bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum NMR metabolomics uncovers multiple metabolic changes in phenobarbital-treated dogs
Authors: Ottka Claudia , Weber Corinna , Müller Elisabeth , Lohi Hannes
Published: June 2021

Introduction

Phenobarbital is a commonly used anticonvulsant for the treatment of canine epileptic seizures. In addition to its central nervous system (CNS) depressing effects, long-term phenobarbital administration affects liver function. However, broader metabolic consequences of phenobarbital treatment are poorly characterized.

Objectives

To identify metabolic changes in the sera of phenobarbital-treated dogs and to investigate the relationship between serum phenobarbital concentration and metabolite levels.

Methods

Leftovers of clinical samples were used: 58 cases with phenobarbital concentrations ranging from 7.8 µg/mL to 50.8 µg/mL, and 25 controls. The study design was cross-sectional. The samples were analyzed by a canine-specific1H NMR metabolomics platform. Differences between the case and control groups were evaluated by logistic regression. The linear relationship between metabolite and phenobarbital concentrations was evaluated using linear regression.

Results

Increasing concentrations of glycoprotein acetyls, LDL particle size, palmitic acid, and saturated fatty acids, and decreasing concentrations of albumin, glutamine, histidine, LDL particle concentration, multiple HDL measures, and polyunsaturated fatty acids increased the odds of the sample belonging to the phenobarbital-treated group, having ap-value < .0033, and area under the curve (AUC) > .7. Albumin and glycoprotein acetyls had the best discriminative ability between the groups (AUC: .94). No linear associations between phenobarbital and metabolite concentrations were observed.

Conclusion

The identified metabolites are known to associate with, for example, liver and CNS function, inflammatory processes and drug binding. The lack of a linear association to phenobarbital concentration suggests that other factors than the blood phenobarbital concentration contribute to the magnitude of metabolic changes.
4-Hydroxyl-N′-[(3-Hydroxy-4-Methoxyphenyl) Methylidene] Benzohydrazide] as Corrosion Inhibitor for Carbon Steel in Dilute H2SO4
Authors: Poojary Nikshith G. , Kumari Preethi , Rao Suma A.
Published: June 2021

The effect of an aromatic hydrazide derivative 4-hydroxyl-N′-[(3-hydroxy-4-methoxyphenyl) methylidene] benzohydrazide] (HMBH) as inhibitor for the corrosion of carbon steel in 0.5 M H2SO4 solution was investigated in the temperature range of 303 K to 323 K using potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS). The concentration of HMBH used was in the range of 0.1 to 1 mM. Inhibition efficiency (% IE) increased with increase in concentration of HMBH and decreased with increase in temperature. Maximum % IE obtained was around 71 with 1 $$\times $$
×
10-3 M HMBH in 0.5 M H2SO4 at 303 K. The Tafel polarization results indicate that HMBH acted as a mixed type of inhibitor. The results of evaluation of thermodynamic and activation parameters suggest the mixed adsorption of HMBH took place by physisorption, and it obeyed Freundlich’s isotherm. Scanning electron microscope (SEM) and atomic force spectroscopy (AFM) images were also recorded to supplement the results of electrochemical studies, and mechanism for corrosion inhibition was suggested.
Radon Inversion Problem for Holomorphic Functions on Circular, Strictly Convex Domains
Authors: Pierzchała P. , Kot P.
Published: June 2021

In this paper we study the so-called Radon inversion problem in bounded, circular, strictly convex domains with $${\mathcal {C}}^2$$

C

2

boundary. We show that given $$p>0$$

p
>
0

and a strictly positive, continuous function $$\Phi $$
Φ
on $$\partial \Omega $$

∂
Ω

, by use of homogeneous polynomials it is possible to construct a holomorphic function $$f \in {\mathcal {O}}(\Omega )$$

f
∈
O
(
Ω
)

such that $$\displaystyle \smallint _0^1 |f(zt)|^pdt = \Phi (z)$$

∫
0
1

|
f

(
z
t
)

|

p

d
t
=
Φ

(
z
)

for all $$z \in \partial \Omega $$

z
∈
∂
Ω

. In our approach we make use of so-called lacunary K-summing polynomials (see definition below) that allow us to construct solutions with in some sense extremal properties.
The INSPIRE Support sub-scale: A critical view of the psychometric properties focusing on dimensionality
Authors: Šaltytė Benth Jūratė , Skar-Fröding Regina , Ruud Torleif , Clausen Hanne Kristin , Heiervang Kristin Sverdvik
Published: June 2021

The statistical methods previously used for assessing dimensionality of the INSPIRE Support sub-scale are often not valid, which may lead to inaccurate conclusions. The first aim of this paper was to present and discuss the methods for assessing the dimensionality of the scale. The second aim was to illustrate these methods using data from a Norwegian translation of the INSPIRE Support sub-scale. Exploratory factor analysis with several extraction and rotation methods was used to identify the dimensionality of the scale. Cronbach’s alpha and omega coefficient were employed to assess the internal consistency. Using the recognized statistical approach, there was no clear structure found in the Support sub-scale, indicating that the scale might be one-dimensional. While single items or sum score of the INSPIRE Support sub-scale might cover important aspects of the personal recovery concept, there is no evidence of the five CHIME dimensions of this scale as published earlier. A more thorough assessment is called for, and results from studies using the five dimensions should be interpreted with caution.
Assessment and source identification of heavy metal contamination of groundwater using geospatial technology in Gadilam River basin, Tamil Nadu, India
Authors: Rizwan K. Mohammed , Thirukumaran V. , Suresh M.
Published: June 2021

