bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal transfer of environmentally relevant polybrominated diphenyl ethers (PBDEs) produces a diabetic phenotype and disrupts glucoregulatory hormones and hepatic endocannabinoids in adult mouse female offspring
Authors: Kozlova Elena V. , Chinthirla Bhuvaneswari D. , Pérez Pedro A. , DiPatrizio Nicholas V. , Argueta Donovan A. , Phillips Allison L. , Stapleton Heather M. , González Gwendolyn M. , Krum Julia M. , Carrillo Valeria , Bishay Anthony E. , Basappa Karthik R. , Currás-Collazo Margarita C.
Published: October 2020

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardant chemicals and environmental contaminants with endocrine-disrupting properties that are associated with diabetes and metabolic syndrome in humans. However, their diabetogenic actions are not completely characterized or understood. In this study, we investigated the effects of DE-71, a commercial penta-mixture of PBDEs, on glucoregulatory parameters in a perinatal exposure model using female C57Bl/6 mice. Results from in vivo glucose and insulin tolerance tests and ex vivo analyses revealed fasting hyperglycemia, glucose intolerance, reduced sensitivity and delayed glucose clearance after insulin challenge, decreased thermogenic brown adipose tissue mass, and exaggerated hepatic endocannabinoid tone in F1 offspring exposed to 0.1 mg/kg DE-71 relative to control. DE-71 effects on F0 dams were more limited indicating that indirect exposure to developing offspring is more detrimental. Other ex vivo glycemic correlates occurred more generally in exposed F0 and F1, i.e., reduced plasma insulin and altered glucoregulatory endocrines, exaggerated sympathoadrenal activity and reduced hepatic glutamate dehydrogenase enzymatic activity. Hepatic PBDE congener analysis indicated maternal transfer of BDE-28 and -153 to F1 at a collective level of 200 ng/g lipid, in range with maximum values detected in serum of human females. Given the persistent diabetogenic phenotype, especially pronounced in female offspring after developmental exposure to environmentally relevant levels of DE-71, additional animal studies should be conducted that further characterize PBDE-induced diabetic pathophysiology and identify critical developmental time windows of susceptibility. Longitudinal human studies should also be conducted to determine the risk of long-lasting metabolic consequences after maternal transfer of PBDEs during early-life development.
Effect of perceived interpersonal closeness on the joint Simon effect in adolescents and adults
Authors: Shafaei Raheleh , Bahmani Zahra , Bahrami Bahador , Vaziri-Pashkam Maryam
Published: October 2020

Here, we explored the role of perceived interpersonal closeness in joint action using the joint Simon task in adolescents and adults. In a two-choice reaction time task, spatially assigned responses to non-spatial stimulus features are faster when the stimulus and response are in congruent locations than not. This phenomenon is called Simon effect and is absent or strongly attenuated when a participant responds to only one of the stimuli. However, the effect reappears when two participants carry out the same go/no-go tasks cooperatively. This re-emergence of the Simon effect in joint action is called the joint Simon effect (JSE). In this study, we first replicated the standard and joint Simon effects in adolescents (n = 43), as well as adults (n = 39) with similar magnitude of the effects in the two age groups. The magnitude of the JSE was positively correlated with the level of closeness as measured by Inclusion of Other in the Self scale. This correlation was not significantly different in adolescents (n = 73) compared to adults (n = 71). Our findings show that joint action is sensitive to the social factor such as interpersonal closeness, and the underlying mechanisms are already mature by adolescence.
Axonal blockage with microscopic magnetic stimulation
Authors: Skach Jordan , Conway Catherine , Barrett Lauryn , Ye Hui
Published: October 2020

Numerous neurological dysfunctions are characterized by undesirable nerve activity. By providing reversible nerve blockage, electric stimulation with an implanted electrode holds promise in the treatment of these conditions. However, there are several limitations to its application, including poor bio-compatibility and decreased efficacy during chronic implantation. A magnetic coil of miniature size can mitigate some of these problems, by coating it with biocompatible material for chronic implantation. However, it is unknown if miniature coils could be effective in axonal blockage and, if so, what the underlying mechanisms are. Here we demonstrate that a submillimeter magnetic coil can reversibly block action potentials in the unmyelinated axons from the marine mollusk Aplysia californica. Using a multi-compartment model of the Aplysia axon, we demonstrate that the miniature coil causes a significant local depolarization in the axon, alters activation dynamics of the sodium channels, and prevents the traveling of the invading action potentials. With improved biocompatibility and capability of emitting high-frequency stimuli, micro coils provide an interesting alternative for electric blockage of axonal conductance in clinical settings.
Spatial cell type composition in normal and Alzheimers human brains is revealed using integrated mouse and human single cell RNA sequencing
Authors: Johnson Travis S. , Xiang Shunian , Helm Bryan R. , Abrams Zachary B. , Neidecker Peter , Machiraju Raghu , Zhang Yan , Huang Kun , Zhang Jie
Published: October 2020

Single-cell RNA sequencing (scRNA-seq) resolves heterogenous cell populations in tissues and helps to reveal single-cell level function and dynamics. In neuroscience, the rarity of brain tissue is the bottleneck for such study. Evidence shows that, mouse and human share similar cell type gene markers. We hypothesized that the scRNA-seq data of mouse brain tissue can be used to complete human data to infer cell type composition in human samples. Here, we supplement cell type information of human scRNA-seq data, with mouse. The resulted data were used to infer the spatial cellular composition of 3702 human brain samples from Allen Human Brain Atlas. We then mapped the cell types back to corresponding brain regions. Most cell types were localized to the correct regions. We also compare the mapping results to those derived from neuronal nuclei locations. They were consistent after accounting for changes in neural connectivity between regions. Furthermore, we applied this approach on Alzheimer’s brain data and successfully captured cell pattern changes in AD brains. We believe this integrative approach can solve the sample rarity issue in the neuroscience.
Assessment of odor hedonic perception: the Sniffin’ sticks parosmia test (SSParoT)
Authors: Liu David T. , Welge-Lüssen Antje , Besser Gerold , Mueller Christian A. , Renner Bertold
Published: October 2020

