bluuebunny/crossref_metadata_2025 huggingface dataset:
High capacity DNA data storage with variable-length Oligonucleotides using repeat accumulate code and hybrid mapping
Authors: Wang Yixin , Noor-A-Rahim Md , Zhang Jingyun , Gunawan Erry , Guan Yong Liang , Poh Chueh Loo
Published: December 2019

Background

With the inherent high density and durable preservation, DNA has been recently recognized as a distinguished medium to store enormous data over millennia. To overcome the limitations existing in a recently reported high-capacity DNA data storage while achieving a competitive information capacity, we are inspired to explore a new coding system that facilitates the practical implementation of DNA data storage with high capacity.

Result

In this work, we devised and implemented a DNA data storage scheme with variable-length oligonucleotides (oligos), where a hybrid DNA mapping scheme that converts digital data to DNA records is introduced. The encoded DNA oligos stores 1.98 bits per nucleotide (bits/nt) on average (approaching the upper bound of 2 bits/nt), while conforming to the biochemical constraints. Beyond that, an oligo-level repeat-accumulate coding scheme is employed for addressing data loss and corruption in the biochemical processes. With a wet-lab experiment, an error-free retrieval of 379.1 KB data with a minimum coverage of 10x is achieved, validating the error resilience of the proposed coding scheme. Along with that, the theoretical analysis shows that the proposed scheme exhibits a net information density (user bits per nucleotide) of 1.67 bits/nt while achieving 91% of the information capacity.

Conclusion

To advance towards practical implementations of DNA storage, we proposed and tested a DNA data storage system enabling high potential mapping (bits to nucleotide conversion) scheme and low redundancy but highly efficient error correction code design. The advancement reported would move us closer to achieving a practical high-capacity DNA data storage system.
RETRACTED ARTICLE: MicroRNA-338-3p suppresses ovarian cancer cells growth and metastasis: implication of Wnt/catenin beta and MEK/ERK signaling pathways
Authors: Zhang Ruitao , Shi Huirong , Ren Fang , Feng Wei , Cao Yuan , Li Gailing , Liu Zheying , Ji Pengcheng , Zhang Minghui
Published: December 2019

Background

Downregulation of microRNA-338-3p (miR-338-3p) was detected in many malignant tumors, which indicated miR-338-3p might serve as a role of antioncogene in those cancers. The present study aimed to explore the roles of miR-338-3p in the growth and metastasis of ovarian cancer cells and elaborate the underlying possible molecular mechanism.

Methods

Multiply biomedical databases query and KEGG pathway enrichment assay were used to infilter possible target genes and downstream pathways regulated by miR-338-3p. Overexpression miR-338-3p lentiviral vectors were transfected into ovarian cancer OVCAR-3 and OVCAR-8 cells, cell proliferation, migration and invasion were analyzed by MTT, colony formation, transwell, Matrigel assay and xenograft mouse model. One 3′-untranslated regions (UTRs) binding target gene of miR-338-3p, MACC1 (MET transcriptional regulator MACC1), and its regulated gene MET and downstream signaling pathway activities were examined by western blot.

Results

Biomedical databases query indicated that miR-338-3p could target MACC1 gene and regulate Met, downstream Wnt/Catenin beta and MEK/ERK pathways. Rescue of miR-338-3p could inhibit the proliferation, migration and invasion of ovarian cancer cells, and suppress the growth and metastasis of xenograft tumor. Restoration of miR-338-3p could attenuate MACC1 and Met overexpression induced growth, epithelial to mesenchymal transition (EMT) and activities of Wnt/Catenin beta and MEK/ERK signaling in vitro and in vivo.

Conclusions

The present data indicated that restoration of miR-338-3p could suppress the growth and metastasis of ovarian cancer cells, which might due to the inhibition of proliferation and EMT induced by MACC1, Met and its downstream Wnt/Catenin beta and MEK/ERK signaling pathways.
Responses of Methanosarcina barkeri to acetate stress
Authors: He Pinjing , Duan Haowen , Han Wenhao , Liu Yang , Shao Liming , Lü Fan
Published: December 2019

Background

Anaerobic digestion of easily degradable biowaste can lead to the accumulation of volatile fatty acids, which will cause environmental stress to the sensitive methanogens consequently. The metabolic characteristics of methanogens under acetate stress can affect the overall performance of mixed consortia. Nevertheless, there exist huge gaps in understanding the responses of the dominant methanogens to the stress, e.g., Methanosarcinaceae. Such methanogens are resistant to environmental deterioration and able to utilize multiple carbon sources. In this study, transcriptomic and proteomic analyses were conducted to explore the responses of Methanosarcina barkeri strain MS at different acetate concentrations of 10, 25, and 50 mM.

Results

The trend of OD600 and the regulation of the specific genes in 50 mM acetate, indicated that high concentration of acetate promoted the acclimation of M. barkeri to acetate stress. Acetate stress hindered the regulation of quorum sensing and thereby eliminated the advantages of cell aggregation, which was beneficial to resist stress. Under acetate stress, M. barkeri allocated more resources to enhance the uptake of iron to maintain the integrities of electron-transport chains and other essential biological processes. Comparing with the initial stages of different acetate concentrations, most of the genes participating in acetoclastic methanogenesis did not show significantly different expressions except hdrB1C1, an electron-bifurcating heterodisulfide reductase participating in energy conversion and improving thermodynamic efficiency. Meanwhile, vnfDGHK and nifDHK participating in nitrogen fixation pathway were upregulated.

