bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of incidence and risk factors of the multidrug resistant gastrointestinal tract infection in children and adolescents undergoing allogeneic and autologous hematopoietic cell transplantation: a nationwide study
Authors: Salamonowicz-Bodzioch Małgorzata , Frączkiewicz Jowita , Czyżewski Krzysztof , Zając-Spychała Olga , Gorczyńska Ewa , Wróbel Grażyna , Kazanowska Bernarda , Sęga-Pondel Dorota , Węcławek-Tompol Jadwiga , Ussowicz Marek , Kałwak Krzysztof , Wysocki Mariusz , Dziedzic Magdalena , Wachowiak Jacek , Zaucha-Prażmo Agnieszka , Kowalczyk Jerzy , Goździk Jolanta , Styczyński Jan
Published: October 2021

The aim of this multi-center study was to evaluate the incidence, clinical course, and risk factors for bacterial multidrug-resistant (MDR) gastrointestinal tract infections (GTI) among children undergoing allogeneic and autologous hematopoietic cell transplantation. A total number of 175 pediatric patients (aged 1–18 years), transplanted between January 2018 and December 2019, who were tested for bacterial colonization/infection were enrolled into this multi-center analysis. Episodes of MDR GTI occurred in 77/175 (44%) patients. In multivariate analysis for higher GTI incidence, the following factors were significant: matched-unrelated donor (MUD) transplantation, HLA mismatch, presence of graft-versus-host disease (GVHD), and gut GVHD. The most common GTI were Clostridium difficile (CDI), multidrug-resistant Enterobacteriaceae (Klebsiella pneumoniae, Escherichia coli extended-spectrum β-lactamase), and Enterococcus HLAR (high-level aminoglycoside-resistant). No MDR GTI–attributed deaths were reported. MDR GTI is a frequent complication after HCT among children, causes prolonged hospitalization, but rarely contributes to death. We identified risk factors of MDR GTI development in children, with focus on GVHD and unrelated donor and HLA mismatch. We conclude that the presence of Clostridiales plays an important anti-inflammatory homeostatic role and decreases incidence of GVHD or alleviate its course.
Monitoring of rheumatoid arthritis: a patient survey on disease insight and possible added value of an innovative inflammation monitoring device
Authors: Wolkorte Ria , Heesink Lieke , Kip Michelle M. A. , Koffijberg Hendrik , Tabak Monique , Grünloh Christiane
Published: October 2021

To enable patients with rheumatoid arthritis (RA) and their healthcare professionals to choose the optimal treatment, it is crucial to accurately assess the current state of inflammatory activity. The objectives of this study were to (1) investigate the perspective of RA patients on their insight into the current status of their disease, and to (2) investigate the patients’ perspective on the possible added value of a monitoring device based on optical spectral transmission—called the HandScan—that measures the location and severity of joint inflammation. A survey was distributed online among patients with RA in the Netherlands. Four-hundred and eight patients with RA completed the survey. Of these, 298 (73%) felt they have sufficient insight into their current disease status. Most respondents perceived either a large (n = 242; 59%) or small (n = 148; 36%) added value of the HandScan in their monitoring process, mostly because the device provides additional knowledge on the presence of inflammation. This perceived added value was higher for respondents experienced with the device (n = 46; p = .04). Respondents preferred monitoring with the device on every (n = 192; 47%) or most (n = 171; 42%) visits to the outpatient clinic, or even more often than on every visit (n = 17; 4%). Monitoring RA using an optical spectral transmission device is seen by patients as a possibly valuable addition to the monitoring process of inflammatory activity during visits to an outpatient clinic. Their main reason was that the device can increase insight into their current disease status. More insight may support patients in discussing treatment options with their rheumatologist.
Spatial extent of precipitation events: when big is getting bigger
Authors: Matte Dominic , Christensen Jens H. , Ozturk Tugba
Published: October 2021

Using a sub-selection of regional climate models at 0.11° ($$\approx$$
≈
12 km) grid resolution from the EURO-CORDEX ensemble, we investigate how the spatial extent of areas associated with the most intensive daily precipitation events changes as a consequence of global warming. We address this by analysing three different warming levels: 1 °C, 2 °C and 3 °C. We find that not only does the intensity of such events increase, but their size will also change as a function of the warming: larger systems becomes more frequent and larger, while systems of lesser extent are reduced in numbers.
Are there predilection sites for intracranial meningioma? A population-based atlas
Authors: Hosainey Sayied Abdol Mohieb , Bouget David , Reinertsen Ingerid , Sagberg Lisa Millgård , Torp Sverre Helge , Jakola Asgeir Store , Solheim Ole
Published: October 2021

