bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telomerase-targeting compounds Imetelstat and 6-thio-dG act synergistically with chemotherapy in high-risk neuroblastoma models
Authors: Fischer-Mertens Janina , Otte Felix , Roderwieser Andrea , Rosswog Carolina , Kahlert Yvonne , Werr Lisa , Hellmann Anna-Maria , Berding Maya , Chiu Bill , Bartenhagen Christoph , Fischer Matthias 
Published: August 2022

Abstract

Background
The majority of high-risk neuroblastomas harbor telomerase activity, and telomerase-interacting compounds, such as 6-thio-2’-deoxyguanosine (6-thio-dG), have been found to impair the growth of telomerase-positive neuroblastoma cell lines. It has remained unclear, however, how such drugs can be combined with other compounds used in current treatment concepts for neuroblastoma patients.

Methods
Growth-inhibitory effects of varying concentrations of 6-thio-dG in combination with etoposide, doxorubicin or ceritinib were determined in eight telomerase-positive neuroblastoma cell lines with distinct genetic backgrounds. Tumor growth inhibition of subcutaneous xenografts from three different cell lines was assessed upon treatment with 6-thio-dG, the competitive telomerase inhibitor imetelstat, etoposide, or combinations of these compounds.

Results
Robust synergistic anti-tumor effects were observed for combinations of 6-thio-dG and etoposide or doxorubicin, but not for 6-thio-dG and ceritinib, in telomerase-positive neuroblastoma cell lines in vitro. Treatment of mouse xenografts with combinations of 6-thio-dG and etoposide significantly attenuated tumor growth and improved mouse survival over etoposide alone in two of three cell line models. Treatment of xenograft tumors by imetelstat monotherapy decreased telomerase activity by roughly 50% and significantly improved survival over control in all three models, whereas treatment with imetelstat plus etoposide led to enhanced survival over etoposide monotherapy in one model. Mechanistically, the synergistic effect was found to be due to both increased apoptosis and cell cycle arrest.

Conclusion
Our study indicates that telomerase is an actionable target in telomerase-positive neuroblastoma, and demonstrates that combination therapies including telomerase-interacting compounds may improve the efficacy of established cytotoxic drugs. Targeting telomerase may thus represent a therapeutic option in high-risk neuroblastoma patients.
Centile Charts of Fetal Kidney and Adrenal Gland Length: A Prospective Study in Indian Population in the State of Bihar
Authors: Aparna S. , Kumar Prem , Kumar Bindey , Agarwal Mukta , Sinha Rishikant 
Published: August 2022

AbstractNormal development of the fetal kidneys and adrenal glands is essential for a good crucial neonatal outcome. There is, however, paucity of data on normal fetal adrenal gland and renal length in populations of North India and this poses a not infrequent dilemma when an anomaly is suspected during the anomaly scan. The objective of this study was to obtain gestation wise data of fetal renal length and adrenal length for 18, 19, 20 and 21 weeks of gestation and construct a gestation age wise size chart. This was a cross sectional study of 128 consecutive normal pregnancies after exclusion of multiple gestations, maternal complications, congenital anomalies and a family history of congenial adrenal hyperplasia. Gestational age of the fetus was calculated from fetal biometry. Measurements were made in the sagittal plane as length including renal and adrenal, longest pole to pole length of kidney and adrenal gland length calculated as the difference between the values. The values were analysed to yield the 95% confidence interval along with the 50th centile for gestational age groups of 18–21 weeks.
Experimental and numerical study for the adsorption behavior of Cu(II) and Mn(II) in quartz sand
Authors: Gharbia Abdalkarim S. , Zákányi Balázs , Tóth Márton 
Published: August 2022