Conclusion

In this work, transcriptomic and proteomic analyses are combined to reveal the responses of M. barkeri to acetate stress in terms of central metabolic pathways, which provides basic clues for exploring the responses of other specific methanogens under high organics load. Moreover, the results can also be used to gain insights into the complex interactions and geochemical cycles among natural or engineered populations. Furthermore, these findings also provide the potential for designing effective and robust anaerobic digesters with high organic loads.
A new methodology for sporogony research of avian haemoproteids in laboratory-reared Culicoides spp., with a description of the complete sporogonic development of Haemoproteus pastoris
Authors: Bukauskaitė Dovilė , Chagas Carolina Romeiro Fernandes , Bernotienė Rasa , Žiegytė Rita , Ilgūnas Mikas , Iezhova Tatjana , Valkiūnas Gediminas
Published: December 2019

Background

Haemosporidian parasites of the genus Haemoproteus (Haemoproteidae) are widespread and cause haemoproteosis in birds and therefore, their diversity, ecology and evolutionary biology have become subjects of intensive research. However, the vectors and transmission patterns of haemoproteids as well as the epidemiology of haemoproteosis remain insufficiently investigated. Several species of Culicoides (Ceratopogonidae) support complete sporogony of haemoproteids belonging to the subgenus Parahaemoproteus. However, experimental research with these fragile insects is difficult to design in the field, particularly because their abundance markedly depends on seasonality. This is an obstacle for continuous sampling of sufficient numbers of naturally infected or experimentally exposed midges from wildlife. We developed simple methodology for accessing sporogonic development of haemoproteids in laboratory-reared Culicoides nubeculosus. This study aimed to describe the mosaic of methods constituting this methodology, which was applied for investigation of the sporogonic development of Haemoproteus (Parahaemoproteus) pastoris, a widespread parasite of the common starling Sturnus vulgaris.

Methods

The methodology consists of the following main stages: (i) laboratory rearing of C. nubeculosus from the egg stage to adult insects; (ii) selection of naturally infected birds, the donors of mature gametocytes to expose biting midges; (iii) experimental exposure of insects and their laboratory maintenance; and (iv) dissection of exposed insects. Biting midges were exposed to H. pastoris (cytochrome b lineage hLAMPUR01) detected in one naturally infected common starling. Engorged insects were dissected at intervals in order to follow sporogony. Microscopic examination and PCR-based methods were used to identify the sporogonic stages and to confirm the presence of the parasite lineage in infected insects, respectively.

Results

Culicoides nubeculosus females were successfully reared and exposed to H. pastoris, which completed sporogonic development 7–9 days post-infection when sporozoites were observed in the salivary glands.

Conclusions

The new methodology is easy to use and non-harmful for birds, providing opportunities to access the sporogonic stages of Parahaemoproteus parasites, which might be used in a broad range of parasitology and genetic studies. Culicoides nubeculosus is an excellent experimental vector of subgenus Parahaemoproteus and is recommended for various experimental studies aiming investigation of sporogony of these pathogens.
Maintenance of active chromatin states by HMGN2 is required for stem cell identity in a pluripotent stem cell model
Authors: Garza-Manero Sylvia , Sindi Abdulmajeed Abdulghani A. , Mohan Gokula , Rehbini Ohoud , Jeantet Valentine H. M. , Bailo Mariarca , Latif Faeezah Abdul , West Maureen P. , Gurden Ross , Finlayson Lauren , Svambaryte Silvija , West Adam G. , West Katherine L.
Published: December 2019

Background

Members of the HMGN protein family modulate chromatin structure and influence epigenetic modifications. HMGN1 and HMGN2 are highly expressed during early development and in the neural stem/progenitor cells of the developing and adult brain. Here, we investigate whether HMGN proteins contribute to the chromatin plasticity and epigenetic regulation that is essential for maintaining pluripotency in stem cells.

Results

We show that loss ofHmgn1orHmgn2in pluripotent embryonal carcinoma cells leads to increased levels of spontaneous neuronal differentiation. This is accompanied by the loss of pluripotency markersNanogandSsea1, and increased expression of the pro-neural transcription factorsNeurog1andAscl1. Neural stem cells derived from theseHmgn-knockout lines also show increased spontaneous neuronal differentiation andNeurog1expression. The loss of HMGN2 leads to a global reduction in H3K9 acetylation, and disrupts the profile of H3K4me3, H3K9ac, H3K27ac and H3K122ac at theNanogandOct4loci. At endodermal/mesodermal genes,Hmgn2-knockout cells show a switch from a bivalent to a repressive chromatin configuration. However, at neuronal lineage genes whose expression is increased, no epigenetic changes are observed and their bivalent states are retained following the loss of HMGN2.

Conclusions

We conclude that HMGN1 and HMGN2 maintain the identity of pluripotent embryonal carcinoma cells by optimising the pluripotency transcription factor network and protecting the cells from precocious differentiation. Our evidence suggests that HMGN2 regulates active and bivalent genes by promoting an epigenetic landscape of active histone modifications at promoters and enhancers.
Association of predicted 10 years cardiovascular mortality risk with duration of HIV infection and antiretroviral therapy among HIV-infected individuals in Durban, South Africa
Authors: Todowede Olamide O. , Sartorius Benn , Magula Nombulelo , Schutte Aletta E.
Published: December 2019

Background

South Africa has the largest population of human immunodeficiency virus (HIV) infected patients on antiretroviral therapy (ART) realising the benefits of increased life expectancy. However, this population may be susceptible to cardiovascular disease (CVD) development, due to the chronic consequences of a lifestyle-related combination of risk factors, HIV infection and ART. We predicted a 10-year cardiovascular mortality risk in an HIV-infected population on long-term ART, based on their observed metabolic risk factor profile.

