bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Race Play a Role in Complications and Outcomes of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms?
Authors: Peseski Andrew M. , Saliba Antoine N. , Althouse Sandra K. , Sayar Hamid
Published: February 2021

Background:

Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are a group of hematologic malignancies with known vascular complications. The role race and ethnicity play in these complications is less defined. We aimed to further evaluate the role of race in patients without a history of previous thrombotic or hemorrhagic events.

Methods:

In this retrospective study, 300 adult patients with MPN were included; 270 (90.0%) were White and 30 (10.0%) were non-White. The non-White group primarily consisted of African American or Black (26 patients), followed by others. Median age at diagnosis was 58 years for White patients and 61.5 years for non-White patients. The interaction between outcomes and vascular events with race was evaluated using multivariate logistical regression models.

Results:

The incidence of thrombotic events was inversely correlated with age at diagnosis, with younger patients demonstrating a higher rate of thrombotic events over time (p < .001). The incidence of thrombotic or hemorrhagic events did not differ between White and non-White patients. A statistically significant difference in median survival was observed between White and non-White patients: 29 years (95% confidence interval [CI]: 21.8–not reached) versus 13 years (95% CI: 5.7–22.7), respectively (p = .016).

Conclusion:

This study did not find a significant difference in the rate of thrombotic or hemorrhagic events between White and non-White patients with MPN but suggested that non-White patients had significantly shorter median survival than White patients. Such observations may inform future studies to further characterize racial disparities in outcomes.
Human Struggle
Authors: Siddiqui Mona
Published: February 2021

Many of the great thinkers and poets in Christianity and Islam led lives marked by personal and religious struggle. Indeed, suffering and struggle are part of the human condition and constant themes in philosophy, sociology and psychology. In this thought-provoking book, acclaimed scholar Mona Siddiqui ponders how humankind finds meaning in life during an age of uncertainty. Here, she explores the theme of human struggle through the writings of iconic figures such as Dietrich Bonhoeffer, Muhammad Ghazali, Rainer Maria Rilke and Sayyid Qutb - people who searched for meaning in the face of adversity. Considering a wide range of thinkers and literary figures, her book explores how suffering and struggle force the faithful to stretch their imagination in order to bring about powerful and prophetic movements for change. The moral and aesthetic impulse of their writings will also stimulate inter-cultural and interdisciplinary conversations on the search for meaning in an age of uncertainty.
Greek Theater in Ancient Sicily
Authors: Bosher Kathryn G. , Winling LaDale
Published: February 2021

Studies of ancient theater have traditionally taken Athens as their creative center. In this book, however, the lens is widened to examine the origins and development of ancient drama, and particularly comedy, within a Sicilian and southern Italian context. Each chapter explores a different category of theatrical evidence, from the literary (fragments of Epicharmus and cult traditions) to the artistic (phylax vases) and the archaeological (theater buildings). Kathryn G. Bosher argues that, unlike in classical Athens, the golden days of theatrical production on Sicily coincided with the rule of tyrants, rather than with democratic interludes. Moreover, this was not accidental, but plays and the theater were an integral part of the tyrants' propaganda system. The volume will appeal widely to classicists and to theater historians.
Negative Actions
Authors: Payton Jonathan D.
Published: February 2021

Negative actions, like intentional omissions or refrainments, seem to be genuine actions. The standard metaphysical theories of action are event-based: they treat actions as events of a special kind. However, it seems that many (and perhaps all) negative actions are not events, but absences thereof. This is the first book-length treatment of the problem of negative action. It surveys the recent literature, and shows how the problem is rooted in interconnected issues in metaphysics, the philosophy of action, and the philosophy of language. In particular, it connects competing views of the ontology of negative actions to competing views of the semantics of 'negative action sentences', and develops unique ontological and semantic theories to solve the problem. It provides a comprehensive picture of the nature of negative actions, our thought and talk about them, and their place in a theory of action.
Progress Unchained
Authors: Bowler Peter J.
Published: February 2021

Progress Unchained reinterprets the history of the idea of progress using parallels between evolutionary biology and changing views of human history. Early concepts of progress in both areas saw it as the ascent of a linear scale of development toward a final goal. The 'chain of being' defined a hierarchy of living things with humans at the head, while social thinkers interpreted history as a development toward a final paradise or utopia. Darwinism reconfigured biological progress as a 'tree of life' with multiple lines of advance not necessarily leading to humans, each driven by the rare innovations that generate entirely new functions. Popular writers such as H. G. Wells used a similar model to depict human progress, with competing technological innovations producing ever-more rapid changes in society. Bowler shows that as the idea of progress has become open-ended and unpredictable, a variety of alternative futures have been imagined.
The Serious Game
Authors: Törnqvist Egil
Published: February 2021

Though Ingmar Bergman became famous as a filmmaker, his roots-and, to some extent, his heart-were in the theater. He directed more than one hundred plays in his career, and The Serious Game takes a close look at fourteen productions he staged at the Royal Dramatic Theatre in Stockholm. Looking closely at the relationship between the verbal and the visual, this book gives even longtime Bergman fans a new understanding of his sensitivity to nuance, his versatility, and his dedication to craftsmanship.
Parameter optimisation of a carrier-based UAV drawbar based on strain fatigue analysis
Authors: Chen H. , Fang X. , Zhang Z. , Xie X. , Nie H. , Wei X.
Published: February 2021

