bluuebunny/crossref_metadata_2025 huggingface dataset:
Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency: Report on 30 Patients
Authors: Hashem Hasan , Bucciol Giorgia , Ozen Seza , Unal Sule , Bozkaya Ikbal Ok , Akarsu Nurten , Taskinen Mervi , Koskenvuo Minna , Saarela Janna , Dimitrova Dimana , Hickstein Dennis D. , Hsu Amy P. , Holland Steven M. , Krance Robert , Sasa Ghadir , Kumar Ashish R. , Müller Ingo , de Sousa Monica Abreu , Delafontaine Selket , Moens Leen , Babor Florian , Barzaghi Federica , Cicalese Maria Pia , Bredius Robbert , van Montfrans Joris , Baretta Valentina , Cesaro Simone , Stepensky Polina , Benedicte Neven , Moshous Despina , Le Guenno Guillaume , Boutboul David , Dalal Jignesh , Brooks Joel P. , Dokmeci Elif , Dara Jasmeen , Lucas Carrie L. , Hambleton Sophie , Wilson Keith , Jolles Stephen , Koc Yener , Güngör Tayfun , Schnider Caroline , Candotti Fabio , Steinmann Sandra , Schulz Ansgar , Chambers Chip , Hershfield Michael , Ombrello Amanda , Kanakry Jennifer A. , Meyts Isabelle
Published: July 2021

Purpose

Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2.

Methods

We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS).

Results

Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2–28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5–16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT.

Conclusion

HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency.

Clinical Implications

HCT is a definitive cure for DADA2 with > 95% survival.
Sublinear search spaces for shortest path planning in grid and road networks
Authors: Blum Johannes , Funke Stefan , Storandt Sabine
Published: July 2021

Shortest path planning is a fundamental building block in many applications. Hence developing efficient methods for computing shortest paths in, e.g., road or grid networks is an important challenge. The most successful techniques for fast query answering rely on preprocessing. However, for many of these techniques it is not fully understood why they perform so remarkably well, and theoretical justification for the empirical results is missing. An attempt to explain the excellent practical performance of preprocessing based techniques on road networks (as transit nodes, hub labels, or contraction hierarchies) in a sound theoretical way are parametrized analyses, e.g., considering the highway dimension or skeleton dimension of a graph. Still, these parameters may be large in case the network contains grid-like substructures—which inarguably is the case for real-world road networks around the globe. In this paper, we use the very intuitive notion of bounded growth graphs to describe road networks and also grid graphs. We show that this model suffices to prove sublinear search spaces for the three above mentioned state-of-the-art shortest path planning techniques. Furthermore, our preprocessing methods are close to the ones used in practice and only require expected polynomial time.
Patients’ and parents’ perspective on the implementation of Patient Reported Outcome Measures in pediatric clinical practice using the KLIK PROM portal
Authors: van Muilekom Maud M. , Teela Lorynn , van Oers Hedy A. , van Goudoever Johannes B. , Grootenhuis Martha A. , Haverman Lotte
Published: July 2021

Introduction

The KLIK Patient Reported Outcome Measures (PROM) portal (www.hetklikt.nu) has been implemented since 2011 in clinical practice in over 20 Dutch hospitals. Patients and/or parents complete PROMs before the outpatient consultation and answers are subsequently discussed by clinicians during consultation. This study aims to provide insight into patients’ and parents’ perspective on the use of the KLIK PROM portal in order to optimize its implementation in pediatric clinical practice.

Methods

Patients (12–19 years) and parents (of children 0–19 years) from the Emma Children’s Hospital were invited to participate. A mixed-method design was used; (1) Focus groups were held and analyzed using thematic analysis in psychology, (2) a questionnaire was sent out and analyzed using descriptive statistics.

Results

(1) Eight patients and 17 parents participated. Patients mentioned that KLIK has an attractive layout. However, PROMs were sometimes considered irrelevant and repetitive. Parents valued that KLIK provides insight into their child’s functioning, but they were not satisfied with the extent to which PROMs were discussed by clinicians. (2) 31 patients and 130 parents completed the questionnaire. Overall, patients and parents reported a satisfaction score of 7.9/10 and 7.3/10, respectively. 81% of patients and 74% of parents indicated that KLIK is easy to use.

Conclusion

Patients and parents are generally satisfied with KLIK, however, points of improvement were mentioned. These are currently being addressed by e.g., upgrading the KLIK website, implementing PROMIS item banks in KLIK to reduce irrelevancy and repetitiveness of PROMs, and implementation strategies to improve the discussion-rate. In this way, implementation of the KLIK PROM portal can be further optimized, with the ultimate goal to improve quality of care.
Assessing measurement invariance in the EORTC QLQ-C30
Authors: van Roij Janneke , Kieffer Jacobien M. , van de Poll-Franse Lonneke , Husson Olga , Raijmakers Natasja J. H. , Gelissen John
Published: July 2021

Purpose

We aimed to investigate measurement invariance (MI) in the European Organisation for research and treatment of cancer quality of life questionnaire core 30 (EORTC QLQ-C30) in a heterogeneous sample of patients with cancer.