Methods

We extracted data from hospital medical charts for 384 randomly selected HIV-infected patients aged ≥ 30 years. We defined metabolic syndrome (MetS) subcomponents using the International Diabetes Federation definition. A validated non-laboratory-based model for predicting a 10-year CVD mortality risk was applied and categorised into five levels, with the thresholds ranging from very low-risk (< 5%) to very high-risk scores (> 30%).

Results

Among the 384 patients, with a mean (± standard deviation) age of 42.90 ± 8.20 years, the proportion of patients that were overweight/obese was 53.3%, where 50.9% had low high-density lipoprotein (HDL) cholesterol and 21 (17.5%) had metabolic syndrome. A total of 144 patients with complete data allowed a definitive prediction of a 10-year CVD mortality risk. 52% (95% CI 44–60) of the patients were stratified to very low risk (< 5%) compared to 8% (95% CI 4–13) that were at a very high risk (> 30%) of 10-year CVD mortality. The CVD risk grows with increasing age (years), 57.82 ± 6.27 among very high risk and 37.52 ± 4.50; p < 0.001 in very low risk patients. Adjusting for age and analysing CVD risk mortality as a continuous risk score, increasing duration of HIV infection (p = 0.002) and ART (p = 0.007) were significantly associated with increased predicted 10 year CVD mortality risk. However, there was no association between these factors and categorised CVD mortality risk as per recommended scoring thresholds.

Conclusions

Approximately 1 in 10 HIV-infected patients is at very high risk of predicted 10-year CVD mortality in our study population. Like uninfected individuals, our study found increased age as a major predictor of 10-year mortality risk and high prevalence of metabolic syndrome. Additional CVD mortality risk due to the duration of HIV infection and ART was seen in our population, further studies in larger and more representative study samples are encouraged. It recommends an urgent need for early planning, prevention and management of metabolic risk factors in HIV populations, at the point of ART initiation.
Effects of virtual reality-based cognitive training in older adults living without and with mild dementia: a pretest–posttest design pilot study
Authors: Zając-Lamparska Ludmiła , Wiłkość-Dębczyńska Monika , Wojciechowski Adam , Podhorecka Marta , Polak-Szabela Anna , Warchoł Łukasz , Kędziora-Kornatowska Kornelia , Araszkiewicz Aleksander , Izdebski Paweł
Published: December 2019

Objective

Modern technologies are increasingly used in the development of cognitive interventions for older adults. Research into possible applications of virtual reality in such interventions has begun only recently. The aim of present study was to evaluate the effects of 8 sessions of VR-based cognitive training using the GRADYS game in healthy older adults (n = 72; aged 60–88) and older adults living with mild dementia (n = 27; aged 60–89).

Results

Older adults with mild dementia demonstrated worse baseline cognitive performance than participants without dementia. Both groups showed progress in training, which was greater in healthy older adults. There were also significant differences in cognitive functioning before and after the training. However, positive changes were revealed almost exclusively in the group of older adults without dementia. Based on the findings, we can recommend the GRADYS game for cognitive enhancement and as a possible counter-measure for cognitive decline experienced in normal cognitive ageing. Our results provide also support for the usefulness of VR technology in cognitive interventions in older adults. The use of the GRADYS game in persons living with dementia, however, would require several of the hardware and software modifications.

Trial registration ISRCTN17613444, date of registration: 10.09.2019. Retrospectively registered
PAD-Beads enrichment enhances detection of PrPSc using real-time quaking-induced conversion
Authors: Hwang Soyoun , Dassanayake Rohana P. , Nicholson Eric M.
Published: December 2019

Objective

Scrapie is a transmissible spongiform encephalopathy (TSE) that naturally occurs in sheep and goats. This fatal neurodegenerative disease results from misfolding of the normal cellular prion protein (PrPC) to a pathogenic prion protein form (PrPSc). This pathogenic form, PrPSc, accumulates in the brain and lymphoid tissues. The presence of PrPSc can be detected by an in vitro conversion assay known as real-time quaking induced conversion (RT-QuIC). RT-QuIC has been used to detect PrPSc in a variety of biological tissues from brains to fluids. While this technique is both rapid and sensitive, enhancing the detection of prions would be valuable in the diagnostic laboratories.

Results

In this study, we assessed whether PrPSc detection sensitivity of RT-QuIC can be increased by enriching PrPSc in scrapie tissue homogenates using commercially available aggregated protein binding ligands coated magnetic beads (PAD-Beads). Coupling of RT-QuIC to PAD-Beads based cleanup allowed detection of PrPSc rapidly and without dilution of scrapie sheep brain homogenates prior to RT-QuIC. The PAD-Beads sample pretreatment step prior to RT-QuIC is a useful enhancement in the diagnosis of TSEs.
Human plasma dynamically quenches the fluorescein at the initial point of oxygen radical absorption capacity (ORAC) assay
Authors: Gunawardena Harshi , Silva Renuka , Ranasinghe Pathmasiri
Published: December 2019

Objective

Oxygen radical absorbance capacity (ORAC) assay measures the quenching of fluorescent probe by peroxyl radicals. Antioxidants present in biological systems block the quenching of fluorescence probe. We experienced the dynamic quenching of fluorescein, the fluorescence probe used in ORAC assay by the human plasma while plasma ORAC assay was optimized. Therefore, for the first time, we report the quenching of fluorescein by human plasma at the initial point of ORAC assay.