Carrier-based unmanned aerial aircraft (UAV) structure is subjected to severe tensile load during takeoff, especially the drawbar, which affects its fatigue performance and structural safety. However, the complex structural features pose great challenges for the engineering design. Considering this situation, a structural design, fatigue analysis, and parameters optimisation joint working platform are urgently needed to solve this problem. In this study, numerical analysis of strain fatigue is carried out based on the laboratory fatigue failure of the carrier-based aircraft drawbar. Taking the sensitivity of drawbar parameters to stress and life into account and optimum design of drawbar with fatigue life as a target using the parametric method, this study also includes cutting-edge parameters of milling cutters, structural details of the drawbar and so on. Then an experimental design is applied using the Latin hypercube sampling method, and a surrogate model based on RBF neural network is established. Lastly, a multi-island genetic algorithm is introduced for optimisation. The results show that the error between the obtained optimal solution and simulation is 0.26%, while the optimised stress level is reduced by 15.7%, and the life of the drawbar is increased by 122%.
Pediatric Hyperacute Arterial Ischemic Stroke Pathways at Canadian Tertiary Care Hospitals
Authors: Gladkikh Maria , McMillan Hugh J. , Andrade Andrea , Boelman Cyrus , Bhathal Ishvinder , Mailo Janette , Mineyko Aleksandra , Moharir Mahendranath , Perreault Sébastien , Smith Jonathan , Pohl Daniela
Published: February 2021

Background:

Childhood acute arterial ischemic stroke (AIS) is diagnosed at a median of 23 hours post-symptom onset, delaying treatment. Pediatric stroke pathways can expedite diagnosis. Our goal was to understand the similarities and differences between Canadian pediatric stroke protocols with the aim of optimizing AIS management.

Methods:

We contacted neurologists at all 16 Canadian pediatric hospitals regarding AIS management. Established protocols were analyzed for similarities and differences in eight domains.

Results:

Response rate was 100%. Seven (44%) centers have an established AIS protocol and two (13%) have a protocol under development. Seven centers do not have a protocol; two redirect patients to adult neurology, five rely on a case-by-case approach for management. Analysis of the seven protocols revealed differences in: 1) IV-tPA dosage: age-dependent 0.75–0.9 mg/kg (N = 1) versus age-independent 0.9 mg/kg (N = 6), with maximum doses of 75 mg (N = 1) or 90 mg (N = 6); 2) IV-tPA lower age cut-off: 2 years (N = 5) versus 3 or 10 years (each N = 1); 3) IV-tPA exclusion criteria: PedNIHSS score <4 (N = 3), <5 (N = 1), <6 (N = 3); 4) first choice of pre-treatment neuroimaging: computed tomography (CT) (N = 3), magnetic resonance imaging (MRI) (N = 2) or either (N = 2); 5) intra-arterial tPA use (N = 3) and; 6) mechanical thrombectomy timeframe: <6 hour (N = 3), <24 hour (N = 2), unspecified (N = 2).

Conclusions:

Although 44% of Canadian pediatric hospitals have established AIS management pathways, several differences remain among centers. Some criteria (dosage, imaging) reflect adult AIS literature. Canadian expert consensus regarding IV-tPA and endovascular treatment should be established to standardize and implement AIS protocols across Canada.
Effect of usinggreen fluorescent proteindouble-stranded RNA as non-target negative control inNasonia vitripennisRNA interference assays
Authors: Rougeot Julien , Wang Yidong , Verhulst Eveline C.
Published: February 2021

RNA interference (RNAi) is a technique used in many insects to study gene function. However, prior research suggests possible off-target effects when usingGreen Fluorescent Protein(GFP) sequence as a non-target control. We used a transcriptomic approach to study the effect ofGFPRNAi (GFP-i) inNasonia vitripennis, a widely used parasitoid wasp model system. Our study identified 3.4% of total genes being differentially expressed in response toGFP-i. A subset of these genes appears involved in microtubule and sperm functions.In silicoanalysis identified 17 potential off-targets, of which only one was differentially expressed afterGFP-i. We suggest the primary cause for differential expression afterGFP-i is the non-specific activation of the RNAi machinery at the injection site, and a potentially disturbed spermatogenesis. Still, we advise that any RNAi study involving the genes deregulated in this study, exercises caution in drawing conclusions and uses a different non-target control.
Emission mechanism for the silicon He-α lines in a photoionization experiment
Authors: Han Bo , Wang Feilu , Salzmann David , Zhong Jiayong , Zhao Gang
Published: February 2021

In this paper, we present a reanalysis of the silicon He-$\mathrm{\alpha}$X-ray spectrum emission in Fujiokaet al.’s 2009 photoionization experiment. The computations were performed with our radiative-collisional code, RCF. The central ingredients of our computations are accurate atomic data, inclusion of satellite lines from doubly excited states and accounting for the reabsorption of the emitted photons on their way to the spectrometer. With all these elements included, the simulated spectrum turns out to be in good agreement with the experimental spectrum.
Social enterprise in a remote Indigenous community – Barunga Festival in Australia's Northern Territory
Authors: Ensign Prescott C.
Published: February 2021

In 2020, the Barunga Festival would have celebrated its 35th anniversary. In mid-June of 2021, as many as 4,000 individuals were expected to descend on an aboriginal community of 300 residents located 400 km south of Darwin. This case describes the challenge to the Festival's promoters as they seek to sustain peak socio-economic impact in their role as community development change agents in a diverse and dynamic environment. The reader is tasked with clarifying goals, deciding what is at stake, and setting a course of action to realize those objectives.
Assessment of the helminth fauna in northern bobwhites (Colinus virginianus) occurring within South Texas
Authors: Shea S.A. , Fedynich A.M. , Wester D.B.
Published: February 2021