Qualitative olfactory dysfunction is characterized as distorted odor perception and can have a profound effect on quality of life of affected individuals. Parosmia and phantosmia represent the two main subgroups of qualitative impairment and are currently diagnosed based on patient history only. We have developed a test method which measures qualitative olfactory function based on the odors of the Sniffin’ Sticks Identification subtest. The newly developed test is called Sniffin’ Sticks Parosmia Test (SSParoT). SSParoT uses hedonic estimates of two oppositely valenced odors (pleasant and unpleasant) to assess hedonic range (HR) and hedonic direction (HD), which represent qualitative olfactory perception. HR is defined as the perceivable hedonic distance between two oppositely valenced odors, while HD serves as an indicator for overall hedonic perception of odors. This multicenter study enrolled a total of 162 normosmic subjects in four consecutive experiments. Cluster analysis was used to group odors from the 16-item Sniffin’ Sticks Identification test and 24-additional odors into clusters with distinct hedonic properties. Eleven odor pairs were found to be suitable for estimation of HR and HD. Analysis showed agreement between test–retest sessions for all odor pairs. SSparoT might emerge as a valuable tool to assess qualitative olfactory function in health and disease.
Investigation of GIM-TEC disturbances before M ≥ 6.0 inland earthquakes during 2003–2017
Authors: Zhu Fuying , Jiang Yingchun
Published: October 2020

With the rapid development of the Global Navigation Satellite System (GNSS) and its wide applications to atmospheric science research, the global ionosphere map (GIM) total electron content (TEC) data are extensively used as a potential tool to detect ionospheric disturbances related to seismic activity and they are frequently used to statistically study the relation between the ionosphere and earthquakes (EQs). Indeed, due to the distribution of ground based GPS receivers is very sparse or absent in large areas of ocean, the GIM-TEC data over oceans are results of interpolation between stations and extrapolation in both space and time, and therefore, they are not suitable for studying the marine EQs. In this paper, based on the GIM-TEC data, a statistical investigation of ionospheric TEC variations of 15 days before and after the 276 M ≥ 6.0 inland EQs is undertaken. After eliminating the interference of geomagnetic activities, the spatial and temporal distributions of the ionospheric TEC disturbances before and after the EQs are investigated and compared. There are no particularly distinct features in the time distribution of the ionospheric TEC disturbances before the inland EQs. However, there are some differences in the spatial distribution, and the biggest difference is precisely in the epicenter area. On the other hand, the occurrence rates of ionospheric TEC disturbances within 5 days before the EQs are overall higher than those after EQs, in addition both of them slightly increase with the earthquake magnitude. These results suggest that the anomalous variations of the GIM-TEC before the EQs might be related to the seismic activities.
Characterizing the evolution life cycle of the Sunkoshi landslide in Nepal with multi-source SAR data
Authors: Ao Meng , Zhang Lu , Dong Yuting , Su Lijun , Shi Xuguo , Balz Timo , Liao Mingsheng
Published: October 2020

A catastrophic landslide disaster happened on 2 August 2014 on the right bank of Sunkoshi River in Nepal, resulting in enormous casualties and severe damages of the Araniko highway. We collected multi-source synthetic aperture radar (SAR) data to investigate the evolution life cycle of the Sunkoshi landslide. Firstly, Distributed Scatterers SAR Interferometry (DS-InSAR) technology is applied to analyze 20 ALOS PALSAR images to retrieve pre-disaster time-series deformation. The results show that the upper part, especially the top of the landslide, has long been active before collapse, with the largest annual LOS deformation rate more than − 30 mm/year. Time series deformations measured illustrate that rainfall might be a key driving factor. Next, two pairs of TerraSAR-X/TanDEM-X bistatic data are processed to identify the landslide affected area by intensity change detection, and to generate pre- and post-disaster DSMs. Surface height change map showed maximum values of − 150.47 m at the source region and 55.65 m in the deposit region, leading to a debris volume of 5.4785 ± 0.6687 million m3. Finally, 11 ALOS-2 PALSAR-2 and 82 Sentinel-1 SAR images are analyzed to derive post-disaster annual deformation rate and long time series displacements of the Sunkoshi landslide. The results illustrated that the upper part of the landslide were still in active deformation with the largest LOS displacement velocity exceeding − 100 mm/year.
Innate connectivity patterns drive the development of the visual word form area
Authors: Li Jin , Osher David E. , Hansen Heather A. , Saygin Zeynep M.
Published: October 2020

