bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal transport and phase transitions of zirconia by on-the-fly machine-learned interatomic potentials
Authors: Verdi Carla , Karsai Ferenc , Liu Peitao , Jinnouchi Ryosuke , Kresse Georg
Published: September 2021

Machine-learned interatomic potentials enable realistic finite temperature calculations of complex materials properties with first-principles accuracy. It is not yet clear, however, how accurately they describe anharmonic properties, which are crucial for predicting the lattice thermal conductivity and phase transitions in solids and, thus, shape their technological applications. Here we employ a recently developed on-the-fly learning technique based on molecular dynamics and Bayesian inference in order to generate an interatomic potential capable to describe the thermodynamic properties of zirconia, an important transition metal oxide. This machine-learned potential accurately captures the temperature-induced phase transitions below the melting point. We further showcase the predictive power of the potential by calculating the heat transport on the basis of Green–Kubo theory, which allows to account for anharmonic effects to all orders. This study indicates that machine-learned potentials trained on the fly offer a routine solution for accurate and efficient simulations of the thermodynamic properties of a vast class of anharmonic materials.
Temporal analog of Fabry-Pérot resonator via coherent population trapping
Authors: Fang Ruihuan , Han Chengyin , Jiang Xunda , Qiu Yuxiang , Guo Yuanyuan , Zhao Minhua , Huang Jiahao , Lu Bo , Lee Chaohong
Published: September 2021

Ramsey spectroscopy via coherent population trapping (CPT) is essential in precision measurements. The conventional CPT-Ramsey fringes contain numbers of almost identical oscillations and so that it is difficult to identify the central fringe. Here we experimentally demonstrate a temporal analog of Fabry–Pérot resonator via double-Λ CPT of laser-cooled 87Rb atoms. By inserting a periodic CPT pulse train between the two CPT-Ramsey pulses, due to the constructive interference of spin coherence, the transmission spectrum appears as a comb of equidistant peaks in frequency domain and thus the central Ramsey fringe can be easily identified. From the five-level Bloch equations for our double-Λ system, we find that the multi-pulse CPT interference can be regarded as a temporal analog of Fabry–Pérot resonator. Because of the small amplitude difference between the two Landé g factors, each peak splits into two when the external magnetic field is not too weak. This splitting is exactly linear with the magnetic field strength and thus can be used for measuring a magnetic field without involving magneto-sensitive transitions.
Optical breast atlas as a testbed for image reconstruction in optical mammography
Authors: Xing Yidan , Duan Yubo , P. Indurkar Padmeya , Qiu Anqi , Chen Nanguang
Published: September 2021

We present two optical breast atlases for optical mammography, aiming to advance the image reconstruction research by providing a common platform to test advanced image reconstruction algorithms. Each atlas consists of five individual breast models. The first atlas provides breast vasculature surface models, which are derived from human breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data using image segmentation. A finite element-based method is used to deform the breast vasculature models from their natural shapes to generate the second atlas, compressed breast models. Breast compression is typically done in X-ray mammography but also necessary for some optical mammography systems. Technical validation is presented to demonstrate how the atlases can be used to study the image reconstruction algorithms. Optical measurements are generated numerically with compressed breast models and a predefined configuration of light sources and photodetectors. The simulated data is fed into three standard image reconstruction algorithms to reconstruct optical images of the vasculature, which can then be compared with the ground truth to evaluate their performance.
Profiling extra cellular matrix associated proteome of human fetal nucleus pulposus in search for regenerative targets
Authors: Rajasekaran Shanmuganathan , Thangavel Chitra , Djuric Niek , Raveendran Muthurajan , Soundararajan Dilip Chand Raja , Nayagam Sharon Miracle , Matchado Monica Steffi , Sri Vijay Anand K. S. , Venkateshwaran Krishna
Published: September 2021

Degeneration of the intervertebral disc is associated with a decrease in extra-cellular matrix (ECM) content due to an imbalance in anabolic and catabolic signaling. Our previous study profiled the core matrisome of fetal NP’s and identified various proteins with anabolic potential for regenerative therapies. This study aims to complement those results by exploring ECM regulators, associated proteins and secreted factors of the fetal nucleus pulposus (NP). Proteomic data of 9 fetal, 7 healthy adults (age 22–79), and 11 degenerated NP’s was analyzed. Based on the selection criteria, a total of 45 proteins were identified, of which 14 were uniquely expressed or upregulated in fetus compared to adult NP’s. Pathway analysis with these proteins revealed a significant upregulation of one pathway and two biological processes, in which 12 proteins were involved. Prolyl 4 hydroxylase (P4HA) 1 and 2, Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) 1, and Heat shock protein 47 (SERPINH1) were involved in ‘collagen biosynthesis’ pathway. In addition, PLOD 1, SERPINH1, Annexin A1 and A4, CD109 and Galectin 3 (LGALS3) were all involved in biological process of ‘tissue development’. Furthermore Annexin A1, A4 and A5, LGALS-3 and SERPINF1 were featured in ‘negative regulation of cell death’. In conclusion, additionally to core ECM proteome, this study reveals ECM regulators and ECM affiliated proteins of interest to study for regenerative therapies, and their potential should be validated in future mechanistic experiments.
RapidEELS: machine learning for denoising and classification in rapid acquisition electron energy loss spectroscopy
Authors: Pate Cassandra M. , Hart James L. , Taheri Mitra L.
Published: September 2021