Populations of northern bobwhites (Colinus virginianus; hereafter bobwhite) have been declining across their geographic range in North America, prompting consideration of the role parasites may play. We conducted this study to learn about the helminth fauna in South Texas, a region that supports a sustainable bobwhite population. Helminths were examined from 356 bobwhites collected during the 2014–2015 (n = 124) and 2015–2016 (n = 232) hunting seasons, when increasing trends in precipitation were observed in comparison with the previous two years. Ten helminth species were found, consisting of 14,127 individuals. Of these, all are heteroxenous parasites and three are pathogenic (Dispharynx nasuta, Tetrameres pattersoni and Oxyspirura petrowi). Aulonocephalus pennula numerically dominated the component community (81% prevalence, 99% of the total helminths found), whereas each of the remaining species occurred rarely (≤9% prevalence) and contributed few individuals (≤0.4%) to the helminth community. Prevalence and abundance of A. pennula were not influenced by host age, sex or body mass, but abundance was higher during the 2014–2015 than the 2015–2016 hunting season. Our findings indicate that the helminth community in bobwhites from South Texas can vary during long-term, highly variable precipitation conditions and these communities are more similar to those found in the Rolling Plains of Texas than those found in the eastern part of the bobwhite's geographic range in the US.
The predictive power of expressed emotion and its components in relapse of schizophrenia: a meta-analysis and meta-regression
Authors: Ma Chak Fai , Chan Sherry Kit Wa , Chung Yik Ling , Ng Siu Man , Hui Christy Lai Ming , Suen Yi Nam , Chen Eric Yu Hai
Published: February 2021

Background

Schizophrenia is a longstanding condition and most patients experience multiple relapse in the course of the condition. High expressed emotion (HEE) has been found to be a predictor of relapse. This meta-analysis and meta-regression examined the association of global EE and relapse specifically focusing on timing of relapse and EE domains.

Methods

Random-effects model was used to pool the effect estimates. Multiple random-effects meta-regression was used to compute the moderator analysis. Putative effect moderators including culture, EE measurements, age, length of condition and study quality were included.

Results

Thirty-three prospective cohort studies comprising 2284 patients were included in the descriptive review and 30 studies were included for meta-analysis and meta-regression. Findings revealed that global HEE significantly predicted more on early relapse (⩽12 months) [OR 4.87 (95% CI 3.22–7.36)] than that on late relapse (>12 months) [OR 2.13 (95% CI 1.36–3.35)]. Higher level of critical comments (CC) significantly predicted relapse [OR 2.22 (95% CI 1.16–4.26)], whereas higher level of warmth significantly protected patients from relapse [OR 0.35 (95% CI 0.15–0.85)]. None of the moderators included significantly change the results.

Conclusions

These findings indicate that there is a dynamic interaction between EE-relapse association with time, and CC and warmth are the two important EE domains to influence relapse among patients with schizophrenia. Results also confirmed the foci of family interventions on reducing CC and improving warmth in relationship.
Spatial agency bias and word order flexibility: A comparison of 14 European languages
Authors: Suitner Caterina , Maass Anne , Navarrete Eduardo , Formanowicz Magdalena , Bratanova Boyka , Cervone Carmen , Hakoköngäs Juho Eemeli , Kuppens Toon , Lipourli Eleni , Rakić Tamara , Scatolon Andrea , Teixeira Catia P. , Wang Zhenlan , Sobral Maria Pedro , Carrier Antonin
Published: February 2021

The spatial agency bias predicts that people whose native language is rightward written will predominantly envisage action along the same direction. Two mechanisms contribute jointly to this asymmetry: (a) an embodied process related to writing/reading; (b) a linguistic regularity according to which sentence subjects (typically the agent) tend to precede objects (typically the recipient). Here we test a novel hypothesis in relation to the second mechanism, namely, that this asymmetry will be most pronounced in languages with rigid word order. A preregistered study on 14 European languages (n= 420) varying in word order flexibility confirmed a rightward bias in drawings of interactions between two people (agent and recipient). This bias was weaker in more flexible languages, confirming that embodied and linguistic features of language interact in producing it.
Weathering Climate Change in Archaeology: Conceptual Challenges and an East African Case Study
Authors: Petek-Sargeant Nik , Lane Paul J.
Published: February 2021

Research on the social dimensions of climate change is increasingly focused on people's experiences, values and relations to the environment as a means to understand how people interpret and adapt to changes. However, a particular challenge has been making seemingly temporally and geographically distant climate change more immediate and local so as to prompt behavioural change. Environmental humanists, anthropologists and historians have tried to address the challenge through analysis of the experiences, philosophies and memories of weather. Archaeology, commonly preoccupied by hard science approaches to climate change, has largely been absent from this conversation. Nevertheless, with its insights into material outcomes of human experiences and relations, it can become integral to the discussion of ‘weathering’ climate change and historicizing weather. Here, drawing on the subtleties of responses by Ilchamus communities in Kenya and using a mix of historical and archaeological sources, we highlight their experiences of weather since the end of the Little Ice Age and explore the potential of building archaeologies of weather.
Post-dispersion humidity condition alters the surface of the testa and the proportion of seeds with physical dormancy in Erythrina speciosa
Authors: Magalhães Camila R. , Garcia Queila S. , Oliveira Denise M.T.
Published: February 2021