What determines the functional organization of cortex? One hypothesis is that innate connectivity patterns, either structural or functional connectivity, set up a scaffold upon which functional specialization can later take place. We tested this hypothesis by asking whether the visual word form area (VWFA), an experience-driven region, was already functionally connected to proto language networks in neonates scanned within one week of birth. Using the data from the Human Connectone Project (HCP) and the Developing Human Connectome Project (dHCP), we calculated intrinsic functional connectivity during resting-state functional magnetic resonance imaging (fMRI), and found that neonates showed similar functional connectivity patterns to adults. We observed that (1) language regions connected more strongly with the putative VWFA than other adjacent ventral visual regions that also show foveal bias, and (2) the VWFA connected more strongly with frontotemporal language regions than with regions adjacent to these language regions. These data suggest that the location of the VWFA is earmarked at birth due to its connectivity with the language network, providing evidence that innate connectivity instructs the later refinement of cortex.
Temporal trends in clozapine use at time of discharge among people with schizophrenia at two public psychiatric hospitals in Taiwan, 2006–2017
Authors: Lin Ching-Hua , Chan Hung-Yu , Hsu Chun-Chi , Chen Feng-Chua
Published: October 2020

Clozapine treatment remains the gold standard for treatment-resistant schizophrenia. This study aimed to describe temporal trends in clozapine use at discharge among patients with schizophrenia at two of the largest public psychiatric hospitals in Taiwan over a twelve-year period. Patients with schizophrenia discharged from the two study hospitals between 2006 and 2017 (n = 24,101) were included in the analysis. Antipsychotic augmentation was defined as concomitant use of a second antipsychotic as augmentation to clozapine treatment. Changes in the rate of clozapine use and antipsychotic augmentation at discharge over time were analyzed using the Cochran-Armitage trend test. Patients discharged on clozapine had significantly longer hospital stays than other patients. The rate of clozapine use at discharge increased from 13.8% to 20.0% over time (Z = 6.88, p < .0001). Concomitant use of anticholinergic medication was more common in patients receiving antipsychotic augmentation than clozapine antipsychotic monotherapy. Among patients discharged on clozapine, the rate of augmentation with a second antipsychotic increased from 19.1% to 36.2% over time (Z = 6.58, p < .0001). Among patients receiving antipsychotic augmentation, use of another second-generation antipsychotic as the augmentation agent grew from 32.6% to 65.5% over time (Z = 8.90, p < .0001). The increase in clozapine use was accompanied by an increase in concomitant use of a second antipsychotic as augmentation during the study period. Further studies are warranted to clarify the risk/benefit of this augmentation strategy. Clozapine may still be underutilized, and educational programs are needed to promote clinical use of clozapine.
An ultra-high-density protein microarray for high throughput single-tier serological detection of Lyme disease
Authors: Jayaraman Vasanth , Krishna Karthik , Yang Yuanyuan , Rajasekaran Karenah J. , Ou Yuzheng , Wang Tianhao , Bei Kang , Krishnamurthy Hari Krishnan , Rajasekaran John J. , Rai Alex J. , Green Daniel A.
Published: October 2020

Current serological immunoassays have inherent limitations for certain infectious diseases such as Lyme disease, a bacterial infection caused by Borrelia burgdorferi in North America. Here we report a novel method of manufacturing high-density multiplexed protein microarrays with the capacity to detect low levels of antibodies accurately from small blood volumes in a fully automated system. A panel of multiple serological markers for Lyme disease are measured using a protein microarray system, Lyme Immunochip, in a single step but interpreted adhering to the standard two-tiered testing algorithm (enzyme immunoassay followed by Western blot). Furthermore, an enhanced IgM assay was supplemented to improve the test’s detection sensitivity for early Lyme disease. With a training cohort (n = 40) and a blinded validation cohort (n = 90) acquired from CDC, the Lyme Immunochip identified a higher proportion of Lyme disease patients than the two-tiered testing (82.4% vs 70.6% in the training set, 66.7% vs 60.0% in the validation set, respectively). Additionally, the Immunochip improved sensitivity to 100% while having a lower specificity of 95.2% using a set of investigational antigens which are being further evaluated with a large cohort of blinded samples from the CDC and Columbia University. This universal microarray platform provides an unprecedented opportunity to resolve a broad range of issues with diagnostic tests, including multiplexing, workflow simplicity, and reduced turnaround time and cost.
Physiological demands and signaling associated with snake venom production and storage illustrated by transcriptional analyses of venom glands
Authors: Perry Blair W. , Schield Drew R. , Westfall Aundrea K. , Mackessy Stephen P. , Castoe Todd A.
Published: October 2020

Despite the extensive body of research on snake venom, many facets of snake venom systems, such as the physiology and regulation of the venom gland itself, remain virtually unstudied. Here, we use time series gene expression analyses of the rattlesnake venom gland in comparison with several non-venom tissues to characterize physiological and cellular processes associated with venom production and to highlight key distinctions of venom gland cellular and physiological function. We find consistent evidence for activation of stress response pathways in the venom gland, suggesting that mitigation of cellular stress is a crucial component of venom production. Additionally, we demonstrate evidence for an unappreciated degree of cellular and secretory activity in the steady state venom gland relative to other secretory tissues and identify vacuolar ATPases as the likely mechanisms driving acidification of the venom gland lumen during venom production and storage.
Cosmological reconstruction and energy constraints in generalized Gauss–Bonnet-scalar–kinetic–matter couplings
Authors: Kaczmarek Adam Z. , Szczęśniak Dominik
Published: October 2020

Recently introduced $$f(\mathcal {G},T)$$

f
(
G
,
T
)

theory is generalized by adding dependence on the arbitrary scalar field $$\phi $$
ϕ
and its kinetic term $$(\nabla \phi )^2$$

(
∇
ϕ
)

2

, to explore non-minimal interactions between geometry, scalar and matter fields in context of the Gauss–Bonnet theories. The field equations for the resulting $$f\left( \mathcal {G},\phi ,(\nabla \phi )^2,T\right) $$

f

G
,
ϕ
,

(
∇
ϕ
)