Methods

Data from 12 studies within the PROFILES registry were used for secondary analyses (n = 7007). We tested MI by successive restrictions on thresholds, loadings, and intercepts across subgroups based on primary cancer sites, age, sex, time since diagnosis, and life stage, using multigroup confirmatory factor analysis (MGCFA) for ordered categorical measures. We also evaluated the impact of potentially miss-specified parameter equality across groups on latent factor means by releasing threshold and loading equality constraints for each item at a time.

Results

Results showed that the highest level of MI (invariance of thresholds, loadings, and intercepts) was found across groups based on time since diagnosis and life stage and to a lesser extent across groups based on sex, age, and primary tumor site. On item level, however, changes in the item’s associated factor means were relatively small and in most cases canceled each other out to some extent.

Conclusions

Given only a few instances of non-invariance in our study, there is reason to be confident that valid conclusions can be drawn from between-group comparisons of QLQ-C30 latent means as operationalized in our study. Nonetheless, further research into MI between other subgroups for the QLQ-C30 (i.e., treatment effects and ethnicity) is warranted. We stress the importance of including MI evaluations in the development and validation of measurement instruments.
Optimal Stability Thresholds in Rotating Fully Anisotropic Porous Medium with LTNE
Authors: Capone Florinda , Gentile Maurizio , Gianfrani Jacopo A.
Published: July 2021

The onset of thermal convection in an anisotropic horizontal porous layer heated from below and rotating about vertical axis, under local thermal non-equilibrium hypothesis is studied. Linear and nonlinear stability analysis of the conduction solution is performed. Coincidence between the linear instability and the global nonlinear stability thresholds with respect to the L2—norm is proved.

Article Highlights

A necessary and sufficient condition for the onset of convection in a rotating
anisotropic porous layer has been obtained.

It has been proved that convection can occur only through a steady motion.
A detailed proof is reported thoroughly.

Numerical analysis shows that permeability promotes convection, while
thermal conductivities and rotation stabilize conduction.
Down to Earth: History and philosophy of geoscience in practice for undergraduate education
Authors: Kleinhans Maarten G.
Published: July 2021

Undergraduate geoscience students are rarely exposed to history and philosophy of science (HPS). I will describe the experiences with a short course unfavourably placed in the first year of a bachelor of earth science. Arguments how HPS could enrich their education in many ways are sketched. One useful didactic approach is to develop a broader interest by connecting HPS themes to practical cases throughout the curriculum, and develop learning activities that allow students to reflect on their skills, methods and their field in relation to other disciplines and interactions with society with abilities gained through exposure to HPS. Given support of the teaching staff, the tenets of philosophy of science in practice, of conceptual history of knowledge, and of ethics of science for society can fruitfully and directly be connected to the existing curriculum. This is ideally followed by a capstone HPS course late in the bachelor programme.
Drag reduction methods at solid-liquid interfaces
Authors: Liu Min , Ma Liran
Published: July 2021

Friction drag is a nonnegligible matter when relative motion happens between solid and liquid phase, which brings many inconveniences in ship navigation, fluid transportation, microfluid devices, etc. Thereby various methods have been developed focusing on friction drag reduction. In this article, a review of several widely studied drag reduction methods is given, specially, their advantages and limitations in practical applications are discussed. Besides, a comparison of different methods is made and the development prospect of drag reduction is concluded.
Bullying experiences, body esteem, body dissatisfaction, and the moderating role of weight status among adolescents
Authors: Fowler Lauren A. , Kracht Chelsea L. , Denstel Kara D. , Stewart Tiffany M. , Staiano Amanda E.
Published: July 2021

Introduction

The present study examined the relationships between bullying victimization experiences, body esteem (BE), and body dissatisfaction (BD) by obesity status.

Methods

Using a cross‐sectional design, adolescents (10‐16y) from the U.S. completed surveys. Weight and height were objectively assessed. Bullying was assessed using the Personal Experiences Checklist, with a total score that included three subscales (cyber, verbal‐relational, and physical). BE was assessed using total score on the BE Scale, and BD was assessed using the Body Image Assessment for Pre‐Adolescents, operationalized as the discrepancy between current and ideal body figure. Linear regression models, controlling for sociodemographics, were used to examine obesity status (with vs. without obesity) and sex as moderators of the relationships between bullying, BE, and BD.

Results

On average, adolescents (n = 328) were 12.6 ± 1.9 y, 45.4% male, 58.2% White, 35.7% Black, and 36.0% had obesity. Obesity status moderated the relationship between bullying experiences and BE, such that these relationships were only significant (B = −0.38, p<.05) among adolescents with obesity compared to adolescents without obesity. In both groups, greater verbal‐relational bullying experiences were associated with lower BE, while greater physical bullying experiences were related to higher BE only among adolescents with obesity. In adolescent girls without obesity, greater cyberbullying experiences were associated with lower BD.