Seeds of Papilionoideae (Leguminosae) species lose water after dispersal, increasing the proportion of water-impermeable seeds (physical dormancy, PY). However, changes in testa structure during this process remain unknown. The present study investigated how variation in relative humidity (RH) during the post-dispersion period affects the proportion of seeds of Erythrina speciosa with PY. Seeds from two populations were stored in drier (40% RH) and wetter (80% RH) environments and periodically subjected to physiological analysis (seed water content, imbibition and germination) and structural analysis of the testa (light and scanning electron microscopy). Drier storage resulted in seed dehydration, increasing the proportion of water-impermeable seeds and closure of cracks in the mucilaginous stratum. In contrast, wetter storage led to an increase in seed water content, a decrease in the proportion of seeds with PY, and the formation of cracks. As a result of variation in environmental humidity, we conclude that changes occur in the mucilaginous stratum of seeds, altering water loss and, consequently, the proportion of seeds with PY. Environments with low humidity cause a decrease in seed water content, the closing of cracks in the mucilaginous stratum, and, consequently, an increase in the proportion of water-impermeable seeds. On the other hand, a high RH environment increases the seed water content and the formation of superficial cracks, through which water enters during imbibition, causing a decrease in the proportion of seeds with PY.
Marked skeletal muscle deficits are associated with 6-minute walk distance in paediatric pulmonary hypertension
Authors: Avitabile Catherine M. , Saavedra Sofia , Sivakumar Nithya , Goldmuntz Elizabeth , Paridon Stephen M. , Zemel Babette S.
Published: February 2021

Background:

Poor growth is common in children with pulmonary hypertension; however, skeletal muscle deficits have not been described and the association between muscle deficits and functional status is unknown.

Methods:

Patients aged 8–18 years with pulmonary hypertension (diagnostic Groups 1, 2, or 3) and World Health Organization functional class I or II underwent dual-energy absorptiometry to measure leg lean mass Z-score (a surrogate for skeletal muscle). Muscle strength was assessed using dynamometry. Physical activity questionnaires were administered. Clinical data, including 6-minute walk distance, were reviewed. Relationships between skeletal muscle, physical activity score, and 6-minute walk distance were assessed by correlations and linear regression.

Results:

Sixteen patients (12.1 ± 3.2 years, 50% female, 56% Group 1, 56% functional class II) were enrolled. Leg lean mass Z-score was significantly less than reference data (−1.40 ± 1.12 versus 0.0 ± 0.9, p < 0.001) and worse in those with functional class II versus I (−2.10 ± 0.83 versus −0.50 ± 0.73, p < 0.01). Leg lean mass Z-score was positively associated with right ventricular systolic function by tricuspid annular plane systolic Z-score (r = 0.54, p = 0.03) and negatively associated with indexed pulmonary vascular resistance (r = −0.78, p < 0.001). Leg lean mass Z-score and forearm strength were positively associated with physical activity score. When physical activity score was held constant, leg lean mass Z-score independently predicted 6-minute walk distance (R2 = 0.39, p = 0.03).

Conclusions:

Youth with pulmonary hypertension demonstrate marked skeletal muscle deficits in association with exercise intolerance. Future studies should investigate whether low leg lean mass is a marker of disease severity or an independent target that can be improved.
The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS): Validation in Arabic and Lebanese Normative Values
Authors: Darwish Hala , Zeinoun Pia , Farran Natali , Ghusn Husam , Yamout Bassem , Khoury Samia J.
Published: February 2021

Objective:

Multiple sclerosis (MS) is often associated with cognitive deficits. Accurate evaluation of the MS patients’ cognitive performance is essential for diagnosis and treatment recommendation. The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS), widely used cognitive testing battery, examines processing speed, verbal and visuospatial learning, and memory. Our study aims to examine the psychometric properties of an Arabic version of the BICAMS and to provide normative values in a Lebanese sample.

Method:

The BICAMS, comprised of the Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R), and a newly developed verbal learning/memory test, the Verbal Memory Arabic Test (VMAT), were administered on healthy subjects and MS patients. The sample consisted of 180 healthy individuals, of whom 63 were retested after 2–3 weeks. Forty-three MS patients matched with 43 healthy subjects based on age, sex, and years of education were assessed. A sample of 10 MS patients was also examined on two occasions. Test–retest reliability and criterion-related validity were examined, and regression-based norms were derived.

Results:

The test–retest correlations showed good evidence of reliability with coefficients ranging between 0.64 and 0.73 in the healthy sample, and between 0.43 and 0.92 in the MS sample. The BICAMS was able to discriminate between MS patients and matched healthy participants on the SDMT and BVMT-R. Normative data were comparable to other studies.

Conclusions:

This new Arabic version of the BICAMS shows initial good psychometric properties. While good evidence of VMAT’s reliability was shown in the healthy participants, less test–retest reliability in this tool was seen in the MS group, and partial criterion-related validity was evident. This renders further examination of the VMAT. We provide regression-based norms for a Lebanese sample and encourage the use of this battery in both research and clinical settings.
Global evaluation of the use of glycaemic impact measurements to food or nutrient intake
Authors: Trumbo Paula R
Published: February 2021

Objective:

Measures of glycaemic impact (e.g. postprandial glucose (PPG), oral glucose tolerance test (OGTT) and glycaemic index (GI)) are used by government health and regulatory agencies and public health associations around the world. The objective of this global review was to identify similarities and differences in the use of glycaemic impact measures for potential considerations for harmonisation.

