bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Absolutely Continuous Spectrum of Generalized Indefinite Strings
Authors: Eckhardt Jonathan , Kostenko Aleksey
Published: June 2021

We investigate absolutely continuous spectrum of generalized indefinite strings. By following an approach of Deift and Killip, we establish stability of the absolutely continuous spectra of two model examples of generalized indefinite strings under rather wide perturbations. In particular, one of these results allows us to prove that the absolutely continuous spectrum of the isospectral problem associated with the conservative Camassa–Holm flow in the dispersive regime is essentially supported on the interval $$[1/4,\infty )$$

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4
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SARS-CoV-2/COVID-19-Auswirkungen auf die Plazenta
Authors: Menter T. , Tzankov A. , Bruder E.
Published: June 2021

Ein besonderes Augenmerk bei der durch das Severe-acute-respiratory-syndrome-Coronavirus‑2 (SARS-CoV-2) hervorgerufenen Coronaviruskrankheit 2019 (COVID-19) wurde von Beginn an auf die Gruppe der Schwangeren gelegt.

Nach einer Einführung zur Immunabwehr der Plazenta und viralen plazentaren Infektionen, beschreiben wir die morphologischen Veränderungen der Plazenta bei SARS-CoV-2-Infektion der Mutter, ziehen Vergleiche zur SARS-Epidemie und diskutieren die Frage der vertikalen Transmission von SARS-CoV‑2 von der Mutter auf das Neugeborene.

Die häufigsten pathologischen Befunde der Plazenta bestehen in Zeichen der maternalen und auch fetalen Malperfusion sowie immunologisch bzw. thromboinflammatorisch vermittelten Veränderungen. Es finden sich Infarkte, deziduale Vaskulopathie sowie Thromben im fetalen Kreislauf und Vermehrung avaskulärer Villi. Daneben zeigen sich in einigen Fällen Entzündungsreaktionen mit Villitis und Intervillositis sowie eine Vaskulitis fetaler Gefäße. Zudem konnte der Nachweis erbracht werden, dass SARS-CoV‑2 die Plazenta direkt infizieren kann. Somit ist auch eine vertikale Transmission möglich.

Ein COVID-19-spezifisches Schädigungsmuster der Plazenta liegt bislang nicht vor, obwohl der Nachweis von fetaler Thrombovaskulitis, Villitis und Intervillositis sowie einer fetalen und maternalen Malperfusion in Analogie zu der bereits bekannten allgemeinen Pathophysiologie von COVID-19 (Entzündungsreaktion und Mikrozirkulationsstörung) interpretiert werden könnte. Der Nachweis viraler RNA in den fetalen Kompartimenten der Plazenta/der Nabelschnur zeugt von der vertikalen SARS-CoV‑2 Transmission.
The course of gait speed during a 400m walk test of mobility limitations in community-dwelling older adults
Authors: Lindemann Ulrich , Krumpoch Sebastian , Becker Clemens , Sieber Cornel C. , Freiberger Ellen
Published: June 2021

Background

The 400‑m walk test (400MWT) of usual gait speed is an assessment of mobility limitations in geriatric medicine and sarcopenic research.

Objective

The aim of this study was to describe the course of gait speed during a 400MWT in community-dwelling older adults in terms of physical, psychological and general health-related outcomes. Possible plateau phases during the 400MWT could enable integrated measurements of short distance walk tests.

Methods

In this study 148 community-dwelling older adults (mean age 80.4 ± 4.4 years, 61% women) performed a 400MWT at comfortable gait speed. Additionally, an 8m walk test was carried out and history of falling, sex, comorbidities, fear of falling, executive function and gait variability were determined as covariates.

Results

Gait speed was higher in the beginning and the end of the 400MWT compared to the middle part with respect to all analyzed covariates. Mean gait speed of the 8 m walk test was significantly faster than mean gait speed of the 400MWT (t (df = 147) = 0.07, p = 0.001).

Conclusion

The course of gait speed during a 400MWT performed by community-dwelling older adults was not affected by sex, gait variability, comorbidity, history of falling, fear of falling or executive function. Gait speed measurements of the 400MWT do not fully represent assessment of supervised short distance gait speed in community-dwelling adults.
Outcomes in Hirschsprung’s disease with coexisting learning disability
Authors: Davidson Joseph R. , Kyrklund Kristiina , Eaton Simon , Pakarinen Mikko P. , Thompson David , Blackburn Simon C. , Cross Kate , De Coppi Paolo , Curry Joe
Published: June 2021

This study describes functional and health-related quality of life (HRQoL) outcomes in patients with Hirschsprung’s disease (HSCR) with associated learning disability or neurodevelopmental delay (LD), completing a core outcome set for HSCR. This was a cross-sectional study from a tertiary pediatric surgery center. Patients treated between 1977 and 2013 were prospectively contacted to complete an outcomes survey. Children under 12 and older patients with LD were assisted to complete these by a proxy. Bowel and urologic function were assessed (Rintala’s BFS and modified DanPSS) along with HRQoL (PedsQL/GIQLI/SF-36). Thirty-two patients with LD were compared to 186 patients with normal cognition. Patients with LD had 76% survival over the follow-up period, compared to 99% in the remainder of the cohort. Poor functional outcomes were common in the patients with LD, considerably higher than cognitively normal patients: with weekly issues withholding stool, soiling and fecal accidents in over half of patients surveyed (44–60%), and urinary incontinence in 46%. Use of permanent stoma was significantly higher (22% vs. 4%; p = 0.001). HRQoL was worse in domains of physical functioning in adults and children but not for social or emotional domains in adults. Subgroup analysis of patients with Down syndrome suggested similar functional results but better QoL. Multivariate analysis demonstrated a dramatically higher incidence of poor continence outcomes in patients with LD (adjusted OR 9.6 [4.0–23]).