Conclusions

The findings suggest different associations between sub‐types of bullying victimization experiences and BE and BD, highlighting the importance of examining these associations separately by obesity status.
Relevance of tissue eosinophilia in subdural hematomata
Authors: Davidson Benjamin , Cusimano Michael , Munoz David G.
Published: July 2021

Chronic subdural hematomata (CSDH) are treated by evacuation. Recurrence occurs in 3-20% of cases, but the factors determining its occurrence have not been determined. Having observed that eosinophil cell infiltrates are often present in the outer membrane of CSDH, our aim was to determine whether such infiltrates are associated with risk of recurrence. Histological sections of the resections from 72 patients with primary CSDH (Mean age 73.4) and 16 with recurrent CSDH (Mean age 72.1) stained with H&E were graded by blinded observers for eosinophilic cell infiltrates using a semiquantitative 0 to 3 scale. The risk of recurrence requiring reoperation (RrR) in primary CSDH was 11.1%, and 12.5% in recurrent CSDH (meaning third surgery was required). A dense (grades 2 or 3) eosinophilic infiltrate was present in 22.2% of primary CSDH; the RrR was 0% in these cases, as compared with 14.8% in cases with sparse (grades 0-1) eosinophilic infiltrate. Among recurrent CSDH cases, 12.5% (2/15) showed a dense eosinophilic infiltrate; the RrR was also 0%, contrasting with 14.3% in those with sparse eosinophilic infiltrate. We conclude that eosinophils either play a role or are a marker of a process leading to stabilizing CSDH, making them less prone to rebleeding. Abstract not previously published

Learning Objectives

Describe the risk of recurrence following surgical evacuation of chronic subdural hematomata

Recognize the variable presence of eosinophils in chronic subdural hematomata

Cite the presence of eosinophils is predictive of absence of recurrence
Presenter: Werner Paulus, University Hospital Muenster, Muenster. Publishing A High-quality, Non-commercial Neuropathology Journal Without a Publisher: The First Nine Months
Authors: Margeta Marta , Gould Peter , Hazrati Lili-Naz , Hirsch-Reinshagen Veronica , Paulus Werner
Published: July 2021

Scholarly communication faces increasing economical and ethical challenges, including pricing policies and overbearing behavior of commercial publishing houses. Based on the hypothesis that a diamond open access neuropathology journal of a high scientific and technical quality can be run entirely by neuropathologists, we launched Free Neuropathology (FNP; freeneuropathology.org) in January 2020. Classical publisher activities, such as copyediting, layout, website maintenance, and journal promotion, are undertaken by neuropathologists and neuroscientists using free open access software. The journal is free for both readers and authors, and papers are published under a Creative Commons BY SA licence, where copyright remains with the authors. Based on 26 articles published by August 2020, it takes FNP 11.1 days from submission to first, and 19.9 days to final, decision. High-quality copyediting, layout, and online publishing in the final format is accomplished in only 8 days. Absence of a commercial publisher enables prioritization of democratic and scientifically-driven decisions on editorial structure, website design, journal promotion, paper formatting, special article series, and number of accepted papers. This new model of journal publishing, which returns the control of scholarly communication to scientists, will be of interest to neuropathologists and wider scientific community alike.

Learning Objectives

Summarize the current state and driving forces behind commercial and non-commercial scientific publishing in neuropathology.

Describe the advantages and challenges of a non-commercial publishing platform for neuropathology.
Comparing Stop Signal Reaction Times in Alzheimer’s and Parkinson’s Disease
Authors: Rahman Simin , Siddique Ummatul , Choudhury Supriyo , Islam Nazrul , Roy Akash , Basu Purba , Anand Sidharth Shankar , Islam Mohammad Ariful , Shahi Mohammad Selim , Nayeem Abu , Chowdhury Md Tauhidul Islam , Chowdhury Mohammad Shah Jahirul Hoque , Taylor John-Paul , Baker Mark R. , Baker Stuart N. , Kumar Hrishikesh
Published: July 2021

Background:

To investigate the relative contributions of cerebral cortex and basal ganglia to movement stopping, we tested the optimum combination Stop Signal Reaction Time (ocSSRT) and median visual reaction time (RT) in patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD) and compared values with data from healthy controls.

Methods:

Thirty-five PD patients, 22 AD patients, and 29 healthy controls were recruited to this study. RT and ocSSRT were measured using a hand-held battery-operated electronic box through a stop signal paradigm.

Result:

The mean ocSSRT was found to be 309 ms, 368 ms, and 265 ms in AD, PD, and healthy controls, respectively, and significantly prolonged in PD compared to healthy controls (p = 0.001). The ocSSRT but not RT could separate AD from PD patients (p = 0.022).

Conclusion:

Our data suggest that subcortical networks encompassing dopaminergic pathways in the basal ganglia play a more important role than cortical networks in movement-stopping. Combining ocSSRT with other putative indices or biomarkers of AD (and other dementias) could increase the accuracy of early diagnosis.
A macro-level investigation of transatlantic controlling shareholder's fiduciary duty
Authors: Anidjar Leon
Published: July 2021

Legal systems around the world apply various strategies to mitigate agency costs between controlling and minority shareholders. A systematic review of the transnational law on the loyalty and care obligations of controlling shareholders reveals various doctrinal choices. This study aims to uncover the evolution of these choices by employing a law-in-context methodology. Accordingly, it seeks to explain the differences in governance selections by exploring the cultural, historical and socio-economic backgrounds of the particular legal systems in which organisations and decisions are embodied. I conduct a macro-level inquiry which focuses on the cultural environment and business history development to understand different doctrinal designs. In particular, I argue that those dissimilarities are a result of unique cultural-non-formal norms of corporate governance regarding the protection afforded to shareholders’ interests and they correspond to the historical development of the law of corporate groups across nations. As the macro-level investigation indicates, any initiative to globally converge corporate law and governance should be carried out with caution because it may distort the delicate normative equilibrium represented in a given jurisdiction.
Phyllozoon and Aulozoon: key components of a novel Ediacaran death assemblage in Bathtub Gorge, Heysen Range, South Australia
Authors: Gehling James G. , Runnegar Bruce
Published: July 2021