Design:

A literature and internet search was conducted to identify country government agencies and health associations that provide guidance or recommendations for PPG, OGTT, GI and glycaemic load.

Results:

Based on this global review, the use of GI for food labelling (e.g. low GI) is limited and its use is voluntary. The application of OGTT as a diagnostic measurement of diabetes and gestational diabetes is widely used and in a consistent manner among the different regions of the world. Time-specific (e.g. 2 h) PPG is commonly used as a target not to exceed in individuals with diabetes and gestational diabetes. PPG is used by regulatory agencies for the substantiation of food labelling. There are differences, however, among regulatory agencies in the specific measure of PPG (i.e. PPG AUC v. peak PPG). Maximum targets for 2-h PPG for individuals with diabetes and gestational diabetes, ranging between 6 and 10 mmol/l, across countries suggest a potential consideration to harmonise PPG targets.

Conclusions:

There is general consistency in the use and/or target levels of glycaemic impact measures; however, there is a potential need to investigate harmonisation strategies on certain aspects of glycaemic impact measures.
Ionospheric D Region Disturbances due to FAC and LEP Associated With Three Severe Geomagnetic Storms as Observed by VLF Signals
Authors: Kerrache F. , Nait Amor S. , Kumar S.
Published: February 2021

The effects of one super and two intense storms on three European very low frequency (VLF) transmitter signals received at Algiers (Algeria) station, are presented. Two VLF transmitters (DHO and GQD) are located almost at the same mid‐latitude and third transmitter (NRK) at a high latitude, allowing us to study the latitudinal dependence of the storm effect on the VLF propagation. Two kind of ionospheric disturbances were considered: Direct effect of the field aligned currents (FACs) and the second concerning with the lightning‐induced electron precipitation (LEP) events. The FACs effect was clearly evident on the recorded signal amplitude during the daytime and nighttime. Our analysis of the short‐duration VLF perturbations due to LEP events showed that the ducted and non‐ducted LEPs are the majority of VLF perturbations and a small fraction of LEP events was associated with magnetospherically reflected waves on the high latitude transmitter path (NRK–Algiers). The coincident observation of LEP on the mid‐latitude transmitters (DHO and GQD) signals implies that the disturbance was large as much as the distance between the two transmitters (728 km). The modeling using Long‐Wave Propagation Capability (LWPC) code of LEP associated VLF perturbations considering Gaussian distribution of electron density enhancements, showed a decrease in the D‐region reference height from its usual value 87 km to 83.3 km for ducted LEP and 80.3 km for non‐ducted LEP event and that the non‐ducted event exhibited a wider disturbed region.
Comparing Non‐Tidal Ocean Loading Around the Southern North Sea With Subdaily GPS/GLONASS Data
Authors: Geng Jianghui , Xin Shaoming , Williams Simon D. P. , Jiang Weiping
Published: February 2021

Observing subdaily surface deformations is important to the interpretation of rapidly developing transient events. However, it is not known whether Global Navigation Satellite System (GNSS) is able to identify millimeter‐level transient displacements over various subdaily timescales. We studied non‐tidal ocean loading (NTOL) using 18 GNSS stations along the southern North Sea for November–December 2013 and compared 3‐h GPS/GLONASS displacements with NTOL predictions. It was found that they overall agreed well with a mean correlation coefficient of 0.6 and their vertical differences had an RMS of 5.7 mm, but a 10‐mm subsidence prediction for December 5th could only be marginally detected. Hence, the spatial coherence among the loading signatures at the 18 stations was harnessed to improve subdaily GNSS, and then the predicted displacements of 5–10‐mm over the subdaily timescales could be discriminated successfully. We envision that adding Galileo/BeiDou signals to GPS/GLONASS can further improve the resolution of subdaily GNSS, which can also enhance the spatial coherence of transient signals captured by regional GNSS stations.
Decadal Changes in Soil and Atmosphere Temperature Differences Linked With Environment Shifts Over Northern Eurasia
Authors: Chen Liangzhi , Aalto Juha , Luoto Miska
Published: February 2021

The difference between soil and air temperatures (ΔT) in a specified time is dependent on meteorological conditions, properties of soil and land covers. Understanding ΔT is critical in assessing land–atmosphere thermal interactions in changing environment. However, systematic knowledge of interannual variations and responses of ΔT to the environmental changes (e.g., snow cover and soil moisture) at decadal scales remain limited. Here, variations of the mean annual air and soil temperatures, and ΔT were investigated at 217 sites in northern Eurasia during 1981–2015. It is found that changes in the mean annual air and soil temperatures were inconsistent as the average increase in soil temperature was generally less than that of air. The relationships between trends in soil and air temperatures were significant in the upper ground (0.2 and 0.8 m) over the seasonal frost region but insignificant in the permafrost regions and deeper ground. During the period, widespread changes in ΔT occurred and closely responded to the environmental changes, but the relationships varied with soil depth. Among the tested factors, trends in snow cover thickness dominantly control trends in ΔT, followed by trends in snow cover duration and solar radiation. Both linear and nonlinear analyses indicate enhanced relationships between trends in snow depth and ΔT as depth increases. This study provides the first view of decadal trends in ΔT and conjunctions with the environmental changes during 1981–2015 over northern Eurasia. The findings are relevant to quantify land–atmosphere thermal interactions given impacts of future environmental changes.
Historical Water Storage Changes Over China's Loess Plateau
Authors: Shao Rui , Zhang Baoqing , He Xiaogang , Su Tongxuan , Li Yao , Long Biao , Wang Xuejin , Yang Wenjing , He Chansheng
Published: February 2021