Conclusions: We provide LD-specific outcomes showing inferior function but similar HRQoL to other patients with HSCR, this is much needed in the counselling of families of these children.

What is Known:• Hirschsprung’s disease is commonly associated with syndromes or other anomalies with resultant cognitive impairments.• The outcomes for these patients specifically have been poorly described in the literature.

What is New:• Objective functional and quality of life surveys demonstrate significant differences from patients without cognitive impairment.• Patients with learning disability Patients with associated LD were almost ten times more likely to have an associated poor functional outcome, with very little impact on proxy-reported quality of life.
Complete genome sequence of a novel fish papillomavirus detected in farmed wels catfish (Silurus glanis)
Authors: Surján András , Fónagy Eszter , Eszterbauer Edit , Harrach Balázs , Doszpoly Andor
Published: June 2021

A novel papillomavirus (PV) was detected in farmed wels catfish (Silurus glanis) in Hungary showing clinical signs resembling those of wels catfish herpesvirus disease. The whole genome of Silurus glanis papillomavirus 1 (SgPV1) was identified using next-generation sequencing. The 5,612-bp complete genome contains four predicted protein coding regions (E1, E2, L1, and L2), which seem to have homologues in every PV genome sequenced to date. Five complete fish PV genome sequences are available in the GenBank database. Their genomes range between 5,748 and 6,086 bp and contain the minimal PV backbone genes E1, E2, L2, and L1, unlike PVs of higher vertebrates, which have larger genomes (6.8-8.6 kbp) and additional (onco)genes. Considering the current species demarcation criteria for the family Papillomaviridae, the establishment of a novel species named "Nunpapillomavirus siluri" is proposed for the SgPV1 in a novel genus, "Nunpapillomavirus", in the subfamily Secondpapillomavirinae.
Geosocial Networking Apps Use Among Sexual Minority Men in Ecuador: An Exploratory Study
Authors: Hermosa-Bosano Carlos , Hidalgo-Andrade Paula , Paz Clara
Published: June 2021

Geosocial networking applications (GSN apps) have become important socialization contexts for sexual minority men (SMM). Despite their popularity, there is limited research carried out in Latin American countries and no single previous study done in Ecuador. To fill this gap, this exploratory study described and analyzed the relationships between the sociodemographic characteristics of SMM using GSN apps, their sought and fulfilled expectations, profile shared and sought characteristics, and the evaluation of their experiences as users including their perceptions of support, and discrimination. We used an online recruited sample of 303 participants enrolled between November 2019 and January 2020. Most respondents used Grindr and reported spending up to 3 h per day using apps. Most common sought expectations were getting distracted, meeting new friends, and meeting people for sexual encounters. The least met expectation was meeting someone to build a romantic relationship with. When asked about their profiles, participants reported sharing mainly their age, photographs, and sexual role. Participants also prioritized these characteristics when looking at others’ profiles. When asked about their experiences, most reported having been discriminated against, weight being the main reason for it. Some participants also indicated having received emotional support from other users. Correlation analyses indicated significant but weak relationships among the variables. Results indicated a positive correlation between time as an active GSN app user and higher experiences of discrimination. Likewise, higher number of used apps related positively with levels of received support. These results provide information that could inform future research in the country and the region regarding GSN apps use among SMM, socialization practices, and modern dating tools.
Clinical Validation of the Champagne Algorithm for Evoked Response Source Localization in Magnetoencephalography
Authors: Bhutada Abhishek S. , Cai Chang , Mizuiri Danielle , Findlay Anne , Chen Jessie , Tay Ashley , Kirsch Heidi E. , Nagarajan Srikantan S.
Published: June 2021

Magnetoencephalography (MEG) is a robust method for non-invasive functional brain mapping of sensory cortices due to its exceptional spatial and temporal resolution. The clinical standard for MEG source localization of functional landmarks from sensory evoked responses is the equivalent current dipole (ECD) localization algorithm, known to be sensitive to initialization, noise, and manual choice of the number of dipoles. Recently many automated and robust algorithms have been developed, including the Champagne algorithm, an empirical Bayesian algorithm, with powerful abilities for MEG source reconstruction and time course estimation (Wipf et al. 2010; Owen et al. 2012). Here, we evaluate automated Champagne performance in a clinical population of tumor patients where there was minimal failure in localizing sensory evoked responses using the clinical standard, ECD localization algorithm. MEG data of auditory evoked potentials and somatosensory evoked potentials from 21 brain tumor patients were analyzed using Champagne, and these results were compared with equivalent current dipole (ECD) fit. Across both somatosensory and auditory evoked field localization, we found there was a strong agreement between Champagne and ECD localizations in all cases. Given resolution of 8mm voxel size, peak source localizations from Champagne were below 10mm of ECD peak source localization. The Champagne algorithm provides a robust and automated alternative to manual ECD fits for clinical localization of sensory evoked potentials and can contribute to improved clinical MEG data processing workflows.
Modeling of levothyroxine in newborns and infants with congenital hypothyroidism: challenges and opportunities of a rare disease multi-center study
Authors: Koch Gilbert , Steffens Britta , Leroux Stephanie , Gotta Verena , Schropp Johannes , Gächter Pascal , Bachmann Freya , Welzel Tatjana , Janner Marco , L’Allemand Dagmar , Konrad Daniel , Szinnai Gabor , Pfister Marc
Published: June 2021