Results

Aqueous whole and non-protein fractions of plasma were used in the analysis. Since the both fractions showed a similar pattern of quenching at the initial stage, quenched percentage of fluorescein was calculated and added to each sample in subsequent analysis. Addition of extra 20% fluorescein allowed plasma samples to quench the required amount of fluorescein and follow the normal decay curves afterwards. Further, change of fluorescein quenching (ΔF/F0) disclosed a dose dependent linear relationship with plasma (R2 = 0.8). It can be speculated that dynamic quenching exhibited by human plasma biomolecule/s at the initial stage would be of non-protein aqueous phase molecule/s. We suggest initiating further studies to detect, identify and quantify the fluorescein quenching biomolecules present in human plasma for further improvements in plasma ORAC assay.
Methylomic profiling in trisomy 21 identifies cognition- and Alzheimer’s disease-related dysregulation
Authors: Haertle Larissa , Müller Tobias , Lardenoije Roy , Maierhofer Anna , Dittrich Marcus , Riemens Renzo J. M. , Stora Samantha , Roche Mathilde , Leber Markus , Riedel-Heller Steffi , Wagner Michael , Scherer Martin , Ravel Aimé , Mircher Clotilde , Cieuta-Walti Cecile , Durand Sophie , van de Hove Daniel L. A. , Hoffmann Per , Ramirez Alfredo , Haaf Thomas , El Hajj Nady , Mégarbané André
Published: December 2019

Background

Trisomy 21 (T21) is associated with intellectual disability that ranges from mild to profound with an average intellectual quotient of around 50. Furthermore, T21 patients have a high risk of developing Alzheimer’s disease (AD) early in life, characterized by the presence of senile plaques of amyloid protein and neurofibrillary tangles, leading to neuronal loss and cognitive decline. We postulate that epigenetic factors contribute to the observed variability in intellectual disability, as well as at the level of neurodegeneration seen in T21 individuals.

Materials and Methods

A genome-wide DNA methylation study was performed using Illumina Infinium® MethylationEPIC BeadChips on whole blood DNA of 3 male T21 patients with low IQ, 8 T21 patients with high IQ (4 males and 4 females), and 21 age- and sex-matched control samples (12 males and 9 females) in order to determine whether DNA methylation alterations could help explain variation in cognitive impairment between individuals with T21. In view of the increased risk of developing AD in T21 individuals, we additionally investigated the T21-associated sites in published blood DNA methylation data from the AgeCoDe cohort (German study on Ageing, Cognition, and Dementia). AgeCoDe represents a prospective longitudinal study including non-demented individuals at baseline of which a part develops AD dementia at follow-up.

Results

Two thousand seven hundred sixteen differentially methylated sites and regions discriminating T21 and healthy individuals were identified. In the T21 high and low IQ comparison, a single CpG located in the promoter of PELI1 was differentially methylated after multiple testing adjustment. For the same contrast, 69 differentially methylated regions were identified. Performing a targeted association analysis for the significant T21-associated CpG sites in the AgeCoDe cohort, we found that 9 showed significant methylation differences related to AD dementia, including one in the ADAM10 gene. This gene has previously been shown to play a role in the prevention of amyloid plaque formation in the brain.

Conclusion

The differentially methylated regions may help understand the interaction between methylation alterations and cognitive function. In addition, ADAM10 might be a valuable blood-based biomarker for at least the early detection of AD.
Human fetal skin-derived stem cell secretome enhances radiation-induced skin injury therapeutic effects by promoting angiogenesis
Authors: Rong Xiaoli , Li Jiannan , Yang Yanyan , Shi Liyan , Jiang Tiechao
Published: December 2019

Background

Radiation dermatitis is a refractory skin injury caused by radiotherapy. Human fetal skin-derived stem cell (hFSSC) is a preferable source for cell therapy and skin tissue regeneration. In the present study, we investigated the repair effect of using hFSSC secretome on a radiation skin injury model in rats.

Methods

We prepared the hFSSC secretome and studied its effects on the proliferation and tube formation of human umbilical vein endothelial cell (HUVEC) in vitro. Furthermore, we used a Sr-90 radiation-induced skin injury model of rats and evaluated the effects of hFSSC secretome on radiation skin injury in vivo.

Results

The results showed that hFSSC secretome significantly promoted the proliferation and tube formation of HUVEC in vitro; in addition, hFSSC secretome-treated rats exhibited higher healing quality and faster healing rate than the other two control groups; the expression level of collagen type III α 1 (Col3A1), transforming growth factor β3 (TGF-β3), angiotensin 1 (Ang-1), angiotensin 2 (Ang-2), vascular endothelial growth factor (VEGF), and placental growth factor (PLGF) was significantly increased, while collagen type I α 2 (Col1A2) and transforming growth factor β1 (TGF-β1) were decreased in hFSSC secretome group.