Since 1999, the Loess Plateau, China, has undergone one of the world's largest revegetation programs (Grain for Green Project, GfGP). Revegetation has profound impacts on hydrological cycle and water balance, especially in arid and semi‐arid areas. As an essential component of water balance, the long‐term change in water storage (ΔS) is generally treated as zero. However, it remains unclear how to define the time scale of “long‐term,” especially over regions undergoing dramatic vegetation restoration. In this study, we quantify ΔS over the Loess Plateau from 1982 to 2009 from a water balance perspective, with a particular focus on the impact of vegetation on ΔS at different time scales. Results show that a 44.78% increase in vegetation coverage could lead to a 37.72% decrease in ΔS. Moreover, the better the vegetation growth, the lower the ratio of ΔS to precipitation (ΔS/P) in the Loess Plateau. ΔS/P achieved a local minimum at the 4‐ to 5‐year scale and reached a plateau after 10 years. We further use the Budyko framework to verify the above conclusions. We find that errors of simulated streamflow over 11/16 of catchments become stable after 4–5 years, and all 16 catchments become stable after 10 years. Ignoring ΔS at a 10‐year scale has the least influence on water budget closure. These findings highlight the importance of considering time scales when ignoring ΔS in the water balance analysis, especially when the length of measurement is limited.
Secondary analyses of global datasets: do obesity and physical activity explain variation in diabetes risk across populations?
Authors: Alkaf Budour , Blakemore Alexandra I. , Järvelin Marjo-Riitta , Lessan Nader
Published: February 2021

Type 2 diabetes rates vary significantly across geographic regions. These differences are sometimes assumed to be entirely driven by differential distribution of environmental triggers, including obesity and insufficient physical activity (IPA). In this review, we discuss data which conflicts with this supposition. We carried out a secondary analysis of publicly available data to unravel the relative contribution of obesity and IPA towards diabetes risk across different populations. We used sex-specific, age-standardized estimates from Non-Communicable Disease Risk Factor Collaboration (NCD-RisC) on diabetes (1980–2014) and obesity (1975–2016) rates, in 200 countries, and from WHO on IPA rates in 168 countries in the year 2016. NCD-RisC and WHO organized countries into nine super-regions. All analyses were region- and sex-specific. Although obesity has been increasing since 1975 in every part of the world, this was not reflected in a proportional increase in diabetes rates in several regions, including Central and Eastern Europe, and High-income western countries region. Similarly, the association of physical inactivity with diabetes is not homogeneous across regions. Countries from different regions across the world could have very similar rates of diabetes, despite falling on opposite ends of IPA rate spectrum. The combined effect of obesity and IPA on diabetes risk was analyzed at the worldwide and country level. The overall findings highlighted the larger impact of obesity on disease risk; low IPA rates do not seem to be protective of diabetes, when obesity rates are high. Despite that, some countries deviate from this overall observation. Sex differences were observed across all our analyses. Overall, data presented in this review indicate that different populations, while experiencing similar environmental shifts, are apparently differentially subject to diabetes risk. Sex-related differences observed suggest that males and females are either subject to different risk factor exposures or have different responses to them.
Age dependency of plasma vitamin B12 status markers in Dutch children and adolescents
Authors: Heiner-Fokkema M. Rebecca , Riphagen Ineke J. , Wiersema Nicole S. , van Zanden Jelmer J. , Kootstra-Ros Jenny E. , Pinxterhuis Tineke H. , Hooimeijer H. Louise , van Spronsen Francjan J. , Muller Kobold Anneke C. , de Jong Wilhelmina H. A.
Published: February 2021

Background

Vitamin B12 deficiency in children may be associated with (severe) neurological manifestations, therefore recognition is important. Diagnosing vitamin B12 deficiency in children is challenging. This study aimed to investigate plasma methylmalonic acid, holotranscobalamin, and total cobalamin in children 0–18 years of age and to estimate age-dependent reference intervals.

Methods

Plasma vitamin B12 markers were measured in collected plasma samples of 170 children 0–18 years visiting a local primary care laboratory. All had within-reference hemoglobin and MCV values. Pediatric plasma vitamin B12 biomarkers were measured and reference values were derived thereof.

Results

Plasma methylmalonic acid was higher in young children, in particular between 1 and 6 months of age; total cobalamin and holotranscobalamin were highest from 0.5 to 4 years and decreased till 10 years of age. Plasma holotranscobalamin was highly correlated with plasma total cobalamin; their ratio was independent of age. Plasma methylmalonic acid was slightly more related to total cobalamin than to holotranscobalamin. A large proportion of mainly young children would be misclassified when adult references are applied.

Conclusions

Pediatric reference values for cobalamin markers are necessary to allow for early recognition and monitoring of children suspect of (clinical) cobalamin deficiency.

