bluuebunny/crossref_metadata_2025 huggingface dataset:
Lost in Time: Temporal Monitoring Elicits Clinical Decrements in Sustained Attention Post-Stroke
Authors: Brosnan M.B. , Dockree P.M. , Harty S. , Pearce D.J. , Levenstein J.M. , Gillebert C.R. , Bellgrove M.A. , O’Connell R.G. , Robertson I.H. , Demeyere N.
Published: March 2021

Objectives:

Mental fatigue, ‘brain fog’, and difficulties maintaining engagement are commonly reported issues in a range of neurological and psychiatric conditions. Traditional sustained attention tasks commonly measure this capacity as the ability to detect target stimuli based on sensory features in the auditory or visual domains. However, with this approach, discrete target stimuli may exogenously capture attention to aid detection, thereby masking deficits in the ability to endogenously sustain attention over time.

Methods:

To address this, we developed the Continuous Temporal Expectancy Task (CTET) where individuals continuously monitor a stream of patterned stimuli alternating at a fixed temporal interval (690 ms) and detect an infrequently occurring target stimulus defined by a prolonged temporal duration (1020 ms or longer). As such, sensory properties of target and non-target stimuli are perceptually identical and differ only in temporal duration. Using the CTET, we assessed stroke survivors with unilateral right hemisphere damage (N = 14), a cohort in which sustained attention deficits have been extensively reported.

Results:

Stroke survivors had overall lower target detection accuracy compared with neurologically healthy age-matched older controls (N = 18). Critically, stroke survivors performance was characterised by significantly steeper within-block performance decrements, which occurred within short temporal windows (˜3 ½ min), and were restored by the break periods between blocks.

Conclusions:

These findings suggest that continuous temporal monitoring taxes sustained attention processes to capture clinical deficits in this capacity over time, and outline a precise measure of the endogenous processes hypothesised to underpin sustained attention deficits following right hemisphere stroke.
Organic food consumption is associated with a healthy lifestyle, socio-demographics and dietary habits: a cross-sectional study based on the Danish Diet, Cancer and Health cohort
Authors: Andersen Julie Louise Munk , Frederiksen Kirsten , Raaschou-Nielsen Ole , Hansen Johnni , Kyrø Cecilie , Tjønneland Anne , Olsen Anja
Published: March 2021

Objective:

To study the association between organic food consumption and lifestyle, socio-demographics and dietary habits.

Design:

Cohort participants completed detailed questionnaires about organic food consumption, diet and lifestyle between 1999 and 2002. Polytomous logistic regression models were used to estimate the association between organic food consumption, and lifestyle, socio-demographics, and dietary habits.

Setting:

This cross-sectional study uses data from the Danish Diet, Cancer and Health cohort.

Participants:

A total of 43 209 men and women aged between 54 and 73 years were included in the study.

Results:

Overall, 15 % reported never consuming organic food, 39 % had low organic food consumption, 37 % had medium organic food consumption and 10 % had high organic food consumption. The relative risk of consuming organic food versus never consuming organic food was highest among women, persons with BMI < 25 kg/m2, persons with low alcohol intake, persons participating in sports, persons who did not smoke or were former smokers, and among persons who adhered to the Danish national dietary guidelines. Associations were more distinct with higher levels of organic food consumption.

Conclusion:

Based on a historical cohort of Danish adults, organic food consumption was associated with a generally healthy lifestyle, more favourable socio-demographics and dietary habits. These findings have to be considered in the adjustment strategy for future studies linking organic food consumption with health outcomes.
FOR BETTER AND FOR WORSE. ABSTRACTIONISM, GOOD COMPANY, AND PLURALISM
Authors: SERENI ANDREA , SFORZA FOGLIANI MARIA PAOLA , ZANETTI LUCA
Published: March 2021