Modeling of retrospectively collected multi-center data of a rare disease in pediatrics is challenging because laboratory data can stem from several decades measured with different assays. Here we present a retrospective pharmacometrics (PMX) based data analysis of the rare disease congenital hypothyroidism (CH) in newborns and infants. Our overall aim is to develop a model that can be applied to optimize dosing in this pediatric patient population since suboptimal treatment of CH during the first 2 years of life is associated with a reduced intelligence quotient between 10 and 14 years. The first goal is to describe a retrospectively collected dataset consisting of 61 newborns and infants with CH up to 2 years of age. Overall, 505 measurements of free thyroxine (FT4) and 510 measurements of thyrotropin or thyroid-stimulating hormone were available from patients receiving substitution treatment with levothyroxine (LT4). The second goal is to introduce a scale/location-scale normalization method to merge available FT4 measurements since 34 different postnatal age- and assay-specific laboratory reference ranges were applied. This method takes into account the change of the distribution of FT4 values over time, i.e. a transformation from right-skewed towards normality during LT4 treatment. The third goal is to develop a practical and useful PMX model for LT4 treatment to characterize FT4 measurements, which is applicable within a clinical setting. In summary, a time-dependent normalization method and a practical PMX model are presented. Since there is no on-going or planned development of new pharmacological approaches for CH, PMX based modeling and simulation can be leveraged to personalize dosing with the goal to enhance longer-term neurological outcome in children with the rare disease CH.
Positional competition in a binary system: the case of Finnish higher education
Authors: Isopahkala-Bouret Ulpukka , Aro Mikko , Ojala Kristiina
Published: June 2021

Positional competition in the labour market entails graduate opportunities that depend not only on graduates’ skills, experience and abilities, but also on how their educational credentials compare to those of others. In this study, we examined the positional competition in the Finnish labour market and compared the influence of different ‘degree types’ on the probability of obtaining high-paid, high-status jobs. We used a register-based 5% sample of 25–45-year-old Finnish higher education (HE) graduates from 2010 to 2012 (N = 63 486). It was expected that the relative position of graduates would be affected by the degree level as well as the educational field and the binary division (university vs. non-university) of HE. Therefore, master’s and bachelor’s degree levels in all educational fields from universities versus universities of applied sciences (UASs) were included. The method of analysis was logistic regression. According to our results, the binary divide structured the opportunities to enter high-paid, high-status jobs within different fields of education. The university master’s degree graduates had the highest probability of succeeding in the Finnish labour market, and their status/rank elevated them above the competition by regulating access to certain professions or occupations through specific qualification requirements (i.e., credential social closure). Moreover, our results demonstrated how the degree rankings and the relative distance between university and UAS degrees vary in different fields. The Finnish case offers a valuable point of comparison to other HE systems with a binary structure.
A series expansion for generalized harmonic functions
Authors: Klintborg Markus , Olofsson Anders
Published: June 2021

We consider a class of generalized harmonic functions in the open unit disc in the complex plane. Our main results concern a canonical series expansion for such functions. Of particular interest is a certain individual generalized harmonic function which suitably normalized plays the role of an associated Poisson kernel.
Therapeutic Effect of IL1β Priming Tonsil Derived-Mesenchymal Stem Cells in Osteoporosis
Authors: Yoo Minjoo , Cho Sungkuk , Shin Sunhye , Kim Jung-Mi , Park Hyeon-Gyeong , Cho Sungyoo , Hwang Yu Kyeong , Park Dae Hwi
Published: June 2021

Background:

Stem cell therapies can be a new therapeutic strategy that may rebalance anabolic and anti-resorptive effects in osteoporosis patients. Tonsil-derived mesenchymal stem cells (TMSCs) can be an alternative therapeutic source for chronic degenerative diseases including osteoporosis. MSCs acquire immune regulatory function under the inflammatory cytokines. Since interleukin (IL) 1β is known to be one of inflammatory cytokines involved in osteoporosis progression, treatment of IL1β with TMSCs may enhance immunomodulatory function and therapeutic effects of TMSCs in osteoporosis.

Methods:

For IL1β priming, TMSCs were cultured in the presence of the medium containing IL1β for 1 day. Characteristics of IL1β priming TMSCs such as multipotent differentiation properties, anti-inflammatory potential, and suppression of osteoclast differentiation were assessed in vitro. For in vivo efficacy study, IL1β priming TMSCs were intravenously infused twice with ovariectomized (OVX) osteoporosis mouse model, and blood serum and bone parameters from micro computed tomography images were analyzed.

Results:

IL1β priming TMSCs had an enhanced osteogenic differentiation and secreted factors that regulate both osteoclastogenesis and osteoblastogenesis. IL1β priming TMSCs also suppressed proliferation of peripheral blood mononuclear cells (PBMCs) and decreased expression of Receptor activator of nuclear factor kappa-Β ligand (RANKL) in PHA-stimulated PBMCs. Furthermore, osteoclast specific genes such as Nuclear factor of activated T cells c1 (NFATc1) were effectively down regulated when co-cultured with IL1β priming TMSCs in RANKL induced osteoclasts. In OVX mice, IL1β priming TMSCs induced low level of serum RANKL/osteoprotegerin (OPG) ratio on the first day of the last administration. Four weeks after the last administration, bone mineral density and serum Gla-osteocalcin were increased in IL1β priming TMSC-treated OVX mice. Furthermore, bone formation and bone resorption markers that had been decreased in OVX mice with low calcium diet were recovered by infusion of IL1β priming TMSCs.