Impact

We analyzed three plasma vitamin B12 status markers, i.e., total cobalamin, holotranscobalamin, and methylmalonic acid, in the plasma of 170 children 0–18 years of age and were able to derive reference intervals thereof. Recognition of vitamin B12 deficiency in children is important but challenging as pediatric reference intervals for plasma vitamin B12 status markers, particularly plasma holotranscobalamin, are not well described. We think that our results may help early recognition and monitoring of children suspect of (clinical) vitamin B12 deficiency.
Molecular medicine tumor board: whole-genome sequencing to inform on personalized medicine for a man with advanced prostate cancer
Authors: Armstrong Andrew J. , Li Xiaotong , Tucker Matthew , Li Shantao , Mu Xinmeng Jasmine , Eng Kenneth Wha , Sboner Andrea , Rubin Mark , Gerstein Mark
Published: February 2021

Purpose

Molecular profiling of cancer is increasingly common as part of routine care in oncology, and germline and somatic profiling may provide insights and actionable targets for men with metastatic prostate cancer. However, all reported cases are of deidentified individuals without full medical and genomic data available in the public domain.

Patient and methods

We present a case of whole-genome tumor and germline sequencing in a patient with advanced prostate cancer, who has agreed to make his genomic and clinical data publicly available.

Results

We describe an 84-year-old Caucasian male with a Gleason 10 oligometastastic hormone-sensitive prostate cancer. Whole-genome sequencing provided insights into his tumor’s underlying mutational processes and the development of an SPOP mutation. It also revealed an androgen-receptor dependency of his cancer which was reflected in his durable response to radiation and hormonal therapy. Potentially actionable genomic lesions in the tumor were identified through a personalized medicine approach for potential future therapy, but at the moment, he remains in remission, illustrating the hormonal sensitivity of his SPOP-driven prostate cancer. We also placed this patient in the context of a large prostate-cancer cohort from the PCAWG (Pan-cancer Analysis of Whole Genomes) group. In this comparison, the patient’s cancer appears typical in terms of the number and type of somatic mutations, but it has a somewhat larger contribution from the mutational process associated with aging.

Conclusion

We combined the expertise of medical oncology and genomics approaches to develop a molecular tumor board to integrate the care and study of this patient, who continues to have an outstanding response to his combined modality treatment. This identifiable case potentially helps overcome barriers to clinical and genomic data sharing.
AKT1-CREB stimulation of PDGFRα expression is pivotal for PTEN deficient tumor development
Authors: Wan Xiaofeng , Zhou Meng , Huang Fuqiang , Zhao Na , Chen Xu , Wu Yuncui , Zhu Wanhui , Ni Zhaofei , Jin Fuquan , Wang Yani , Hu Zhongdong , Chen Xianguo , Ren Min , Zhang Hongbing , Zha Xiaojun
Published: February 2021

As evidenced by the behavior of loss-of-function mutants of PTEN in the context of a gain-of-function mutation of AKT1, the PTEN-AKT1 signaling pathway plays a critical role in human cancers. In this study, we demonstrated that a deficiency in PTEN or activation of AKT1 potentiated the expression of platelet-derived growth factor receptor α (PDGFRα) based on studies on Pten−/− mouse embryonic fibroblasts, human cancer cell lines, the hepatic tissues of Pten conditional knockout mice, and human cancer tissues. Loss of PTEN enhanced PDGFRα expression via activation of the AKT1-CREB signaling cascade. CREB transactivated PDGFRα expression by direct binding of the promoter of the PDGFRα gene. Depletion of PDGFRα attenuated the tumorigenicity of Pten-null cells in nude mice. Moreover, the PI3K-AKT signaling pathway has been shown to positively correlate with PDGFRα expression in multiple cancers. Augmented PDGFRα was associated with poor survival of cancer patients. Lastly, combination treatment with the AKT inhibitor MK-2206 and the PDGFR inhibitor CP-673451 displayed synergistic anti-tumor effects. Therefore, activation of the AKT1-CREB-PDGFRα signaling pathway contributes to the tumor growth induced by PTEN deficiency and should be targeted for cancer treatment.
Upregulation of LINC01426 promotes the progression and stemness in lung adenocarcinoma by enhancing the level of SHH protein to activate the hedgehog pathway
Authors: Liu Xiaoli , Yin Zuwei , Xu Linping , Liu Huaimin , Jiang Lifeng , Liu Shuochuan , Sun Xu
Published: February 2021

Long noncoding RNAs (lncRNAs) play crucial roles in regulating a variety of biological processes in lung adenocarcinoma (LUAD). In our study, we mainly explored the functional roles of a novel lncRNA long intergenic non-protein coding RNA 1426 (LINC01426) in LUAD. We applied bioinformatics analysis to find the expression of LINC01426 was upregulated in LUAD tissue. Functionally, silencing of LINC01426 obviously suppressed the proliferation, migration, epithelial–mesenchymal transition (EMT), and stemness of LUAD cells. Then, we observed that LINC01426 functioned through the hedgehog pathway in LUAD. The effect of LINC01426 knockdown could be fully reversed by adding hedgehog pathway activator SAG. In addition, we proved that LINC01426 could not affect SHH transcription and its mRNA level. Pull-down sliver staining and RIP assay revealed that LINC01426 could interact with USP22. Ubiquitination assays manifested that LINC01426 and USP22 modulated SHH ubiquitination levels. Rescue assays verified that SHH overexpression rescued the cell growth, migration, and stemness suppressed by LINC01426 silencing. In conclusion, LINC01426 promotes LUAD progression by recruiting USP22 to stabilize SHH protein and thus activate the hedgehog pathway.
Alternative splicing of ceramide synthase 2 alters levels of specific ceramides and modulates cancer cell proliferation and migration in Luminal B breast cancer subtype
Authors: Pani Trishna , Rajput Kajal , Kar Animesh , Sharma Harsh , Basak Rituparna , Medatwal Nihal , Saha Sandhini , Dev Gagan , Kumar Sharwan , Gupta Siddhi , Mukhopadhyay Arnab , Malakar Dipankar , Maiti Tushar Kanti , Arimbasseri Aneeshkumar G. , Deo S. V. S. , Sharma Ravi Datta , Bajaj Avinash , Dasgupta Ujjaini
Published: February 2021