AbstractHeavy metals such as Cu(II) and Mn(II) are prevalent in the environment. The effect of heavy metals on the soils environment is based on the ability of soils to mobilize these contaminants. According to the soil decontamination perspective, examining the reaction technique between heavy metals and soil is indispensable. This study carried out experiments to investigate Cu(II) and Mn(II) adsorption behaviour in quartz sand. The isothermal adsorption results for Cu(II) and Mn(II) presented that the adsorption capacity reached the peak value when the initial concentration was about 10 mg/L. The declines of H+ ions could uprise the adsorption rate activity for Cu(II) and Mn(II) and decrease the soil ability of the desorption for Cu(II) and Mn(II) ions. The adsorption rate of Cu(II) and Mn(II) is lower than the desorption rate under the situation of a low pH range with a solid acidic and low concentration of Cu(II) and Mn(II). The Freundlich and Langmuir adsorption isotherm models were applied to investigate the adsorption isotherm of Cu(II) and Mn(II). The study results confirmed that the Freundlich model synchronous the best with the observed experimental data compared with the Langmuir solution.
Autonomy in Japan: What does it Look Like?
Authors: Akabayashi Akira , Nakazawa Eisuke 
Published: August 2022

AbstractThis paper analysed the nature of autonomy, in particular respect for autonomy in medical ethics/bioethics in Japan. We have undertaken a literature survey in Japanese and English and begin with the historical background and explanation of the Japanese wordJiritsu (autonomy). We go on to identify patterns of meaning that researchers use in medical ethics / bioethics discussions in Japan, namely, Beauchamp and Childress’s individual autonomy, relational autonomy, and O’Neill’s principled autonomy as the three major ways that autonomy is understood. We examine papers discussing these interpretations. We propose using the term ‘a form of autonomy’ first used by Edmund Pellegrino in 1992 and examine the nature of ‘a form of autonomy.’ We finally conclude that the crux of what Pellegrino calls ‘something close to autonomy,’ or ‘a form of autonomy' might best be understood as the minimization of physician paternalism and the maximization of respect for patient preference. Simultaneously, we introduce a family-facilitated approach to informed consent and respond to criticism by Laura Sullivan. Finally, we discuss cross-cultural approaches and global bioethics. Furthermore, we use the term ‘Bioethics across the Globe’ instead of ‘Global Bioethics’, calling for international scholars to write works to provide an in-depth understanding of each country. We conclude that deep understanding of others is pivotal for dialogue to be of value. We hope this article will deepen the reader’s understanding of Japan and will contribute to the progress of bioethics worldwide.
Asymptotic geometry and Delta-points
Authors: Abrahamsen Trond A. , Lima Vegard , Martiny André , Perreau Yoël 
Published: August 2022

AbstractWe study Daugavet- and $$\Delta$$
Δ
-points in Banach spaces. A norm one element x is a Daugavet-point (respectively, a $$\Delta$$
Δ
-point) if in every slice of the unit ball (respectively, in every slice of the unit ball containing x) you can find another element of distance as close to 2 from x as desired. In this paper, we look for criteria and properties ensuring that a norm one element is not a Daugavet- or $$\Delta$$
Δ
-point. We show that asymptotically uniformly smooth spaces and reflexive asymptotically uniformly convex spaces do not contain $$\Delta$$
Δ
-points. We also show that the same conclusion holds true for the James tree space as well as for its predual. Finally, we prove that there exists a superreflexive Banach space with a Daugavet- or $$\Delta$$
Δ
-point provided there exists such a space satisfying a weaker condition.
Changes in regulators of lipid metabolism in the brain: a study of animal models of depression and hypothyroidism
Authors: Głombik Katarzyna , Detka Jan , Kukla-Bartoszek Magdalena , Maciejska Alicja , Budziszewska Bogusława 
Published: August 2022

AbstractMetabolic disturbances in the brain are assumed to be early changes involved in the pathogenesis of depression, and these alterations may be intensified by a deficiency of thyroid hormones. In contrast to glucose metabolism, the link between altered brain lipids and the pathogenesis of depression is poorly understood, therefore in the present study, we determine transcription factors and enzymes regulating cholesterol and fatty acid biosynthesis in the brain structures in an animal model of depression, hypothyroidism and the coexistence of these diseases.In used model of depression, a decrease in the active form of the transcription factor SREBP-2 in the hippocampus was demonstrated, thus suggesting a reduction in cholesterol biosynthesis. In turn, in the hypothyroidism model, the reduction of cholesterol biosynthesis in the frontal cortex was demonstrated by both the reduction of mature SREBP-2 and the concentration of enzymes involved in cholesterol biosynthesis. The lower expression of LDL receptors in the frontal cortex indicates the restriction of cholesterol uptake into the cells in the model of coexistence of depression and hypothyroidism. Moreover, the identified changes in the levels of SNAP-25, GLP-1R and GLP-2R pointed to disturbances in synaptic plasticity and neuroprotection mechanisms in the examined brain structures.In conclusion, a reduction in cholesterol synthesis in the hippocampus in the model of depression may be the reason for the reduction of synaptic plasticity, whereas a lower level of LDL-R occurring in the frontal cortex in rats from the model of depression and hypothyroidism coexistence could be the reason of anxiogenic and depression-like behaviors.
A multi-level analytic framework for disaster situational awareness using Twitter data
Authors: Zhai Wei 
Published: August 2022