A thriving literature has developed over logical and mathematical pluralism – i.e. the views that several rival logical and mathematical theories can be equally correct. These have unfortunately grown separate; instead, they both could gain a great deal by a closer interaction. Our aim is thus to present some novel forms of abstractionist mathematical pluralism which can be modeled on parallel ways of substantiating logical pluralism (also in connection with logical anti-exceptionalism). To do this, we start by discussing the Good Company Problem for neo-logicists recently raised by Paolo Mancosu (2016), concerning the existence of rival abstractive definitions of cardinal number which are nonetheless equally able to reconstruct Peano Arithmetic. We survey Mancosu’s envisaged possible replies to this predicament, and suggest as a further path the adoption of some form of mathematical pluralism concerning abstraction principles. We then explore three possible ways of substantiating such pluralism—Conceptual Pluralism,Domain Pluralism,Pluralism about Criteria—showing how each of them can be related to analogous proposals in the philosophy of logic. We conclude by considering advantages, concerns, and theoretical ramifications for these varieties of mathematical pluralism.
Assessing the Measurement Invariance of the Gratitude Questionnaire–5 in Chinese and American Adolescents
Authors: Ling Yu , Yang Qin , Zeng Yifang , Huebner E. Scott
Published: March 2021

Given the possibility of cultural differences in the meaning and levels of gratitude among children, we evaluated the measurement invariance of the Gratitude Questionnaire–5 (GQ–5) and differences in latent means across adolescents from two distinct cultures, China and America. Data were obtained from 1,991 Chinese and 1,685 American adolescents. Confirmatory factor analysis and multigroup confirmatory factor analysis were performed to examine the factor structure and the measurement equivalence across Chinese and American adolescents. The Cronbach’s alpha and Item-total Correlations of the GQ–5 were also evaluated. Results of confirmatory factor analyses provided support for the expected one-factor structure. Also, a series of multi-group confirmatory factor analyses supported full configural invariance, full metric invariance, and partial scalar invariance between the two groups. Furthermore, the findings suggested that the GQ–5 is suitable for conducting mean level comparisons. The subsequent comparison of latent means revealed that the Chinese adolescents reported significantly lower gratitude than American adolescents.
The Politics of Wrongful Conviction Legislation
Authors: Hicks William D. , Mullinix Kevin J. , Norris Robert J.
Published: March 2021

Wrongful convictions are an increasing salient feature of criminal justice discourse in the United States. Many states have adopted reforms to mitigate the likelihood of wrongful convictions, discover errors, and provide redress in the wake of exonerations, yet we know little about why some are seemingly more committed to reducing such errors than others. We argue that public opinion is consequential for policy reform, but its effects are contingent on the electoral vulnerability of state lawmakers. We also suggest that advocacy organizations play a critical role in policy adoption. Incorporating data from all 50 states from 1989 to 2018, we investigate the adoption of five types of wrongful conviction reforms: (1) changes to eyewitness identification practices, (2) mandatory recording of interrogations, (3) the preservation of biological evidence, (4) access to postconviction DNA testing, and (5) exoneree compensation. Our results highlight a more nuanced view of how public opinion shapes policy.
Weedy rice (Oryzaspp.) diversity in southern Brazil
Authors: Piveta Leonard Bonilla , Noldin José Alberto , Roma-Burgos Nilda , Viana Vívian Ebeling , Benedetti Lariza , Pinto Jesus Juares Oliveira , Lamego Fabiane Pinto , Avila Luis Antonio de
Published: March 2021

Weedy rice (Oryzaspp.) is one of the most troublesome weeds affecting rice (Oryza sativaL.) production in many countries. Weedy rice control is difficult in rice fields, because the weed and crop are phenotypically and morphologically similar. Weedy rice can be a source of genetic diversity for cultivated rice. Thus, this study aimed to characterize the morphological diversity of weedy rice in southern Brazil. Qualitative and quantitative traits of 249 accessions from eight rice-growing mesoregions in Rio Grande do Sul (RS) and Santa Catarina (SC) states were analyzed. For each accession, 24 morphological descriptors (14 qualitative and 10 quantitative) were evaluated. All 249 accessions from RS and SC are ofindicalineage. Considering all the phenotypic traits evaluated, the accessions separated into 14 distinct groups. One of the largest groups consisted of plants that were predominantly tall with green leaves, intermediate shattering, and variable flowering time. Distinct subgroups exist within larger clusters, showing discernible phenotypic diversity within the main clusters. The variability in flowering time was high (77 to 110 d after emergence), indicating high potential for flowering synchrony with rice cultivars and, consequently, gene flow. This indicates the need to remove escapes when planting herbicide-resistant rice. Thus, weedy rice populations in southern Brazil are highly diverse, and this diversity could result in variable response to weed management.
Evolution of the Thermal and Dehydration State of Sediments Entering the North Sumatra Subduction Zone
Authors: Stevens Duncan E. , Henstock Timothy J. , McNeill Lisa C.
Published: March 2021