Meningioma is the most common benign intracranial tumor and is believed to arise from arachnoid cap cells of arachnoid granulations. We sought to develop a population-based atlas from pre-treatment MRIs to explore the distribution of intracranial meningiomas and to explore risk factors for development of intracranial meningiomas in different locations. All adults (≥ 18 years old) diagnosed with intracranial meningiomas and referred to the department of neurosurgery from a defined catchment region between 2006 and 2015 were eligible for inclusion. Pre-treatment T1 contrast-enhanced MRI-weighted brain scans were used for semi-automated tumor segmentation to develop the meningioma atlas. Patient variables used in the statistical analyses included age, gender, tumor locations, WHO grade and tumor volume. A total of 602 patients with intracranial meningiomas were identified for the development of the brain tumor atlas from a wide and defined catchment region. The spatial distribution of meningioma within the brain is not uniform, and there were more tumors in the frontal region, especially parasagittally, along the anterior part of the falx, and on the skull base of the frontal and middle cranial fossa. More than 2/3 meningioma patients were females (p < 0.001) who also were more likely to have multiple meningiomas (p < 0.01), while men more often have supratentorial meningiomas (p < 0.01). Tumor location was not associated with age or WHO grade. The distribution of meningioma exhibits an anterior to posterior gradient in the brain. Distribution of meningiomas in the general population is not dependent on histopathological WHO grade, but may be gender-related.
Rumour prevention in social networks with layer 2 blockchains
Authors: Thakur Subhasis , Breslin John G.
Published: October 2021

Social bots can cause social, political, and economical disruptions by spreading rumours. The state-of-the-art methods to prevent social bots from spreading rumours are centralised and such solutions may not be accepted by users who may not trust a centralised solution being biased. In this paper, we developed a decentralised method to prevent social bots. In this solution, the users of a social network create a secure and privacy-preserving decentralised social network and may accept social media content if it is sent by its neighbour in the decentralised social network. As users only choose their trustworthy neighbours from the social network to be part of its neighbourhood in the decentralised social network, it prevents the social bots to influence a user to accept and share a rumour. We prove that the proposed solution can significantly reduce the number of users who are share rumour.
Dilution Versus Unfair Advantage: Myths and Realities
Authors: Basma Dima
Published: October 2021

Recent developments in the commercial marketplace have rendered the classification of trademarks as mere tools for remedying information asymmetry and assuring quality inaccurate. The value of trademarks as communicative tools has increased, and they are now being used by their owners to transmit images, value propositions and associations to consumers in order to drive purchases. However, while this new function of trademarks is a reality that can hardly be ignored, finding a convincing normative justification to legally support its integration into the trademark system remains problematic. Thus, building on the normative justifications advanced by the European Union (EU) to justify extended trademark protection, this paper evaluates the dilutive harm theory, including blurring and tarnishment, in addition to the misappropriation rationale. The paper reviews EU case law in this respect and sheds light on the current muddled state of law in dealing with extended trademark protection. Based on this analysis, the paper offers a workable framework which can be utilized by courts to address cases related to modern trademark functions. The paper concludes that the misappropriation rationale should be the principal ground for extending trademark protection, and that harm resulting from blurring and tarnishment should act as an ancillary for misappropriation claims.
Explaining classification performance and bias via network structure and sampling technique
Authors: Espín-Noboa Lisette , Karimi Fariba , Ribeiro Bruno , Lerman Kristina , Wagner Claudia
Published: October 2021

Social networks are very important carriers of information. For instance, the political leaning of our friends can serve as a proxy to identify our own political preferences. This explanatory power is leveraged in many scenarios ranging from business decision-making to scientific research to infer missing attributes using machine learning. However, factors affecting the performance and the direction of bias of these algorithms are not well understood. To this end, we systematically study how structural properties of the network and the training sample influence the results of collective classification. Our main findings show that (i) mean classification performance can empirically and analytically be predicted by structural properties such as homophily, class balance, edge density and sample size, (ii) small training samples are enough for heterophilic networks to achieve high and unbiased classification performance, even with imperfect model estimates, (iii) homophilic networks are more prone to bias issues and low performance when group size differences increase, (iv) when sampling budgets are small, partial crawls achieve the most accurate model estimates, and degree sampling achieves the highest overall performance. Our findings help practitioners to better understand and evaluate their results when sampling budgets are small or when no ground-truth is available.
Extreme Weather Events and Internal Migration: Evidence from Mongolia
Authors: Roeckert Julian , Kraehnert Kati
Published: October 2021

This article examines the effects of extreme weather events on internal migration in Mongolia. Our focus is on dzuds, extremely harsh winters characterized by very cold temperature, snowfall anomalies, and/or storms causing very high livestock mortality. We exploit exogenous variation in the intensity of extreme winter events across time and space to identify their causal impacts on permanent domestic migration. Our database is a time series of migration and population data at provincial and district level from official population registries, spanning the 1992-2018 period. Results obtained with a two-way fixed effects panel estimator show that extreme winter events cause significant and sizeable permanent out-migration from affected provinces for up to two years after an event. These effects are confirmed when considering net change rates in the overall population at the district level. The occurrence of extreme winter events is also a strong predictor for declines in the local population of pastoralist households, the socio-economic group most affected by those events. This suggests that the abandonment of pastoralist livelihoods is an important channel through which climate affects within-country migration.
The Language of Violent Jihad
Authors: Baker Paul , Vessey Rachelle , McEnery Tony
Published: October 2021

How do violent jihadists use language to try to persuade people to carry out violent acts? This book analyses over two million words of texts produced by violent jihadists to identify and examine the linguistic strategies employed. Taking a mixed methods approach, the authors combine quantitative methods from corpus linguistics, which allows the identification of frequent words and phrases, alongside close reading of texts via discourse analysis. The analysis compares language use across three sets of texts: those which advocate violence, those which take a hostile but non-violent standpoint, and those which take a moderate perspective, identifying the different uses of language associated with different stages of radicalization. The book also discusses how strategies including use of Arabic, romanisation, formal English, quotation, metaphor, dehumanisation and collectivisation are used to create in- and out-groups and justify violence.
Rural Older Adults in Disasters: A Study of Recovery From Hurricane Michael
Authors: Fletcher Patricia A. , Worthen Dreamal L. , McSweeney-Feld Mary Helen , Gibson Allison , Seblova Dominika , Pagán Lisandra , Troya M. Isabela , Fang Mei Lan , Owusu Brenda , Lane Charlene , Wada Mineko , Harrell Erin R. , Viana Aline
Published: October 2021

Objective:

This study aims for a greater understanding of how older adults (age 65 and older) in Jackson County, Florida, are prepared for and cope with the effects of a natural disaster.