AbstractDuring a natural disaster, mining messages from social media platforms can facilitate local agencies, rescue teams, humanitarian aid organizations, etc., to track the situational awareness of the public. However, for different stakeholders, the concerns about people’s situational awareness in a natural disaster event are different. Therefore, I developed a Twitter-based analytic framework to take perception-level situational awareness, humanitarian-level situational awareness, and action-level situational awareness into consideration. Specifically, perception-level situational awareness mainly reflects people’s perception of the ongoing natural disaster event (i.e., if people are discussing the disaster event). Decision-makers can rapidly have a big picture of severely impacted regions. Humanitarian-level situational awareness represents tweets that are associated with the humanitarian categories based on the definition from the United Nations Office for the Coordination of Humanitarian Affairs. The detection of humanitarian-level situational awareness can help response teams understand the specific situations and needs of local communities. In terms of the action-level situational awareness, I extracted noun-verb pairs in each tweet to explicitly represent the specific event described in a given tweet, so that the response teams can quickly act on the situation case by case. Moreover, to shed light on disaster resilience and social vulnerability, I further examined the demographic characteristics of three levels of situational awareness. I empirically demonstrated the analytic framework using geo-tagged tweets during 2018 Hurricane Michael.
Major vacuolar TPC1 channel in stress signaling: what matters, K+, Ca2+ conductance or an ion-flux independent mechanism?
Authors: Pottosin Igor , Dobrovinskaya Oxana 
Published: August 2022

AbstractTwo-pore cation channel, TPC1, is ubiquitous in the vacuolar membrane of terrestrial plants and mediates the long distance signaling upon biotic and abiotic stresses. It possesses a wide pore, which transports small mono- and divalent cations. K+ is transported more than 10-fold faster than Ca2+, which binds with a higher affinity within the pore. Key pore residues, responsible for Ca2+ binding, have been recently identified. There is also a substantial progress in the mechanistic and structural understanding of the plant TPC1 gating by membrane voltage and cytosolic and luminal Ca2+. Collectively, these gating factors at resting conditions strongly reduce the potentially lethal Ca2+ leak from the vacuole. Such tight control is impressive, bearing in mind high unitary conductance of the TPC1 and its abundance, with thousands of active channel copies per vacuole. But it remains a mystery how this high threshold is overcome upon signaling, and what type of signal is emitted by TPC1, whether it is Ca2+ or electrical one, or a transduction via protein conformational change, independent on ion conductance. Here we discuss non-exclusive scenarios for the TPC1 integration into Ca2+, ROS and electrical signaling.
The Impact of Implied Constraints on MaxSAT B2B Instances
Authors: Bofill Miquel , Coll Jordi , Giráldez-Cru Jesús , Suy Josep , Villaret Mateu 
Published: August 2022

AbstractThe B2B scheduling optimization problem consists of finding a schedule of a set of meetings between pairs of participants, minimizing their number of idle time periods. Recent works have shown that SAT-based approaches are state-of-the-art on this problem. One interesting feature of such approaches is the use of implied constraints. In this work, we provide an experimental setting to study the impact of using these implied constraints in MaxSAT B2B instances. To this purpose and due to the reduced number of existing real-world B2B instances, we propose a random B2B instance generation model, which reproduces certain features of these problems. In our experimental analysis, we show that the impact of using some implied constraints in the MaxSAT encodings depends on the characteristics of the problem, and we also analyze the benefits of combining them. Finally, we give some insights on how a MaxSAT solver is able to exploit these implied constraints.
Money Laundering Considerations in Blockchain-based Maritime Trade and Commerce
Authors: Chuah Jason C.T. 
Published: August 2022