The purpose of this study is to determine the groundwater quality of the Gadilam River basin on the basis of Geographic Information Technology (GIS) taxonomy evaluation and risk assessment and statistical analysis. The Gadilam River originates from the district of Kallakurichi and flows into the district of Viluppuram finally confluence at Bay of Bengal in the district of Cuddalore. Groundwater supplies are serving the entire drinking needs of the residents of the Gadilam River basin, and pollution of its toxic elements has been raised in recent years. A total of 120 groundwater samples, excluding reserved forest areas, were obtained from the Gadilam River basin. 50 samples of the Archaean formation, 34 samples of the Quaternary formation, 35 additional Tertiary formation samples and one Cretaceous formation sample. During the monsoon season (Nov. 2018), groundwater samples were taken, which is after the Gaja cyclone’s diastral effects. At the time of the sample acquisition, pH, EC and TDS were measured using the Elico field kit. Using the Atomic Absorption Spectrometer, the heavy metals Zn, Cr, Cu, Pb, Co, Fe, Mn and Ni were analyzed. The spatial distribution maps of the GIS shows that in all the samples the concentrations of chromium, lead, cobalt, nickel are high (above the permitted limit). In 93.40%of the area, the manganese concentrations are higher, dropping under the unauthorized cap for human use in compliance with WHO requirements. In addition, statistical analysis indicates that groundwater pollution of the roots of Pb and Cr is from foreign sources and geogenic origin cannot be avoided. The country's rocks and industrial effluents can trigger Zn and Co. The anthropogenic operations may be due to Cu. The taxonomy diagram showing all groundwater samples is classified as ‘near neutral high metal.’ Industrial waste, household sewage, has boosted the emission of heavy metals. Groundwater risk assessment study of heavy metals using SMCE approach reveals that dense residential area in the Archaean formation, lineaments intersection with river portion and sea shore area in Quaternary formation and nearby SIPCOT industry and Lignite mining area in Tertiary formation is noted in the ‘Extreme risk dangerous’ areas.
Transferable face image privacy protection based on federated learning and ensemble models
Authors: Yang Jingjing , Liu Jiaxing , Han Runkai , Wu Jinzhao
Published: June 2021

Face image features represent significant user privacy concerns. Face images cannot be privately transferred under existing privacy protection methods, and data across various social networks are unevenly distributed. This paper proposes a method for face image privacy protection based on federated learning and ensemble models. A federated learning model based on distributed data sets was established by means of federated learning. On the client side, a local facial recognition model was obtained by local face data training and used as the input of PcadvGAN to train PcadvGAN for several rounds. On the server side, a parameter aggregator based on a differential evolutionary algorithm was established as the discriminator of PcadvGAN server, and a client facial recognition model was ensembled simultaneously. The discriminator of the PcadvGAN server experienced mutation, crossover, and interaction with the ensemble model to reveal the optimal global weight of the PcadvGAN model. Finally, the global optimal aggregation parameter matrix of PcadvGAN was obtained by calculation. The server and the client shared the global optimal aggregation parameter matrix, enabling each client to generate private face images with high transferability and practicality. Targeted attack and non-targeted attack experiments demonstrated that the proposed method can generate high-quality, transferable, robust, private face images with only minor perturbations more effectively than other existing methods.
What Is the Relation between Circular Economy and Sustainability? Answers from Frontrunner Companies Engaged with Circular Economy Practices
Authors: Walker Anna M. , Opferkuch Katelin , Roos Lindgreen Erik , Raggi Andrea , Simboli Alberto , Vermeulen Walter J.V. , Caeiro Sandra , Salomone Roberta
Published: June 2021

The circular economy (CE) concept has become a major interest for companies, promising new business opportunities and a decrease in environmental impacts. Though research on circular business models has recently increased, few scholars have investigated how companies engaged with CE view the connection between CE and sustainability. To address this gap, this paper uses a semi-quantitative survey and semi-structured interviews conducted with companies based in Italy and the Netherlands. Purposive sampling was employed to target firms associated with national and international CE networks, as these companies already engage with CE practices. The survey was distributed online to over 800 firms, of which 155 provided information on their understanding of the CE concept and its relationship with sustainability. The survey results are complemented through findings from 43 interviews with a subset of the survey respondents. The survey answers show that companies view CE as one of the tools to achieve sustainable development, particularly in the environmental domain, where the focus lies on environmentally friendly resource use. Yet, the respondents are less confident whether CE increases economic and social benefits of firms. Interviews show that a majority of respondents position sustainability as the overarching concept. However, most companies advocate that the private sector should strive for both sustainability and circularity, though the distinction between the two concepts in daily business operations seems synthetic and futile to some. These findings provide an important stepping stone for better understanding how firms could apply CE practices to move towards a more sustainable society.
The Music of Frank Bridge
Authors: Huss Fabian
Published: June 2021

The English composer, violist, and conductor Frank Bridge (1879-1941), a student of Sir Charles Villiers Stanford, was one of the first modernists in British music, developing the most radical and lastingly modern musical language of his generation. Bridge was also one of the most accomplished British composers of chamber music in the twentieth century. After the lyrical romanticism of the early period, a notable expansion of style can be observed as early as 1913, leading eventually to the radical language of the Piano Sonata and Third String Quartet, drawing on influences such as Debussy, Stravinsky and the Second Viennese School composers. However, Bridge became frustrated that his later, more complex music was often ignored in favour of his earlier 'Edwardian' works; this neglect of his mature music contributed to the growing obscurity into which his music and reputation fell in his last years and after his death. Symptomatically, Bridge is still often remembered primarily for privately tutoring Benjamin Britten, who later championed his teacher's music and paid homage to him in the 'Variations on a Theme of Frank Bridge' (1937).