Shallow slip on the plate‐boundary fault during the 2004 Mw 9.2 Aceh‐Andaman Earthquake, offshore North Sumatra, has been linked to thick incoming sediments on the oceanic plate with advanced diagenetic and sediment property changes at the depths of plate boundary fault development. We couple age control, physical, and thermal property measurements from International Ocean Discovery Program (IODP) drilling with multichannel seismic reflection data to reconstruct the thermal structure and evolution of the incoming sediment column, up to the point of accretion/subduction. Lithospheric thermal rejuvenation around 58 Ma is required to explain anomalously high heat flux at IODP Site U1480, and heat flux within the trench is suppressed by very high sediment accumulation rates during the development of a thick trench wedge. Accumulation of up to ∼4.5 km of thick Nicobar Fan and trench wedge sediments produces temperatures >150°C within the basal sediments where the décollement develops, resulting in total pre‐subduction diagenetic dehydration of basal sediments. The smectite‐illite transformation within these basal sediments produces sufficient fluid to explain a polarity reversal on a pre‐décollement reflector. We suggest that the boundary between basal‐pelagic and siliciclastic‐fan sediments has trapped fluid over the last ∼1 Myr, as a result of primary lithological properties, diagenetic fluid release, and cementation, controlling décollement formation at this weakened level. Pre‐subduction dehydration of large portions of the accreted sediment column strengthens the décollement beneath the prism, extending co‐seismic velocity‐weakening behavior close to the trench, which may occur at other subduction zones with similar sediment compositions, thicknesses, and/or temperatures.
Spatiotemporal Clustering of Seismicity During the 2018 Kilauea Volcanic Eruption
Authors: Ortega‐Romo Angie D. , Chen Xiaowei
Published: March 2021

The intense volcanic and seismic activity at Kilauea volcano, Hawaii in 2018 provides an opportunity to understand the characteristics and driving forces of volcano earthquake clusters. Nearest neighbor distance analysis of a high‐resolution earthquake catalog reveals two modes of clustering: M1 and M2. M1 clusters focus on events within short space and time windows, and are concentrated within isolated fault patches. Examination of three structures shows a gradual increase of source radius (assuming a constant stress drop) and spatial migration of seismicity, likely representing aseismic growth of peripheral faults. M2 clusters focus on temporal clustering of all seismicity within the caldera and most clusters represent complete seismicity cycles between major collapse events. Beginning in late June, the M2 cluster duration gradually increased. The event numbers show a strong linear relationship with the tilt rates on the transverse component, suggesting earthquake rates are controlled by the deformation rate within the caldera.
Uptake of Water‐soluble Gas‐phase Oxidation Products Drives Organic Particulate Pollution in Beijing
Authors: Gkatzelis Georgios I. , Papanastasiou Dimitrios K. , Karydis Vlassis A. , Hohaus Thorsten , Liu Ying , Schmitt Sebastian H. , Schlag Patrick , Fuchs Hendrik , Novelli Anna , Chen Qi , Cheng Xi , Broch Sebastian , Dong Huabin , Holland Frank , Li Xin , Liu Yuhan , Ma Xuefei , Reimer David , Rohrer Franz , Shao Min , Tan Zhaofeng , Taraborrelli Domenico , Tillmann Ralf , Wang Haichao , Wang Yu , Wu Yusheng , Wu Zhijun , Zeng Limin , Zheng Jun , Hu Min , Lu Keding , Hofzumahaus Andreas , Zhang Yuanhang , Wahner Andreas , Kiendler‐Scharr Astrid
Published: March 2021