The recognition of fossiliferous horizons both below and above the classical Ediacara levels of the Flinders Ranges, South Australia, significantly expands the potential of this candidate World Heritage succession. Here we document a small window into the biology and taphonomy of the late Ediacaran seafloor within the new Nilpena Sandstone Member of the Rawnsley Quartzite in Bathtub Gorge, northern Heysen Range. A 1 m2 slab extracted from the gorge, now on permanent display at the South Australian Museum, has a death assemblage dominated by the erniettomorph Phyllozoon hanseni Jenkins and Gehling 1978 and a newly named macroscopic tubular body fossil – Aulozoon soliorum gen. et sp. nov. – on its fine sandstone bed sole. The orientations and juxtaposition of these taxa suggest overprinting of an in situ benthic Phyllozoon community by sand-filled tubes of Aulozoon carried in by a storm wave-base surge. Phyllozoon hanseni is a widespread species that is restricted to the Nilpena Sandstone Member of the Rawnsley Quartzite, whereas Dickinsonia costata ranges from the underlying Ediacara Sandstone Member into the Nilpena Sandstone Member. Fundamental differences in the ways these two vendobiont taxa are constructed and preserved may provide insights into their biology and phylogenetic affinities. In the Nilpena Sandstone Member, D. costata is joined by Dickinsonia rex Jenkins 1992, which appears to be confined to the member, and is here re-described to clarify its taxonomic status and stratigraphic distribution.
Active ageing in Europe: are changes in social capital associated with engagement, initiation and maintenance of activity in later life?
Authors: Boerio Pryanka , Garavaglia Emma , Gaia Alessandra
Published: July 2021

The demographic landscape of European countries is rapidly changing because of population ageing; in this context, societies are called to offer older people opportunities to age actively. Although ‘active ageing’ has been broadly explored, there is still room to further our knowledge on the individual conditions that may favour or hinder activity in later life. This study aims to contribute to the literature in this field by focusing on the role of social capital. Specifically, it explores, through logistic regression models, how social capital and changes in social capital are associated with engagement in, the initiation of and continued participation in various domains of activity: volunteering and charity work, active participation in political or community-related organisations, informal care-giving and paid work. The data analysed stem from the Survey of Health, Ageing and Retirement in Europe (SHARE). We focused on people aged 55+ participating in Waves 4–6. The key findings are: (a) having a larger social network is positively associated with participation in and the initiation of activities; (b) receiving social support (rarely) may stimulate reciprocity and thus care-giving; and (c) an increase in social network size is positively associated with initiation and maintenance of activities during later life.
A lithostratigraphical and chronological study of Oligocene-Miocene sequences on eastern King George Island, South Shetland Islands (Antarctica), and correlation of glacial episodes with global isotope events
Authors: Smellie John L. , McIntosh William C. , Whittle Rowan , Troedson Alexa , Hunt Richard J.
Published: July 2021

King George Island (South Shetland Islands, Antarctic Peninsula) is renowned for its terrestrial palaeoenvironmental record, which includes evidence for potentially up to four Cenozoic glacial periods. An advantage of the glacigenic outcrops on the island is that they are associated with volcanic formations that can be isotopically dated. As a result of a new mapping and chronological study, it can now be shown that the published stratigraphy and ages of many geological units on eastern King George Island require major revision. The Polonez Glaciation is dated asc.26.64 ± 1.43 Ma (Late Oligocene (Chattian Stage)) and includes the outcrops previously considered as evidence for an Eocene glacial ('Krakow Glaciation'). It was succeeded by two important volcanic episodes (Boy Point and Cinder Spur formations) formed during a relatively brief interval (< 2 Ma), which also erupted within the Oligocene Chattian Stage. The Melville Glaciation is dated asc.21–22 Ma (probably 21.8 Ma; Early Miocene (Aquitanian Stage)), and the Legru Glaciation is probably ≤c.10 Ma (Late Miocene or younger). As a result of this study, the Polonez and Melville glaciations can now be correlated with increased confidence with the Oi2b and Mi1a isotope zones, respectively, and thus represent major glacial episodes.
Labour Rights Protection and Its Enforcement under the USMCA: Insights from a Comparative Legal Analysis
Authors: Corvaglia Maria Anna
Published: July 2021

Chapter 23, exclusively dedicated to labor protection, has been widely described as one of the most distinctive features of the new US–Mexico–Canada Agreement (USMCA). This paper challenges the current narrative surrounding the USMCA by critically analysing Chapter 23 of the agreement, looking at the legal innovative design of its substantive commitments of labour protection and their enforceability. In light of this objective, a comparative analysis will be conducted. The provisions of Chapter 23 USMCA will be compared with labour provisions in previous US Preferential Trade Agreements (PTAs), namely, the NAFTA side agreement on labour rights and the TPP. Second, a comparative analysis will be conducted comparing USMCA Chapter 23 with labour provisions in EU Trade Agreements negotiated with USMCA parties. The paper demonstrates that although the USMCA does not radically innovate from the level of substantive labour protection reached in recent US and EU PTAs, the enforcement mechanism in the USMCA is significantly strengthened, with controversial and innovative features.
Structural Validity and Reliability of the Indonesian Version of PID-5
Authors: Adhiatma Widhi , Halim Magdalena S.
Published: July 2021