This book, the first detailed, and long-overdue, study of Bridge's music and its relevant socio-cultural and aesthetic contexts, encourages a more thorough understanding of Bridge's style and development and will appeal to readers with interests in British music, early twentieth-century modernism and post-romanticism as well as genre and style. Fabian Huss is Visiting Fellow at the University of Bristol and has published widely on British music (particularly E. J. Moeran), with an emphasis on cultural history, and aesthetic and analytical issues.
Machiavelli's Gospel
Authors: Parsons William B.
Published: June 2021

Recent scholarship on The Prince interprets the classic work in the context of Machiavelli's sixteenth-century Italy, but this scholarship neglects the source on which the moral and political world of the sixteenth century was based, the Christian Bible. In this study of The Prince, William Parsons plumbs Machiavelli's allusions to the Bible, along with his statements on the church,and shows that Machiavelli was a careful reader of the Bible and an astute observer of the church. Machiavelli's teaching in The Prince, Parsons contends, might be instructively compared with that of the church's teacher, Jesus Christ. Parsons undertakes what recent interpreters of The Prince have not done: contrast Machiavelli's advice with the teachings of Christ. The result is a new reading of The Prince, revealing in Machiavelli's political thought a systematic critique of the teachings of the New Testament and its model for human life, Christ. In this study of the one of greatest works on politics ever written, Parsons not only challenges the most recent interpretations of The Prince but also gives new understanding to the reading that made Machiavelli famous. William Parsons is associate professor of political science at Carroll College.
“You stole my work! And you stole it poorly!” Choreography, Copyright, and the Problem of Inexpert Iterations
Authors: Gover K.E.
Published: June 2021

Dance theorists and legal scholars argue that choreography is by nature ill-suited to the conceptual framework provided by copyright, even as there is widespread agreement that works of dance deserve the legal protection and cultural endorsement that its inclusion represents. I reexamine the factors that are often cited as barriers to choreography's suitability for copyright. I argue that choreography is better suited to the copyright regime than it appears, so long as we recognize that the artistic standard for substantial similarity should be different from the legal standard.
Cautionary Contours: Joann Kealiinohomoku's Silhougraphs® and Dance Analysis in Black and White
Authors: Hamera Judith
Published: June 2021

Joann Kealiinohomoku's Silhougraphs®, traces of the silhouettes of dancers, were her attempt to operationalize her cultural relativist commitments and create a new method of dance analysis. Silhougraphs illuminate underexamined scholarly presumptions, methods, and tools that both contributed to and paralleled the emergence of dance studies as a discipline. Silhougraphs are also a cautionary tale demonstrating the ways culturally sensitive research commitments and methods can unintentionally yet decisively reiterate tools and logics of racist typologies.
Sensitivity of Climate Feedbacks to Vertical Resolution in a General Circulation Model
Authors: Ingram William , Bushell Andrew C.
Published: June 2021

Many of the current, Coupled Model Intercomparison Project 6 (CMIP6), General Circulation Models (GCMs) show climate sensitivity higher than currently accepted uncertainty ranges. There is a weak correlation between increases in vertical resolution and in climate sensitivity from CMIP5. In particular, the MO Hadley Centre GCM’s vertical resolution has more than doubled, and its climate sensitivity has also increased substantially. We therefore compare estimates of climate sensitivity from the CMIP6 model HadGEM3‐GC3.1‐LL, with 85 levels, and a version with 242 levels. This is far higher resolution than in any previously published simulations with a mainstream GCM, though still less than many scales important for clouds. The climate sensitivity and feedbacks, including the cloud feedback, change little. This suggests that vertical resolution did not drive recent increases in GCM climate sensitivity, though this result should be further tested in other GCMs and over a broader range of resolutions.
Design and fabrication of a vigorous “cavitation-on-a-chip” device with a multiple microchannel configuration
Authors: Rokhsar Talabazar Farzad , Jafarpour Mohammad , Zuvin Merve , Chen Hongjian , Gevari Moein Talebian , Villanueva Luis Guillermo , Grishenkov Dmitry , Koşar Ali , Ghorbani Morteza
Published: June 2021

Hydrodynamic cavitation is one of the major phase change phenomena and occurs with a sudden decrease in the local static pressure within a fluid. With the emergence of microelectromechanical systems (MEMS), high-speed microfluidic devices have attracted considerable attention and been implemented in many fields, including cavitation applications. In this study, a new generation of ‘cavitation-on-a-chip’ devices with eight parallel structured microchannels is proposed. This new device is designed with the motivation of decreasing the upstream pressure (input energy) required for facile hydrodynamic cavitation inception. Water and a poly(vinyl alcohol) (PVA) microbubble (MB) suspension are used as the working fluids. The results show that the cavitation inception upstream pressure can be reduced with the proposed device in comparison with previous studies with a single flow restrictive element. Furthermore, using PVA MBs further results in a reduction in the upstream pressure required for cavitation inception. In this new device, different cavitating flow patterns with various intensities can be observed at a constant cavitation number and fixed upstream pressure within the same device. Moreover, cavitating flows intensify faster in the proposed device for both water and the water–PVA MB suspension in comparison to previous studies. Due to these features, this next-generation ‘cavitation-on-a-chip’ device has a high potential for implementation in applications involving microfluidic/organ-on-a-chip devices, such as integrated drug release and tissue engineering.
Chromosome 1q21 abnormalities in multiple myeloma
Authors: Schmidt Timothy M. , Fonseca Rafael , Usmani Saad Z.
Published: June 2021