Conclusions

In conclusion, our results provided the first evidence on the effects of hFSSC secretome towards radiation-induced skin injury. We found that hFSSC secretome significantly enhanced radiation dermatitis angiogenesis, and the therapeutic effects could match with the characteristics of fetal skin. It may act as a kind of novel cell-free therapeutic approach for radiation-induced cutaneous wound healing.
Genetic tool for fate mapping of Oct4 (Pou5f1)-expressing cells and their progeny past the pluripotency stage
Authors: Kuzmin Andrey A. , Ermakova Veronika V. , Sinenko Sergey A. , Ponomartsev Sergey V. , Starkova Tatiana Y. , Skvortsova Elena V. , Cherepanova Olga , Tomilin Alexey N.
Published: December 2019

Background

Methods based on site-specific recombinases are widely used in studying gene activities in vivo and in vitro. In these studies, constitutively active or inducible variants of these recombinases are expressed under the control of either lineage-specific or ubiquitous promoters. However, there is a need for more advanced schemes that combine these features with possibilities to choose a time point from which lineage tracing starts in an autonomous fashion. For example, the key mammalian germline gatekeeper gene Oct4 (Pou5f1) is expressed in the peri-implantation epiblast which gives rise to all cells within embryos. Thus the above techniques are hardly applicable to Oct4 tracing past the epiblast stage, and the establishment of genetic tools addressing such a limitation is a highly relevant pursuit.

Methods

The CRISPR/Cas9 tool was used to manipulate the genome of mouse embryonic stem cells (ESCs), and various cell culture technics—to maintain and differentiate ESCs to neural cell, lentivirus-based reprogramming technique—to generate induced pluripotent stem cells (iPSCs).

Results

In this paper, we have developed a two-component genetic system (referred to as O4S) that allows tracing Oct4 gene activity past the epiblast stage of development. The first component represents a knock-in of an ubiquitous promoter-driven inducible Cre, serving as a stop signal for downstream tdTomato. Upon activation of Cre activity with 4-hydroxytamoxifen (4-OHT) at any given time point, the recombinase excises a stop signal and poses the second component of the system—the FlpO recombinase, knocked into 3’UTR of Oct4, to be expressed upon activation of the latter gene. Oct4-driven expression of FlpO, in turn, triggers the tdTomato expression and thus, permanently marks Oct4+ cells and their progeny. We have validated the O4S system in cultured ESCs and shown that it is capable, for example, to timely capture an activation of Oct4 gene during the reprogramming of somatic cells into iPSCs.

Conclusions

The developed O4S system can be used to detect Oct4 activation event, both permanent and transient, in somatic cell types outside the germline. The approach can be equally adjusted to other genes, provided the first component of the system is placed under transcriptional control of these genes, thus, making it a valuable tool for cell fate mapping in mice.
Activation of type I interferon antiviral response in human neural stem cells
Authors: Lin Jhao-Yin , Kuo Rei-Lin , Huang Hsing-I
Published: December 2019

Background

Neural stem cells (NSCs) residing in the central nervous system play an important role in neurogenesis. Several viruses can infect these neural progenitors and cause severe neurological diseases. The innate immune responses against the neurotropic viruses in these tissue-specific stem cells remain unclear.

Methods

Human NSCs were transfected with viral RNA mimics or infected with neurotropic virus for detecting the expression of antiviral interferons (IFNs) and downstream IFN-stimulated antiviral genes.

Results

NSCs are able to produce interferon-β (IFN-β) (type I) and λ1 (type III) after transfection with poly(I:C) and that downstream IFN-stimulated antiviral genes, such as ISG56 and MxA, and the viral RNA sensors RIG-I, MDA5, and TLR3, can be expressed in NSCs under poly(I:C) or IFN-β stimulation. In addition, our results show that the pattern recognition receptors RIG-I and MDA5, as well as the endosomal pathogen recognition receptor TLR3, but not TLR7 and TLR8, are involved in the activation of IFN-β transcription in NSCs. Furthermore, NSCs infected with the neurotropic viruses, Zika and Japanese encephalitis viruses, are able to induce RIG-I-mediated IFN-β expression.

Conclusion

Human NSCs have the ability to activate IFN signals against neurotropic viral pathogens.
Cardiac hypertrophy with obesity is augmented after pregnancy in C57BL/6 mice
Authors: Che Chen , Dudick Kayla , Shoemaker Robin
Published: December 2019

Background

Over a third of reproductive-age women in the USA are obese, and the prevalence of cardiovascular disease (CVD) is rising in premenopausal women. Cardiac hypertrophy is an independent predictor of CVD. In contrast to pregnancy, where transiently increased left ventricular (LV) mass is not associated with cardiac damage, obesity-mediated cardiac hypertrophy is pathological. There is a paucity of data describing the effect of obesity during pregnancy on maternal cardiovascular health. The purpose of this study was to determine the long-term effect of obesity during pregnancy on cardiac function and structure in mice.

Methods

Female C57BL/6 J mice were fed a high-fat (HF) or a low-fat (LF) diet for 20 weeks. After 4 weeks, LF- and HF-fed female mice were either crossed with males to become pregnant or remained non-pregnant controls. Following delivery, pups were euthanized, and females maintained on respective diets. After 20 weeks of diet feeding, cardiac function was quantified by echocardiography, and plasma leptin and adiponectin concentrations quantified in LF- and HF-fed postpartum and nulliparous females. mRNA abundance of genes regulating cardiac hypertrophy and remodeling was quantified from left ventricles using the NanoString nCounter Analysis System. Cardiac fibrosis was assessed from picrosirius red staining of left ventricles.

