent polyps remained high-flow. Flow signal of polyps as detected by OCTA could be a predictive factor for treatment response in patients with PCV. Monitoring changes in flow signal after treatment is clinically relevant.
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Potential association of LOXL1 with peritoneal dissemination in gastric cancer possibly via promotion of EMT

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journal.pone.0241140.g004&size=inline

by Qingjiang Hu, Takaaki Masuda, Shotaro Kuramitsu, Taro Tobo, Kuniaki Sato, Shinya Kidogami, Sho Nambara, Masami Ueda, Yusuke Tsuruda, Yosuke Kuroda, Shuhei Ito, Eiji Oki, Masaki Mori, Koshi Mimori

Background

Peritoneal dissemination (PD) frequently occurs in gastric cancer (GC) and is incurable. In this study, we aimed to identify novel PD-associated genes and clarify their clinical and biological significance in GC.

Materials and methods

We identified LOXL1 as a PD-associated candidate gene by in silico analysis of GC datasets (highly disseminated peritoneal GC cell line and two freely available GC datasets, GSE15459 and TCGA). Next, we evaluated the clinical significance of LOXL1 expression using RT-qPCR and immunohistochemistry staining (IHC) in a validation cohort (Kyushu cohort). Moreover, we performed gene expression analysis, including gene set enrichment analysis (GSEA) with GSE15459 and TCGA datasets. Finally, we performed a series of in vitro experiments using GC cells.

Results

In silico analysis showed that LOXL1 was overexpressed in tumor tissues of GC patients with PD and in highly disseminated peritoneal GC cell s, relative to that in the control GC patients and cells, respectively. High expression of LOXL1 was a poor prognostic factor in the TCGA dataset. Next, IHC showed that LOXL1 was highly expressed in GC cells. High LOXL1 mRNA expression was associated with poorly differentiated histological type, lymph node metastasis, and was an independent poor prognostic factor in the Kyushu validation cohort. Moreover, LOXL1 expression was positively correlated with the EMT (epithelial-mesenchymal transition) gene set in GSEA. Finally, LOXL1-overexpressing GC cells changed their morphology to a spindle-like form. LOXL1 overexpression reduced CDH1 expression; increased the expression of VIM, CDH2, SNAI2, and PLS3; and promoted the migration capacity of GC cells.

Conclusions

LOXL1 is associated with PD in GC, possibly through the induction of EMT.

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Do chronic illnesses and poverty go hand in hand?

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journal.pone.0241232.g002&size=inline

by Ruwan Jayathilaka, Sheron Joachim, Venuri Mallikarachchi, Nishali Perera, Dhanushika Ranawaka

In the global context, the health and quality of life of people are adversely affected by either one or more types of chronic diseases. The chronic pain associated with diagnosed patients may include heavy medical expenditure along with the physical and mental suffering they undergo. Usually, unbearable amounts of medical expenses are incurred, to improve or sustain the health condition of the patient. Consequently, the heavy financial burden tends to push households from a comfortable or secure life, or even from bad to worse, towards the probability of becoming poor. Hence, this study is conducted to identify the impact chronic illnesses have on poverty using data from a national survey referred as the Household Income and Expenditure Survey (HIES), with data gathered by the Department of Census and Statistics (DCS) of Sri Lanka in 2016. As such, this study is the first of its kind in Sri Lanka, declaring the originality of the study based on data collected from the local arena. Ac cordingly, the study discovered that married females who do not engage in any type of economic activity, in the age category of 40–65, having an educational level of tertiary level or below and living in the urban sector have a higher likelihood of suffering from chronic diseases. Moreover, it was inferred that, if a person is deprived from access to basic education in the level of education, lives in the rural or estate sector, or suffers from a brain disease, cancer, heart disease or kidney disease, he is highly likely to be poor. Some insights concluded from this Sri Lankan case study can also be applied in the context of other developing countries, to minimise chronic illnesses and thereby the probability of falling into poverty.
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Psychosocial factors affecting sleep misperception in middle-aged community-dwelling adults

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journal.pone.0241237.t003&size=inline

by Sungjong Park, Kyungmee Park, Jee-Seon Shim, Yoosik Youm, Junsol Kim, Eun Lee, Hyeon Chang Kim

Sleep misperception has long been a major issue in the field of insomnia research. Most studies of sleep misperception examine sleep underestimation by comparing the results of polysomnography conducted in a laboratory environment with patients' sleep diary entries. We aimed to investigate psychosocial characteristics of adults who underestimated or overestimated sleep time in a nonclinical, middle-aged community-dwelling population. We collected one week of sleep data with wrist-worn accelerometers. We used egocentric social network analysis to analyze the effects of psychosocial factors. Among 4,060 study participants, 922 completed the accelerometer substudy. Underestimation was defined as an accelerometer-measured sleep time ≥ 6 h and a subjective sleep time
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Serotonin stimulated parathyroid hormone related protein induction in the mammary epithelia by transglutaminase-dependent serotonylation