Gain of chromosome 1q (+1q) is one of the most common recurrent cytogenetic abnormalities in multiple myeloma (MM), occurring in approximately 40% of newly diagnosed cases. Although it is often considered a poor prognostic marker in MM, +1q has not been uniformly adopted as a high-risk cytogenetic abnormality in guidelines. Controversy exists regarding the importance of copy number, as well as whether +1q is itself a driver of poor outcomes or merely a common passenger genetic abnormality in biologically unstable disease. Although the identification of a clear pathogenic mechanism from +1q remains elusive, many genes at the 1q21 locus have been proposed to cause early progression and resistance to anti-myeloma therapy. The plethora of potential drivers suggests that +1q is not only a causative factor or poor outcomes in MM but may be targetable and/or predictive of response to novel therapies. This review will summarize our current understanding of the pathogenesis of +1q in plasma cell neoplasms, the impact of 1q copy number, identify potential genetic drivers of poor outcomes within this subset, and attempt to clarify its clinical significance and implications for the management of patients with multiple myeloma.
Geometrically encoded SERS nanobarcodes for the logical detection of nasopharyngeal carcinoma-related progression biomarkers
Authors: Lin Duo , Hsieh Chang-Lin , Hsu Keng-Chia , Liao Pei-Hsuan , Qiu Sufang , Gong Tianxun , Yong Ken-Tye , Feng Shangyuan , Kong Kien Voon
Published: June 2021

The limited availability of nasopharyngeal carcinoma-related progression biomarker array kits that offer physicians comprehensive information is disadvantageous for monitoring cancer progression. To develop a biomarker array kit, systematic identification and differentiation of a large number of distinct molecular surface-enhanced Raman scattering (SERS) reporters with high spectral temporal resolution is a major challenge. To address this unmet need, we use the chemistry of metal carbonyls to construct a series of unique SERS reporters with the potential to provide logical and highly multiplex information during testing. In this study, we report that geometric control over metal carbonyls on nanotags can produce 14 distinct barcodes that can be decoded unambiguously using commercial Raman spectroscopy. These metal carbonyl nanobarcodes are tested on human blood samples and show strong sensitivity (0.07 ng/mL limit of detection, average CV of 6.1% and >92% degree of recovery) and multiplexing capabilities for MMPs.
Is the oral microbiome a source to enhance mucosal immunity against infectious diseases?
Authors: Zenobia Camille , Herpoldt Karla-Luise , Freire Marcelo
Published: June 2021

Mucosal tissues act as a barrier throughout the oral, nasopharyngeal, lung, and intestinal systems, offering first-line protection against potential pathogens. Conventionally, vaccines are applied parenterally to induce serotype-dependent humoral response but fail to drive adequate mucosal immune protection for viral infections such as influenza, HIV, and coronaviruses. Oral mucosa, however, provides a vast immune repertoire against specific microbial pathogens and yet is shaped by an ever-present microbiome community that has co-evolved with the host over thousands of years. Adjuvants targeting mucosal T-cells abundant in oral tissues can promote soluble-IgA (sIgA)-specific protection to confer increased vaccine efficacy. Th17 cells, for example, are at the center of cell-mediated immunity and evidence demonstrates that protection against heterologous pathogen serotypes is achieved with components from the oral microbiome. At the point of entry where pathogens are first encountered, typically the oral or nasal cavity, the mucosal surfaces are layered with bacterial cohabitants that continually shape the host immune profile. Constituents of the oral microbiome including their lipids, outer membrane vesicles, and specific proteins, have been found to modulate the Th17 response in the oral mucosa, playing important roles in vaccine and adjuvant designs. Currently, there are no approved adjuvants for the induction of Th17 protection, and it is critical that this research is included in the preparedness for the current and future pandemics. Here, we discuss the potential of oral commensals, and molecules derived thereof, to induce Th17 activity and provide safer and more predictable options in adjuvant engineering to prevent emerging infectious diseases.
A global analysis of the impact of COVID-19 stay-at-home restrictions on crime
Authors: Nivette Amy E. , Zahnow Renee , Aguilar Raul , Ahven Andri , Amram Shai , Ariel Barak , Burbano María José Arosemena , Astolfi Roberta , Baier Dirk , Bark Hyung-Min , Beijers Joris E. H. , Bergman Marcelo , Breetzke Gregory , Concha-Eastman I. Alberto , Curtis-Ham Sophie , Davenport Ryan , Díaz Carlos , Fleitas Diego , Gerell Manne , Jang Kwang-Ho , Kääriäinen Juha , Lappi-Seppälä Tapio , Lim Woon-Sik , Revilla Rosa Loureiro , Mazerolle Lorraine , Meško Gorazd , Pereda Noemí , Peres Maria F. T. , Poblete-Cazenave Rubén , Rose Simon , Svensson Robert , Trajtenberg Nico , van der Lippe Tanja , Veldkamp Joran , Perdomo Carlos J. Vilalta , Eisner Manuel P.
Published: June 2021