Methods:

A multidisciplinary, international research team developed a survey examining: (1) resources available to individuals aged 65+ in rural communities for preparing for a disaster; (2) challenges they face when experiencing a disaster; and (3) their physical, social, emotional, and financial needs when it strikes. The survey was administered with older adults (65+) in Jackson County, Florida, following Hurricane Michael in 2018. The descriptive, multivariate logistic, and linear regression analyses were performed to examine the relationship between respondents’ demographic information and needs, concerns, and consequences of disaster.

Results:

Results indicated (n = 139) rural community-dwelling older adults rely on social support, community organizations, and trusted disaster relief agencies to prepare for and recover from disaster-related events.

Conclusions:

Such findings can be used to inform the development of new interventions, programs, policies, practices, and tools for emergency management and social service agencies to improve disaster preparedness and resiliency among older populations in rural communities.
The Rights of the Families of Missing Persons: Going Beyond International Humanitarian Law
Authors: Baranowska Grażyna
Published: October 2021

The main aim of the article is to test how states implement international humanitarian law (IHL) with regard to the families of missing persons. The article shows relevant IHL shortcomings and compares them with rules applicable in cases of enforced disappearance. The national legislation collected in the section titled ‘The Missing and Their Families’ of the National Implementation Database of the International Committee of the Red Cross is then examined. The analysis addresses three core questions that are particularly relevant for families of missing persons: (1) Who is considered a missing person under each law? Approaching this question allows the testing of whether states follow the understanding of ‘missing persons’ under IHL treaty law. The second and third questions address two issues that are crucial for families of missing persons that are not addressed in IHL: (2) How is the legal status of the missing person regulated? (3) Are family members provided with measures of reparation and/or assistance? This approach reveals that states rarely apply the IHL understanding of ‘missing persons’ and predominantly exceed IHL by addressing some of the identified shortcomings. It further shows that states provide families of missing persons either with reparation measures – in cases of human rights violations – or, less often, with measures of assistance in post-conflict situations.
Gender differences in dietary behaviours, health-related habits and prevalence of non-communicable diseases in Botswana
Authors: Letamo Gobopamang , Keetile Mpho , Navaneetham Kannan , Medupe Keitumetse
Published: October 2021

The aim of this study was to assess gender differences in the prevalence non-communicable diseases (NCDs) and in associated health-related habits, weight status and common risk factors in Botswana. Data were from the cross-sectional, population-based Botswana STEPS Survey II conducted in 2014. A total sample of 2947 survey participants aged 25–64 years were included the study. The results showed that a statistically significant higher percentage of men used tobacco compared with women (34.4%, 95% CI: 33.5–35.1 vs 4.4%, 95% CI: 4.3–4.5). Men also had consistently and statistically significantly greater heavy alcohol consumption and lower fruit and/or vegetable consumption than women. Physical inactivity among women was higher than in men. Controlling for other factors, men had a higher probability of being overweight (28.7%, 95% CI: 28.6–28.8 vs 18.3%, 95% CI: 18.0–18.6) and obese (25.8%, 95% CI: 25.4–26.2 vs 10.2%, 95% CI: 9.9–10.5) than women. Women were at a greater risk of developing NCDs compared with men since their adjusted prevalence of having at least three common risk factors was higher than men’s. Women had a higher adjusted predicted prevalence of suffering from hypertension than men (39.4%, 95% CI: 38.9–40.0 vs 26.1%, 95% CI: 25.5–26.8). Appropriate policies and programmes need to be adopted to urgently address the problem of NCDs in Botswana.
Conserving migratory waterbirds and the coastal zone: the future of South-east Asia's intertidal wetlands
Authors: Yong Ding Li , Kee Jing Ying , Aung Pyae Phyo , Jain Anuj , Yeap Chin-Aik , Au Nyat Jun , Jearwattanakanok Ayuwat , Lim Kim Keang , Yu Yat-Tung , Fu Vivian W. K. , Insua-Cao Paul , Sawa Yusuke , Crosby Mike , Chan Simba , Crockford Nicola J.
Published: October 2021