AbstractThere is much to be welcomed concerning the role blockchain technology can play in modernising and enhancing international trade, creating a more level playing field and reducing costs. However, it goes without say that the technology also brings with it the risk of abuse leading to trade-based money laundering. This article explores how anti-money-laundering legislation should respond to the use of blockchain technology in shipping and trade. Maritime trade poses unique challenges because of several significant factors: the fact that it concerns large sums but many linked trading transactions over the same goods; its use of documents and involvement of numerous faceless entities; and its cross-border setting. Drawing on tried and tested forms of blockchain technology-based trade transactions, this work examines the fault lines in the current regulatory system and questions how best these gaps should be remedied. It also stresses that even states that have banned the issue and trade of cryptoassets might not be immune to these new challenges.
Diachronic Development of the K-suffixes: Evidence from Classical New Persian, Contemporary Written Persian, and Contemporary Spoken Persian
Authors: Nourzaei Maryam 
Published: August 2022

AbstractThis paper aims to investigate the usage and frequency of what we refer to as K-suffixes in Classical New Persian of the ninth to thirteenth centuries, Contemporary Written Persian of the late nineteenth to mid-twentieth centuries, and Contemporary Spoken Persian. It shows that K-suffixes are most likely to be the reflexes of earlier evaluative morphemes, traditionally called “diminutives,” and are characterized by a high degree of multifunctionality. While evaluative functions continue to dominate in the Classical New Persian works, they have largely been lost in contemporary spoken Persian, and the suffix is now systematically used to express definiteness. The development of the K-suffix as a definiteness marker in contemporary colloquial Persian appears to be innovative, and is mainly dependent on genre, speaker, and speech situation.Data for Classical New Persian is taken from critical editions of works from the ninth to thirteenth centuries. The data for Contemporary Written Persian comes from comprehensive books of fiction from the late nineteenth to mid-twentieth centuries, and for Contemporary Spoken Persian from an extensive corpus of spoken Persian narratives and a questionnaire answered by fifteen speakers. The results suggest that evaluative morphology can develop into definiteness marking, with the development passing through a stage of combination with a deictic marker.This paper concludes that the development of definiteness marking can proceed down a new pathway that is different from the one normally assumed for demonstrative-based definite marking, though the endpoint may be similar. The study contributes the second detailed documentation of this process for any Iranian language, and one of the few well-documented cases of a non-demonstrative origin of definiteness marking worldwide.
Voluntary physical activity in early life attenuates markers of fatty liver disease in adult male rats fed a high-fat diet
Authors: Abdulqader Farqad , Yu Lennex , Vickers Mark H. , Firth Elwyn C. , McGlashan Sue R. 
Published: August 2022

AbstractPaediatric fatty liver disease (FLD) can develop into steatohepatitis, cirrhosis and hepatocellular carcinoma in adulthood. We assessed if early life physical exercise reduced the effects of high-fat (HF) diet-induced steatosis. Male HF-fed rats with access to a running wheel from weaning until day (D)60 (early exercise) or from D67 to D120 (late exercise) were compared with control HF- or chow-fed groups with no wheel. At D63 and D120, liver histopathology (Kleiner score), type I collagen and plasma enzymes were assessed. At D63, early life activity significantly reduced histopathology scores (total, portal inflammation, steatosis, ballooning, but not lobular inflammation or fibrosis) and the number of rats affected. At D120, HF control scores were higher than in chow-fed controls, but the effect of activity was selective: early exercise reduced portal inflammation, steatosis, ballooning and fibrosis, but late activity affected only portal inflammation and ballooning. The chow-fed portal inflammation score was significantly less than all HF groups, but lobular inflammation was lower in the HF control group only. The fibrosis score in the HF early exercise and control chow group were lower than in the late exercise and sedentary HF groups, indicating that early life exercise was more effective than when activity was introduced later in life. Plasma biomarkers showed minor between-group differences. The retained effect on liver histopathology rat at D120 after only early life exposure activity suggests that timing of introduction of exercise is critical in reducing FLD scores and prevalence in children, young adults and possibly into adulthood.
Complex spatiotemporal changes in land-use and ecosystem services in the Jeju Island UNESCO heritage and biosphere site (Republic of Korea)
Authors: Kim Jihwan , Choi Heejoon , Shin Wonhyeop , Yun Jiweon , Song Youngkeun 
Published: August 2022