The stay-at-home restrictions to control the spread of COVID-19 led to unparalleled sudden change in daily life, but it is unclear how they affected urban crime globally. We collected data on daily counts of crime in 27 cities across 23 countries in the Americas, Europe, the Middle East and Asia. We conducted interrupted time series analyses to assess the impact of stay-at-home restrictions on different types of crime in each city. Our findings show that the stay-at-home policies were associated with a considerable drop in urban crime, but with substantial variation across cities and types of crime. Meta-regression results showed that more stringent restrictions over movement in public space were predictive of larger declines in crime.
Generation and characterization of iPSC-derived renal proximal tubule-like cells with extended stability
Authors: Chandrasekaran Vidya , Carta Giada , da Costa Pereira Daniel , Gupta Rajinder , Murphy Cormac , Feifel Elisabeth , Kern Georg , Lechner Judith , Cavallo Anna Lina , Gupta Shailesh , Caiment Florian , Kleinjans Jos C. S. , Gstraunthaler Gerhard , Jennings Paul , Wilmes Anja
Published: June 2021

The renal proximal tubule is responsible for re-absorption of the majority of the glomerular filtrate and its proper function is necessary for whole-body homeostasis. Aging, certain diseases and chemical-induced toxicity are factors that contribute to proximal tubule injury and chronic kidney disease progression. To better understand these processes, it would be advantageous to generate renal tissues from human induced pluripotent stem cells (iPSC). Here, we report the differentiation and characterization of iPSC lines into proximal tubular-like cells (PTL). The protocol is a step wise exposure of small molecules and growth factors, including the GSK3 inhibitor (CHIR99021), the retinoic acid receptor activator (TTNPB), FGF9 and EGF, to drive iPSC to PTL via cell stages representing characteristics of early stages of renal development. Genome-wide RNA sequencing showed that PTL clustered within a kidney phenotype. PTL expressed proximal tubular-specific markers, including megalin (LRP2), showed a polarized phenotype, and were responsive to parathyroid hormone. PTL could take up albumin and exhibited ABCB1 transport activity. The phenotype was stable for up to 7 days and was maintained after passaging. This protocol will form the basis of an optimized strategy for molecular investigations using iPSC derived PTL.
High burden of cerebral white matter lesion in 9 Asian cities
Authors: Lam Bonnie Yin Ka , Yiu Brian , Ampil Encarnita , Chen Christopher Li-Hsian , Dikot Yustiani , Dominguez Jacqueline C. , Ganeshbhai Patel Vishal , Hilal Saima , Kandiah Nagaendran , Kim SangYun , Lee Jun-Young , Ong Anam Paulus , Senanarong Vorapun , Leung Kam Tat , Wang Huali , Yang Yuan-Han , Yong Tingting , Arshad Faheem , Alladi Suvarna , Wong Samuel , Ko Ho , Lau Alexander Yuk Lun , Mok Vincent Chung Tong
Published: June 2021

Age-related white matter lesion (WML) is considered a manifestation of sporadic cerebral small vessel disease and an important pathological substrate for dementia. Asia is notable for its large population with a looming dementia epidemic. Yet, the burden of WML and its associated risk factors across different Asian societies are unknown. Subjects from 9 Asian cities (Bangkok, Bandung, Beijing, Bengaluru, Hong Kong, Kaohsiung, Manila, Seoul, and Singapore) were recruited (n = 5701) and classified into (i) stroke/transient ischemic attack (TIA), (ii) Alzheimer’s disease (AD)/mild cognitive impairment (MCI), or (iii) control groups. Data on vascular risk factors and cognitive performance were collected. The severity of WML was visually rated on MRI or CT. The prevalence of moderate-to-severe WML was the highest in subjects with stroke/TIA (43.3%). Bandung Indonesia showed the highest prevalence of WML, adjusted for age, sex, education, disease groups, and imaging modality. Hypertension and hyperlipidemia were significant risk factors for WML, and WML was negatively associated with MMSE in all groups. WML is highly prevalent in Asia and is associated with increasing age, hypertension, hyperlipidemia, and worse cognitive performance. Concerted efforts to prevent WML will alleviate the huge dementia burden in the rapidly aging Asian societies.
Impact of kidney transplantation on the risk of retinal vein occlusion in end-stage renal disease
Authors: Lee Jangwook , Choe Hye Rim , Park Sang Hyun , Do Han Kyung , Kim Dong Ki , Joo Kwon Wook , Kim Yon Su , Lee Eun Kyoung , Park Un Chul , Yu Hyeong Gon , Lee Hajeong , Kim Yong Chul , Oh Baek-Lok
Published: June 2021

It has been known that retinal vein occlusion (RVO) is associated with chronic kidney disease, especially end-stage renal disease (ESRD). However, little is known about the effect of kidney transplantation (KT) on RVO incidence in ESRD patients. This study aimed to compare the incidence of RVO in KT recipients (n = 10,498), matched ESRD patients (n = 10,498), and healthy controls (HCs, n = 10,498), using a long-term population-based cohort. The incidence of RVO was 2.74, 5.68, and 1.02 per 1000 patient-years, for the KT group, the ESRD group, and the HCs group, respectively. Adjusted hazard ratios for RVO development compared to the HCs group, were 1.53 and 3.21, in the KT group and the ESRD group, respectively. In the KT group, multivariable regression analysis indicated that an age over 50, a Charlson Comorbidity Index score over 4, and a history of desensitization therapy were associated with an increased risk of RVO. In summary, KT recipients have a lower risk for development of RVO than ESRD patients treated with dialysis. However, the risk is still higher compared to healthy people who have normal kidney functions.
Development of a reference standard for the detection and quantification of Mycobacterium avium subsp. paratuberculosis by quantitative PCR
Authors: Beinhauerova Monika , Beinhauerova Martina , McCallum Sarah , Sellal Eric , Ricchi Matteo , O’Brien Rory , Blanchard Beatrice , Slana Iva , Babak Vladimir , Kralik Petr
Published: June 2021