Abstract. Many studies have evaluated the Personality Inventory for DSM-5 (PID-5) validity and reliability. Unfortunately, research on PID-5 in Southeast Asian countries is still limited. This study aimed to identify the structural validity and reliability of the Indonesian version of PID-5. We involved 963 participants, and 68 of these participants filled the PID-5 twice. Facets and domains showed a satisfactory test–retest reliability (median r for facets = .84; median r for domains = .88), and acceptable McDonald’s omega indices (median ω for facets = .85; median ω for domains = .79). The hierarchical factor structure suggested that five-factor solution was interpretable, and this model showed a high congruency to its original version (ϕ = .97). Unfortunately, we could not achieve a model fit of this five-factor model. We hypothesized that the cultural influence and sample characteristics might explain this poor model fit. Finally, cautious administration and interpretation of PID-5 in Indonesia are highly recommended.
Remote and Local Processes Controlling Decadal Sea Ice Variability in the Weddell Sea
Authors: Morioka Yushi , Behera Swadhin K.
Published: July 2021

Sea ice in the Weddell Sea plays important roles in the albedo, air‐sea heat, freshwater, and gas exchanges and the formation of the Antarctic Bottom Water on the continental shelf that regulates global climate through deep thermohaline circulation. Sea ice extent (SIE) in the Weddell Sea does not show any significant trend in the four‐decade satellite observation period but does experience large interannual‐to‐decadal variability. Physical processes underlying this variability are difficult to examine because of a paucity of prolonged observations. Using a coupled general circulation model, we corroborate the observational finding that decadal increases in SIE are preceded by weakening of the mean westerly winds linked to the Southern Annular Mode. Weakening of the westerly winds over the Weddell Sea reduces the northward Ekman current and suppresses upwelling of warm water from the subsurface ocean; this lowers the upper‐ocean temperature, causing an increase in sea ice. In a sensitivity experiment where the interannual sea surface temperature variations are suppressed outside the South Atlantic and the Weddell Sea, decadal increase in the SIE over the Weddell Sea is induced by a decrease in the upper‐ocean temperature owing to enhanced horizontal advection by the Weddell Gyre. The strengthening of the Weddell Gyre increases the upper‐ocean salinity as a result of enhanced evaporation and brine rejection associated with the sea ice increase. These results demonstrate that both the remote atmospheric forcing and local ice‐ocean interaction are crucial for generation of decadal sea ice variability in the Weddell Sea.
SnowSchool Spans the States
Authors: Tripathy-Lang Alka
Published: July 2021

The nonprofit, donation-fueled program engages K–12 students by combining the fun of playing in snow with the science of the cryosphere.
Linking AMOC Variations With the Multidecadal Seesaw in Tropical Cyclone Activity Between Eastern North Pacific and Atlantic
Authors: Gong Zhanqiu , Liu Yusen , Sun Cheng , Zhang Jing , Li Jianping , Shi Chunming
Published: July 2021

Tropical cyclone (TC) over the North Atlantic is an important extreme weather event, causing great social and economic damages to the American coastal regions. In this study, we find that the North Atlantic TC activity (genesis frequency and accumulated cyclone energy) has significant multidecadal variability, which exhibits an out‐of‐phase relationship with that over the eastern North Pacific, referring to as the inter‐basin seesaw in TC activity. By using five indicators of the Atlantic Meridional Overturning Circulation (AMOC) strength, we link this TC activity seesaw pattern to the AMOC and the associated North Atlantic sea surface temperature anomalies. Both observation and Atlantic pacemaker experiment indicate that the AMOC induces the North Atlantic sea surface temperature warming and eastern North Pacific cooling, which lead to contrasting backgrounds (vertical wind shear, maximum potential intensity, and humidity) for the TC formation and development, resulting in the seesaw pattern in TC activity. Our results provide additional evidence for the reversed relationship in TC activity between the two ocean basins and attribute this seesaw to the variations in the AMOC. More importantly, the atmospheric‐NAO‐based AMOC indicator shows a leading role in depicting the multidecadal seesaw, which has great potential in improving the decadal prediction of North Atlantic/eastern North Pacific TCs.
Lightning Activity Over Chilean Territory
Authors: Montana J. , Morales C. , Nicora M. G. , Ardila J. , Schurch R. , Aranguren D.
Published: July 2021