Despite the recent decrease in pollution events in Chinese urban areas, the World Health Organization air quality guideline values are still exceeded. Observations from monitoring networks show a stronger decrease of organic aerosol directly emitted to the atmosphere relative to secondary organic aerosol (SOA) generated from oxidation processes. Here, the uptake of water‐soluble gas‐phase oxidation products is reported as a major SOA contribution to particulate pollution in Beijing, triggered by the increase of aerosol liquid water. In pollution episodes, this pathway is enough to explain the increase in SOA mass, with formaldehyde, acetaldehyde, glycolaldehyde, formic acid, and acetic acid alone explaining 15%–25% of the SOA increase. Future mitigation strategies to reduce non‐methane volatile organic compound emissions should be considered to reduce organic particulate pollution in China.
Lightning in the Arctic
Authors: Holzworth Robert H. , Brundell James B. , McCarthy Michael P. , Jacobson Abram R. , Rodger Craig J. , Anderson Todd S.
Published: March 2021

World Wide Lightning Location Network (WWLLN) data on global lightning are used to investigate the increase of total lightning strokes at Arctic latitudes. We use the summertime data from June, July, and August (JJA) which average >200,000 strokes each year above 65°N for the years 2010–2020. We minimize the possible influence of WWLLN network detection efficiency increases by normalizing our results to the total global strokes during northern summer each year. The ratio of strokes occurring above a given latitude, compared to total global strokes, increases with time, indicating that the Arctic is becoming more influenced by lightning. We compare the increasing fraction of strokes with the NOAA global temperature anomaly, and find that the fraction of strokes above 65°N to total global strokes increases linearly with the temperature anomaly and grew by a factor of 3 as the anomaly increased from 0.65°C to 0.95°C.
Atmosphere‐Ocean Feedback From Wind‐Driven Sea Spray Aerosol Production
Authors: Revell L. E. , Wotherspoon N. E. , Jones O. J. , Bhatti Y. A. , Williams J. H. T. , Mackie S. L. , Mulcahy J. P.
Published: March 2021

Marine aerosol production is influenced by wind speed, particularly over the Southern Ocean which is the windiest region on Earth year‐round. Using climate model simulations with artificially enhanced sea spray aerosol (SSA), we show that Southern Ocean wind speeds are sensitive to SSA via surface cooling resulting from enhanced aerosol concentrations. The near‐surface westerly jet weakens, therefore reducing SSA production. Comparing coupled and atmosphere‐only simulations indicates that SSA partially regulates its own production via a feedback between the atmosphere and ocean. The decrease in radiative forcing in the coupled model is approximately one‐quarter of that simulated by the atmosphere‐only model, and the extent of the feedback also depends on the SSA source function used. Our results highlight the importance of understanding SSA emissions and their parameterization in climate models. Including a temperature dependence in SSA parameterizations can play a large role in the climate feedback, but further investigation is needed.
The Synergistic Role of Sulfuric Acid, Bases, and Oxidized Organics Governing New‐Particle Formation in Beijing
Authors: Yan Chao , Yin Rujing , Lu Yiqun , Dada Lubna , Yang Dongsen , Fu Yueyun , Kontkanen Jenni , Deng Chenjuan , Garmash Olga , Ruan Jiaxin , Baalbaki Rima , Schervish Meredith , Cai Runlong , Bloss Matthew , Chan Tommy , Chen Tianzeng , Chen Qi , Chen Xuemeng , Chen Yan , Chu Biwu , Dällenbach Kaspar , Foreback Benjamin , He Xucheng , Heikkinen Liine , Jokinen Tuija , Junninen Heikki , Kangasluoma Juha , Kokkonen Tom , Kurppa Mona , Lehtipalo Katrianne , Li Haiyan , Li Hui , Li Xiaoxiao , Liu Yiliang , Ma Qingxin , Paasonen Pauli , Rantala Pekka , Pileci Rosaria E. , Rusanen Anton , Sarnela Nina , Simonen Pauli , Wang Shixian , Wang Weigang , Wang Yonghong , Xue Mo , Yang Gan , Yao Lei , Zhou Ying , Kujansuu Joni , Petäjä Tuukka , Nie Wei , Ma Yan , Ge Maofa , He Hong , Donahue Neil M. , Worsnop Douglas R. , Veli‐Matti Kerminen  , Wang Lin , Liu Yongchun , Zheng Jun , Kulmala Markku , Jiang Jingkun , Bianchi Federico
Published: March 2021