Quantitative PCR (qPCR) has become a frequently employed direct method for the detection and quantification of Mycobacterium avium subsp. paratuberculosis (MAP). The quantity of MAP determined by qPCR, however, may be affected by the type of qPCR quantification standard used (PCR product, plasmid, genomic DNA) and the way in which standard DNA quantity is determined (absorbance, fluorescence). In practice, this can be reflected in the inability to properly compare quantitative data from the same qPCR assays in different laboratories. Thus, the aim of this study was to prepare a prototype of an international MAP reference standard, which could be used to calibrate routinely used qPCR quantification standards in various laboratories to promote clinical data comparability. Considering stability, storage and shipment issues, a lyophilised fecal suspension artificially contaminated with a MAP reference strain was chosen as the most suitable form of the standard. The effect of five types of lyophilisation matrices on standard stability was monitored on 2-weeks interval basis for 4 months by F57 qPCR. The lyophilisation matrix with 10% skimmed milk provided the best recovery and stability in time and was thus selected for subsequent comparative testing of the standard involving six diagnostic and research laboratories, where DNA isolation and qPCR assay procedures were performed with the parallel use of the identical supplied genomic DNA solution. Furthermore, the effect of storage conditions on the standard stability was tested for at least 6 months. The storage at room temperature in the dark and under light, at + 4 °C, − 20 °C and − 80 °C showed no significant changes in the stability, and also no substantial changes in MAP viability were found using phage amplification assay. The prepared MAP quantification standard provided homogeneous and reproducible results demonstrating its suitability for utilisation as an international reference qPCR standard.
Global climate shift in 1970s causes a significant worldwide increase in precipitation extremes
Authors: Sarkar Subharthi , Maity Rajib
Published: June 2021

The shift in climate regimes around 1970s caused an overall enhancement of precipitation extremes across the globe with a specific spatial distribution pattern. We used gridded observational-reanalysis precipitation dataset and two important extreme precipitation measures, namely Annual Maximum Daily Precipitation (AMDP) and Probable Maximum Precipitation (PMP). AMDP is reported to increase for almost two-third of the global land area. The variability of AMDP is found to increase more than its mean that eventually results in increased PMP almost worldwide, less near equator and maximum around mid-latitudes. Continent-wise, such increase in AMDP and PMP is true for all continents except some parts of Africa. The zone-wise analysis (dividing the globe into nine precipitation zones) reveals that zones of ‘moderate precipitation’ and ‘moderate seasonality’ exhibit the maximum increases in PMP. Recent increased in pole-ward heat and moisture transport as a result of Arctic Amplification may be associated with such spatial redistribution of precipitation extremes in the northern hemisphere.
Lipid profile of bovine grade-1 blastocysts produced either in vivo or in vitro before and after slow freezing process
Authors: Janati Idrissi Sarah , Le Bourhis Daniel , Lefevre Antoine , Emond Patrick , Le Berre Laurene , Desnoës Olivier , Joly Thierry , Buff Samuel , Maillard Virginie , Schibler Laurent , Salvetti Pascal , Elis Sebastien
Published: June 2021

Currently, in vitro embryo production (IVP) is successfully commercially applied in cattle. However, the high sensitivity of embryos to cryopreservation in comparison to in vivo (IVD) embryos slows the dissemination of this biotechnology. Reduced cryotolerance is frequently associated with lipid accumulation in the cytoplasm mainly due to in vitro culture conditions. The objective of this study was to evaluate the lipid composition of biopsied and sexed embryos, produced either in vivo or in vitro from the same Holstein heifers before and after a slow freezing protocol. Lipid extracts were analysed by liquid chromatography-high resolution mass spectrometry, which enabled the detection of 496 features. Our results highlighted a lipid enrichment of IVP embryos in triglycerides and oxidised glycerophospholipids and a reduced abundance in glycerophospholipids. The slow freezing process affected the lipid profiles of IVP and IVD embryos similarly. Lysophosphatidylcholine content was reduced when embryos were frozen/thawed. In conclusion, the embryonic lipid profile is impacted by IVP and slow freezing protocols but not by sex. Lysophosphatidylcholine seemed highly sensitive to cryopreservation and might contribute to explain the lower quality of frozen embryos. Further studies are required to improve embryo freezability by modulating the lipidome.
Mycoplasma pneumoniae CARDS toxin exploits host cell endosomal acidic pH and vacuolar ATPase proton pump to execute its biological activities
Authors: Ramasamy Kumaraguruparan , Balasubramanian Sowmya , Kirkpatrick Alejandra , Szabo Daniel , Pandranki Lavanya , Baseman Joel B. , Kannan T. R.
Published: June 2021