Conclusion:

IL1β priming can endow constant therapeutic efficacy with TMSCs, which may contribute to improve bone density and maintain bone homeostasis in postmenopausal osteoporosis. Therefore, IL1β priming TMSCs can be a new therapeutic option for treating postmenopausal osteoporosis.
Smart Bionic Surfaces with Switchable Wettability and Applications
Authors: Li Shuyi , Fan Yuyan , Liu Yan , Niu Shichao , Han Zhiwu , Ren Luquan
Published: June 2021

In order to satisfy the needs of different applications and more complex intelligent devices, smart control of surface wettability will be necessary and desirable, which gradually become a hot spot and focus in the field of interface wetting. Herein, we review interfacial wetting states related to switchable wettability on superwettable materials, including several classical wetting models and liquid adhesive behaviors based on the surface of natural creatures with special wettability. This review mainly focuses on the recent developments of the smart surfaces with switchable wettability and the corresponding regulatory mechanisms under external stimuli, which is mainly governed by the transformation of surface chemical composition and geometrical structures. Among that, various external stimuli such as physical stimulation (temperature, light, electric, magnetic, mechanical stress), chemical stimulation (pH, ion, solvent) and dual or multi-triggered stimulation have been sought out to realize the regulation of surface wettability. Moreover, we also summarize the applications of smart surfaces in different fields, such as oil/water separation, programmable transportation, anti-biofouling, detection and delivery, smart soft robotic etc. Furthermore, current limitations and future perspective in the development of smart wetting surfaces are also given. This review aims to offer deep insights into the recent developments and responsive mechanisms in smart biomimetic surfaces with switchable wettability under external various stimuli, so as to provide a guidance for the design of smart surfaces and expand the scope of both fundamental research and practical applications.
Actuation of Liquid Flow by Guided Acoustic Waves on Punched Steel Tapes with Protruding Loops
Authors: Backer Alexander , Landskron Johannes , Drese Klaus Stefan , Lindner Gerhard
Published: June 2021

In a biomimetic approach the feasibility of liquid flow actuation by vibrating protruding structures excited via guided acoustic waves is investigated. Inspired by periodically beating cilia the loop part of a punched metallic hook-and-loop tape with tilted protruding loops was used as a waveguide for plate waves in water. Such waves were excited in the frequency range of 110 Hz to 220 Hz by directly coupling the tape to a loudspeaker membrane. A flow generated in the tilt direction of the loops with velocities up to 60 mm·s−1 was visualized by ink droplets deposited on the tape. The phenomenon persisted, when the protruding length of the loops was reduced by decreasing the protrusion angle. However, after closing the punch holes near the loops with sticking tape streaming could not be observed any longer. The same happened with open punch holes when the ink was replaced by glycerol. Low-frequency acoustic streaming around vibrating sharp edges is proposed as an explanation for the observed phenomena. Applications are expected with respect to the modification of flow profiles and the enhancement of transport processes along and across liquid-solid boundaries.
The Divine Goodness of Jesus
Authors: Moser Paul
Published: June 2021

In this book, Paul Moser explores Jesus' role as God's filial inquirer and clarifies a method of inquiry regarding Jesus, one that offers a compelling explanation regarding his experiential impact and his audience's response. Moser's method values the roles of history and moral/religious experience in inquiry about him, and it saves inquirers from distorting biases in their inquiry. His study illuminates Jesus' puzzling features, including his challenging question for inquirers of him (Who do you say I am?), his distinctive experience of God as father, his reference to himself as 'the son of man', his attitude toward his suffering and death, his unique role in the kingdom of God, and his understanding of his allegedly miraculous signs and of his parables and good news. The book also makes sense of evidence for the reality and the main purpose of Jesus.
RNAi of vacuolar-type H+-ATPase genes causes growth delay and molting defect inHenosepilachna vigintioctopunctata
Authors: Zeng Jie , Mu Li-Li , Jin Lin , Ali Anjum Ahmad , Li Guo-Qing
Published: June 2021

Henosepilachna vigintioctopunctatais one of the most serious insect pests to a large number of nightshades and cucurbits. RNA interference (RNAi) triggered by double-stranded RNA (dsRNA) offers a reduced risk approach to control the beetle. Identification of amenable target genes and determination of appropriate life stage for dsRNA treatment are two critical steps in order to improve RNAi efficiency. In the present paper, we identified three vATPase genes, namelyHvvATPaseC,HvvATPaseEandHvvATPaseH. We found that the three transcripts were widely expressed in the eggs, first- to fourth-instar larvae, prepupae, pupae and adults. They were abundantly transcribed in the hindgut and Malpighian tubules, in contrast to the epidermis and fat body. Three days' ingestion of dsvATPaseC, dsvATPaseEand dsvATPaseHby the fourth-instar larvae significantly decreased corresponding transcript level by 90.1, 88.9 and 97.2%, greatly reduced larval fresh weight by 28.0, 29.9 and 28.0%, and caused 66.7, 100 and 78.7% larval lethality respectively. Comparably, 3 days' exposure of the third-instar larvae to dsvATPaseCsignificantly reducedHvvATPaseCmRNA level by 89.5%, decreased approximately 80% of the larval fresh weight, and killed 100% of the treated larvae. Therefore, the three vATPase genes, especiallyHvvATPaseE, are potential amenable target genes and young larvae are more susceptible to dsRNA. Our findings will enable the development of the dsRNA-based pesticide to controlH. vigintioctopunctata.
TREND EXTRACTION FROM ECONOMIC TIME SERIES WITH MISSING OBSERVATIONS BY GENERALIZED HODRICK–PRESCOTT FILTERS
Authors: Yamada Hiroshi
Published: June 2021