This work presents the spatial distribution and temporal variability of lightning activity over the continental territory of Chile by means of Thunderstorms days (Td), on the basis of 7 years (2012–2018) of lightning measurement from World Wide Lightning Location Network (WWLLN). Td are obtained separately for the 15 geopolitical regions of Chile, reporting the higher lightning activity in the northeastern region of the country with 85 thunderstorms days per year. These values are mainly located in the mountains between 2,000 and 5,000 m.a.s.l. where extensive mining activity is located and there are electrical facilities of great importance for Chile. The Td values obtained in this study update the information presented by the World Meteorological Organization (WMO) in 1953, so far the only one available for the entire Chilean territory. From the diurnal cycle analysis, there is a marked mono‐modal behavior of lightning activity in the afternoon for latitudes between S and S (regions XV, I, and II) and a different behavior of lightning activity over the region between S and S (regions X, XI, and XII) known as Chilean Patagonia, due to special weather conditions in that area. Further more, the seasonal analysis showed that the highest lightning activity occurs in January and February and the lowest activity takes place between June and August. Once again, the Chilean Patagonia showed a different behavior because the highest activity is presented in May and August, and the lowest in September. The analysis and results presented here contribute to the knowledge of lightning activity in the region that has not been characterized before and can serve as a basis for future research to determine the behavior of this natural phenomenon.
Riehl and Malkus Revisited: The Role of Cloud Radiative Effects
Authors: Needham Michael R. , Randall David A.
Published: July 2021

The intertropical convergence zone (ITCZ) exports energy and imports moisture. This has been understood for decades. By analyzing a set of uniform, nonrotating aquaplanet simulations, we show that energy export and moisture convergence are general characteristics of warm humid regions, and not just of the ITCZ. Using an analysis method based on the column relative humidity, we find that the absorption of longwave radiation by clouds supplies the energy that is exported from humid regions. The longwave absorption also induces a thermally direct circulation that lifts water vapor and converges moisture into regions that are already quite humid. An additional set of simulations shows that strong atmospheric energy convergence is absent when radiation is homogenized across the domain.
High expression of Sterol-O-Acyl transferase 1 (SOAT1), an enzyme involved in cholesterol metabolism, is associated with earlier biochemical recurrence in high risk prostate cancer
Authors: Eckhardt Carolin , Sbiera Iuliu , Krebs Markus , Sbiera Silviu , Spahn Martin , Kneitz Burkhard , Joniau Steven , Fassnacht Martin , Kübler Hubert , Weigand Isabel , Kroiss Matthias
Published: July 2021

Background

Prostate cancer (PCa) is the most frequent cancer in men. The prognosis of PCa is heterogeneous with many clinically indolent tumors and rare highly aggressive cases. Reliable tissue markers of prognosis are lacking. Active cholesteryl ester synthesis has been associated with prostate cancer aggressiveness. Sterol-O-Acyl transferases (SOAT) 1 and 2 catalyze cholesterol esterification in humans.

Objective

To investigate the value of SOAT1 and SOAT2 tissue expression as prognostic markers in high risk PCa.

Patients and methods

Formalin-fixed paraffin-embedded tissue samples from 305 high risk PCa cases treated with radical prostatectomy were analyzed for SOAT1 and SOAT2 protein expression by semi-quantitative immunohistochemistry. The Kaplan–Meier method and Cox proportional hazards modeling were used to compare outcome.

Main outcome measure

Biochemical recurrence (BCR) free survival.

Results

SOAT1 expression was high in 73 (25%) and low in 219 (75%; not evaluable: 13) tumors. SOAT2 was highly expressed in 40 (14%) and at low levels in 249 (86%) samples (not evaluable: 16). By Kaplan–Meier analysis, we found significantly shorter median BCR free survival of 93 months (95% confidence interval 23.6–123.1) in patients with high SOAT1 vs. 134 months (112.6–220.2, Log-rank p < 0.001) with low SOAT1. SOAT2 expression was not significantly associated with BCR. After adjustment for age, preoperative PSA, tumor stage, Gleason score, resection status, lymph node involvement and year of surgery, high SOAT1 but not SOAT2 expression was associated with shorter BCR free survival with a hazard ratio of 2.40 (95% CI 1.57–3.68, p < 0.001). Time to clinical recurrence and overall survival were not significantly associated with SOAT1 and SOAT2 expression

Conclusions

SOAT1 expression is strongly associated with BCR free survival alone and after multivariable adjustment in high risk PCa. SOAT1 may serve as a histologic marker of prognosis and holds promise as a future treatment target.
RETRACTED ARTICLE: PIK3R3, part of the regulatory domain of PI3K, is upregulated in sarcoma stem-like cells and promotes invasion, migration, and chemotherapy resistance
Authors: Yoon Changhwan , Lu Jun , Ryeom Sandra W. , Simon M. Celeste , Yoon Sam S.
Published: July 2021

To identify drivers of sarcoma cancer stem-like cells (CSCs), we compared gene expression using RNA sequencing between HT1080 fibrosarcoma and SK-LMS-1 leiomyosarcoma spheroids (which are enriched for CSCs) compared with the parent populations. The most overexpressed survival signaling-related gene in spheroids was phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), a regulatory subunit of PI3K, which functions in tumorigenesis and metastasis. In a human sarcoma microarray, PIK3R3 was also overexpressed by 4.1-fold compared with normal tissues. PIK3R3 inhibition using shRNA in the HT1080, SK-LMS-1, and DDLS8817 dedifferentiated liposarcoma in spheroids and in CD133+ cells (a CSC marker) reduced expression of CD133 and the stem cell factor Nanog and blocked spheroid formation by 61–71%. Mechanistic studies showed that in spheroid cells, PIK3R3 activated AKT and ERK signaling. Inhibition of PIK3R3, AKT, or ERK using shRNA or inhibitors decreased expression of Nanog, spheroid formation by 68–73%, and anchorage-independent growth by 76–91%. PIK3R3 or ERK1/2 inhibition similarly blocked sarcoma spheroid cell migration, invasion, secretion of MMP-2, xenograft invasion into adjacent normal tissue, and chemotherapy resistance. Together, these results show that signaling through the PIK3R3/ERK/Nanog axis promotes sarcoma CSC phenotypes such as migration, invasion, and chemotherapy resistance, and identify PIK3R3 as a potential therapeutic target in sarcoma.
Impact of indoor temperature instability on diurnal and day-by-day variability of home blood pressure in winter: a nationwide Smart Wellness Housing survey in Japan
Authors: Umishio Wataru , Ikaga Toshiharu , Kario Kazuomi , Fujino Yoshihisa , Suzuki Masaru , Ando Shintaro , Hoshi Tanji , Yoshimura Takesumi , Yoshino Hiroshi , Murakami Shuzo ,   on behalf of the SWH survey group
Published: July 2021