Results

HF-fed postpartum mice had markedly greater weight gain and fat mass expansion with obesity, associated with significantly increased LV mass, cardiac output, and stroke volume compared with HF-fed nulliparous mice. Plasma leptin, but not adiponectin, concentrations were correlated with LV mass in HF-fed females. HF feeding increased LV posterior wall thickness; however, LV chamber diameter was only increased in HF-fed postpartum females. Despite the marked increase in LV mass in HF-fed postpartum mice, mRNA abundance of genes regulating fibrosis and interstitial collagen content was similar between HF-fed nulliparous and postpartum mice. In contrast, only HF-fed postpartum mice exhibited altered expression of genes regulating the extracellular matrix.

Conclusions

These results suggest that the combined effects of pregnancy and obesity augment cardiac hypertrophy and promote remodeling. The rising prevalence of CVD in premenopausal women may be attributed to an increased prevalence of women entering pregnancy with an overweight or obese BMI.
Learning important features from multi-view data to predict drug side effects
Authors: Liang Xujun , Zhang Pengfei , Li Jun , Fu Ying , Qu Lingzhi , Chen Yongheng , Chen Zhuchu
Published: December 2019

The problem of drug side effects is one of the most crucial issues in pharmacological development. As there are many limitations in current experimental and clinical methods for detecting side effects, a lot of computational algorithms have been developed to predict side effects with different types of drug information. However, there is still a lack of methods which could integrate heterogeneous data to predict side effects and select important features at the same time. Here, we propose a novel computational framework based on multi-view and multi-label learning for side effect prediction. Four different types of drug features are collected and graph model is constructed from each feature profile. After that, all the single view graphs are combined to regularize the linear regression functions which describe the relationships between drug features and side effect labels. L1 penalties are imposed on the regression coefficient matrices in order to select features relevant to side effects. Additionally, the correlations between side effect labels are also incorporated into the model by graph Laplacian regularization. The experimental results show that the proposed method could not only provide more accurate prediction for side effects but also select drug features related to side effects from heterogeneous data. Some case studies are also supplied to illustrate the utility of our method for prediction of drug side effects.
Role of F-18 FDG PET/CT in non-conjunctival origin ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphomas
Authors:   On behalf of Catholic University Lymphoma Group, Park Hye Lim , O Joo Hyun , Park Sonya Youngju , Jung Seung-Eun , Park Gyeongsin , Choi Byung-Ock , Kim Sung Hoon , Jeon Young-Woo , Cho Seok-Goo , Yang Suk-Woo
Published: December 2019

Background

Despite the widespread use of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in the diagnosis and response assessment of patients with lymphoma, few studies have assessed its value in ocular adnexal lymphomas. The purpose of this study was to evaluate the role of FDG PET/CT in staging of non-conjunctival origin ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphomas (OAML). In addition, the diagnostic sensitivity of FDG PET/CT was compared with magnetic resonance imaging (MRI). FDG PET/CT of 123 consecutive patients with pathologically proven OAML between January 2009 and February 2016 were retrospectively reviewed. The patients with MALT lymphoma originating from conjunctiva were excluded. A total 50 patients with non-conjunctival origin OAML were assessed. Maximum standardized uptake value (SUVmax) and additional PET parameters were measured for all lesions. Sensitivity for primary tumor detection was compared with MRI.

Results

Ten patients had bilateral OAML and total 60 OAML lesions were analyzed. MRI was missing in one patient. The tumor locations were as follows: eyelid, 9; lacrimal gland, 18; orbit, 33. Fifty lesions (83.3%) were FDG-avid tumors with mean ± SD SUVmax 4.8 ± 2.4 (range 2.0~11.1). The mean SUVmax according to tumor location were as follows: eyelid, 3.7 ± 1.1 (2.8~5.3); lacrimal gland, 3.6 ± 1.4 (2.1~6.4); orbit, 5.7 ± 2.6 (2.0~11.1). Mean SUVmax among the 3 locations were statistically different (P = 0.010). The sensitivity was calculated as 83.1% (49/59) for FDG PET/CT and 89.8% (53/59) for MRI, which were statistically comparable (P = 0.219 by McNemar’s test). Seven of 50 patients (14%) were upstaged by detection of extraocular lesions by FDG PET/CT (1 kidney and lung, 1 tonsil, 4 cervical LNs, 1 sacral foramen).

Conclusion

83.3% of the non-conjunctival origin OAML were FDG-avid tumors, with FDG PET/CT showing comparable sensitivity to that of MRI. FDG PET/CT detected unsuspected extraocular lymphoma involvement in 14% of the patients. FDG PET/CT performed for staging of non-conjunctival origin OAML may thus guide therapeutic management.
Multimodal image-guided surgery of HER2-positive breast cancer using [111In]In-DTPA-trastuzumab-IRDye800CW in an orthotopic breast tumor model
Authors: Deken Marion M. , Bos Desirée L. , Tummers Willemieke S. F. J. , March Taryn L. , van de Velde Cornelis J. H. , Rijpkema Mark , Vahrmeijer Alexander L.
Published: December 2019

Background

Combining modalities using dual-labeled antibodies may allow preoperative and intraoperative tumor localization and could be used in image-guided surgery to improve complete tumor resection. Trastuzumab is a monoclonal antibody against the human epidermal growth factor-2 (HER2) receptor and dual-labeled trastuzumab with both a fluorophore (IRDye800CW) and a radioactive label (111In) can be used for multimodal imaging of HER2-positive breast cancer. The aim of this study was to demonstrate the feasibility of HER2-targeted multimodal imaging using [111In]In-DTPA-trastuzumab-IRDye800CW in an orthotopic breast cancer model.