Intense and frequent new particle formation (NPF) events have been observed in polluted urban environments, yet the dominant mechanisms are still under debate. To understand the key species and governing processes of NPF in polluted urban environments, we conducted comprehensive measurements in downtown Beijing during January–March, 2018. We performed detailed analyses on sulfuric acid cluster composition and budget, as well as the chemical and physical properties of oxidized organic molecules (OOMs). Our results demonstrate that the fast clustering of sulfuric acid (H2SO4) and base molecules triggered the NPF events, and OOMs further helped grow the newly formed particles toward climate‐ and health‐relevant sizes. This synergistic role of H2SO4, base species, and OOMs in NPF is likely representative of polluted urban environments where abundant H2SO4 and base species usually co‐exist, and OOMs are with moderately low volatility when produced under high NOx concentrations.
Vegetation‐Climate Feedbacks Enhance Spatial Heterogeneity of Pan‐Amazonian Ecosystem States Under Climate Change
Authors: Wu Minchao , Smith Benjamin , Schurgers Guy , Ahlström Anders , Rummukainen Markku
Published: March 2021

Amazonian ecosystems range from rainforest to open dryland vegetation, with a following decrease in biomass along the moisture gradient. Biomass can vary greatly at the ecological transition zone between grass dominated savannahs and the forest. It is not well understood if the transition zone could expand under climate change, and thereby reduce ecosystem stability and carbon storage in biomass. Here, we quantify such changes by using a high‐resolution regional Earth system model under RCP 8.5 climate scenario. We disentangle the effects of climate, CO2, and land use by considering vegetation‐climate feedbacks. Our results suggest that future climate change combined with elevated atmospheric CO2 concentration tends to induce a larger spatial gradient of ecosystem states, increasing the transition area by ∼110% at the end of the century. Vegetation feedbacks generally amplify the climate effect by intensifying the climate‐induced warming and drought, further enhancing spatial heterogeneity.
Nanosecond Electromagnetic Pulses Generated by Electric Discharges: Observation With Clouds of Charged Water Droplets and Implications for Lightning
Authors: Gushchin M. E. , Korobkov S. V. , Zudin I. Yu. , Nikolenko A. S. , Mikryukov P. A. , Syssoev V. S. , Sukharevsky D. I. , Orlov A. I. , Naumova M. Yu. , Kuznetsov Yu. A. , Belov A. S. , Shvets N. N. , Mareev E. A.
Published: March 2021

Effects of lightning‐induced generation of high‐frequency and microwave radiation are of great interest for studying fundamental physics of lightning and its applications for monitoring of the thunderstorm activity and protection of equipment against electromagnetic interference. Ultrawideband electromagnetic pulses (UWB EMPs) of spark discharges about 1 m long were detected in a frequency band of up to 10 GHz in laboratory experiments using a cloud of water droplets charged up to the electric potential exceeding 1 MV. Electromagnetic pulses with characteristic front buildup durations from 50  to 100 ps were produced by streamer flashes, at the stage of leader propagation and the main stage of the discharge (i.e., the return stroke). Electric and magnetic fields of pulses were measured, and the radiation polarization was determined. The UWB EMP waveforms and the spectra obtained experimentally are consistent with colliding streamer models.
Mapping the Thermal Lithosphere and Melting Across the Continental US
Authors: Porter Ryan , Reid Mary
Published: March 2021