The Hodrick–Prescott (HP) filter has been a popular method of trend extraction from economic time series. However, it is impractical without modification if some observations are not available. This paper improves the HP filter so that it can be applied in such situations. More precisely, this paper introduces two alternative generalized HP filters that are applicable for this purpose. We provide their properties and a way of specifying those smoothing parameters that are required for their application. In addition, we numerically examine their performance. Finally, based on our analysis, we recommend one of them for applied studies.
Intravascular ultrasonography-guided measurement and transcatheter closure of highly calcified patent ductus arteriosus in an older adult
Authors: Kawai Yoko , Nakamura Takeshi , Matoba Satoaki
Published: June 2021

In older adults with patent ductus arteriosus, CT is widely used for duct visualisation because angiography images can be inadequate for evaluation. We report the case of a 73-year-old woman with a highly calcified patent ductus arteriosus whose CT images were insufficient for accurate measurement. Intravascular ultrasonography is useful for sizing of and guiding device closure of the duct.
Fishy SPS Measures? The WTO's Korea – Radionuclides Dispute
Authors: Brewster Rachel , Fischer Carolyn
Published: June 2021

The Korea–Radionuclides case addresses Korean SPS measures imposed on Japanese fishery products after the Fukushima Dai-ichi nuclear plant meltdown in 2011. Japan challenged these measures as more restrictive than necessary under the SPS Agreement. The panel agreed with Japan, but this ruling was largely reversed by the Appellate Body. Korea's victory at the Appellate Body was based on procedure. The panel accepted Korea's appropriate level of protection (ALOP), which included both quantitative and qualitative elements. However, the Appellate Body found that the panel only addressed the quantitative aspect of Korea's ALOP and reversed on that basis. The Appellate Body's ruling did not affirmatively find that Korea's SPS measures were legal under WTO rules. Instead, the Appellate Body found that panel had not sufficiently addressed Korea's arguments and, thereby, the panel could not determine that the SPS measures were more restrictive than necessary. The case highlights the need for the Appellate Body to be able to conduct its own factual analysis, a power it could be given if the dispute settlement system is reformed. Without independent fact-finding power, the Appellate Body cannot correct panels’ mistakes, and respondents can prevail based on panel error.
Acquisition and Online Display of High‐Resolution Backscattered Electron and X‐Ray Maps of Meteorite Sections
Authors: Ogliore Ryan C.
Published: June 2021

Analyses of meteorites in thin or thick section begins with a detailed mineralogic/petrologic study of the sample. Backscattered electron and X‐ray imaging in a scanning electron microscope is critical for the characterization and study of the meteorite sections at sub‐μm to cm size scales. Here, I describe techniques to acquire backscattered electron and X‐ray images of an entire one‐inch thin or thick section at high resolution, assemble large mosaic mosaic maps of the data, and display the maps conveniently online in a web browser. The code to acquire, stitch, and display the maps is made available as an open‐source project on GitHub.
NK-/T-cell lymphomas
Authors: Wang Hua , Fu Bi-bo , Gale Robert Peter , Liang Yang
Published: June 2021

Natural killer/T-cell lymphoma (NKTL) is a sub-type of Epstein–Barr virus (EBV)-related non-Hodgkin lymphomas common in Asia and Latin America but rare elsewhere. Its pathogenesis is complex and incompletely understood. Lymphoma cells are transformed from NK- or T-cells, sometimes both. EBV-infection and subsequent genetic alterations in infected cells are central to NKTL development. Hemophagocytic syndrome is a common complication. Accurate staging is important to predict outcomes but there is controversy which system is best. More than two-thirds of NKTL lympohmas are localized at diagnosis, are frequently treated with radiation therapy only and have 5-year survival of about 70 percent. Persons with advanced NKTLs receive radiation therapy synchronously or metachronously with diverse multi-drug chemotherapy typically includingl-asparginase with 5-year survival of about 40 percent. Some persons with widespread NKTL receive chemotherapy only. There are few data on safety and efficacy of high-dose therapy and a haematopoietic cell autotransplant. Immune therapies, histone deacetylase (HDAC)-inhibitors and other drugs are in early clinical trials. There are few randomized controlled clinical trials in NKTLs and no therapy strategy is clearlybest; more effective therapy(ies) are needed. Some consensus recommendations are not convincingly evidence-based. Mechanisms of multi-drug resistance are considered. We discuss these issues including recent advances in our understanding of and therapy of NKTLs.
Avian extremity reconstruction via osseointegrated leg-prosthesis for intuitive embodiment
Authors: Hochgeschurz Sarah , Bergmeister Konstantin D. , Brånemark Rickard , Aman Martin , Rocchi Attillio , Restitutti Flavia , Gumpenberger Michaela , Sporer Matthias E. , Gstoettner Clemens , Kramer Anne-Margarete , Lang Susanna , Podesser Bruno K. , Aszmann Oskar C.
Published: June 2021