Home blood pressure (HBP) variability is an important factor for cardiovascular events. While several studies have examined the effects of individual attributes and lifestyle factors on reducing HBP variability, the effects of living environment remain unknown. We hypothesized that a stable home thermal environment contributes to reducing HBP variability. We conducted an epidemiological survey on HBP and indoor temperature in 3785 participants (2162 households) planning to have their houses retrofitted with insulation. HBP was measured twice in the morning and evening for 2 weeks in winter. Indoor temperature was recorded with each HBP observation. We calculated the morning-evening (ME) difference as an index of diurnal variability and the standard deviation (SD), coefficient of variation (CV), average real variability (ARV) and variability independent of the mean (VIM) as indices of day-by-day variability. The association between BP variability and temperature instability was analyzed using multiple linear regression models. The mean ME difference in indoor/outdoor temperature (a decrease in temperature overnight) was 3.2/1.5 °C, and the mean SD of indoor/outdoor temperature was 1.6/2.5 °C. Linear regression analyses showed that the ME difference in indoor temperature was closely correlated with the ME difference in systolic BP (0.85 mmHg/°C, p < 0.001). The SD of indoor temperature was also associated with the SD of systolic BP (0.61 mmHg/°C, p < 0.001). The CV, ARV, and VIM showed similar trends as the SD of BP. In contrast, outdoor temperature instability was not associated with either diurnal or day-by-day HBP variability. Therefore, residents should keep the indoor temperature stable to reduce BP variability.
Antibody toolkit reveals N-terminally ubiquitinated substrates of UBE2W
Authors: Davies Christopher W. , Vidal Simon E. , Phu Lilian , Sudhamsu Jawahar , Hinkle Trent B. , Chan Rosenberg Scott , Schumacher Frances-Rose , Zeng Yi Jimmy , Schwerdtfeger Carsten , Peterson Andrew S. , Lill Jennie R. , Rose Christopher M. , Shaw Andrey S. , Wertz Ingrid E. , Kirkpatrick Donald S. , Koerber James T.
Published: July 2021

The ubiquitin conjugating enzyme UBE2W catalyzes non-canonical ubiquitination on the N-termini of proteins, although its substrate repertoire remains unclear. To identify endogenous N-terminally-ubiquitinated substrates, we discover four monoclonal antibodies that selectively recognize tryptic peptides with an N-terminal diglycine remnant, corresponding to sites of N-terminal ubiquitination. Importantly, these antibodies do not recognize isopeptide-linked diglycine (ubiquitin) modifications on lysine. We solve the structure of one such antibody bound to a Gly-Gly-Met peptide to reveal the molecular basis for its selective recognition. We use these antibodies in conjunction with mass spectrometry proteomics to map N-terminal ubiquitination sites on endogenous substrates of UBE2W. These substrates include UCHL1 and UCHL5, where N-terminal ubiquitination distinctly alters deubiquitinase (DUB) activity. This work describes an antibody toolkit for enrichment and global profiling of endogenous N-terminal ubiquitination sites, while revealing functionally relevant substrates of UBE2W.
Atomic-scale unveiling of multiphase evolution during hydrated Zn-ion insertion in vanadium oxide
Authors: Byeon Pilgyu , Hong Youngjae , Bae Hyung Bin , Shin Jaeho , Choi Jang Wook , Chung Sung-Yoon
Published: July 2021

An initial crystalline phase can transform into another phases as cations are electrochemically inserted into its lattice. Precise identification of phase evolution at an atomic level during transformation is thus the very first step to comprehensively understand the cation insertion behavior and subsequently achieve much higher storage capacity in rechargeable cells, although it is sometimes challenging. By intensively using atomic-column-resolved scanning transmission electron microscopy, we directly visualize the simultaneous intercalation of both H2O and Zn during discharge of Zn ions into a V2O5 cathode with an aqueous electrolyte. In particular, when further Zn insertion proceeds, multiple intermediate phases, which are not identified by a macroscopic powder diffraction method, are clearly imaged at an atomic scale, showing structurally topotactic correlation between the phases. The findings in this work suggest that smooth multiphase evolution with a low transition barrier is significantly related to the high capacity of oxide cathodes for aqueous rechargeable cells, where the crystal structure of cathode materials after discharge differs from the initial crystalline state in general.
The genomic landscape of 85 advanced neuroendocrine neoplasms reveals subtype-heterogeneity and potential therapeutic targets
Authors: van Riet Job , van de Werken Harmen J. G. , Cuppen Edwin , Eskens Ferry A. L. M. , Tesselaar Margot , van Veenendaal Linde M. , Klümpen Heinz-Josef , Dercksen Marcus W. , Valk Gerlof D. , Lolkema Martijn P. , Sleijfer Stefan , Mostert Bianca
Published: July 2021