Recent advances in detectors for imaging and spectroscopy have afforded in situ, rapid acquisition of hyperspectral data. While electron energy loss spectroscopy (EELS) data acquisition speeds with electron counting are regularly reaching 400 frames per second with near-zero read noise, signal to noise ratio (SNR) remains a challenge owing to fundamental counting statistics. In order to advance understanding of transient materials phenomena during rapid acquisition EELS, trustworthy analysis of noisy spectra must be demonstrated. In this study, we applied machine learning techniques to denoise high frame rate spectra, benchmarking with slower frame rate “ground truths”. The results provide a foundation for reliable use of low SNR data acquired in rapid, in-situ spectroscopy experiments. Such a tool-set is a first step toward both automation in microscopy as well as use of these methods to interrogate otherwise poorly understood transformations.
Multi-product biorefinery from Arthrospira platensis biomass as feedstock for bioethanol and lactic acid production
Authors: Esquivel-Hernández Diego A. , Pennacchio Anna , Torres-Acosta Mario A. , Parra-Saldívar Roberto , de Souza Vandenberghe Luciana Porto , Faraco Vincenza
Published: September 2021

With the aim to reach the maximum recovery of bulk and specialty bioproducts while minimizing waste generation, a multi-product biorefinery for ethanol and lactic acid production from the biomass of cyanobacteriumArthrospira platensiswas investigated. Therefore, the residual biomass resulting from different pretreatments consisting of supercritical fluid extraction (SF) and microwave assisted extraction with non-polar (MN) and polar solvents (MP), previously applied onA. platensisto extract bioactive metabolites, was further valorized. In particular, it was used as a substrate for fermentation withSaccharomyces cerevisiaeLPB-287 andLactobacillus acidophilusATCC 43121 to produce bioethanol (BE) and lactic acid (LA), respectively. The maximum concentrations achieved were 3.02 ± 0.07 g/L of BE by the MN process at 120 rpm 30 °C, and 9.67 ± 0.05 g/L of LA by the SF process at 120 rpm 37 °C. An economic analysis of BE and LA production was carried out to elucidate the impact of fermentation scale, fermenter costs, production titer, fermentation time and cyanobacterial biomass production cost. The results indicated that the critical variables are fermenter scale, equipment cost, and product titer; time process was analyzed but was not critical. As scale increased, costs tended to stabilize, but also more product was generated, which causes production costs per unit of product to sharply decrease. The median value of production cost was US$ 1.27 and US$ 0.39, for BE and LA, respectively, supporting the concept of cyanobacterium biomass being used for fermentation and subsequent extraction to obtain ethanol and lactic acid as end products fromA. platensis.
Neuronally-derived tau is increased in experienced breachers and is associated with neurobehavioral symptoms
Authors: Edwards Katie A. , Greer Kisha , Leete Jacqueline , Lai Chen , Devoto Christina , Qu Bao-Xi , Yarnell Angela M. , Polejaeva Elena , Dell Kristine C. , LoPresti Matthew L. , Walker Peter , Wassermann Eric M. , Carr Walter , Stone James R. , Ahlers Stephen T. , Vorn Rany , Martin Carina , Gill Jessica M.
Published: September 2021

Military and law enforcement breachers are exposed to many low-level blasts during their training and occupational experiences in which they detonate explosives to force entry into secured structures. There is a concern that exposure to these repetitive blast events in career breachers could result in cumulative neurological effects. This study aimed to determine concentrations of neurofilament light (NF-L), tau, and amyloid-beta 42 (Aβ42) in serum and in neuronal-derived extracellular vesicles (EVs) in an experienced breacher population, and to examine biomarker associations with neurobehavioral symptoms. Thirty-four participants enrolled in the study: 20 experienced breachers and 14 matched military or civilian law enforcement controls. EV tau concentrations were significantly elevated in experienced breachers (0.3301 ± 0.5225) compared to controls (−0.4279 ± 0.7557; F = 10.43, p = 0.003). No statistically significant changes were observed in EV levels of NF-L or Aβ42 or in serum levels of NF-L, tau, or Aβ42 (p’s > 0.05). Elevated EV tau concentrations correlated with increased Neurobehavioral Symptom Inventory (NSI) score in experienced breachers (r = 0.596, p = 0.015) and predicted higher NSI score (F(1,14) = 7.702, p = 0.015, R2 = 0.355). These findings show that neuronal-derived EV concentrations of tau are significantly elevated and associated with neurobehavioral symptoms in this sample of experienced breachers who have a history of many low-level blast exposures.
Spatial distribution and regional difference of carbon emissions efficiency of industrial energy in China
Authors: Liu Fang , Tang Lu , Liao Kaicheng , Ruan Lijuan , Liu Pingsheng
Published: September 2021

The three-stage super-efficiency slack-based measure and data envelopment analysis (SBM-DEA) model with undesirable outputs is used to calculate carbon emissions efficiency of industrial energy (CEEIE) of 30 provinces in China from 2000 to 2017. Then ArcGIS software is used to illustrate the spatial distribution of CEEIE, and Dagum Gini ratio is calculated to decompose the regional difference. The results show that the spatial distribution of CEEIE changes from disorder to order and provinces characterized with high or low CEEIE cluster in space over time. The total Dagum Gini coefficient indicates that the interprovincial difference in CEEIE across China is gradually expanding, which is mainly induced by the difference between regions. Our findings attach more importance to interregional integration policies for carbon emissions reduction in China.
Cerebral blood flow and cognitive outcome after pediatric stroke in the middle cerebral artery
Authors: Steiner Leonie , Federspiel Andrea , Jaros Jasmine , Slavova Nedelina , Wiest Roland , Steinlin Maja , Grunt Sebastian , Everts Regula
Published: September 2021