The thermal regime of continental lithosphere plays a fundamental role in controlling the behavior of tectonic plates. In this work, we assess the thermal state of the North American upper mantle by combining shear‐wave velocity models, calculated using data from the EarthScope facility, with empirically derived anelasticity models and basalt thermobarometry. We estimate the depth of the thermal lithosphere‐asthenosphere boundary (LAB), defined as the intersection of a geotherm with the 1300°C adiabat. Results show lithospheric thicknesses across the contiguous US vary between ∼40 km and >200 km. The thinnest thermal lithosphere is observed in the tectonically active western US and the thickest lithosphere in the midcontinent. By combining geotherm estimates with solidus curves for peridotite, we show that a pervasive partial melt zone is common within the western US upper mantle and that partial melt is absent in the eastern and central US without significant metasomatism.
Phase‐Resolved Wave Boundary Layer Dynamics in a Shallow Estuary
Authors: Cowherd Marianne , Egan Galen , Monismith Stephen , Fringer Oliver
Published: March 2021

We present in situ observations of near‐bed velocity profiles with high temporal and spatial resolution from a Nortek Vectrino Profiler deployed in South San Francisco Bay. Using Hilbert analysis, we ensemble‐averaged near‐bed velocity profiles by wave phase and calculated wave phase‐dependent boundary layer thickness for varying wave and current conditions. We also applied mixing length relationships to derive a boundary layer thickness‐based eddy‐viscosity and compared this estimate to one obtained from the k–ɛ turbulence model. From the eddy viscosity estimates, we find that while turbulence responds instantaneously to shear, boundary layer thickness lags by a scaling estimate based on the turbulence response timescale. This analysis provides a method for wave phase decomposition of field‐based velocity profile time series and shows that there is a finite‐time response between turbulence dissipation and boundary layer thickness.
DMSP Observations of High‐Latitude Dayside Aurora (HiLDA)
Authors: Cai L. , Kullen A. , Zhang Y. , Karlsson T. , Vaivads A.
Published: March 2021

We report two events of high‐latitude dayside aurora (HiLDA), a large‐scale aurora in the dayside polar cap, observed by the Defense Meteorological Satellite Program (DMSP) spacecraft in the northern and southern hemispheres, respectively. While HiLDA in the northern hemisphere was reported before under interplanetary magnetic field (IMF) positive By conditions, we show for the first time a HiLDA event in the southern hemisphere when the IMF negative By component was dominant. Our observations also show that HiLDA is highly dynamical: change in its forms, size, location, and development of fine structures during its long lifetime of hours. The co‐occurrence of HiLDA and the duskside oval‐aligned transpolar aurora (TPA) may be a common feature during IMF By dominant conditions. Both are associated with the high‐latitude reconnection and the cusp. Based on the linear Knight relation, we estimate the distribution of the electron density in the magnetospheric source region of HiLDA. These results indicate that HiLDA maps most probably to the high‐latitude lobe tailward of the cusp, where the electron density is down to 0.03−3 cm−3. The lobe electrons are accelerated by the field‐aligned potential drop (up to 10 kV) set up in the poleward part of upward Region 0 field‐aligned current (FAC). The total energy flux of HiLDA electrons can be up to 50 mW/m2, indicating HiLDA precipitation as a potential energy source that impacts the polar ionosphere‐thermosphere system.
On Alfvénic Slow Wind: A Journey From the Earth Back to the Sun
Authors: D’Amicis R. , Perrone D. , Bruno R. , Velli M.
Published: March 2021