Metastatic and locally-advanced neuroendocrine neoplasms (aNEN) form clinically and genetically heterogeneous malignancies, characterized by distinct prognoses based upon primary tumor localization, functionality, grade, proliferation index and diverse outcomes to treatment. Here, we report the mutational landscape of 85 whole-genome sequenced aNEN. This landscape reveals distinct genomic subpopulations of aNEN based on primary localization and differentiation grade; we observe relatively high tumor mutational burdens (TMB) in neuroendocrine carcinoma (average 5.45 somatic mutations per megabase) withTP53,KRAS,RB1,CSMD3,APC,CSMD1,LRATD2,TRRAP and MYCas major drivers versus an overall low TMB in neuroendocrine tumors (1.09). Furthermore, we observe distinct drivers which are enriched in somatic aberrations in pancreatic (MEN1,ATRX,DAXX,DMDandCREBBP) and midgut-derived neuroendocrine tumors (CDKN1B). Finally, 49% of aNEN patients reveal potential therapeutic targets based upon actionable (and responsive) somatic aberrations within their genome; potentially directing improvements in aNEN treatment strategies.
Evading strength-corrosion tradeoff in Mg alloys via dense ultrafine twins
Authors: Yan Changjian , Xin Yunchang , Chen Xiao-Bo , Xu Daokui , Chu Paul K. , Liu Chaoqiang , Guan Bo , Huang Xiaoxu , Liu Qing
Published: July 2021

Conventional ultrafine-grains can generate high strength in Mg alloys, but significant tradeoff of corrosion resistance due to inclusion of a large number of non-equilibrium grain boundaries. Herein, an ultrafine-grain structure consisting of dense ultrafine twins is prepared, yielding a high strength up to 469 MPa and decreasing the corrosion rate by one order of magnitude. Generally, the formation of dense ultrafine twins in Mg alloys is rather difficult, but a carefully designed multi-directional compression treatment effectively stimulates twinning nucleation within twins and refines grain size down to 300 nm after 12-passes compressions. Grain-refinement by low-energy twins not only circumvents the detrimental effects of non-equilibrium grain boundaries on corrosion resistance, but also alters both the morphology and distribution of precipitates. Consequently, micro-galvanic corrosion tendency decreases, and severe localized corrosion is suppressed completely. This technique has a high commercial viability as it can be readily implemented in industrial production.
Adaptive ecological niche migration does not negate extinction susceptibility
Authors: Woodhouse A. , Jackson S. L. , Jamieson R. A. , Newton R. J. , Sexton P. F. , Aze T.
Published: July 2021

Extinction rates in the modern world are currently at their highest in 66 million years and are likely to increase with projections of future climate change. Our knowledge of modern-day extinction risk is largely limited to decadal-centennial terrestrial records, while data from the marine realm is typically applied to high-order (> 1 million year) timescales. At present, it is unclear whether fossil organisms with common ancestry and ecological niche exhibit consistent indicators of ecological stress prior to extinction. The marine microfossil record, specifically that of the planktonic foraminifera, allows for high-resolution analyses of large numbers of fossil individuals with incredibly well-established ecological and phylogenetic history. Here, analysis of the isochronous extinction of two members of the planktonic foraminiferal genusDentoglobigerinashows disruptive selection differentially compounded by permanent ecological niche migration, “pre-extinction gigantism”, and photosymbiont bleaching prior to extinction. Despite shared ecological and phylogenetic affinity, and timing of extinction, the marked discrepancies observed within the pre-extinction phenotypic responses are species-specific. These behaviours may provide insights into the nature of evolution and extinction in the open ocean and can potentially assist in the recognition and understanding of marine extinction risk in response to global climate change.
Mathematical model of the feedback between global supply chain disruption and COVID-19 dynamics
Authors: Li Xingyu , Ghadami Amin , Drake John M. , Rohani Pejman , Epureanu Bogdan I.
Published: July 2021

The pandemic of COVID-19 has become one of the greatest threats to human health, causing severe disruptions in the global supply chain, and compromising health care delivery worldwide. Although government authorities sought to contain the spread of SARS-CoV-2, by restricting travel and in-person activities, failure to deploy time-sensitive strategies in ramping-up of critical resource production exacerbated the outbreak. Here, we developed a mathematical model to analyze the effects of the interaction between supply chain disruption and infectious disease dynamics using coupled production and disease networks built on global data. Analysis of the supply chain model suggests that time-sensitive containment strategies could be created to balance objectives in pandemic control and economic losses, leading to a spatiotemporal separation of infection peaks that alleviates the societal impact of the disease. A lean resource allocation strategy can reduce the impact of supply chain shortages from 11.91 to 1.11% in North America. Our model highlights the importance of cross-sectoral coordination and region-wise collaboration to optimally contain a pandemic and provides a framework that could advance the containment and model-based decision making for future pandemics.