Methods

Trastuzumab was conjugated withp-isothiocyanatobenzyl (ITC)-diethylenetriaminepentaacetic acid (DTPA) and IRDye800CW-NHS ester and subsequently labeled with111In. In a dose escalation study, the biodistribution of 10, 30, and 100 μg [111In]In-DTPA-trastuzumab-IRDye800CW was determined 48 h after injection in BALB/c nude mice with orthotopic high HER2-expressing tumors. Also, a biodistribution study was performed in a low HER2-expressing breast cancer model. In addition, multimodal image-guided surgery was performed in each group. Autoradiography, fluorescence microscopy, and immunohistochemically stained slices of the tumors were compared for co-localization of tumor tissue, HER2 expression, fluorescence, and radiosignal.

Results

Based on the biodistribution data, a 30 μg dose of dual-labeled trastuzumab (tumor-to-blood ratio 13 ± 2) was chosen for all subsequent studies. [111In]In-DTPA-trastuzumab-IRDye800CW specifically accumulated in orthotopic HER2-positive BT474 tumors (101 ± 7 %IA/g), whereas uptake in orthotopic low HER2-expressing MCF7 tumor was significantly lower (1.2 ± 0.2 %IA/g,p= 0.007). BT474 tumors could clearly be visualized with both micro-SPECT/CT, fluorescence imaging and subsequently, image-guided resection was performed. Immunohistochemical analyses of BT474 tumors demonstrated correspondence in fluorescence, radiosignal, and high HER2 expression.

Conclusions

Dual-labeled trastuzumab showed specific accumulation in orthotopic HER2-positive BT474 breast tumors with micro-SPECT/CT and fluorescence imaging and enabled image-guided tumor resection. In the clinical setting, [111In]In-DTPA-trastuzumab-IRDye800CW could be valuable for preoperative detection of (metastatic) tumors by SPECT/CT imaging, and intraoperative localization by using a gamma probe and fluorescence image-guided surgery to improve radical resection of tumor tissue in patients with HER2-positive tumors.
Impact of a multidisciplinary care bundle for necrotizing skin and soft tissue infections: a retrospective cohort study
Authors:   the Henri Mondor Hospital Necrotizing Fasciitis group, Urbina Tomas , Hua Camille , Sbidian Emilie , Bosc Romain , Tomberli Françoise , Lepeule Raphael , Decousser Jean-Winoc , Mekontso Dessap Armand , Chosidow Olivier , de Prost Nicolas
Published: December 2019

Background

Necrotizing skin and soft tissue infections (NSTIs) require both prompt medical and surgical treatment. The coordination of multiple urgent interventions by care bundles has improved outcome in other settings. This study aimed to assess the impact of a multidisciplinary care bundle on management and outcome of patients with NSTIs.

Methods

Patients with NSTIs admitted between 2006 and 2017 were compared according to admission before or after bundle implementation (2012–2013). This bundle consisted mainly in (1) the creation of a multidisciplinary task force; (2) management guidelines on empirical antibiotics, intensive care unit admission criteria, a triage algorithm to accelerate operating room access; and (3) an active communication policy. Patient recruitment and management were compared between pre- and post-implementation periods. Main outcome was day 60-censored hospital survival.

Results

Overall, 224 patients were admitted: 60 before, 35 during, and 129 after bundle implementation. Admission after implementation was associated with increased yearly admissions (10 [8–13] vs 30 [24–43] patients/year, p = 0.014) and decreased mortality (30 vs 15%, HR = 0.49 [0.26–0.92]; p = 0.026) but was no longer a protective factor for mortality after adjustment on confounding factors (adjusted HR = 0.90 [0.43–1.88], p = 0.780). There was no significant difference regarding time to surgery (0 [0–1] vs 0 [0–1] days, p = 0.192) or rate of antibiotic treatment within 24 h (98% vs 99%, p > 0.99).

Conclusions

Implementation of a multidisciplinary care bundle for NSTIs was feasible, but in a retrospective study from an already experienced center was not associated with significantly increased survival after adjustment.
How to detect a positive response to a fluid bolus when cardiac output is not measured?
Authors: Ait-Hamou Zakaria , Teboul Jean-Louis , Anguel Nadia , Monnet Xavier
Published: December 2019

Background

Volume expansion is aimed at increasing cardiac output (CO), but this variable is not always directly measured. We assessed the ability of changes in arterial pressure, pulse pressure variation (PPV) and heart rate (HR) or of a combination of them to detect a positive response of cardiac output (CO) to fluid administration.

Methods

We retrospectively included 491 patients with circulatory failure. Before and after a 500-mL normal saline infusion, we measured CO (PiCCO device), HR, systolic (SAP), diastolic (DAP), mean (MAP) and pulse (PP) arterial pressure, PPV, shock index (HR/SAP) and the PP/HR ratio.