Global dysregulation of RNA splicing and imbalanced sphingolipid metabolism has emerged as promoters of cancer cell transformation. Here, we present specific signature of alternative splicing (AS) events of sphingolipid genes for each breast cancer subtype from the TCGA-BRCA dataset. We show thatceramide synthase 2(CERS2) undergoes a unique cassette exon event specifically in Luminal B subtype tumors. We validated this exon 8 skipping event in Luminal B cancer cells compared to normal epithelial cells, and in patient-derived tumor tissues compared to matched normal tissues. Differential AS-based survival analysis shows that this AS event ofCERS2is a poor prognostic factor for Luminal B patients. As Exon 8 corresponds to catalytic Lag1p domain, overexpression of AS transcript ofCERS2in Luminal B cancer cells leads to a reduction in the level of very-long-chain ceramides compared to overexpression of protein-coding (PC) transcript ofCERS2. We further demonstrate that this AS event-mediated decrease of very-long-chain ceramides leads to enhanced cancer cell proliferation and migration. Therefore, our results show subtype-specific AS of sphingolipid genes as a regulatory mechanism that deregulates sphingolipids like ceramides in breast tumors, and can be explored further as a suitable therapeutic target.
BCAT1 decreases the sensitivity of cancer cells to cisplatin by regulating mTOR-mediated autophagy via branched-chain amino acid metabolism
Authors: Luo Lifang , Sun Wenjing , Zhu Weijian , Li Shuhan , Zhang Wenqi , Xu Xiaohui , Fang Daoquan , Grahn Tan Hooi Min , Jiang Lei , Zheng Yihu
Published: February 2021

Cisplatin is one of the most effective chemotherapy drugs and is widely used in the treatment of cancer, including hepatocellular carcinoma (HCC) and cervical cancer, but its therapeutic benefit is limited by the development of resistance. Our previous studies demonstrated that BCAT1 promoted cell proliferation and decreased cisplatin sensitivity in HCC cells. However, the exact role and mechanism of how BCAT1 is involved in cisplatin cytotoxicity remain undefined. In this study, we revealed that cisplatin triggered autophagy in cancer cells, with an increase in BCAT1 expression. The cisplatin-induced up-regulation of BCAT1 decreased the cisplatin sensitivity by regulating autophagy through the mTOR signaling pathway. In addition, branched-chain amino acids or leucine treatment inhibited cisplatin- or BCAT1-mediated autophagy and increased cisplatin sensitivity by activating mTOR signaling in cancer cells. Moreover, inhibition of autophagy by chloroquine increased cisplatin sensitivity in vivo. Also, the knockdown of BCAT1 or the administration of leucine activated mTOR signaling, inhibited autophagy, and increased cisplatin sensitivity in cancer cells in vivo. These findings demonstrate a new mechanism, revealing that BCAT1 decreases cisplatin sensitivity in cancer cells by inducing mTOR-mediated autophagy via branched-chain amino acid leucine metabolism, providing an attractive pharmacological target to improve the effectiveness of chemotherapy.
IP3R1 regulates Ca2+ transport and pyroptosis through the NLRP3/Caspase-1 pathway in myocardial ischemia/reperfusion injury
Authors: Mo Guixi , Liu Xin , Zhong Yiyue , Mo Jian , Li Zhiyi , Li Daheng , Zhang Liangqing , Liu Yijun
Published: February 2021

Intracellular ion channel inositol 1,4,5-triphosphate receptor (IP3R1) releases Ca2+ from endoplasmic reticulum. The disturbance of IP3R1 is related to several neurodegenerative diseases. This study investigated the mechanism of IP3R1 in myocardial ischemia/reperfusion (MI/R). After MI/R modeling, IP3R1 expression was silenced in myocardium of MI/R rats to explore its role in the concentration of myocardial enzymes, infarct area, Ca2+ level, NLRP3/Caspase-1, and pyroptosis markers and inflammatory factors. The adult rat cardiomyocytes were isolated and cultured to establish hypoxia/reperfusion (H/R) cell model. The expression of IP3R1 was downregulated or ERP44 was overexpressed in H/R-induced cells. Nifedipine D6 was added to H/R-induced cells to block Ca2+ channel or Nigericin was added to activate NLRP3. IP3R1 was highly expressed in myocardium of MI/R rats, and silencing IP3R1 alleviated MI/R injury, reduced Ca2+ overload, inflammation and pyroptosis in MI/R rats, and H/R-induced cells. The binding of ERP44 to IP3R1 inhibited Ca2+ overload, alleviated cardiomyocyte inflammation, and pyroptosis. The increase of intracellular Ca2+ level caused H/R-induced cardiomyocyte pyroptosis through the NLRP3/Caspase-1 pathway. Activation of NLRP3 pathway reversed the protection of IP3R1 inhibition/ERP44 overexpression/Nifedipine D6 on H/R-induced cells. Overall, ERP44 binding to IP3R1 inhibits Ca2+ overload, thus alleviating pyroptosis and MI/R injury.