Mycoplasma pneumoniae is the leading cause of bacterial community-acquired pneumonia among hospitalized children in the United States. It is also responsible for a spectrum of other respiratory tract disorders and extrapulmonary manifestations in children and adults. The main virulence factor of M. pneumoniae is a 591 amino acid multifunctional protein called Community Acquired Respiratory Distress Syndrome (CARDS) toxin. The amino terminal region of CARDS toxin (N-CARDS) retains ADP-ribosylating activity and the carboxy region (C-CARDS) contains the receptor binding and vacuolating activities. After internalization, CARDS toxin is transported in a retrograde manner from endosome through the Golgi complex into the endoplasmic reticulum. However, the mechanisms and criteria by which internalized CARDS toxin is transported and activated to execute its cytotoxic effects remain unknown. In this study, we used full-length CARDS toxin and its mutant and truncated derivatives to analyze how pharmacological drugs that alter pH of intracellular vesicles and electrical potential across vesicular membranes affect translocation of CARDS toxin in mammalian cells. Our results indicate that an acidic environment is essential for CARDS toxin retrograde transport to endoplasmic reticulum. Moreover, retrograde transport facilitates toxin clipping and is required to induce vacuole formation. Additionally, toxin-mediated cell vacuolation is strictly dependent on the function of vacuolar type-ATPase.
The international ENIGMA-II substudy on postoperative cognitive disorders (ISEP)
Authors: Haller Guy , Chan Matthew T. V. , Combescure Christophe , Lopez Ursula , Pichon Isabelle , Licker Marc , Fournier Roxane , Myles Paul
Published: June 2021

There is a large controversy as to whether nitrous oxide (N2O) added to the anaesthetic gas mixture is harmful or harmless for postoperative cognitive function recovery. We performed a nested study in the ENIGMA-II trial and compared postoperative neurocognitive recovery of patients randomly receiving N2O (70%) or Air (70%) in 30% O2 during anesthesia. We included adults having non cardiac surgery. We compared recovery scores for episodic memory, decision making/processing speed and executive functions measured with the computerised Cambridge Neuropsychological Test Automated Battery (CANTAB). Assessments were performed at baseline, seven and ninety days. At first interim analysis, following recruitment of 140 participants, the trial was suspended. We found that the mean (95%CI) changes of scores for episodic memory were in the Pocock futility boundaries. Decision making/processing speed did not differ either between groups (P > 0.182). But for executive functions at seven days, the mean number (95% CI) of problems successfully solved and the number of correct box choices made was higher in the N2O group, P = 0.029. N2O with the limitations of an interim analysis appears to have no harmful effect on cognitive functions (memory/processing speed). It may improve the early recovery process of executive functions. This preliminary finding warrants further investigations.
Common neurobiological correlates of resilience and personality traits within the triple resting-state brain networks assessed by 7-Tesla ultra-high field MRI
Authors: Altinok Dilsa Cemre Akkoc , Rajkumar Ravichandran , Nießen Dominik , Sbaihat Hasan , Kersey Margo , Shah N. Jon , Veselinović Tanja , Neuner Irene
Published: June 2021

Despite numerous studies investigating resilience and personality trials, a paucity of information regarding their neurobiological commonalities at the level of the large resting-state networks (rsNWs) remains. Here we address this topic using the advantages of ultra-high-field (UHF) 7T-MRI, characterized by higher signal-to-noise ratio and increased sensitivity. The association between resilience, personality traits and three fMRI measures (fractional amplitude of low-frequency fluctuations (fALFF), degree centrality (DC) and regional homogeneity (ReHo)) determined for three core rsNWs (default mode (DMN), salience (SN), and central executive network (CEN)) were examined in 32 healthy volunteers. The investigation revealed a significant role of SN in both resilience and personality traits and a tight association of the DMN with resilience. DC in CEN emerged as a significant moderator for the correlations of resilience with the personality traits of neuroticism and extraversion. Our results indicate that the common neurobiological basis of resilience and the Big Five personality traits may be reflected at the level of the core rsNWs.
Pure hydroxyapatite synthesis originating from amorphous calcium carbonate
Authors: Sawada Michika , Sridhar Kandi , Kanda Yasuharu , Yamanaka Shinya
Published: June 2021

We report a synthesis strategy for pure hydroxyapatite (HAp) using an amorphous calcium carbonate (ACC) colloid as the starting source. Room-temperature phosphorylation and subsequent calcination produce pure HAp via intermediate amorphous calcium phosphate (ACP). The pre-calcined sample undergoes a competitive transformation from ACC to ACP and crystalline calcium carbonate. The water content, ACC concentration, Ca/P molar ratio, and pH during the phosphorylation reaction play crucial roles in the final phase of the crystalline phosphate compound. Pure HAp is formed after ACP is transformed from ACC at a low concentration (1 wt%) of ACC colloid (1.71 < Ca/P < 1.88), whereas Ca/P = 1.51 leads to pure β-tricalcium phosphate. The ACP phases are precursors for calcium phosphate compounds and may determine the final crystalline phase.
Circulation derived from 4D flow MRI correlates with right ventricular dysfunction in patients with tetralogy of Fallot
Authors: Tsuchiya Nanae , Nagao Michinobu , Shiina Yumi , Miyazaki Shohei , Inai Kei , Murayama Sadayuki , Sakai Shuji
Published: June 2021