2

,
T

theory are obtained and show that particles follow non-geodesic trajectories in a perfect fluid surrounding. The energy conditions in the Friedmann–Lemaître–Robertson–Walker (FLRW) spacetime are discussed for the generic function $$f\left( \mathcal {G},\phi ,(\nabla \phi )^2,T\right) $$

f

G
,
ϕ
,

(
∇
ϕ
)

2

,
T

. As an application of the introduced extensions, using the reconstruction techniques we obtain functions that satisfy common cosmological models, along with the equations describing energy conditions for the reconstructed $$f\left( \mathcal {G},\phi ,(\nabla \phi )^2,T\right) $$

f

G
,
ϕ
,

(
∇
ϕ
)

2

,
T

gravity. The detailed discussion of the energy conditions for the de Sitter and power-law spacetimes is provided in terms of the fixed kinetic term i.e. in the $$f\left( \mathcal {G},\phi ,T\right) $$

f

G
,
ϕ
,
T

case. Moreover, in order to check viability of the reconstructed models, we discuss the energy conditions in the specific cases, namely the $$f(R,\phi ,(\nabla \phi )^2)$$

f
(
R
,
ϕ
,

(
∇
ϕ
)

2

)

and $$f=\gamma (\phi ,X)\mathcal {G}+\mu T^{1/2}$$

f
=
γ

(
ϕ
,
X
)

G
+
μ

T

1
/
2

approaches. We show, that for the appropriate choice of parameters and constants, the energy conditions can be satisfied for the discussed scenarios.
High colloidal stability ZnO nanoparticles independent on solvent polarity and their application in polymer solar cells
Authors: Lee Woojin , Yeop Jiwoo , Heo Jungwoo , Yoon Yung Jin , Park Song Yi , Jeong Jaeki , Shin Yun Seop , Kim Jae Won , An Na Gyeong , Kim Dong Suk , Park Jongnam , Kim Jin Young
Published: October 2020

Significant aggregation between ZnO nanoparticles (ZnO NPs) dispersed in polar and nonpolar solvents hinders the formation of high quality thin film for the device application and impedes their excellent electron transporting ability. Herein a bifunctional coordination complex, titanium diisopropoxide bis(acetylacetonate) (Ti(acac)2) is employed as efficient stabilizer to improve colloidal stability of ZnO NPs. Acetylacetonate functionalized ZnO exhibited long-term stability and maintained its superior optical and electrical properties for months aging under ambient atmospheric condition. The functionalized ZnO NPs were then incorporated into polymer solar cells with conventional structure as n-type buffer layer. The devices exhibited nearly identical power conversion efficiency regardless of the use of fresh and old (2 months aged) NPs. Our approach provides a simple and efficient route to boost colloidal stability of ZnO NPs in both polar and nonpolar solvents, which could enable structure-independent intense studies for efficient organic and hybrid optoelectronic devices.
Association of gamma-glutamyl transferase with subclinical coronary atherosclerosis and cardiac outcomes in non-alcoholics
Authors: Kim Yong-Giun , Park Gyung-Min , Lee Seung Bum , Yang Dong Hyun , Kang Joon-Won , Lim Tae-Hwan , Kim Hong-Kyu , Choe Jaewon , Lee Seung-Whan , Kim Young-Hak
Published: October 2020

In an asymptomatic population, we determined the relationship between serum gamma-glutamyl transferase (GGT) and subclinical atherosclerosis, using coronary computed tomography angiography (CCTA). This was a retrospective observational cohort study which analyzed 5120 consecutive asymptomatic individuals with no prior history of coronary artery disease or significant alcohol intake who voluntarily underwent CCTA as part of a general health examination. All subjects were stratified into tertiles based on GGT levels. Degree and extent of subclinical coronary atherosclerosis were evaluated using CCTA. Cardiac events were a composite of all-cause death, myocardial infarction, unstable angina, and coronary revascularization. After adjustment for cardiovascular risk factors, there were no significant differences among GGT tertiles in terms of adjusted odds ratios for non-calcified and mixed plaques. The risk of any atherosclerotic and calcified plaques, significant stenosis, multi-vessel disease, and significant stenosis in the left main or proximal left anterior descending artery was higher in the third GGT tertile than in the first tertile (all p < 0.05). Over a median 5.4-year follow-up, the third GGT tertile had significant adjusted hazards ratios for cardiac events than did the first GGT tertile, even after stepwise adjustment for cardiovascular risk factors (all p < 0.01). In asymptomatic individuals, elevated GGT was independently associated with high-risk feature atherosclerosis and poorer cardiac outcomes.
Graphene oxide and its derivatives as promising In-vitro bio-imaging platforms
Authors: Esmaeili Yasaman , Bidram Elham , Zarrabi Ali , Amini Abbas , Cheng Chun
Published: October 2020

Intrinsic fluorescence and versatile optical properties of Graphene Oxide (GO) in visible and near-infrared range introduce this nanomaterial as a promising candidate for numerous clinical applications for early-diagnose of diseases. Despite recent progresses in the impact of major features of GO on the photoluminescence properties of GO, their modifications have not yet systematically understood. Here, to study the modification effects on the fluorescence behavior, poly ethylene glycol (PEG) polymer, metal nanoparticles (Au and Fe3O4) and folic acid (FA) molecules were used to functionalize the GO surface. The fluorescence performances in different environments (water, DMEM cell media and phosphate buffer with two different pH values) were assessed through fluorescence spectroscopy and fluorescent microscopy, while Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) and Scanning electron microscopy (SEM) were utilized to evaluate the modifications of chemical structures. The modification of GO with desired molecules improved the photoluminescence property. The synthesized platforms of GO-PEG, GO-PEG-Au, GO-PEG-Fe3O4and GO-PEG-FA illustrated emissions in three main fluorescence regions (blue, green and red), suitable for tracing and bio-imaging purposes. Considering MTT results, these platforms potentially positioned themselves as non-invasive optical sensors for the diagnosis alternatives of traditional imaging agents.
Optimizing target nodes selection for the control energy of directed complex networks
Authors: Chen Hong , Yong Ee Hou
Published: October 2020