Comparative studies of fast and slow solar wind streams performed over the past decades have illustrated several differences between the plasma regimes for these different flows, examples including features such as temperatures, particle distribution function anisotropies, and the nature of the embedded turbulence, specifically the Alfvénicity of the fluctuations. Though this two‐state classification of the solar wind primarily based on flow speed has been widely adopted, more in depth studies have found that slow solar wind should be further categorized, flow speed not being a sufficient descriptor of the plasma state. Within this framework, slow solar wind streams with a strong Alfvénic character have been identified and characterized, showing that in many ways they resemble fast solar wind. The similarities between fast and slow Alfvénic wind regimes have been explained in terms of a similar solar origin, with the latter corresponding to slow winds emanating from rapidly diverging low‐latitude small coronal holes. The aim of this review is to describe the state of art of our understanding of Alfvénic slow solar wind streams. The results presented cover observations performed at different heliocentric distances spanning from Wind at L1 to Helios and Parker Solar Probe in the inner heliosphere, as well as a discussion of their source regions.
Differential Exhumation of the Eastern Cordillera in the Central Andes: Evidence for South‐Verging Backthrusting (Abancay Deflection, Peru)
Authors: Gérard Benjamin , Robert Xavier , Audin Laurence , Valla Pierre G. , Bernet Matthias , Gautheron Cécile
Published: March 2021

Located at the northern tip of the Altiplano, the Abancay Deflection marks abruptly the latitudinal segmentation of the Central Andes spreading over the Altiplano to the south and the Eastern Cordillera northward. The striking morphological contrast between the low‐relief Altiplano and the high‐relief Eastern Cordillera makes this area a well‐suited place to determine spatiotemporal variations in surface and/or rock uplift and discuss the latest phase of the formation of the Central Andes. Here, we aim to quantify exhumation and uplift patterns in the Abancay Deflection since 40 Ma and present new apatite (U–Th)/He and fission track data from four altitudinal profiles and additional individual samples. Age–elevation relationships and thermal modeling both document that the Abancay Deflection experienced a moderate, spatially uniform, and steady exhumation at 0.2 ± 0.1 km/Myr between 40 and ∼5 Ma implying common large‐scale exhumation mechanism(s). From ∼5 Ma, while the northern part of the Eastern Cordillera and the Altiplano registered similar ongoing slow exhumation, the southern part of the Eastern Cordillera experienced one order‐of‐magnitude of exhumation acceleration (1.2 ± 0.4 km/Myr). This differential exhumation since ∼5 Ma implies active tectonics, river capture, and incision affecting the southern Eastern Cordillera. 3D thermokinematic modeling favors a tectonic decoupling between the Altiplano and the Eastern Cordillera through backthrusting activity of the Apurimac fault. We speculate that the Abancay Deflection, with its “bulls‐eye” structure and significant exhumation rate since 5 Ma, may represent an Andean protosyntaxis, similar to the syntaxes described in the Himalaya or Alaska.
Mineral Dissolution and Precipitation Under Stress: Model Formulation and Application to Metamorphic Reactions
Authors: Malvoisin Benjamin , Baumgartner Lukas P.
Published: March 2021

Reactions in the Earth's crust occur through a dissolution‐precipitation process in the presence of fluid. Dissolution releases aqueous species which are transported to the locus of precipitation. This replacement process generates creep deformation (i.e., dissolution‐precipitation creep) due to volume change during reaction and stress‐controlled mass re‐distribution in the rock. Reaction under stress also modifies the rock microstructure and the pressure record during metamorphism. A quantitative model for dissolution‐precipitation creep is developed here by considering both dissolution and precipitation at grain interfaces to simulate replacement reactions under stress. A new creep law is obtained for pressure solution, allowing for the reaction‐ and the diffusion‐controlled cases to be modeled with a single expression. It is extended to replacement reactions by introducing volume change during reaction. Deformation mechanism maps are generated with the new creep law, indicating that, when fluid is present, dissolution‐precipitation creep is the dominant deformation mechanism in the Earth's crust. Numerical model reveals that grain shape preferred orientation only develops near thermodynamic equilibrium. This is consistent with measurements of porphyroblasts preferred orientation in rocks from the Nufenen Pass (Switzerland) having experienced prograde metamorphism. Kinetics play a key role on the thermodynamic pressure of metamorphic reaction. Near the equilibrium, reaction is controlled by either σ1 or σ3 depending on the total volume change during reaction whereas it is controlled by the mean stress far from the equilibrium.
How Much Did the Colombian Andes Rise by the Collision of the Caribbean Oceanic Plateau?
Authors: León Santiago , Monsalve Gaspar , Bustamante Camilo
Published: March 2021