South-east Asia's diverse coastal wetlands, which span natural mudflats and mangroves to man-made salt pans, offer critical habitat for many migratory waterbird species in the East Asian–Australasian Flyway. Species dependent on these wetlands include nearly the entire population of the Critically Endangered spoon-billed sandpiper Calidris pygmaea and the Endangered spotted greenshank Tringa guttifer, and significant populations of several other globally threatened and declining species. Presently, more than 50 coastal Important Bird and Biodiversity Areas (IBAs) in the region (7.4% of all South-east Asian IBAs) support at least one threatened migratory species. However, recent studies continue to reveal major knowledge gaps on the distribution of migratory waterbirds and important wetland sites along South-east Asia's vast coastline, including undiscovered and potential IBAs. Alongside this, there are critical gaps in the representation of coastal wetlands across the protected area networks of many countries in this region (e.g. Viet Nam, Indonesia, Malaysia), hindering effective conservation. Although a better understanding of the value of coastal wetlands to people and their importance to migratory species is necessary, governments and other stakeholders need to do more to strengthen the conservation of these ecosystems by improving protected area coverage, habitat restoration, and coastal governance and management. This must be underpinned by the judicious use of evidence-based approaches, including satellite-tracking of migratory birds, ecological research and ground surveys.
Diversifying the Social Policy Curriculum: A Collaborative Approach
Authors: Adewumi Barbara , Mitton Lavinia
Published: October 2021

This article offers a practical methodological ‘toolkit’ for creating more diverse reading lists for social policy teaching. It reports on the findings of the award-winning ‘Reading List Diversity Mark Project’, carried out at the University of Kent in 2018–20, which investigated how many Black, Asian and other ethnic minority authors were included on undergraduate reading lists. Through the application of critical race theory (CRT), we argue that inclusive curricula matter. We then analyse the reasons for the marginalisation of race and ethnicity in the social policy curriculum. A distinctive aspect of the project was the nature of our staff-student collaboration and we discuss how this shaped its design and outcomes. We argue that our approach could be implemented at other institutions and conclude with suggestions about how to achieve a more diverse social policy curriculum.
The geopolitics of negative emissions technologies: learning lessons from REDD+ and renewable energy for afforestation, BECCS, and direct air capture
Authors: Kreuter Judith , Lederer Markus
Published: October 2021

Non-technical summary

Negative emissions technologies (NETs) have received increasing interest in recent years as a potential part of a portfolio of measures to address anthropogenic climate change, in particular following the 2015 UN Framework Convention on Climate Change Paris Agreement and the 2018 Intergovernmental Panel on Climate Change Special Report ‘Global Warming of 1.5 °C’. This increasing significance for global climate policy is faced with a multitude of open questions regarding, among others, the geopolitical implications of large-scale use of NETs. This paper outlines what we can learn for the possible geopolitical futures of NETs from existing international ‘green’ approaches.

Technical summary

We contribute to assessing political implications of NET scenarios, addressing the following question: What are potential geopolitical challenges, conflicts, and consequences of a large-scale deployment of three NETs, namely afforestation, bio-energy with carbon capture and storage (BECCS), and direct air capture and carbon storage (DACCS)? We turn to the two cases of renewable energies and reducing emissions from deforestation and forest degradation for answers. We find that, first, not only afforestation, but also BECCS and even DACCS would have a geopolitical impact due to their requirements of territory – in the latter two cases, for instance, due to requirements for appropriate carbon storage space. Second, the material requirements of various NETs might also impact geopolitical constellations and induce conflict, providing certain countries and regions of the world with new leverage in the case of large-scale deployment, for instance those which can provide raw materials for fertilizer (for afforestation and BECCS) or energy generation (for DACCS). Third, discursive construction of space and identity might lead to very interesting new patterns of contestation, for instance if specific nation-states can successfully construct an identity of front-running climate protectors and use this to put pressure on other states.

Social media summary

What might be geopolitical implications of using NETs on a large scale to counteract anthropogenic climate change?
A Geochemical Comparison of Three Terrestrial Sites of Serpentinization: The Tablelands, the Cedars, and Aqua de Ney
Authors: Cook Melissa C. , Blank Jennifer G. , Rietze Amanda , Suzuki Shino , Nealson Kenneth H. , Morrill Penny L.
Published: October 2021

Although the Earth's subsurface hosts an abundance of microbial life, the influence of geochemistry on these communities remains poorly constrained. Ophiolites, sites where oceanic ultramafic minerals can be hydrated to serpentine minerals and metal oxides, create unique conditions capable of sustaining life. The fluid geochemistry of the Tablelands (NL, CAN), The Cedars (CA, USA), and Aqua de Ney (CA, USA), were studied to better characterize the range of fluid compositions observed at terrestrial sites of serpentinization. Fluids from these sites shared many commonalities including being ultra‐basic and reducing as well as having elevated levels of Cl−, Na+, K+, and Br− and depleted concentrations of Mg2+. They also exhibited a wide range of geochemistry. Isotopic and compositional data suggested the CH4 from The Cedars was a mixture of microbial and non‐microbial sources while the CH4 from the Tablelands was non‐microbial in origin. Aqua de Ney was the only site where the CH4 plotted in the abiogenic field. Despite being a known product of serpentinization, no H2 was detected at Aqua de Ney, likely due to the formation of abiogenic CH4 as well as the reaction of H2 and SO42− in the system to produce H2S. These unique sites of terrestrial serpentinization help to better understand the range of geochemistry at sites of serpentinization and its influence on the microbial communities in the subsurface.
Direct protein–protein interaction between Npas4 and IPAS mutually inhibits their critical roles in neuronal cell survival and death
Authors: Kasai Shuya , Li Xianyu , Torii Satoru , Yasumoto Ken-ichi , Sogawa Kazuhiro
Published: October 2021