The energy needed in controlling a complex network is a problem of practical importance. Recent works have focused on the reduction of control energy either via strategic placement of driver nodes, or by decreasing the cardinality of nodes to be controlled. However, optimizing control energy with respect to target nodes selection has yet been considered. In this work, we propose an iterative method based on Stiefel manifold optimization of selectable target node matrix to reduce control energy. We derive the matrix derivative gradient needed for the search algorithm in a general way, and search for target nodes which result in reduced control energy, assuming that driver nodes placement is fixed. Our findings reveal that the control energy is optimal when the path distances from driver nodes to target nodes are minimized. We corroborate our algorithm with extensive simulations on elementary network topologies, random and scale-free networks, as well as various real networks. The simulation results show that the control energy found using our algorithm outperforms heuristic selection strategies for choosing target nodes by a few orders of magnitude. Our work may be applicable to opinion networks, where one is interested in identifying the optimal group of individuals that the driver nodes can influence.
Quantitative MRI using relaxometry in malignant gliomas detects contrast enhancement in peritumoral oedema
Authors: Blystad I. , Warntjes J. B. M. , Smedby Ö , Lundberg P. , Larsson E.-M. , Tisell A.
Published: October 2020

Malignant gliomas are primary brain tumours with an infiltrative growth pattern, often with contrast enhancement on magnetic resonance imaging (MRI). However, it is well known that tumour infiltration extends beyond the visible contrast enhancement. The aim of this study was to investigate if there is contrast enhancement not detected visually in the peritumoral oedema of malignant gliomas by using relaxometry with synthetic MRI. 25 patients who had brain tumours with a radiological appearance of malignant glioma were prospectively included. A quantitative MR-sequence measuring longitudinal relaxation (R1), transverse relaxation (R2) and proton density (PD), was added to the standard MRI protocol before surgery. Five patients were excluded, and in 20 patients, synthetic MR images were created from the quantitative scans. Manual regions of interest (ROIs) outlined the visibly contrast-enhancing border of the tumours and the peritumoral area. Contrast enhancement was quantified by subtraction of native images from post GD-images, creating an R1-difference-map. The quantitative R1-difference-maps showed significant contrast enhancement in the peritumoral area (0.047) compared to normal appearing white matter (0.032), p = 0.048. Relaxometry detects contrast enhancement in the peritumoral area of malignant gliomas. This could represent infiltrative tumour growth.
Effect of androgen deprivation therapy on cardiovascular function in Chinese patients with advanced prostate cancer: a prospective cohort study
Authors: Ng Chi-fai , Chiu Peter K. F. , Yee Chi-hang , Lau Becky S. Y. , Leung Steven C. H. , Teoh Jeremy Y. C.
Published: October 2020

Androgen deprivation therapy (ADT) is the standard treatment for advanced prostate cancer, but its effect on cardiovascular and metabolic function in Asian patients is still inconclusive. We prospectively assess the effects of ADT on 36 patients with advanced prostate cancer, with reference to another 24 prostate cancer patients not requiring ADT, for 2 years. Patients’ anthropometric, metabolic and vascular parameters were assessed every six-monthly. The baseline parameters of the two groups were comparable. There was a significant negative effect of the usage of ADT on the changes in BMI (p = 0.020), waist to hip ratio (p = 0.005), body fat percentage (p = 0.012), and high-density-lipoprotein (p = 0.012). ADT-patients were 4.9 times more likely to have metabolic syndrome at 24 months. (CI 0.889–27.193, p = 0.068). The Framingham risk score (p = 0.018) and pulse-wave-velocity (p = 0.024) for ADT-group were also significantly higher than controls, which signified increase in cardiovascular risk. Although there was no statistically significant difference in ischemic cardiovascular events between two groups, a trend for more events in ADT-group was observed. Therefore, Asian patients have increased cardiovascular and metabolic risks after being treated with ADT for two years. Appropriate counselling and monitoring of associated complications with ADT are essential.
Using advanced oxidation protein products and ischaemia-modified albumin to monitor oxidative stress levels in patients with drug-induced liver injury
Authors: Xiao Lan-Lan , Zhang Fen , Zhao Ya-Lei , Zhang Ling-Jian , Xie Zhong-Yang , Huang Kai-Zhou , Ouyang Xiao-Xi , Wu Xiao-Xin , Xu Xiao-Wei , Li Lan-Juan
Published: October 2020