Results

The fluid-induced changes in HR were not correlated with the fluid-induced changes in CO. The area under the receiver operating characteristic curve (AUROC) for changes in HR as detectors of a positive fluid response (CO increase ≥ 15%) was not different from 0.5. The fluid-induced changes in SAP, MAP, PP, PPV, shock index (HR/SAP) and the PP/HR ratio were correlated with the fluid-induced changes in CO, but with r < 0.4. The best detection was provided by increases in PP, but it was rough (AUROC = 0.719 ± 0.023, best threshold: increase ≥ 10%, sensitivity = 72 [66–77]%, specificity = 64 [57–70]%). Neither the decrease in shock index nor the changes in other indices combining changes in HR, shock index, PPV and PP provided a better detection of a positive fluid response than changes in PP.

Conclusion

A positive response to fluid was roughly detected by changes in PP and not detected by changes in HR. Changes in combined indices including the shock index and the PP/HR ratio did not provide a better diagnostic accuracy.
Associations between microRNA (miR-25, miR-32, miR-125, and miR-222) polymorphisms and recurrent implantation failure in Korean women
Authors: Lee Jeong Yong , Ahn Eun Hee , Kim Jung Oh , Park Han Sung , Ryu Chang Soo , Kim Ji Hyang , Kim Young Ran , Lee Woo Sik , Kim Nam Keun
Published: December 2019

Background

Recurrent implantation failure (RIF) is the failure of embryos to implant more than two times in a given individual. There is debate about a precise definition for RIF, but we consider more than two implantation failures for individuals who undergo in vitro fertilization-embryo transfer (IVF-ET) to constitute RIF. There are many potential reasons for RIF, including embryonic factors, immunological factors, uterine factors, coagulate factors, and genetic factors. Genetic variation has been suggested as one of the contributing factors leading to RIF, and a number of single-nucleotide polymorphisms (SNPs) have been reported to be associated with RIF. The recent elucidation of miRNA functions has provided new insight into the regulation of gene expression.

Methods

We investigated associations between polymorphisms in four miRNAs and RIF in 346 Korean women: 118 patients with RIF and 228 controls. We determined the genotypes of the miRNAs in the study participants by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis. We analyzed the effects of genotypes, allele combinations, and environmental and clinical factors on the risk of RIF.

Results

The miR-25 T/miR-125aT/miR-222G (odds ratio (OR), 0.528; 95% confidence interval (CI), 0.282–0.990; P = 0.044) and miR-25 T/miR-125aT allele combinations were associated with a reduced risk of RIF. The miR-25 T/miR-32C/miR-125aC/miR-222 T allele combination was associated with an increased risk of RIF. The miR-222GT+TT genotypes interacted with high prothrombin time (≥ 12 s) to increase the risk of RIF.

Conclusions

MicroRNA polymorphisms are significantly different between patients that experience RIF and healthy controls. Combinations of microRNA polymorphisms were associated with the risk of RIF. Interactions between environmental factors and genotypes increased the risk of RIF in Korean women.
Parental opinions regarding consent for observational research of no or minimal risk in the pediatric intensive care unit
Authors: Hodson Jessica , Garros Christiana , Jensen Jodie , Duff Jonathan P. , Garcia Guerra Gonzalo , Joffe Ari R.
Published: December 2019

Background

The aim of the study was to determine opinions and knowledge regarding the process of obtaining informed consent to participate in observational research in pediatric intensive care.

Methods

Survey 1 asked decision makers what model(s) of consent was acceptable for each type of observational research both before and after background information. Survey 2 asked decision makers about the experience of being asked for consent to observational research, and knowledge regarding the consent process both before and after background information.

Results

Cooperation rate was 100/117 (85%). The proportion in favor of any of the offered alternatives to signed informed consent for observational research, after receiving all the background information, was 74-80%, lowest for observational prospective research with a minimal risk intervention 37/50 (74%; 95% CI 60–84%). The proportion who agreed they felt overwhelmed by being approached for consent to observational research was 26 (52%; 95% CI 39-65%). Most respondents (from 60 to 74%) felt they understood the concepts regarding observational research; however, after reading background information, most (from 60 to 74%) felt their understanding had improved “a great deal”.

Conclusion

Understanding of risk, practical difficulties, consent bias, and Research Ethics Board safeguards was poor. Future study is needed to confirm our finding that most agreed with alternative methods of consent for observational research.
Laparoscopic treatment in a patient with median arcuate ligament syndrome identified at the onset of superior mesenteric artery dissection: a case report
Authors: Okada Haruhiko , Ehara Kazuhisa , Ro Hisashi , Yamada Masaki , Saito Tetsuya , Negami Naoki , Ishido Yasunori , Sato Masahiko
Published: December 2019

Background

Median arcuate ligament syndrome (MALS) is a rare clinical entity caused mainly by extrinsic compression of the celiac axis by the median arcuate ligament (MAL). Severe celiac artery stenosis can lead to the development of collateral circulation, aneurysms, and, rarely, superior mesenteric artery (SMA) dissection. The treatment of MALS involves the surgical release of the MAL. However, a standard procedure with the use of laparoscopy has not been established, and intraoperative complications can lead to severe vascular injury.

Case presentation

The patient was a 43-year-old man with MALS identified at the onset of SMA dissection. After treatment for the SMA dissection, he underwent laparoscopic MAL release. Using the technique of laparoscopic gastrectomy within the surgical field, we performed laparoscopic MAL release and ganglionectomy safely with a good view. Immediate symptomatic improvement was acquired, and no recurrence was observed at the 20-month follow-up.

Conclusion

We reported a rare case of MALS and SMA dissection. A horizontal 3D laparoscopic approach of the celiac axis allows for safe, meticulous, and radical MAL release and ganglionectomy.