For large avians such as vultures, limb loss leads to loss of ambulation and eventually death from malnutrition. Prosthetic devices may replace the limb, however, conventional prosthetic sockets are not feasible in feathered limbs and the extreme stress and strain of unreflected daily use in animals. Osseointegration is a novel technique, where external prosthetic parts are connected directly to a bone anchor to provide a solid skeletal-attachment. This concept provides a high degree of embodiment since osseoperception will provide direct intuitive feedback allowing natural use of the limb in gait and feeding. Here we demonstrate for the first time an osseointegrated bionic reconstruction of a limb in a vulture after a tarsometatarsal amputation with a longterm follow-up.
Selective control of the contact and transport between droplet pairs by electrowetting-on-dielectric for droplet-array sandwiching technology
Authors: Konishi Satoshi , Ohya Chikara , Yamada Tatsuhiro
Published: June 2021

Methodological advances in on-chip technology enable high-throughput drug screening, such as droplet-array sandwiching technology. Droplet-array sandwiching technology involves upper and lower substrates with a droplet-array designed for a one-step process. This technology is, however, limited to batch manipulation of the droplet-array. Here, we propose a method for selective control of individual droplets, which allows different conditions for individual droplet pairs. Electrowetting-on-dielectric (EWOD) technology is introduced to control the height of the droplets so that the contact between droplet-pairs can be individually controlled. Circular patterns 4 mm in diameter composed of electrodes for EWOD and hydrophilic–hydrophobic patterns for droplet formation 4 μl in volume were developed. We demonstrate the selective control of the droplet height by EWOD for an applied voltage up to 160 V and selective control of the contact and transport of substances. Presented results will provide useful method for advanced drug screening, including cell-based screening.
Multiple functions of reversine on the biological characteristics of sheep fibroblasts
Authors: Guo Yu , Zhu Huan , Li Xiangchen , Ma Caiyun , Sun Tingting , Wang Yuanyuan , Wang Chunjing , Guan Weijun , Liu Changqing
Published: June 2021

Previous reports have demonstrated that Reversine can reverse differentiation of lineage-committed cells to mesenchymal stem cells and suppress tumors growth. However, the molecular mechanisms of antitumor activity and promoting cellular dedifferentiation for reversine have not yet been clearly elucidated. In the present study, it was demonstrated that reversine of 5 μM could induce multinucleated cells through cytokinesis failure rather than just arrested in G2 or M phase. Moreover, reversine reversed the differentiation of sheep fibroblasts into MSC-like style, and notably increased the expression of pluripotent marker genes Oct4 and MSCs-related surface antigens. The fibroblasts treated with reversine could transdifferentiate into all three germ layers cells in vitro. Most importantly, the induced β-like cells and hepatocytes had similar metabolic functions with normal cells in vivo. In addition, reversine promoted fibroblasts autophagy, ROS accumulation, mitochondrial dysfunction and cell apoptosis via the mitochondria mediated intrinsic pathway. The results of high-throughput RNA sequencing showed that most differentially expressed genes (DEGs) involved in Mismatch repair, Nucleotide excision repair and Base excision repair were significantly up-regulated in reversine treated fibroblasts, which means that high concentration of reversine will cause DNA damage and activate the DNA repair mechanism. In summary, reversine can increase the plasticity of sheep fibroblasts and suppress cell growth via the mitochondria mediated intrinsic pathway.
Uncovering of cytochrome P450 anatomy by SecStrAnnotator
Authors: Midlik Adam , Navrátilová Veronika , Moturu Taraka Ramji , Koča Jaroslav , Svobodová Radka , Berka Karel
Published: June 2021

Protein structural families are groups of homologous proteins defined by the organization of secondary structure elements (SSEs). Nowadays, many families contain vast numbers of structures, and the SSEs can help to orient within them. Communities around specific protein families have even developed specialized SSE annotations, always assigning the same name to the equivalent SSEs in homologous proteins. A detailed analysis of the groups of equivalent SSEs provides an overview of the studied family and enriches the analysis of any particular protein at hand. We developed a workflow for the analysis of the secondary structure anatomy of a protein family. We applied this analysis to the model family of cytochromes P450 (CYPs)—a family of important biotransformation enzymes with a community-wide used SSE annotation. We report the occurrence, typical length and amino acid sequence for the equivalent SSE groups, the conservation/variability of these properties and relationship to the substrate recognition sites. We also suggest a generic residue numbering scheme for the CYP family. Comparing the bacterial and eukaryotic part of the family highlights the significant differences and reveals a well-known anomalous group of bacterial CYPs with some typically eukaryotic features. Our workflow for SSE annotation for CYP and other families can be freely used at addresshttps://sestra.ncbr.muni.cz.
Loss of the transcriptional repressor Rev-erbα upregulates metabolism and proliferation in cultured mouse embryonic fibroblasts
Authors: Gillis Sean P. , Yao Hongwei , Rizal Salu , Maeda Hajime , Chang Julia , Dennery Phyllis A.
Published: June 2021