Inhibitory PAS domain protein (IPAS) is a bifunctional protein that acts as a transcriptional repressor in hypoxia and as a pro-apoptotic protein involved in neuronal cell death. Npas4 (NXF or LE-PAS) is a transcriptional factor that protects nerve cells from endogenous and foreign neurotoxins. Here we show that IPAS and Npas4 antagonize each other through their direct interaction. Coimmunoprecipitation experiments revealed that multiple binding sites on each protein were involved in the interaction. CoCl2 treatment of PC12 cells that induces IPAS repressed the transactivation activity of Npas4, and IPAS siRNA treatment reduced the CoCl2-induced repression. CoCl2-induced apoptosis was suppressed by the addition of KCl that induces Npas4. The protective effect of KCl was attenuated by siRNA-mediated gene silencing of Npas4. Npas4 and IPAS proteins were induced and localized in the cytoplasm of the dopaminergic neurons in the substantia nigra pars compacta after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. Npas4−/− mice exhibited greater sensitivity to MPTP in nigral dopaminergic neurons. Together, these results strongly suggest that neuroprotective activity of Npas4 was, at least partly, exerted by inhibiting the pro-apoptotic activity of IPAS through direct interaction.
Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut
Authors: Laursen Martin F. , Sakanaka Mikiyasu , von Burg Nicole , Mörbe Urs , Andersen Daniel , Moll Janne Marie , Pekmez Ceyda T. , Rivollier Aymeric , Michaelsen Kim F. , Mølgaard Christian , Lind Mads Vendelbo , Dragsted Lars O. , Katayama Takane , Frandsen Henrik L. , Vinggaard Anne Marie , Bahl Martin I. , Brix Susanne , Agace William , Licht Tine R. , Roager Henrik M.
Published: October 2021

Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune development, and the gut microbiota can impact host physiology in various ways, such as through the production of metabolites. However, few breastmilk-dependent microbial metabolites mediating host–microbiota interactions are currently known. Here, we demonstrate that breastmilk-promotedBifidobacteriumspecies convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactic acid, phenyllactic acid and 4-hydroxyphenyllactic acid) via a previously unrecognized aromatic lactate dehydrogenase (ALDH). The ability ofBifidobacteriumspecies to convert aromatic amino acids to their lactic acid derivatives was confirmed using monocolonized mice. Longitudinal profiling of the faecal microbiota composition and metabolome of Danish infants (n = 25), from birth until 6 months of age, showed that faecal concentrations of aromatic lactic acids are correlated positively with the abundance of human milk oligosaccharide-degradingBifidobacteriumspecies containing the ALDH, includingBifidobacterium longum,B. breveandB. bifidum. We further demonstrate that faecal concentrations ofBifidobacterium-derived indolelactic acid are associated with the capacity of these samples to activate in vitro the aryl hydrocarbon receptor (AhR), a receptor important for controlling intestinal homoeostasis and immune responses. Finally, we show that indolelactic acid modulates ex vivo immune responses of human CD4+T cells and monocytes in a dose-dependent manner by acting as an agonist of both the AhR and hydroxycarboxylic acid receptor 3 (HCA3). Our findings reveal that breastmilk-promotedBifidobacteriumspecies produce aromatic lactic acids in the gut of infants and suggest that these microbial metabolites may impact immune function in early life.
Steroid sulfatase deficiency causes cellular senescence and abnormal differentiation by inducing Yippee-like 3 expression in human keratinocytes
Authors: Baek Hyoung-Seok , Kwon Tae-Uk , Shin Sangyun , Kwon Yeo-Jung , Chun Young-Jin
Published: October 2021

Human steroid sulfatase (STS) is an enzyme that catalyzes the hydrolysis of dehydroepiandrosterone sulfate (DHEAS), estrone sulfate (E1S), and cholesterol sulfate. Abnormal expression of STS causes several diseases including colorectal, breast, and prostate cancer and refractory skin disease. In particular, accumulation of intracellular cholesterol sulfate by STS deficiency leads to a skin disorder with abnormal keratinization called X-linked ichthyosis (XLI). To determine the detailed mechanisms of XLI, we performed RNA sequencing (RNA-seq) analysis using human keratinocyte HaCaT cells treated with cholesterol and cholesterol sulfate. Of the genes with expression changes greater than 1.5-fold, Yippee-like 3 (YPEL3), a factor expected to affect cell differentiation, was found. Induction of YPEL3 causes permanent growth arrest, cellular senescence, and inhibition of metastasis in normal and tumor cells. In this study, we demonstrate that YPEL3 expression was induced by STS deficiency and, using the CRISPR/Cas9 system, a partial knock-out (STS+/−) cell line was constructed to establish a disease model for XLI studies. Furthermore, we show that increased expression of YPEL3 in STS-deficient cell lines promoted cellular senescence and expression of keratinization-related proteins such as involucrin and loricrin. Our results suggest that upregulation of YPEL3 expression by STS deficiency may play a crucial role in inducing cellular senescence and abnormal differentiation in human keratinocytes.
Leveraging internet search data to assess prevalence, interest, and unmet needs of sarcoidosis in Germany
Authors: Hilker Charlotte , Tizek Linda , Rüth Melvin , Schielein Maximilian , Biedermann Tilo , Zink Alexander
Published: October 2021