Adaptive recovery of cerebral perfusion after pediatric arterial ischemic stroke (AIS) is sought to be crucial for sustainable rehabilitation of cognitive functions. We therefore examined cerebral blood flow (CBF) in the chronic stage after stroke and its association with cognitive outcome in patients after pediatric AIS. This cross-sectional study investigated CBF and cognitive functions in 14 patients (age 13.5 ± 4.4 years) after pediatric AIS in the middle cerebral artery (time since AIS was at least 2 years prior to assessment) when compared with 36 healthy controls (aged 13.8 ± 4.3 years). Cognitive functions were assessed with neuropsychological tests, CBF was measured with arterial spin labeled imaging in the anterior, middle, and posterior cerebral artery (ACA, MCA, PCA). Patients had significantly lower IQ scores and poorer cognitive functions compared to healthy controls (p < 0.026) but mean performance was within the normal range in all cognitive domains. Arterial spin labeled imaging revealed significantly lower CBF in the ipsilesional MCA and PCA in patients compared to healthy controls. Further, we found significantly higher interhemispheric perfusion imbalance in the MCA in patients compared to controls. Higher interhemispheric perfusion imbalance in the MCA was significantly associated with lower working memory performance. Our findings revealed that even years after a pediatric stroke in the MCA, reduced ipsilesional cerebral blood flow occurs in the MCA and PCA and that interhemispheric imbalance is associated with cognitive performance. Thus, our data suggest that cerebral hypoperfusion might underlie some of the variability observed in long-term outcome after pediatric stroke.
Understanding collective regularity in human mobility as a familiar stranger phenomenon
Authors: Leng Yan , Santistevan Dominiquo , Pentland Alex
Published: September 2021

Beyond the physical structures that contain daily routines, urban city dwellers repeatedly encounter strangers that similarly shape their environments. Familiar strangers are neither formal acquaintances nor completely anonymous faces in daily urban life. Due to data limitations, there is a lack of research focused on uncovering the structure of the “Familiar Stranger” phenomenon at a large scale while simultaneously investigating the social relationships between such strangers. Using countrywide mobile phone records from Andorra, we empirically show the existence of such a phenomenon as well as details concerning these strangers’ relative social relations. To understand the social and spatial components of familiar strangers more deeply, we study the temporal regularity and spatial structure of collective urban mobility to shed light on the mechanisms that guide these interactions. Furthermore, we explore the relationship between social distances and the number of encounters to show that more significant physical encounters correspond to a shorter social distance. Understanding these social and physical networks has essential implications for epidemics spreading, urban planning, and information diffusion.
Functional and histologic imaging of urinary bladder wall after exposure to psychological stress and protamine sulfate
Authors: Saito Tetsuichi , Hitchens T. Kevin , Foley Lesley M. , Singh Nishant , Mizoguchi Shinsuke , Kurobe Masahiro , Gotoh Daisuke , Ogawa Teruyuki , Minagawa Tomonori , Ishizuka Osamu , Chermansky Christopher , Kaufman Jonathan , Yoshimura Naoki , Tyagi Pradeep
Published: September 2021

To quantify the urinary bladder wall T1 relaxation time (T1) before and after the instillation contrast mixture in rats previously subjected to water avoidance stress (WAS) and/or acute exposure to protamine sulfate (PS). Female Wistar rats were randomized to receive either sham (control) or 1 h of WAS for ten consecutive days before the evaluation of nocturnal urination pattern in metabolic cages. T1 mapping of urinary bladder wall at 9.4 T was performed pre- and post- instillation of 4 mM Gadobutrol in a mixture with 5 mM Ferumoxytol. Subsequently, either T1 mapping was repeated after brief intravesical PS exposure or the animals were sacrificed for histology and analyzing the mucosal levels of mRNA. Compared to the control group, WAS exposure decreased the single void urine volume and shortened the post-contrast T1 relaxation time of mucosa- used to compute relatively higher ingress of instilled Gadobutrol. Compromised permeability in WAS group was corroborated by the urothelial denudation, edema and ZO-1 downregulation. PS exposure doubled the baseline ingress of Gadobutrol in both groups. These findings confirm that psychological stress compromises the paracellular permeability of bladder mucosa and its non-invasive assay with MRI was validated by PS exposure.
A negative association between prevalence of diabetes and urban residential area greenness detected in nationwide assessment of urban Bangladesh
Authors: Khan Jahidur Rahman , Sultana Amena , Islam Md. Mazharul , Biswas Raaj Kishore
Published: September 2021