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journal.pone.0241192.g004&size=inline

by Celeste M. Sheftel, Laura L. Hernandez

Mammary-derived serotonin has been implicated in breast-to-bone communication during lactation by increasing parathyroid hormone related-protein (PTHrP) in the mammary gland. It is well established that PTHrP acts on the bone to liberate calcium for milk synthesis during lactation; however, the mechanism of serotonin's regulation of PTHrP has not been fully elucidated. Recently, serotonylation has been shown to be involved in a variety of physiological processes mediated by serotonin. Therefore, we investigated whether serotonylation is involved in serotonin's regulation of PTHrP in the mammary gland using lactogenically differentiated mouse mammary epithelial cells. We investigated the effect of increased intracellular serotonin using the antidepressant fluoxetine or 5-hydroxytryptophan (serotonin precursor), with or without transglutaminase inhibition and the corresponding action on PTHrP induction and activity. Treatment with fluoxetine or 5-hydroxytryptophan significantly inc reased intracellular serotonin concentrations and subsequently increased PTHrP gene expression, which was reduced with transglutaminase inhibition. Furthermore, we determined that transglutaminase activity is increased with lactogenic differentiation and 5-hydroxytryptophan or fluoxetine treatment. We investigated whether RhoA, Rac1, and Rab4 were potential serotonylation target proteins. We speculate that RhoA is potentially a serotonylation target protein. Our data suggest that serotonin regulates PTHrP induction in part through the process of serotonylation under lactogenic conditions in mouse mammary epithelial cells.
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Mechanisms of gait phase entrainment in healthy subjects during rhythmic electrical stimulation of the medial gastrocnemius

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journal.pone.0241339.g012&size=inline

by Jenna E. Thorp, Peter Gabriel Adamczyk

Studies have shown that human gait entrains to rhythmic bursts of ankle torque for perturbation intervals both slightly shorter and slightly longer than the natural stride period while walking on a treadmill and during overground walking, with phase alignment such that the torque adds to ankle push-off. This study investigated whether human gait also entrains to align the phase of rhythmic electrical stimulation of the gastrocnemius muscle with the timing of ankle push-off. In addition, this study investigated the muscle response to electrical stimulation at different phases of the gait cycle. We found that for both treadmill and overground walking entrainment was observed with phasing that aligned the stimuli with ankle push-off or just before foot contact. Achilles tendon wave speed measurements showed a significant difference (increase) in tendon load when electrical stimulation was applied just after foot contact and during swing phase, with a greater increase for higher amplitud es of electrical stimulation. However, stimulation did not increase tendon load when the timing coincided with push-off. Stride period measurements also suggest the effect of electrical stimulation is sensitive to the gait phase it is applied. These results confirmed that timing aligned with push-off is an attractor for electrical stimulation-induced perturbations of the medial gastrocnemius, and that the muscle response to stimulation is sensitive to timing and amplitude. Future research should investigate other muscles and timings and separate sensory vs. motor contributions to these phenomena.
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New insights into the existing image encryption algorithms based on DNA coding

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journal.pone.0241184.g011&size=inline

by Xianglian Xue, Dongsheng Zhou, Changjun Zhou

Because a DNA nucleotide sequence has the characteristics of large storage capacity, high parallelism, and low energy consumption, DNA cryptography is favored by information security researchers. Image encryption algorithms based on DNA coding have become a research hotspot in the field of image encryption and security. In this study, based on a comprehensive review of the existing studies and their results, we present new insights into the existing image encryption algorithms based on DNA coding. First, the existing algorithms were summarized and classified into five types, depending on the type of DNA coding: DNA fixed coding, DNA dynamic coding, different types of base complement operation, different DNA sequence algebraic operations, and combinations of multiple DNA operations. Second, we analyzed and studied each classification algorithm using simulation and obtained their advantages and disadvantages. Third, the DNA coding mechanisms, DNA algebraic operations, and DNA algebraic combination operations were compared and discussed. Then, a new scheme was proposed by combining the optimal coding mechanism with the optimal DNA coding operation. Finally, we revealed the shortcomings of the existing studies and the future direction for improving image encryption methods based on DNA coding.
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Lithium intoxication

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Lithium intoxication is a tricky issue, with a variety of different forms which may call for different therapies (acute, chronic, or acute-on-chronic intoxication).  To further complicate matters, the pathophysiology of lithium toxicity isn't understood – particularly, how lithium levels might relate to chronic neurotoxicity (SILENT syndrome).  Finally, as is often the case in toxicology, there […]

EMCrit Project by Josh Farkas.