Sarcoidosis is a multisystemic disease of connective tissue with granuloma formation of unknown etiology and unclear prevalence. Internet search data has been shown to correlate with disease incidences and the population’s interest as well as seasonal variations. Accordingly, aim of this study was to leverage internet search data on sarcoidosis-related keywords to identify unmet needs, geographical and seasonal factors influencing sarcoidosis and estimating its prevalence. In this retrospective longitudinal study, Google Ads Keyword Planner was used to determine the internet search volume of terms related to sarcoidosis across Germany as a whole and in 17 major German cities between July 2015 and June 2019. Identified keywords were qualitatively categorized, converted into number of searches per 100,000 inhabitants and analyzed including regional and seasonal differences. With 3,068,200 queries and 425 different sarcoidosis-related search terms in the studied time period, the search volume was very high for a rare disease. Most searches (67.9%) related to general disease information with “sarcoidosis”, "Löfgren's syndrome", "sarcoidosis lung", "Morbus Boeck" and "neurosarcoidosis" as the top five keywords. Searches per 100,000 inhabitants were comparable in all 17 cities but higher than in Germany as a whole. Overall, the search volume increased from 2015 to 2019 and peaked annually in European springtime with annual lows in European autumn and winter months. The overall high search volume suggests an unmet need for sarcoidosis-related information and a diagnostic gap. Seasonal fluctuations indicate environmental as well as climatic factors that may influence sarcoidosis.
Analysis of newly developed fractal-fractional derivative with power law kernel for MHD couple stress fluid in channel embedded in a porous medium
Authors: Arif Muhammad , Kumam Poom , Kumam Wiyada , Akgul Ali , Sutthibutpong Thana
Published: October 2021

Fractal-fractional derivative is a new class of fractional derivative with power Law kernel which has many applications in real world problems. This operator is used for the first time in such kind of fluid flow. The big advantage of this operator is that one can formulate models describing much better the systems with memory effects. Furthermore, in real world there are many problems where it is necessary to know that how much information the system carries. To explain the memory in a system fractal-fractional derivatives with power law kernel is analyzed in the present work. Keeping these motivation in mind in the present paper new concept of fractal-fractional derivative for the modeling of couple stress fluid (CSF) with the combined effect of heat and mass transfer have been used. The magnetohydrodynamics (MHD) flow of CSF is taken in channel with porous media in the presence of external pressure. The constant motion of the left plate generates the CSF motion while the right plate is kept stationary. The non-dimensional fractal-fractional model of couple stress fluid in Riemann–Liouville sense with power law is solved numerically by using the implicit finite difference method. The obtained solutions for the present problem have been shown through graphs. The effects of various parameters are shown through graphs on velocity, temperature and concentration fields. The velocity, temperature and concentration profiles of the MHD CSF in channel with porous media decreases for the greater values of both fractional parameter $$\alpha$$
α
and fractal parameter $$\beta$$
β
respectively. From the graphical results it can be noticed that the fractal-fractional solutions are more general as compared to classical and fractional solutions of CSF motion in channel. Furthermore, the fractal-fractional model of CSF explains good memory effect on the dynamics of couple stress fluid in channel as compared to fractional model of CSF. Finally, the skin friction, Nusselt number and Sherwood number are evaluated and presented in tabular form.
Cytokine signature and COVID-19 prediction models in the two waves of pandemics
Authors: Cabaro Serena , D’Esposito Vittoria , Di Matola Tiziana , Sale Silvia , Cennamo Michele , Terracciano Daniela , Parisi Valentina , Oriente Francesco , Portella Giuseppe , Beguinot Francesco , Atripaldi Luigi , Sansone Mario , Formisano Pietro
Published: October 2021

In Europe, multiple waves of infections with SARS-CoV-2 (COVID-19) have been observed. Here, we have investigated whether common patterns of cytokines could be detected in individuals with mild and severe forms of COVID-19 in two pandemic waves, and whether machine learning approach could be useful to identify the best predictors. An increasing trend of multiple cytokines was observed in patients with mild or severe/critical symptoms of COVID-19, compared with healthy volunteers. Linear Discriminant Analysis (LDA) clearly recognized the three groups based on cytokine patterns. Classification and Regression Tree (CART) further indicated that IL-6 discriminated controls and COVID-19 patients, whilst IL-8 defined disease severity. During the second wave of pandemics, a less intense cytokine storm was observed, as compared with the first. IL-6 was the most robust predictor of infection and discriminated moderate COVID-19 patients from healthy controls, regardless of epidemic peak curve. Thus, serum cytokine patterns provide biomarkers useful for COVID-19 diagnosis and prognosis. Further definition of individual cytokines may allow to envision novel therapeutic options and pave the way to set up innovative diagnostic tools.
Prognostic value of pre-irradiation FET PET in patients with not completely resectable IDH-wildtype glioma and minimal or absent contrast enhancement
Authors: Rosen Jurij , Stoffels Gabriele , Lohmann Philipp , Bauer Elena K. , Werner Jan-Michael , Wollring Michael , Rapp Marion , Felsberg Jörg , Kocher Martin , Fink Gereon R. , Langen Karl-Josef , Galldiks Norbert
Published: October 2021