Residential area greenness may influence diabetes, but limited studies have explored this relationship in developing countries. This study assessed the association between residential area greenness and diabetes among urban adults in Bangladesh. The mediation effect of the body mass index (BMI) was also assessed. A total of 2367 adults aged ≥ 35 years were extracted from a nationally representative survey. Diabetes was characterised as fasting plasma glucose level be ≥ 7.0 mmol/L or taking prescribed medications to reduce blood sugar level. Residential area greenness was estimated by enhanced vegetation index. Binary logistic regression models were employed to estimate the association between residential area greenness and diabetes adjusting for sociodemographic factors. Mediation analysis was performed to assess whether BMI mediated the association between greenness and diabetes. Greater area greenness was associated with lower odds of diabetes (adjusted odds ratio 0.805, 95% confidence interval 0.693–0.935, p = 0.0052). BMI significantly mediated 36.4% of the estimated association between greenness and diabetes. Presence of areas of greenness adjacent to living area tends to be associated with lower diabetes prevalence. Findings emphasised the importance of preserving the local environment to tackle the growing diabetes prevalence in Bangladesh.
A novel thermostable prokaryotic fucoidan active sulfatase PsFucS1 with an unusual quaternary hexameric structure
Authors: Mikkelsen Maria Dalgaard , Cao Hang Thi Thuy , Roret Thomas , Rhein-Knudsen Nanna , Holck Jesper , Tran Van Thi Thanh , Nguyen Thuan Thi , Tran Vy Ha Nguyen , Lezyk Mateusz Jakub , Muschiol Jan , Pham Thinh Duc , Czjzek Mirjam , Meyer Anne S.
Published: September 2021

Fucoidans are sulfated, fucose-rich marine polysaccharides primarily found in cell walls of brown seaweeds (macroalgae). Fucoidans are known to possess beneficial bioactivities depending on their structure and sulfation degree. Here, we report the first functional characterization and the first crystal structure of a prokaryotic sulfatase, PsFucS1, belonging to sulfatase subfamily S1_13, able to release sulfate from fucoidan oligosaccharides. PsFucS1 was identified in the genome of aPseudoalteromonassp. isolated from sea cucumber gut. PsFucS1 (57 kDa) is Ca2+dependent and has an unusually high optimal temperature (68 °C) and thermostability. Further, the PsFucS1 displays a unique quaternary hexameric structure comprising a tight trimeric dimer complex. The structural data imply that this hexamer formation results from an uncommon interaction of each PsFucS1 monomer that is oriented perpendicular to the common dimer interface (~ 1500 Å2) that can be found in analogous sulfatases. The uncommon interaction involves interfacing (1246 Å2) through a bundle of α-helices in the N-terminal domain to form a trimeric ring structure. The high thermostability may be related to this unusual quaternary hexameric structure formation that is suggested to represent a novel protein thermostabilization mechanism.
Cytotoxicity of snake venom Lys49 PLA2-like myotoxin on rat cardiomyocytes ex vivo does not involve a direct action on the contractile apparatus
Authors: López-Dávila Alfredo Jesús , Weber Natalie , Kraft Theresia , Matinmehr Faramarz , Arias-Hidalgo Mariela , Fernández Julián , Lomonte Bruno , Gutiérrez José María
Published: September 2021

Viperid snake venoms contain a unique family of cytotoxic proteins, the Lys49 PLA2 homologs, which are devoid of enzymatic activity but disrupt the integrity of cell membranes. They are known to induce skeletal muscle damage and are therefore named ‘myotoxins’. Single intact and skinned (devoid of membranes and cytoplasm but with intact sarcomeric proteins) rat cardiomyocytes were used to analyze the cytotoxic action of a myotoxin, from the venom of Bothrops asper. The toxin induced rapid hypercontraction of intact cardiomyocytes, associated with an increase in the cytosolic concentration of calcium and with cell membrane disruption. Hypercontraction of intact cardiomyocytes was abrogated by the myosin inhibitor para-aminoblebbistatin (AmBleb). No toxin-induced changes of key parameters of force development were observed in skinned cardiomyocytes. Thus, although myosin is a key effector of the observed hypercontraction, a direct effect of the toxin on the sarcomeric proteins -including the actomyosin complex- is not part of the mechanism of cytotoxicity. Owing to the sensitivity of intact cardiomyocytes to the cytotoxic action of myotoxin, this ex vivo model is a valuable tool to explore in further detail the mechanism of action of this group of snake venom toxins.
Prevalence of depression and suicide ideation in Hong Kong doctors: a cross-sectional study
Authors: Ng Amy Pui Pui , Chin Weng Yee , Wan Eric Yuk Fai , Chen Julie , Lau Chak Sing
Published: September 2021

Depression amongst physicians can lead to poor individual and institutional outcomes. This study examined the prevalence and factors associated with depression and suicidal ideation amongst doctors in Hong Kong. Doctors who graduated from medical school at the University of Hong Kong between 1995 and 2014 were invited to participate in a survey measuring depressive symptoms, suicidal ideation and thoughts of self-harm, lifestyle behaviours, career satisfaction and socio-demographic characteristics. Data collection occurred between January and April 2016. The prevalence of screened-positive depression was 16.0% and 15.3% of respondents reported having suicidal ideation. Amongst those with positive depression screening scores, less than half reported having a diagnosed mood disorder. Sleeping fewer hours was associated with higher depression scores (P < 0.001) and an increased odds of meeting the cut-off for depression (P < 0.001). Factors associated with suicidal ideation included being unmarried (P = 0.012) and sleeping fewer hours (P = 0.022). Hong Kong doctors appear to have high rates of undiagnosed depression, and high levels of depressive symptoms and suicidal ideations. There is a need for greater awareness of the morbidity due to depression and to promote better mental health help-seeking among physicians. Barriers to mental health help-seeking need to be addressed and appropriate resources allocated to reduce suffering.
Coexisting commensurate and incommensurate charge ordered phases in CoO
Authors: Negi Devendra , Singh Deobrat , Ahuja Rajeev , van Aken Peter A.
Published: September 2021