We used 4D-flow MRI to investigate circulation, an area integral of vorticity, in the main pulmonary artery (MPA) as a new hemodynamic parameter for assessing patients with a repaired Tetralogy of Fallot (TOF). We evaluated the relationship between circulation, right ventricular (RV) function and the pulmonary regurgitant fraction (PRF). Twenty patients with a repaired TOF underwent cardiac MRI. Flow-sensitive 3D-gradient sequences were used to obtain 4D-flow images. Vortex formation in the MPA was visualized, with short-axis and longitudinal vorticities calculated by software specialized for 4D flow. The RV indexed end-diastolic/end-systolic volumes (RVEDVi/RVESVi) and RV ejection fraction (RVEF) were measured by cine MRI. The PR fraction (PRF) and MPA area were measured by 2D phase-contrast MRI. Spearman ρ values were determined to assess the relationships between circulation, RV function, and PRF. Vortex formation in the MPA occurred in 15 of 20 patients (75%). The longitudinal circulation (11.7 ± 5.1 m2/s) was correlated with the RVEF (ρ = − 0.85, p = 0.0002), RVEDVi (ρ = 0.62, p = 0.03), and RVESVi (ρ = 0.76, p = 0.003) after adjusting for the MPA size. The short-axis circulation (9.4 ± 3.4 m2/s) in the proximal MPA was positively correlated with the MPA area (ρ = 0.61, p = 0.004). The relationships between the PRF and circulation or RV function were not significant. Increased longitudinal circulation in the MPA, as demonstrated by circulation analysis using 4D flow MRI, was related to RV dysfunction in patients with a repaired TOF.
Metabolomics analysis of the soapberry (Sapindus mukorossi Gaertn.) pericarp during fruit development and ripening based on UHPLC-HRMS
Authors: Xu Yuanyuan , Gao Yuan , Chen Zhong , Zhao Guochun , Liu Jiming , Wang Xin , Gao Shilun , Zhang Duanguang , Jia Liming
Published: June 2021

Soapberry (Sapindus mukorossi Gaertn.) is a multi-functional tree with widespread application in toiletries, biomedicine, biomass energy, and landscaping. The pericarp of soapberry can be used as a medicine or detergent. However, there is currently no systematic study on the chemical constituents of soapberry pericarp during fruit development and ripening, and the dynamic changes in these constituents still unclear. In this study, a non-targeted metabolomics approach using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was used to comprehensively profile the variations in metabolites in the soapberry pericarp at eight fruit growth stages. The metabolome coverage of UHPLC-HRMS on a HILIC column was higher than that of a C18 column. A total of 111 metabolites were putatively annotated. Principal component analysis and hierarchical clustering analysis of pericarp metabolic composition revealed clear metabolic shifts from early (S1–S2) to late (S3–S5) development stages to fruit ripening stages (S6–S8). Furthermore, pairwise comparison identified 57 differential metabolites that were involved in 18 KEGG pathways. Early fruit development stages (S1–S2) were characterized by high levels of key fatty acids, nucleotides, organic acids, and phosphorylated intermediates, whereas fruit ripening stages (S6–S8) were characterized by high contents of bioactive and valuable metabolites, such as troxipide, vorinostat, furamizole, alpha-tocopherol quinone, luteolin, and sucrose. S8 (fully developed and mature stage) was the most suitable stage for fruit harvesting to utilize the pericarp. To the best of our knowledge, this was the first metabolomics study of the soapberry pericarp during whole fruit growth. The results could offer valuable information for harvesting, processing, and application of soapberry pericarp, as well as highlight the metabolites that could mediate the biological activity or properties of this medicinal plant.
Effects of human serum albumin on post-mortem changes of malathion
Authors: Yamagishi Yoshikazu , Iwase Hirotaro , Ogra Yasumitsu
Published: June 2021

Malathion, diethyl 2-[(dimethoxyphosphinothioyl)thio]butanedioate, is one of most widely used organophosphoryl pesticide, and it has been detected in several clinical cases of accidental exposure and suicide. It is reported that the observed malathion concentration in blood of persons who suffer from malathion poisoning is smaller than the expected concentration. Because malathion is bound to human serum albumin (HSA), recovery of malathion in the free form is insufficient. We detected malathion adducts in HSA by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF–MS). The mass spectra showed that malathion was preferably bound to the lysine (K) and cysteinylproline (CP) residues of HSA. The K- and CP-adducts of malathion were increased in vitro with a dose-dependent fashion when its concentration was smaller than the lethal dose. Further, the K-adduct was also detected in post-mortem blood of an autopsied subject suffering from intentional malathion ingestion. These results suggest that the K-adduct seems to be available to use a biomarker of malathion poisoning, and the determination of the K-adduct could make possible to estimate the amount of malathion ingestion.
IKKε isoform switching governs the immune response against EV71 infection
Authors: Chang Ya-Ling , Liao Yu-Wen , Chen Min-Hsuan , Chang Sui-Yuan , Huang Yao-Ting , Ho Bing-Ching , Yu Sung-Liang
Published: June 2021

The reciprocal interactions between pathogens and hosts are complicated and profound. A comprehensive understanding of these interactions is essential for developing effective therapies against infectious diseases. Interferon responses induced upon virus infection are critical for establishing host antiviral innate immunity. Here, we provide a molecular mechanism wherein isoform switching of the host IKKε gene, an interferon-associated molecule, leads to alterations in IFN production during EV71 infection. We found that IKKε isoform 2 (IKKε v2) is upregulated while IKKε v1 is downregulated in EV71 infection. IKKε v2 interacts with IRF7 and promotes IRF7 activation through phosphorylation and translocation of IRF7 in the presence of ubiquitin, by which the expression of IFNβ and ISGs is elicited and virus propagation is attenuated. We also identified that IKKε v2 is activated via K63-linked ubiquitination. Our results suggest that host cells induce IKKε isoform switching and result in IFN production against EV71 infection. This finding highlights a gene regulatory mechanism in pathogen-host interactions and provides a potential strategy for establishing host first-line defense against pathogens.