In glioma patients, complete resection of the contrast-enhancing portion is associated with improved survival, which, however, cannot be achieved in a considerable number of patients. Here, we evaluated the prognostic value of O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in not completely resectable glioma patients with minimal or absent contrast enhancement before temozolomide chemoradiation. Dynamic FET PET scans were performed in 18 newly diagnosed patients with partially resected (n = 8) or biopsied (n = 10) IDH-wildtype astrocytic glioma before initiation of temozolomide chemoradiation. Static and dynamic FET PET parameters, as well as contrast-enhancing volumes on MRI, were calculated. Using receiver operating characteristic analyses, threshold values for which the product of paired values for sensitivity and specificity reached a maximum were obtained. Subsequently, the prognostic values of FET PET parameters and contrast-enhancing volumes on MRI were evaluated using univariate Kaplan–Meier and multivariate Cox regression (including the MTV, age, MGMT promoter methylation, and contrast-enhancing volume) survival analyses for progression-free and overall survival (PFS, OS). On MRI, eight patients had no contrast enhancement; the remaining patients had minimal contrast-enhancing volumes (range, 0.2–5.3 mL). Univariate analyses revealed that smaller pre-irradiation FET PET tumor volumes were significantly correlated with a more favorable PFS (7.9 vs. 4.2 months; threshold, 14.8 mL; P = 0.012) and OS (16.6 vs. 9.0 months; threshold, 23.8 mL; P = 0.002). In contrast, mean tumor-to-brain ratios and time-to-peak values were only associated with a longer PFS (P = 0.048 and P = 0.045, respectively). Furthermore, the pre-irradiation FET PET tumor volume remained significant in multivariate analyses (P = 0.043), indicating an independent predictor for OS. Our results suggest that pre-irradiation FET PET parameters have a prognostic impact in this subgroup of patients.
DNA damage response of haematopoietic stem and progenitor cells to high-LET neutron irradiation
Authors: Engelbrecht Monique , Ndimba Roya , de Kock Maryna , Miles Xanthene , Nair Shankari , Fisher Randall , du Plessis Peter , Bolcaen Julie , Botha Matthys Hendrik , Zwanepoel Elbie , Sioen Simon , Baeyens Ans , Nieto-Camero Jaime , de Kock Evan , Vandevoorde Charlot
Published: October 2021

The radiosensitivity of haematopoietic stem and progenitor cells (HSPCs) to neutron radiation remains largely underexplored, notwithstanding their potential role as target cells for radiation-induced leukemogenesis. New insights are required for radiation protection purposes, particularly for aviation, space missions, nuclear accidents and even particle therapy. In this study, HSPCs (CD34+CD38+ cells) were isolated from umbilical cord blood and irradiated with 60Co γ-rays (photons) and high energy p(66)/Be(40) neutrons. At 2 h post-irradiation, a significantly higher number of 1.28 ± 0.12 γ-H2AX foci/cell was observed after 0.5 Gy neutrons compared to 0.84 ± 0.14 foci/cell for photons, but this decreased to similar levels for both radiation qualities after 18 h. However, a significant difference in late apoptosis was observed with Annexin-V+/PI+ assay between photon and neutron irradiation at 18 h, 43.17 ± 6.10% versus 55.55 ± 4.87%, respectively. A significant increase in MN frequency was observed after both 0.5 and 1 Gy neutron irradiation compared to photons illustrating higher levels of neutron-induced cytogenetic damage, while there was no difference in the nuclear division index between both radiation qualities. The results point towards a higher induction of DNA damage after neutron irradiation in HSPCs followed by error-prone DNA repair, which contributes to genomic instability and a higher risk of leukemogenesis.
A new ant-butterfly symbiosis in the forest canopy fills an evolutionary gap
Authors: Pérez-Lachaud Gabriela , Rocha Franklin H. , Pozo Carmen , Kaminski Lucas A. , Seraphim Noemy , Lachaud Jean-Paul
Published: October 2021

Myrmecophilous butterflies can establish complex symbiotic relationships with ants. A caterpillar wandering among the brood of the aggressive ponerine antNeoponera villosawas found inside the core of a nest built in the myrmecophytic bromeliadAechmea bracteata. This is the first caterpillar found living inside a ponerine ant nest. Its DNA barcode was sequenced, and an integrative approach was used to identify it asPseudonymphidia agave, a poorly known member of the subtribe Pachythonina in the riodinid tribe Nymphidiini. The cuticle of the tank-like caterpillar lacks projections or tubercles and is covered dorsally by specialized flat setae that form an armor of small plates. Ant-organs potentially related to caterpillar-ant signaling, such as perforated cupola organs and tentacle nectary organs, are present. These morphological traits, together with evidence of social integration (direct contact with host brood, protective morphology, slow movement, no host aggressiveness), suggest thatP. agaveis a symbiotic, social parasite ofN. villosa, preying on its host brood. However, several knowledge gaps remain, including oviposition site, dependence on bromeliad association, steps to colony integration, and larval diet through development. Carnivory has been reported in all known members of the subtribe Pachythonina (caterpillars prey on honeydew-producing hemipterans) suggesting a shift to myrmecophagy inside the ant nests as a possible evolutionary transition.
A novel method of identifying inner ear malformation types by pattern recognition in the mid modiolar section
Authors: Dhanasingh Anandhan , Erpenbeck Daniel , Assadi Masoud Zoka , Doyle Úna , Roland Peter , Hagr Abdulrahman , Van Rompaey Vincent , Van de Heyning Paul
Published: October 2021