The subtle interplay of strong electronic correlations in a distorted crystal lattice often leads to the evolution of novel emergent functionalities in the strongly correlated materials (SCM). Here, we unravel such unprecedented commensurate (COM) and incommensurate (ICOM) charge ordered (CO) phases at room temperature in a simple transition-metal mono-oxide, namely CoO. The electron diffraction pattern unveils a COM ($$q_{1}$$

q
1

=$$\frac{1}{2}(1,1,{\bar{1}})$$

1
2

(
1
,
1
,

1

¯

)

and ICOM ($$q_{2}=0.213(1,1,{\bar{1}})$$

q
2

=
0.213

(
1
,
1
,

1

¯

)

) periodic lattice distortion. Transmission electron microscopy (TEM) captures unidirectional and bidirectional stripe patterns of charge density modulations. The widespread phase singularities in the phase-field of the order parameter (OP) affirms the abundant topological disorder. Using, density functional theory (DFT) calculations, we demystify the underlying electronic mechanism. The DFT study shows that a cation disordering ($$\mathrm {Co}_{1-\textit{x}}\mathrm {O}, \text {with }{} \textit{x} = 4.17 \%$$

Co

1
-
x

O
,
with

x
=
4.17
%

) stabilizes Jahn-Teller (JT) distortion and localized aliovalent $$\mathrm {Co}^{3+}$$

Co

3
+

states in CoO. Therefore, the lattice distortion accompanied with mixed valence states ($$\mathrm {Co}^{3+}, \mathrm {Co}^{2+}$$

Co

3
+

,

Co

2
+

) states introduces CO in CoO. Our findings offer an electronic paradigm to engineer CO to exploit the associated electronic functionalities in widely available transition-metal mono-oxides.
The immunomodulatory effects of long-term supplementation with Lactobacillus casei Shirota depend on ovalbumin presentation in BALB/c mice
Authors: Chen Li-Han , Pan Chun-Hsu , Huang Shih-Yi , Chan Ching-Hung , Huang Hui-Yu
Published: September 2021

Immunomodulation is an ability of several particular probiotics. However, it still remains unclear whether the immunomodulatory effects of specific probiotics vary for different antigen presentation models with the same antigen. To investigate this matter, six groups of BALB/c mice (n = 10) were exposed to one of two antigen presentation models: ovalbumin (OVA) by injection alone, or injection plus intranasal administration. Moreover, the mice were fed distilled water or Lactobacillus casei Shirota fermented beverage (LcSFB) at low (2.5 × 109 CFU/kg body weight) or high doses (5 × 109 CFU/kg body weight) by gavage for 8 weeks. LcSFB enhanced the proliferation of splenocytes, production of OVA-specific immunoglobulin (Ig)-G and IgA, and the ratio of T-helper (Th)-2/Th1 cytokines in mice injected with OVA. Conversely, in the mice treated with OVA by injection plus intranasal administration, LcSFB attenuated the immune responses against OVA by reducing the proliferation of splenocytes, levels of OVA-specific IgE, IgG, and IgM, and ratio of Th2/Th1 cytokines. Moreover, LcSFB increased the percentage of regulatory T cells in the injection plus intranasal administration group. Taken together, this work indicates the immunoregulatory effects of LcSFB depend on how the antigen is presented. Therefore, the use of probiotics to boost the immune system must be carefully considered.
Noise reduction by adaptive-SIN filtering for retinal OCT images
Authors: Hu Yan , Ren Jianfeng , Yang Jianlong , Bai Ruibing , Liu Jiang
Published: September 2021

Optical coherence tomography (OCT) images is widely used in ophthalmic examination, but their qualities are often affected by noises. Shearlet transform has shown its effectiveness in removing image noises because of its edge-preserving property and directional sensitivity. In the paper, we propose an adaptive denoising algorithm for OCT images. The OCT noise is closer to the Poisson distribution than the Gaussian distribution, and shearlet transform assumes additive white Gaussian noise. We hence propose a square-root transform to redistribute the OCT noise. Different manufacturers and differences between imaging objects may influence the observed noise characteristics, which make predefined thresholding scheme ineffective. We propose an adaptive 3D shearlet image filter with noise-redistribution (adaptive-SIN) scheme for OCT images. The proposed adaptive-SIN is evaluated on three benchmark datasets using quantitative evaluation metrics and subjective visual inspection. Compared with other algorithms, the proposed algorithm better removes noise in OCT images and better preserves image details, significantly outperforming in terms of both quantitative evaluation and visual inspection. The proposed algorithm effectively transforms the Poisson noise to Gaussian noise so that the subsequent shearlet transform could optimally remove the noise. The proposed adaptive thresholding scheme optimally adapts to various noise conditions and hence better remove the noise. The comparison experimental results on three benchmark datasets against 8 compared algorithms demonstrate the effectiveness of the proposed approach in removing OCT noise.
Cortical thickness is differently associated with ALDH2 rs671 polymorphism according to level of amyloid deposition
Authors: Cho Yong Hyuk , Lee Heirim , Kim Na-Rae , Choi Jin Wook , Roh Hyun Woong , Ha Jae Ho , Hong Chang Hyung , Seo Sang Won , Choi Seong Hye , Kim Eun-Joo , Kim Byeong C. , Kim Seong Yoon , Cheong Jaeyoun , Park Bumhee , Son Sang Joon
Published: September 2021