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How health condition labels affect behavioural intentions

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journal.pone.0240985.g002&size=inline

by Rae Thomas, Mark T. Spence, Rajat Roy, Elaine Beller

Objectives

We examined the effect of 'labels' versus 'descriptions' across four asymptomatic health conditions: pre-diabetes, pre-hypertension, mild hyperlipidaemia, and chronic kidney disease stage 3A, on participants' intentions to pursue further tests. There were four secondary objectives: 1) assessing confidence and satisfaction in their intention to test further; 2) revealing psychological drivers affecting intentions; 3) exploring whether intentions, confidence and satisfaction differ by label vs. description and health condition; and 4) producing a perceptual map of illnesses by label condition.

Methods

Practitioner validated health-related scenarios were used. Two variants of each condition were developed. Participants were recruited through Qualtrics from Australia, Ireland and Canada and randomly assigned two 'labelled' or two 'descriptive' scenarios.

Results

There was no significant difference in intentions to test between label and descr iption conditions (95% CI -0.76 to 0.33 points, p = 0.4). Confidence and satisfaction were both positively associated with intentions: regression coefficient (β) for confidence β = 0.58 points (95% CI 0.49 to 0.68, p p Conclusions

Unlike studies investigating symptomatic illnesses, the disease label effect on behavioural intentions was not supported suggesting that reducing demand for medical services for borderline cases cannot be achieved by labelling. The average intention to test score was higher in this sample than previous symptomatic health-related studies and there was a positive relationship between increased intentions and confidence/satisfaction in one's decision. Exploratory insights suggested perceptions of the four labelled asymptomatic illnesses all shifted toward greater levels of dread and concern compared to their respective description condition.

Trial registration

ACTRN12618000392268.

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Automated classification of bacterial cell sub-populations with convolutional neural networks

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journal.pone.0241200.g006&size=inline

by Denis Tamiev, Paige E. Furman, Nigel F. Reuel

Quantification of phenotypic heterogeneity present amongst bacterial cells can be a challenging task. Conventionally, classification and counting of bacteria sub-populations is achieved with manual microscopy, due to the lack of alternative, high-throughput, autonomous approaches. In this work, we apply classification-type convolutional neural networks (cCNN) to classify and enumerate bacterial cell sub-populations (B. subtilis clusters). Here, we demonstrate that the accuracy of the cCNN developed in this study can be as high as 86% when trained on a relatively small dataset (81 images). We also developed a new image preprocessing algorithm, specific to fluorescent microscope images, which increases the amount of training data available for the neural network by 72 times. By summing the classified cells together, the algorithm provides a total cell count which is on parity with manual counting, but is 10.2 times more consistent and 3.8 times faster. Finally, this work presents a complete solution framework for those wishing to learn and implement cCNN in their synthetic biology work.
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The association between change of soluble tumor necrosis factor receptor R1 (sTNF-R1) measurements and cardiovascular and all-cause mortality—Results from the population-based (Cardiovascular Disease, Living and Ageing in Halle) CARLA study 2002–2016

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journal.pone.0241213.g002&size=inline

by Lamiaa Hassan, Daniel Medenwald, Daniel Tiller, Alexander Kluttig, Beatrice Ludwig-Kraus, Frank Bernhard Kraus, Karin H. Greiser, Rafael Mikolajczyk

Aims

Single measurements of higher levels of soluble tumor necrosis factor receptor I (sTNF-R1) have been shown to be associated with increased risk of mortality. However, up to date, little is known about the underlying temporal dynamics of sTNF-R1 concentrations and their relation with mortality. We aimed to characterize the effect of changes in sTNFR-1 levels on all-cause and cardiovascular mortality, independent from other established risk factors for mortality, including other inflammatory markers.

Methods

We used data of the population based cohort study CARLA and included 1408 subjects with sTNF-R1 measured at baseline (2002–2006) and first follow-up (2007–2010). Cox proportional hazard models were used to assess the association of baseline and follow-up sTNF-R1 measurements with all-cause and cardiovascular mortality during ~10 years since the first follow-up after adjusting for relevant confounders.

Results

Based on 211 deaths among 1408 subjects, per ea ch doubling of the baseline sTNF-R1, the risk of all-cause mortality was increased by about 30% (Hazard ratio 1.28, 95% Confidence Interval 0.6–2.7), while per each doubling of the follow-up level of sTNF-R1 mortality was 3-fold (3.11, 1.5–6.5) higher in a model including both measurements and adjusting for confounders. The results were mainly related to the cardiovascular mortality (5.9, 2.1–16.8 per each doubling of follow up sTNF-R1 value).

Conclusion

Solely the follow-up value, rather than its change from baseline, predicted future mortality. Thus, while sTNF-R1 levels are associated with mortality, particularly cardiovascular, over a long-time period in the general population, if they change, the earlier measurements play no or little role.

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