Identification of the inner ear malformation types from radiographs is a complex process. We hypothesize that each inner ear anatomical type has a uniqueness in its appearance in radiographs. The outer contour of the inner ear was captured from the mid-modiolar section, perpendicular to the oblique-coronal plane, from which the A-value was determined from CT scans with different inner ear anatomical types. The mean A-value of normal anatomy (NA) and enlarged vestibular aqueduct syndrome (EVAS) anatomical types was greater than for Incomplete Partition (IP) type I, II, III and cochlear hypoplasia. The outer contour of the cochlear portion within the mid-modiolar section of NA and EVAS resembles the side view of Aladdin’s lamp; IP type I resembles the side-view of the Sphinx pyramid and type II a Pomeranian dog’s face. The steep spiraling cochlear turns of IP type III resemble an Auger screw tip. Drawing a line parallel to the posterior margin of internal auditory canal (IAC) in axial-view, bisecting the cavity into cochlear and vestibular portions, identifies common-cavity; whereas a cavity that falls under the straight-line leaving no cochlear portion identifies cochlear aplasia. An atlas of the outer contour of seventy-eight inner ears was created for the identification of the inner malformation types precisely.
Prime factorization using quantum variational imaginary time evolution
Authors: Selvarajan Raja , Dixit Vivek , Cui Xingshan , Humble Travis S. , Kais Sabre
Published: October 2021

The road to computing on quantum devices has been accelerated by the promises that come from using Shor’s algorithm to reduce the complexity of prime factorization. However, this promise hast not yet been realized due to noisy qubits and lack of robust error correction schemes. Here we explore a promising, alternative method for prime factorization that uses well-established techniques from variational imaginary time evolution. We create a Hamiltonian whose ground state encodes the solution to the problem and use variational techniques to evolve a state iteratively towards these prime factors. We show that the number of circuits evaluated in each iteration scales as $$O(n^{5}d)$$

O
(

n
5

d
)

, where n is the bit-length of the number to be factorized and d is the depth of the circuit. We use a single layer of entangling gates to factorize 36 numbers represented using 7, 8, and 9-qubit Hamiltonians. We also verify the method’s performance by implementing it on the IBMQ Lima hardware to factorize 55, 65, 77 and 91 which are greater than the largest number (21) to have been factorized on IBMQ hardware.
Sensitive detection of tamsulosin hydrochloride based on dual-emission ratiometric fluorescence probe consisting of amine-carbon quantum dots and rhodamine B
Authors: Mousavi Aida , Zare-Dorabei Rouholah , Mosavi Seyed Hossein
Published: October 2021

In this work, amine-carbon quantum dots (CQDs)/rhodamine B (RhB) ratiometric fluorescent (RF) sensor was employed for effective and selective determination of tamsulosin hydrochloride (TMS) based on a dual-emission fluorescence system. Although the function of amine-CQDs is to transfer the specific interaction between TMS and sensor into detectable fluorescence (FL) signals, RhB as a reference unit has been employed to omit internal and external effects. The FL signal was quenched by adding the TMS at 442 nm; nevertheless, it did not change at 569 nm. The material characterization and investigation of the sensing mechanism were done. The optimization of pH, the volumetric ratio of CQDs to RhB, and interaction time parameters were carried out by the one-variable-at-a-time (OVAT) method. The quantitative analysis of the concentration of TMS for this RF sensor in a linear range of 0.446–7.083 μg mL−1 (1.091–17.338 μM) was obtained (R2 = 0.9969, n = 3) under optimum conditions. The limit of detection and quantitation values were estimated to be 0.033 μg mL−1 (0.081 μM) and 0.109 μg mL−1 (0.267 μM), respectively. The repeatability of intra-day and inter-day were less than one percent. This inexpensive RF probe was well applied to determine TMS in biological fluids, and acceptable achievements were obtained.
ANXA2 is correlated with the molecular features and clinical prognosis of glioma, and acts as a potential marker of immunosuppression
Authors: Ma Kaiming , Chen Xin , Liu Weihai , Yang Yang , Chen Suhua , Sun Jianjun , Ma Changcheng , Wang Tao , Yang Jun
Published: October 2021

Recent studies have shown that ANXA2 is important in the development of many cancers, while its role in glioma-related immune response remains unclear. We aimed to comprehensively investigate its biological characteristics and clinical value in glioma. We analyzed 699 glioma samples from The Cancer Genome Atlas as training cohort and 325 samples from the Chinese Glioma Genome Atlas as validation cohort. All the statistical analyses and figures were generated with R. ANXA2 was overexpressed significantly in high-grade glioma, isocitrate dehydrogenase wild-type and mesenchymal-subtype glioma. ANXA2 was a special indicator of mesenchymal subtype. The survival analysis showed that highly-expressed ANXA2 was related to worse survival status as an independent factor of poor prognosis. Further gene ontology analysis showed that ANXA2 was mainly involved in immune response and inflammatory activities of glioma. Subsequent correlation analysis showed that ANXA2 was positively correlated with HCK, LCK, MHC II, STAT1 and interferon but negatively with IgG. Meanwhile, ANXA2 was positively related to the infiltration of tumor-related macrophages, regulatory T cells and myeloid-derived suppressor cells. Our study revealed that ANXA2 is a biomarker closely related to the malignant phenotype and poor prognosis of glioma, and plays an important role in immune response, inflammatory activity and immunosuppression.