Accumulating evidence indicates that amyloid-beta (Aβ) deposition and biogenic aldehyde accumulation contribute to the pathogenesis of neurodegenerative diseases. Human aldehyde dehydrogenase 2 (ALDH2) metabolizes biogenic aldehydes produced in the brain to prevent damage. However, r671G>A, a single nucleotide polymorphism of ALDH2, causes aldehyde accumulation and decreased ALDH2 activity. We aimed to investigate whether Aβ deposition and rs671 polymorphism have an interaction effect on cortical thickness (CTh). We grouped 179 participants in the Biobank Innovations for chronic Cerebrovascular disease With ALZheimer's disease Study as follows: amyloid (–) [A(–)] and amyloid (+) [A(+)] groups based on the Aβ deposition degree; A-carrier (AC) and GG (GG) groups based on the presence/absence of the rs671 A allele; and their combinations, i.e., A(–)AC, A(–)GG, A(+)AC, and A(+)GG groups. A multiple regression analysis identified nine regions of interest. Compared with the A(–)GG group, the A(–)AC group showed thinner CTh in all regions. There were no significant differences between the A(+)AC and A(+)GG groups. We observed an interaction effect of amyloid deposition and rs671 polymorphism on CTh. The CTh in the A(–) group appeared to be strongly influenced by rs671 polymorphism, which could have contributed to cortical thinning and biogenic aldehyde accumulation in the AC group. Additionally, CTh in the A(+) group appeared to be strongly influenced by amyloid deposition.
Suppression of autophagy promotes fibroblast activation in p53-deficient colorectal cancer cells
Authors: Inoue Takanori , Hayashi Yoshito , Tsujii Yoshiki , Yoshii Shunsuke , Sakatani Akihiko , Kimura Keiichi , Uema Ryotaro , Kato Minoru , Saiki Hirotsugu , Shinzaki Shinichiro , Iijima Hideki , Takehara Tetsuo
Published: September 2021

Deficiency of p53 in cancer cells activates the transformation of normal tissue fibroblasts into carcinoma-associated fibroblasts; this promotes tumor progression through a variety of mechanisms in the tumor microenvironment. The role of autophagy in carcinoma-associated fibroblasts in tumor progression has not been elucidated. We aimed to clarify the significance of autophagy in fibroblasts, focusing on the TP53 status in co-cultured human colorectal cancer cell lines (TP53-wild-type colon cancer, HCT116; TP53-mutant colon cancer, HT29; fibroblast, CCD-18Co) in vitro. Autophagy in fibroblasts was significantly suppressed in association with ACTA2, CXCL12, TGFβ1, VEGFA, FGF2, and PDGFRA mRNA levels, when co-cultured with p53-deficient HCT116sh p53 cells. Exosomes isolated from the culture media of HCT116sh p53 cells significantly suppressed autophagy in fibroblasts via inhibition of ATG2B. Exosomes derived from TP53-mutant HT29 cells also suppressed autophagy in fibroblasts. miR-4534, extracted from the exosomes of HCT116sh p53 cells, suppressed ATG2B in fibroblasts. In conclusion, a loss of p53 function in colon cancer cells promotes the activation of surrounding fibroblasts through the suppression of autophagy. Exosomal miRNAs derived from cancer cells may play a pivotal role in the suppression of autophagy.
Methylprednisolone stimulated gene expression (GILZ, MCL-1) and basal cortisol levels in multiple sclerosis patients in relapse are associated with clinical response
Authors: Evangelopoulos Maria Eleftheria , Nasiri-Ansari Narjes , Kassi Eva , Papadopoulou Anna , Evangelopoulos Dimitrios Stergios , Moutsatsou Paraskevi
Published: September 2021

Glucocorticoids (GCs) are the main treatment of relapse in multiple sclerosis (MS). Decreased sensitivity to GCs in MS patients has been associated with lack of the suppressive effect of GCs on inflammatory molecules as well as increased resistance to apoptosis. We investigated GC-sensitivity by measuring the effect of intravenous methylprednisolone (IVMP) treatment on transactivation of anti-inflammatory and apoptotic genes (GILZ, MCL-1 and NOXA respectively), in accordance to clinical outcome. Thirty nine MS patients were studied: 15 with clinically isolated syndrome (CIS), 12 with relapsing remitting (RRMS) and 12 with secondary progressive (SPMS) under relapse. Patients underwent treatment with IVMP for 5 days. Blood was drawn before IVMP treatment on day 1 and 1 h after IVMP treatment on days 1 and 5. GIlZ, MCL-1 and NOXA were determined by qPCR. The Expanded Disability Status was evaluated and patients were divided according to their clinical response to IVMP. GILZ and MCL-1 gene expression were significantly higher following first IVMP treatment in responders, compared to non-responders. Furthermore, serum basal cortisol and 1,25-OH Vitamin D levels were significantly higher in clinical-responders as compared to non-clinical responders. Our findings suggest that the differential GILZ and MCL-1 gene expression between clinical-responders and non-clinical responders may implicate the importance of GILZ and MCL-1 as possible markers for predicting glucocorticoid sensitivity and response to GC-therapy in MS patients following first IVMP injection.
Analysis of body condition indices reveals different ecotypes of the Antillean manatee
Authors: Castelblanco-Martínez D. N. , Slone D. H. , Landeo-Yauri S. S. , Ramos E. A. , Alvarez-Alemán A. , Attademo F. L. N. , Beck C. A. , Bonde R. K. , Butler S. M. , Cabrias-Contreras L. J. , Caicedo-Herrera D. , Galves J. , Gómez-Camelo I. V. , González-Socoloske D. , Jiménez-Domínguez D. , Luna F. O. , Mona-Sanabria Y. , Morales-Vela J. B. , Olivera-Gómez L. D. , Padilla-Saldívar J. A. , Powell J. , Reid J. P. , Rieucau G. , Mignucci-Giannoni A. A.
Published: September 2021