SummaryJeju Island, designated by UNESCO as a world heritage site, continues to face the anthropogenic pressures of reckless development for regional tourism and economic revitalization purposes. Because land use/land cover (LULC) affects ecosystem services and human well-being, it is crucial to comprehensively identify the causes of changes in LULC based on long-term analyses. This study examined LULC changes on Jeju Island over 47 years from 1973 to 2019 and quantified changes in four ecosystem services: habitat quality, carbon stock, water yield and cumulative viewshed. From 1973 to 1998, forest land increased from 22% to 56%, but these restoration efforts were conducted in grassland, reducing that land type from 42% to 17%. This process increased the areas of highest habitat quality from 68% to 73%, and carbon stock increased from 20 to 30 million tonnes. Between 1998 and 2009, the area of cropland more than doubled from 21% to 44%. As a result, the areas of highest habitat quality decreased from 73% to 49%, and carbon stock decreased from 3.0 million tonnes to 2.3 million tonnes. Our analysis could help stakeholders and policymakers to develop their management planning and improve ecosystem services through restoration and conservation policies on Jeju Island.
Field Research When There Is Limited Access to the Field: Lessons from Japan
Authors: Amano Kenya , Dominguez Melanie Sayuri , Fraser Timothy , Gagnon Etienne , Incerti Trevor , Jang Jinhyuk , McClean Charles T. , Mitchell Austin M. , Miyano Sayumi , Moreshead Colin , Saijo Harunobu , Stanescu Diana , Teraoka Ayumi , Yamagishi Hikaru , Willis Charmaine N. , Woo Yujin , Crabtree Charles 
Published: August 2022

ABSTRACTHow can scholars conduct field research when there is limited access to the field? This article first identifies how limited and uncertain field access can affect field research and then provides recommendations to address these challenges. We focus on conducting field research in Japan because of our substantive expertise, but we believe that the problems and solutions outlined in this article are applicable to a broad range of countries. Our hope is that this article contributes to the developing literature on conducting research during times of emergency and to the larger literature on best practices for field research.
Group intervention for sexual minority adults with common mental health problems: preliminary evaluation
Authors: Hambrook David G. , Aries Damian , Benjamin Lewis , Rimes Katharine A. 
Published: August 2022

AbstractBackground:Stigma against lesbian, gay, bisexual or queer (LGBQ) people may increase their risk of mental illness and reduce their access to and/or benefit from evidence-based psychological treatments. Little is known about the feasibility, acceptability and effectiveness of adapted psychological interventions for sexual minority individuals in the UK.Aims:To describe and evaluate a novel LGBQ Wellbeing group therapy for sexual minority adults experiencing common mental health problems, provided in a UK Improving Access to Psychological Therapies (IAPT) service.Method:An eight-session LGBQ Wellbeing group intervention was developed drawing on CBT and LGBQ affirmative principles. We compare the socio-demographic and clinical characteristics of patients who completed and dropped out of the groups, and explore changes in self-reported symptoms of depression, anxiety and functional impairment.Results:Over eight courses provided, 78 service-users attended at least one session, of whom 78.2% completed the intervention (drop-out rate 21.8%). Older participants were more likely to drop out. There was a lower proportion of female and bisexual or ethnic/racial minority individuals than would be expected. There were significant reductions in severity of depression, anxiety and functional impairment following the group, and more than half of those who completed the intervention needed no further treatment.Conclusions:There was preliminary evidence of the feasibility of, and potential clinical benefit in, a group therapy intervention for sexual minority adults experiencing common mental health problems. Future research should investigate access and outcomes for participants with additional social disadvantage, e.g. those who are female, older, bisexual or ethnic/racial minority.