The transcriptional repressor Rev-erbα is known to down-regulate fatty acid metabolism and gluconeogenesis gene expression. In animal models, disruption of Rev-erbα results in global changes in exercise performance, oxidative capacity, and blood glucose levels. However, the complete extent to which Rev-erbα-mediated transcriptional repression of metabolism impacts cell function remains unknown. We hypothesized that loss of Rev-erbα in a mouse embryonic fibroblast (MEF) model would result in global changes in metabolism. MEFs lacking Rev-erbα exhibited a hypermetabolic phenotype, demonstrating increased levels of glycolysis and oxidative phosphorylation. Rev-erbα deletion increased expression of hexokinase II, transketolase, and ribose-5-phosphate isomerase genes involved in glycolysis and the pentose phosphate pathway (PPP), and these effects were not mediated by the transcriptional activator BMAL1. Upregulation of oxidative phosphorylation was not accompanied by an increase in mitochondrial biogenesis or numbers. Rev-erbα repressed proliferation via glycolysis, but not the PPP. When treated with H2O2, cell viability was reduced in Rev-erbα knockout MEFs, accompanied by increased ratio of oxidized/reduced NADPH, suggesting that perturbation of the PPP reduces capacity to mount an antioxidant defense. These findings uncover novel mechanisms by which glycolysis and the PPP are modulated through Rev-erbα, and provide new insights into how Rev-erbα impacts proliferation.
Evaluation of the prognostic value of CBXs in gastric cancer patients
Authors: He Mengya , Yue Limin , Wang Haiyan , Yu Feiyan , Yu Mingyang , Ni Peng , Zhang Ke , Chen Shuaiyin , Duan Guangcai , Zhang Rongguang
Published: June 2021

Chromobox (CBX) proteins were suggested to exert epigenetic regulatory and transcriptionally repressing effects on target genes and might play key roles in the carcinogenesis of a variety of carcinomas. Nevertheless, the functions and prognostic significance of CBXs in gastric cancer (GC) remain unclear. The current study investigated the roles of CBXs in the prognosis of GC using the Oncomine, The Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, The Cancer Genome Atlas (TCGA), and cBioPortal databases. CBX1/2/3/4/5 were significantly upregulated in GC tissues compared with normal tissues, and CBX7 was downregulated. Multivariate analysis showed that high mRNA expression levels of CBX3/8 were independent prognostic factors for prolonged OS in GC patients. In addition, the genetic mutation rate of CBXs was 37% in GC patients, and genetic alterations in CBXs showed no association with OS or disease-free survival (DFS) in GC patients. These results indicated that CBX3/8 can be prognostic biomarkers for the survival of GC patients.
Assessment of a complete and classified platelet proteome from genome-wide transcripts of human platelets and megakaryocytes covering platelet functions
Authors: Huang Jingnan , Swieringa Frauke , Solari Fiorella A. , Provenzale Isabella , Grassi Luigi , De Simone Ilaria , Baaten Constance C. F. M. J. , Cavill Rachel , Sickmann Albert , Frontini Mattia , Heemskerk Johan W. M.
Published: June 2021

Novel platelet and megakaryocyte transcriptome analysis allows prediction of the full or theoretical proteome of a representative human platelet. Here, we integrated the established platelet proteomes from six cohorts of healthy subjects, encompassing 5.2 k proteins, with two novel genome-wide transcriptomes (57.8 k mRNAs). For 14.8 k protein-coding transcripts, we assigned the proteins to 21 UniProt-based classes, based on their preferential intracellular localization and presumed function. This classified transcriptome-proteome profile of platelets revealed: (i) Absence of 37.2 k genome-wide transcripts. (ii) High quantitative similarity of platelet and megakaryocyte transcriptomes (R = 0.75) for 14.8 k protein-coding genes, but not for 3.8 k RNA genes or 1.9 k pseudogenes (R = 0.43–0.54), suggesting redistribution of mRNAs upon platelet shedding from megakaryocytes. (iii) Copy numbers of 3.5 k proteins that were restricted in size by the corresponding transcript levels (iv) Near complete coverage of identified proteins in the relevant transcriptome (log2fpkm > 0.20) except for plasma-derived secretory proteins, pointing to adhesion and uptake of such proteins. (v) Underrepresentation in the identified proteome of nuclear-related, membrane and signaling proteins, as well proteins with low-level transcripts. We then constructed a prediction model, based on protein function, transcript level and (peri)nuclear localization, and calculated the achievable proteome at ~ 10 k proteins. Model validation identified 1.0 k additional proteins in the predicted classes. Network and database analysis revealed the presence of 2.4 k proteins with a possible role in thrombosis and hemostasis, and 138 proteins linked to platelet-related disorders. This genome-wide platelet transcriptome and (non)identified proteome database thus provides a scaffold for discovering the roles of unknown platelet proteins in health and disease.
Characterization of hyperglycemia due to sub-chronic administration of red ginseng extract via comparative global proteomic analysis
Authors: Na Ann-Yae , Jo Jung Jae , Kwon Oh Kwang , Cho Piljoung , Gao Yan , Kim Ju-Hyun , Kim Kyu Min , Ki Sung Hwan , Lee Sangkyu
Published: June 2021