Assessing the body condition of wild animals is necessary to monitor the health of the population and is critical to defining a framework for conservation actions. Body condition indices (BCIs) are a non-invasive and relatively simple means to assess the health of individual animals, useful for addressing a wide variety of ecological, behavioral, and management questions. The Antillean manatee (Trichechus manatus manatus) is an endangered subspecies of the West Indian manatee, facing a wide variety of threats from mostly human-related origins. Our objective was to define specific BCIs for the subspecies that, coupled with additional health, genetic and demographic information, can be valuable to guide management decisions. Biometric measurements of 380 wild Antillean manatees captured in seven different locations within their range of distribution were obtained. From this information, we developed three BCIs (BCI1 = UG/SL, BCI2 = W/SL3, BCI3 = W/(SL*UG2)). Linear models and two-way ANCOVA tests showed significant differences of the BCIs among sexes and locations. Although our three BCIs are suitable for Antillean manatees, BCI1 is more practical as it does not require information about weight, which can be a metric logistically difficult to collect under particular circumstances. BCI1 was significantly different among environments, revealing that the phenotypic plasticity of the subspecies have originated at least two ecotypes—coastal marine and riverine—of Antillean manatees.
Histological findings of sperm storage in green turtle (Chelonia mydas) oviduct
Authors: Kitayama Chiyo , Tomiyasu Jumpei , Bochimoto Hiroki , Kondo Satomi , Tokuda Kazuyuki , Ogawa Ryuta , Okubo Saki , Kondoh Daisuke
Published: September 2021

Green turtles (Chelonia mydas) are seasonal breeders with a time lag between mating and nesting periods. We therefore investigated whether female turtles store sperm like some other animals by histologically and ultrastructurally analyzing oviducts collected from three mature female free-ranging green turtles during the breeding season in the Ogasawara Islands, Japan. The oviduct comprised an infundibulum, magnum, isthmus, uterus, and vagina. Sperm was found in the isthmus of all turtles examined. Some spermatozoa were found in the duct and acini of glands in the isthmus of two turtles with oviducts containing eggs, and a few were also located in the transition area between the uterus and vagina of one of the turtles. On the other hand, we also found abundant spermatozoa on the luminal surface of the isthmus of one turtle captured during mating. In most reptiles, fertilization occurs in the infundibulum or albumen region, and thus the isthmus near those areas might be suitable for storing sperm in female turtles.
Multi-phenotype genome-wide association studies of the Norfolk Island isolate implicate pleiotropic loci involved in chronic kidney disease
Authors: Tran Ngan K. , Lea Rodney A. , Holland Samuel , Nguyen Quan , Raghubar Arti M. , Sutherland Heidi G. , Benton Miles C. , Haupt Larisa M. , Blackburn Nicholas B. , Curran Joanne E. , Blangero John , Mallett Andrew J. , Griffiths Lyn R.
Published: September 2021

Chronic kidney disease (CKD) is a persistent impairment of kidney function. Genome-wide association studies (GWAS) have revealed multiple genetic loci associated with CKD susceptibility but the complete genetic basis is not yet clear. Since CKD shares risk factors with cardiovascular diseases and diabetes, there may be pleiotropic loci at play but may go undetected when using single phenotype GWAS. Here, we used multi-phenotype GWAS in the Norfolk Island isolate (n = 380) to identify new loci associated with CKD. We performed a principal components analysis on different combinations of 29 quantitative traits to extract principal components (PCs) representative of multiple correlated phenotypes. GWAS of a PC derived from glomerular filtration rate, serum creatinine, and serum urea identified a suggestive peak (pmin = 1.67 × 10–7) that mapped to KCNIP4. Inclusion of other secondary CKD measurements with these three kidney function traits identified the KCNIP4 locus with GWAS significance (pmin = 1.59 × 10–9). Finally, we identified a group of two SNPs with increased minor allele frequencies as potential functional variants. With the use of genetic isolate and the PCA-based multi-phenotype GWAS approach, we have revealed a potential pleotropic effect locus for CKD. Further studies are required to assess functional relevance of this locus.
Three-dimensional morphology of bacterial community developed on the index-matched materials
Authors: Okano Chigusa , Takabe Kyosuke , Hirayama Tomohiro , Nomura Nobuhiko , Yawata Yutaka
Published: September 2021

Herein, we demonstrate that the use of index-matching materials (IMMs) allows direct visualization of microbial cells maintained at a solid–liquid interface through confocal reflection microscopy (CRM). The refractive index mismatch induces a background reflection at the solid–liquid interface that dwarfs the reflection signals from the cells and results in low-contrast images. We found that the IMMs sufficiently suppressed the background reflection at the solid–liquid interface, facilitating the imaging of microbes at the solid surface using CRM. The use of IMMs allowed quantitative analysis of the morphology of the mesh-like structure of Pseudomonas aeruginosa biofilms formed under denitrifying conditions, which led us to propose a novel structural model of the highly porous biofilm structure. These results indicate that the use of CRM coupled with an IMM offers a unique and promising tool for probing the dynamics of biofilm formation, along with visualization of environmental organisms and newly isolated bacteria, for which transformation methods are difficult to establish.
Promoting physical distancing during COVID-19: a systematic approach to compare behavioral interventions
Authors: Blanken Tessa F. , Tanis Charlotte C. , Nauta Floor H. , Dablander Fabian , Zijlstra Bonne J. H. , Bouten Rick R. M. , Oostvogel Quinten H. , Boersma Meier J. , van der Steenhoven Maya V. , van Harreveld Frenk , de Wit Sanne , Borsboom Denny
Published: September 2021