Increased oxidative stress levels play a key role in idiosyncratic drug-induced liver injury (DILI) pathogenesis. To investigated whether advanced oxidation protein products (AOPPs) and ischaemia-modified albumin (IMA) can be used to monitor oxidative stress in DILI patients and to assess disease severity. We performed spectrophotometric assays to assess AOPPs and IMA in 68 DILI patients with severity grade 0–2 (non-severe group), 60 with severity grade 3–5 (severe group), and 38 healthy controls. The results showed that baseline AOPPs and IMA serum levels and AOPPs/albumin and IMA/albumin ratios were significantly higher in DILI patients than in healthy controls. Besides, in comparison to the non-severe group, the severe group showed higher baseline AOPPs and IMA serum levels and AOPPs/albumin and IMA/albumin ratios. AOPPs and IMA serum levels and AOPPs/albumin and IMA/albumin ratios decreased after treatment in both patient groups. Combining the correlation analysis and areas under the receiver operating curve (AUROCs) analysis results, that IMA outperformed to be one is the most reliable marker to assess disease severity of DILI. Our findings indicated that AOPPs and IMA can serve as key biomarkers for monitoring oxidative stress levels in DILI patients and can indicate disease severity. The IMA outperformed to be one of the most reliable oxidative stress biomarkers to assess disease severity of DILI.
TLR9–IL-2 axis exacerbates allergic asthma by preventing IL-17A hyperproduction
Authors: Murakami Yusuke , Ishii Takashi , Nunokawa Hiroki , Kurata Keigo , Narita Tomoya , Yamashita Naomi
Published: October 2020

Allergic asthma is one of most famous allergic diseases, which develops lung and airway inflammation. Recent studies have revealed the relationship between the pathology of allergic asthma and the increase of host-derived DNA in inflamed lung, but the role of the DNA-recognizing innate immune receptor for the inflammation is unknown well. Here we investigated the role of Toll-Like Receptor 9 in the pathogenesis of allergic asthma without synthesized CpG-ODNs. To examine that, we analyzed the pathology and immunology of house-dust-mite (HDM)-induced allergic asthma in Tlr9–/– mice and TLR9-inhibitory-antibody-treated mice. In Tlr9–/– mice, airway hyperresponsiveness (AHR) and the number of eosinophils decreased, and production of the Th2 cytokines IL-13, IL-5, and IL-4 was suppressed, compared with in wild-type mice. Interestingly, unlike Th2 cytokine production, IL-17A production was increased in Tlr9–/– mice. Furthermore, production of IL-2, which decreases IL-17A production, was reduced in Tlr9–/– mice. Blockade of TLR9 by treatment with TLR9-inhibitory-antibody, NaR9, effectively suppressed the development of allergic asthma pathology. IL-17A production in NaR9-treated mice was enhanced, which is comparable to Tlr9-/- mice. These results suggest that the TLR9–IL-2 axis plays an important role in Th2 inflammation by modulating IL-17A production in HDM-induced allergic asthma and that targeting of TLR9 might be a novel therapeutic method for allergic asthma.
Deep time-delay Markov network for prediction and modeling the stress and emotions state transition
Authors: Prasetio Barlian Henryranu , Tamura Hiroki , Tanno Koichi
Published: October 2020

To recognize stress and emotion, most of the existing methods only observe and analyze speech patterns from present-time features. However, an emotion (especially for stress) can change because it was triggered by an event while speaking. To address this issue, we propose a novel method for predicting stress and emotions by analyzing prior emotional states. We named this method the deep time-delay Markov network (DTMN). Structurally, the proposed DTMN contains a hidden Markov model (HMM) and a time-delay neural network (TDNN). We evaluated the effectiveness of the proposed DTMN by comparing it with several state transition methods in predicting an emotional state from time-series (sequences) speech data of the SUSAS dataset. The experimental results show that the proposed DTMN can accurately predict present emotional states by outperforming the baseline systems in terms of the prediction error rate (PER). We then modeled the emotional state transition using a finite Markov chain based on the prediction result. We also conducted an ablation experiment to observe the effect of different HMM values and TDNN parameters on the prediction result and the computational training time of the proposed DTMN.
Identification of DHX9 as a cell cycle regulated nucleolar recruitment factor for CIZ1
Authors: Thacker Urvi , Pauzaite Tekle , Tollitt James , Twardowska Maria , Harrison Charlotte , Dowle Adam , Coverley Dawn , Copeland Nikki A.
Published: October 2020

CIP1-interacting zinc finger protein 1 (CIZ1) is a nuclear matrix associated protein that facilitates a number of nuclear functions including initiation of DNA replication, epigenetic maintenance and associates with the inactive X-chromosome. Here, to gain more insight into the protein networks that underpin this diverse functionality, molecular panning and mass spectrometry are used to identify protein interaction partners of CIZ1, and CIZ1 replication domain (CIZ1-RD). STRING analysis of CIZ1 interaction partners identified 2 functional clusters: ribosomal subunits and nucleolar proteins including the DEAD box helicases, DHX9, DDX5 and DDX17. DHX9 shares common functions with CIZ1, including interaction with XIST long-non-coding RNA, epigenetic maintenance and regulation of DNA replication. Functional characterisation of the CIZ1-DHX9 complex showed that CIZ1-DHX9 interact in vitro and dynamically colocalise within the nucleolus from early to mid S-phase. CIZ1-DHX9 nucleolar colocalisation is dependent upon RNA polymerase I activity and is abolished by depletion of DHX9. In addition, depletion of DHX9 reduced cell cycle progression from G1 to S-phase in mouse fibroblasts. The data suggest that DHX9-CIZ1 are required for efficient cell cycle progression at the G1/S transition and that nucleolar recruitment is integral to their mechanism of action.
Volumetric breast density estimation on MRI using explainable deep learning regression
Authors: van der Velden Bas H. M. , Janse Markus H. A. , Ragusi Max A. A. , Loo Claudette E. , Gilhuijs Kenneth G. A.
Published: October 2020