Ginseng (Panax ginseng Meyer) is commonly used as an herbal remedy worldwide. Few studies have explored the possible physiological changes in the liver although patients often self-medicate with ginseng preparations, which may lead to exceeding the recommended dose for long-term administration. Here, we analyzed changes in the hepatic proteins of mouse livers using quantitative proteomics after sub-chronic administration of Korean red ginseng (KRG) extract (control group and 0.5, 1.0, and 2.0 g/kg KRG) using tandem mass tag (TMT) 6‐plex technology. The 1.0 and 2.0 g/kg KRG groups exhibited signs of liver injury, including increased levels of aspartate transaminase (AST) and alanine aminotransferase (ALT) in the serum. Furthermore, serum glucose levels were significantly higher following KRG administration compared with the control group. Based on the upregulated proteins found in the proteomic analysis, we found that increased cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) levels promoted greater hydrogen sulfide (H2S) synthesis in the liver. This investigation provides novel evidence that sub-chronic administration of KRG can elevate H2S production by increasing protein expression of CBS and CSE in the liver.
Author Correction: A combination of electrochemistry and mass spectrometry to monitor the interaction of reactive species with supported lipid bilayers
Authors: Ravandeh M. , Kahlert H. , Jablonowski H. , Lackmann J.-W. , Striesow J. , Agmo Hernández V. , Wende K.
Published: June 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Extended live-cell barcoding approach for multiplexed mass cytometry
Authors: Muftuoglu Muharrem , Li Li , Liang Shaoheng , Mak Duncan , Lin Angelique J. , Fang Junxiang , Burks Jared K. , Chen Ken , Andreeff Michael
Published: June 2021

Sample barcoding is essential in mass cytometry analysis, since it can eliminate potential procedural variations, enhance throughput, and allow simultaneous sample processing and acquisition. Sample pooling after prior surface staining termed live-cell barcoding is more desirable than intracellular barcoding, where samples are pooled after fixation and permeabilization, since it does not depend on fixation-sensitive antigenic epitopes. In live-cell barcoding, the general approach uses two tags per sample out of a pool of antibodies paired with five palladium (Pd) isotopes in order to preserve appreciable signal-to-noise ratios and achieve higher yields after sample deconvolution. The number of samples that can be pooled in an experiment using live-cell barcoding is limited, due to weak signal intensities associated with Pd isotopes and the relatively low number of available tags. Here, we describe a novel barcoding technique utilizing 10 different tags, seven cadmium (Cd) tags and three Pd tags, with superior signal intensities that do not impinge on lanthanide detection, which enables enhanced pooling of samples with multiple experimental conditions and markedly enhances sample throughput.
Metabolic responses to polychromatic LED and OLED light at night
Authors: Ishihara Asuka , Park Insung , Suzuki Yoko , Yajima Katsuhiko , Cui Huiyun , Yanagisawa Masashi , Sano Takeshi , Kido Junji , Tokuyama Kumpei
Published: June 2021

Light exposure at night has various implications for human health, but little is known about its effects on energy metabolism during subsequent sleep. We investigated the effects of polychromatic white light using conventional light-emitting diodes (LED) and an alternative light source, organic light-emitting diodes (OLED), producing reduced spectral content in the short wavelength of blue light (455 nm). Ten male participants were exposed to either LED, OLED (1000 lx), or dim (< 10 lx) light for 4 h before sleep in a metabolic chamber. Following OLED exposure, energy expenditure and core body temperature during sleep were significantly decreased (p < 0.001). Fat oxidation during sleep was significantly reduced (p = 0.001) after the exposure to LED compared with OLED. Following exposure to OLED, fat oxidation positively correlated with the 6-sulfatoxymelatonin levels, suggesting that the role of melatonin in lipolysis differs depending on the light. These findings advance our knowledge regarding the role of light in energy metabolism during sleep and provide a potential alternative to mitigate the negative consequences of light exposure at night.
Feasibility of a home-based foot–ankle exercise programme for musculoskeletal dysfunctions in people with diabetes: randomised controlled FOotCAre (FOCA) Trial II
Authors: Silva Érica Q. , Santos Danilo P. , Beteli Raquel I. , Monteiro Renan L. , Ferreira Jane S. S. P. , Cruvinel-Junior Ronaldo H. , Donini Asha , Verissímo Jady L. , Suda Eneida Y. , Sacco Isabel C. N.
Published: June 2021

This study sought to assess the feasibility of design, adherence, satisfaction, safety and changes in outcomes followed by a home-based foot–ankle exercise guided by a booklet in individuals with diabetic peripheral neuropathy (DPN). 20 participants were allocated usual care [control group (CG)] or usual care plus home-based foot–ankle exercises [intervention group (IG)] for 8 weeks. For feasibility, we assessed contact, preliminary screening and recruitment rates, adherence, and using a 5-point Likert scale to satisfaction and safety of the booklet. In the IG, we assessed preliminary changes in DPN symptoms, DPN severity (classified by a fuzzy model) and foot–ankle range of motion between baseline and Week 8. In the first 20 weeks, 1310 individuals were screened for eligibility by phone contact. Contact rate was 89% (contacted participants/20w), preliminary screening success 28% (participants underwent screening/20w), and recruitment rate 1.0 participants/week (eligible participants/20w). The recruitment rate was less than the ideal rate of 5 participants/week. The adherence to the exercises programme was 77%, and the dropout was 11% and 9% for the IG and CG, respectively. In the IG, participants’ median level of satisfaction was 4 (IQR: 4–5) and perceived safety was 3 (IQR: 3–5). IG significantly decreased the DPN severity (p = 0.020), increased hallux relative to forefoot (first metatarsal) range of motion (ROM) (p < 0.001) and decreased maximum forefoot relative to hindfoot (midfoot motion) dorsiflexion during gait (p = 0.029). The home-based programme was feasible, satisfactory, safe and showed preliminary positive changes in DPN severity and foot motion during gait.

Trial Registration ClinicalTrials.gov, NCT04008745. Registered 02/07/2019. https://clinicaltrials.gov/ct2/show/NCT04008745.