In the wake of the COVID-19 pandemic, physical distancing behavior turned out to be key to mitigating the virus spread. Therefore, it is crucial that we understand how we can successfully alter our behavior and promote physical distancing. We present a framework to systematically assess the effectiveness of behavioral interventions to stimulate physical distancing. In addition, we demonstrate the feasibility of this framework in a large-scale natural experiment (N = 639) conducted during an art fair. In an experimental design, we varied interventions to evaluate the effect of face masks, walking directions, and immediate feedback on visitors’ contacts. We represent visitors as nodes, and their contacts as links in a contact network. Subsequently, we used network modelling to test for differences in these contact networks. We find no evidence that face masks influence physical distancing, while unidirectional walking directions and buzzer feedback do positively impact physical distancing. This study offers a feasible way to optimize physical distancing interventions through scientific research. As such, the presented framework provides society with the means to directly evaluate interventions, so that policy can be based on evidence rather than conjecture.
Optimized design parameters for CRISPR Cas9 and Cas12a homology-directed repair
Authors: Schubert Mollie S. , Thommandru Bernice , Woodley Jessica , Turk Rolf , Yan Shuqi , Kurgan Gavin , McNeill Matthew S. , Rettig Garrett R.
Published: September 2021

CRISPR–Cas proteins are RNA-guided nucleases used to introduce double-stranded breaks (DSBs) at targeted genomic loci. DSBs are repaired by endogenous cellular pathways such as non-homologous end joining (NHEJ) and homology-directed repair (HDR). Providing an exogenous DNA template during repair allows for the intentional, precise incorporation of a desired mutation via the HDR pathway. However, rates of repair by HDR are often slow compared to the more rapid but less accurate NHEJ-mediated repair. Here, we describe comprehensive design considerations and optimized methods for highly efficient HDR using single-stranded oligodeoxynucleotide (ssODN) donor templates for several CRISPR–Cas systems including S.p. Cas9, S.p. Cas9 D10A nickase, and A.s. Cas12a delivered as ribonucleoprotein (RNP) complexes. Features relating to guide RNA selection, donor strand preference, and incorporation of blocking mutations in the donor template to prevent re-cleavage were investigated and were implemented in a novel online tool for HDR donor template design. These findings allow for high frequencies of precise repair utilizing HDR in multiple mammalian cell lines. Tool availability: https://www.idtdna.com/HDR
A comparative shape analysis of the cervical spine between individuals with cervicogenic headaches and asymptomatic controls
Authors: Masharawi Youssef , Mansour Aumayma Murad , Peled Natan , Weisman Asaf
Published: September 2021

As some researchers theorized that cervicogenic headache (CEH) might be related to bony and discal features of the cervical spine, this retrospective study examined the shapes of the cervical vertebrae and intervertebral discs (IVDs) of individuals with CEH and compared them to asymptomatic controls. Scans of 40 subjects in their late 20’s–mid 30’s affected with CEH and 40 asymptomatic controls were obtained (overall = 19,040 measurements, age-sex matched, 20 males and 20 females in each group). The following cervical spine variables were measured: Supine lordosis, vertebral body-heights, A-P lengths, mediolateral widths and sagittal-wedging; IVDs heights and sagittal-wedging; pedicle heights, widths and transverse angles; laminar widths and transverse angles; articular facet angles, spinal canal, and transverse foramen lengths, widths, and areas. Both groups had similar shape variation along the cervical in all the measured parameters. There were no significant left–right differences in all measured parameters and no significant differences between the CEH and control groups concerning sex and age. Cervical IVDs were lordotic in shape, whereas their adjacent vertebral bodies were kyphotic in shape except for C2. In conclusion, the shape of the cervical spine and IVDs in subjects in their late 20’s–mid 30’s affected with CEH is identical to asymptomatic controls.
Real-time particle size analysis using focused beam reflectance measurement as a process analytical technology tool for continuous microencapsulation process
Authors: Muhaimin Muhaimin , Chaerunisaa Anis Yohana , Bodmeier Roland
Published: September 2021

The online real-time particle size analysis of the microencapsules manufacturing process using the continuous solvent evaporation method was performed using focused beam reflectance measurement (FBRM). In this paper, we use FBRM measurements to investigate the effects of polymer type and compare the size distributions to those obtained using other sizing methods such as optical microscope and laser diffraction. FBRM was also utilized to measure the length-weighted chord length distribution (CLD) and particle size distribution (PSD) online during particle solidification, which could not be done with laser diffraction or nested sieve analysis. The chord lengths and CLD data were taken at specific times using an online FBRM probe mounted below the microparticle. The timing of the FBRM determinations was coordinated with the selection of microparticle samples for particle size analysis by optical microscope and laser diffraction calculation as a reference. For all three produced batches tested, FBRM, laser diffraction, and sieve analysis yielded similar results. Hardening time for the transformation of emulsion droplets into solid microparticles occurred within the first 10.5, 19, 25, 30, and 55 min, according to FBRM results. The FBRM CLDs revealed that a larger particle size mean resulted in a longer CLD and a lower peak of particle number. The FBRM data revealed that the polymer type had a significant impact on microparticle CLD and the transformation process.