To purpose of this paper was to assess the feasibility of volumetric breast density estimations on MRI without segmentations accompanied with an explainability step. A total of 615 patients with breast cancer were included for volumetric breast density estimation. A 3-dimensional regression convolutional neural network (CNN) was used to estimate the volumetric breast density. Patients were split in training (N = 400), validation (N = 50), and hold-out test set (N = 165). Hyperparameters were optimized using Neural Network Intelligence and augmentations consisted of translations and rotations. The estimated densities were evaluated to the ground truth using Spearman’s correlation and Bland–Altman plots. The output of the CNN was visually analyzed using SHapley Additive exPlanations (SHAP). Spearman’s correlation between estimated and ground truth density was ρ = 0.81 (N = 165, P < 0.001) in the hold-out test set. The estimated density had a median bias of 0.70% (95% limits of agreement = − 6.8% to 5.0%) to the ground truth. SHAP showed that in correct density estimations, the algorithm based its decision on fibroglandular and fatty tissue. In incorrect estimations, other structures such as the pectoral muscle or the heart were included. To conclude, it is feasible to automatically estimate volumetric breast density on MRI without segmentations, and to provide accompanying explanations.
Spatiotemporal mapping of malaria prevalence in Madagascar using routine surveillance and health survey data
Authors: Arambepola Rohan , Keddie Suzanne H. , Collins Emma L. , Twohig Katherine A. , Amratia Punam , Bertozzi-Villa Amelia , Chestnutt Elisabeth G. , Harris Joseph , Millar Justin , Rozier Jennifer , Rumisha Susan F. , Symons Tasmin L. , Vargas-Ruiz Camilo , Andriamananjara Mauricette , Rabeherisoa Saraha , Ratsimbasoa Arsène C. , Howes Rosalind E. , Weiss Daniel J. , Gething Peter W. , Cameron Ewan
Published: October 2020

Malaria transmission in Madagascar is highly heterogeneous, exhibiting spatial, seasonal and long-term trends. Previous efforts to map malaria risk in Madagascar used prevalence data from Malaria Indicator Surveys. These cross-sectional surveys, conducted during the high transmission season most recently in 2013 and 2016, provide nationally representative prevalence data but cover relatively short time frames. Conversely, monthly case data are collected at health facilities but suffer from biases, including incomplete reporting and low rates of treatment seeking. We combined survey and case data to make monthly maps of prevalence between 2013 and 2016. Health facility catchment populations were estimated to produce incidence rates from the case data. Smoothed incidence surfaces, environmental and socioeconomic covariates, and survey data informed a Bayesian prevalence model, in which a flexible incidence-to-prevalence relationship was learned. Modelled spatial trends were consistent over time, with highest prevalence in the coastal regions and low prevalence in the highlands and desert south. Prevalence was lowest in 2014 and peaked in 2015 and seasonality was widely observed, including in some lower transmission regions. These trends highlight the utility of monthly prevalence estimates over the four year period. By combining survey and case data using this two-step modelling approach, we were able to take advantage of the relative strengths of each metric while accounting for potential bias in the case data. Similar modelling approaches combining large datasets of different malaria metrics may be applicable across sub-Saharan Africa.
Diagnostic ability of maximum blink interval together with Japanese version of Ocular Surface Disease Index score for dry eye disease
Authors: Hirosawa Kunihiko , Inomata Takenori , Sung Jaemyoung , Nakamura Masahiro , Okumura Yuichi , Midorikawa-Inomata Akie , Miura Maria , Fujio Kenta , Akasaki Yasutsugu , Fujimoto Keiichi , Zhu Jun , Eguchi Atsuko , Nagino Ken , Kuwahara Mizu , Shokirova Hurramhon , Yanagawa Ai , Murakami Akira
Published: October 2020

Various symptoms of the dry eye disease (DED) interfere with the quality of life and reduce work productivity. Therefore, screening, prevention, and treatment of DED are important. We aimed to investigate the potential diagnostic ability of the maximum blink interval (MBI) (the length of time participants could keep their eyes open) with disease-specific questionnaire for DED. This cross-sectional study included 365 patients (252 with DED and 113 without DED) recruited between September 2017 and December 2019. Discriminant validity was assessed by comparing the non-DED and DED groups based on the MBI with a Japanese version of the Ocular Surface Disease Index (J-OSDI) and tear film breakup time (TFBUT) with J-OSDI classifications. The MBI with J-OSDI showed good discriminant validity by known-group comparisons. The positive and predictive values of MBI with J-OSDI were 96.0% (190/198 individuals) and 37.1% (62/167 individuals), respectively. The area under the receiver operating characteristic curve (AUC) of MBI with J-OSDI was 0.938 (95% confidence interval 0.904–0.971), the sensitivity was 75.4% (190/252 individuals), and the specificity was 92.9% (105/113 individuals), which are similar to the diagnostic ability of TFBUT with J-OSDI (AUC 0.954). In conclusion, MBI with J-OSDI may be a simple, non-invasive screening test for DED.
Characterization of rare spindle and root cell transcriptional profiles in the stria vascularis of the adult mouse cochlea
Authors: Gu Shoujun , Olszewski Rafal , Taukulis Ian , Wei Zheng , Martin Daniel , Morell Robert J. , Hoa Michael
Published: October 2020

The stria vascularis (SV) in the cochlea generates and maintains the endocochlear potential, thereby playing a pivotal role in normal hearing. Knowing transcriptional profiles and gene regulatory networks of SV cell types establishes a basis for studying the mechanism underlying SV-related hearing loss. While we have previously characterized the expression profiles of major SV cell types in the adult mouse, transcriptional profiles of rare SV cell types remained elusive due to the limitation of cell capture in single-cell RNA-Seq. The role of these rare cell types in the homeostatic function of the adult SV remain largely undefined. In this study, we performed single-nucleus RNA-Seq on the adult mouse SV in conjunction with sample preservation treatments during the isolation steps. We distinguish rare SV cell types, including spindle cells and root cells, from other cell types, and characterize their transcriptional profiles. Furthermore, we also identify and validate novel specific markers for these rare SV cell types. Finally, we identify homeostatic gene regulatory networks within spindle and root cells, establishing a basis for understanding the functional roles of these cells in hearing. These novel findings will provide new insights for future work in SV-related hearing loss and hearing fluctuation.
Machine learning for recognizing minerals from multispectral data
Authors: Jahoda Pavel , Drozdovskiy Igor , Payler Samuel J. , Turchi Leonardo , Bessone Loredana , Sauro Francesco
Published: October 2020

Combining Deep Learning algorithms, together with data fusion from multi-method spectroscopy, could drastically increase the accuracy of automatic mineral recognition compared to existing approaches.
In vivo evaluation of a pro-healing polydopamine coated stent through an in-stent restenosis rat model
Authors: Hertault Adrien , Chai Feng , Maton Mickael , Sobocinski Jonathan , Woisel Patrice , Maurel Blandine , Lyskawa Joël , Blanchemain Nicolas
Published: October 2020

Drug-eluting stents have demonstrated efficiency in in-stent restenosis (ISR) but induced a risk of late acute thrombosis by delaying strut re-endothelialization.
Synthesis of fulvene-containing boron complexes with aggregation-induced emission and mechanochromic luminescence
Authors: Yan Cai-Xin , Lin Qian-Qian , Li Sha , Wu Cheng-Juan , Li Yan-An , Fan Jian-Zhong , Ma Jian-Ping , Geng Yan , Dong Yu-Bin
Published: October 2020

Donor–acceptor fulvene-containing boron complexes exhibit aggregation-induced emission (AIE), bioimaging properties, and mechanochromic luminescence.
Monodisperse CoSb nanocrystals as high-performance anode material for Li-ion batteries
Authors: Wang Shutao , He Meng , Walter Marc , Kravchyk Kostiantyn V. , Kovalenko Maksym V.
Published: October 2020

20 nm CoSb NCs delivered a high initial Li-ion storage capacity of 544 mA h g−1 at a current density of 660 mA g−1, and at least 82% of this capacity was retained after 1000 cycles.
Synthesis of trisubstituted alkenes by Ni-catalyzed hydroalkylation of internal alkynes with cycloketone oxime esters
Authors: Lu Xiao-Yu , Liu Chuang-Chuang , Jiang Run-Chuang , Yan Lu-Yu , liu Qi-Le , Wang Qing-Qing , Li Jia-Mei
Published: October 2020

A method for Ni-catalyzed hydroalkylation of internal alkynes with cycloketone oxime esters was developed.
Synthesis and characterization of a strong ferromagnetic and high hardness intermetallic compound Fe2B
Authors: Zhao Xingbin , Li Li , Bao Kuo , Zhu Pinwen , Tao Qiang , Ma Shuailing , Liu Bo , Ge Yufei , Li Da , Cui Tian
Published: October 2020

Fe2B is a promising strong ferromagnetic material with high hardness, which makes it a good candidate for multifunction applications in a harsh environment. This work bridges the chasm between strong ferromagnetism and high hardness communities.
Cr3+based nanocrystalline luminescent thermometers operating in a temporal domain
Authors: Elzbieciak-Piecka Karolina , Drabik Joanna , Jaque Daniel , Marciniak Lukasz
Published: October 2020

Cr3+doped nanocrystals were examined as a noncontact temperature sensor in a lifetime-based approach.
Mechanochemical disulfide reduction reveals imprints of noncovalent sulfur⋯oxygen chalcogen bonds in protein-inspired mimics in aqueous solution
Authors: Dopieralski Przemyslaw , Zoloff Michoff Martin E. , Marx Dominik
Published: October 2020

Chalcogen bonds in proteins are found to impact on the mechanochemical reduction of disulfide bridges in aqueous environments.
C3N4-Photocatalyzed aerobic oxidative cleavage of CC bonds in alkynes with diazonium salts leading to two different aldehydes or esters in one pot
Authors: Wang Jingjing , Ni Bangqing , Niu Tengfei , Ji Fei
Published: October 2020

C3N4-Photocatalyzed oxidative cleavage of CC bonds in alkynes with diazonium salts to obtain two different aldehydes or esters.
Polyphenol rich extracts of finger millet and kodo millet ameliorate high fat diet-induced metabolic alterations
Authors: Khare Pragyanshu , Maurya Ruchika , Bhatia Ruchika , Mangal Priyanka , Singh Jagdeep , Podili Koteswaraiah , Bishnoi Mahendra , Kondepudi Kanthi Kiran
Published: October 2020

Taxifolin (98%) and catechin (86.6%) are the major polyphenols in KM-PRE and FM-PRE. FM-PRE and KM-PRE prevent obesity, hepatic steatosis, and gut bacterial dysbiosis however, the effects of KM-PRE are more profound compared to FM-PRE.
Gallium chiral nanoshaping for circular polarization handling
Authors: Cuscunà Massimo , Manoccio Mariachiara , Esposito Marco , Scuderi Mario , Nicotra Giuseppe , Tarantini Iolena , Melcarne Angelo , Tasco Vittorianna , Losurdo Maria , Passaseo Adriana
Published: October 2020

Core/shell nanohelices with VIS-CD are grown using FIBID, with the Ga+ source shaping the metallic core and the gas precursor the dielectric shell