The quantification of topographic growth at convergent margins is of primary importance to assessing the linkages between tectonic processes and landscape evolution. Traditionally, this task has relied on the applicability of conventional paleobotanical and isotopic methods to estimate paleoelevations, which is not always straightforward. Here, we use recent calibrations based on trace elements of arc‐related magmatic rocks to estimate crustal thickening and surface uplift of the northern Colombian Andes during the early Andean orogeny at ca. 70‐60 Ma. Increased Sr/Y and (La/Yb)N ratios of arc‐related intrusives suggest a ∼20 km crustal thickening that was probably accompanied by an isostatically compensated topographic uplift of up to ∼2 km along the proto‐Central Cordillera and the Santa Marta Range. This kilometer‐scale uplift was coeval with a regional shift from marine to continental deposition in foreland basins and was triggered by the collision of the Caribbean oceanic plateau.
Activation of Nm23-H1 to suppress breast cancer metastasis via redox regulation
Authors: Kim Bokyung , Lee Kong-Joo
Published: March 2021

Non-metastatic protein 23 H1 (Nm23-H1), a housekeeping enzyme, is a nucleoside diphosphate kinase-A (NDPK-A). It was the first identified metastasis suppressor protein. Nm23-H1 prolongs disease-free survival and is associated with a good prognosis in breast cancer patients. However, the molecular mechanisms underlying the role of Nm23-H1 in biological processes are still not well understood. This is a review of recent studies focusing on controlling NDPK activity based on the redox regulation of Nm23-H1, structural, and functional changes associated with the oxidation of cysteine residues, and the relationship between NDPK activity and cancer metastasis. Further understanding of the redox regulation of the NDPK function will likely provide a new perspective for developing new strategies for the activation of NDPK-A in suppressing cancer metastasis.
High prevalence of TP53 loss and whole-genome doubling in early-onset colorectal cancer
Authors: Kim Jeong Eun , Choi Jaeyong , Sung Chang-Ohk , Hong Yong Sang , Kim Sun Young , Lee Hyunjung , Kim Tae Won , Kim Jong-Il
Published: March 2021

The global incidence of early-onset colorectal cancer (EO-CRC) is rapidly rising. However, the reason for this rise in incidence as well as the genomic characteristics of EO-CRC remain largely unknown. We performed whole-exome sequencing in 47 cases of EO-CRC and targeted deep sequencing in 833 cases of CRC. Mutational profiles of EO-CRC were compared with previously published large-scale studies. EO-CRC and The Cancer Genome Atlas (TCGA) data were further investigated according to copy number profiles and mutation timing. We classified colorectal cancer into three subgroups: the hypermutated group consisted of mutations in POLE and mismatch repair genes; the whole-genome doubling group had early functional loss of TP53 that led to whole-genome doubling and focal oncogene amplification; the genome-stable group had mutations in APC and KRAS, similar to conventional colon cancer. Among non-hypermutated samples, whole-genome doubling was more prevalent in early-onset than in late-onset disease (54% vs 38%, Fisher’s exact P = 0.04). More than half of non-hypermutated EO-CRC cases involved early TP53 mutation and whole-genome doubling, which led to notable differences in mutation frequencies between age groups. Alternative carcinogenesis involving genomic instability via loss of TP53 may be related to the rise in EO-CRC.
Genetic and clinical characteristics of treatment-resistant depression using primary care records in two UK cohorts
Authors: Fabbri Chiara , Hagenaars Saskia P. , John Catherine , Williams Alexander T. , Shrine Nick , Moles Louise , Hanscombe Ken B. , Serretti Alessandro , Shepherd David J. , Free Robert C. , Wain Louise V. , Tobin Martin D. , Lewis Cathryn M.
Published: March 2021

Treatment-resistant depression (TRD) is a major contributor to the disability caused by major depressive disorder (MDD). Primary care electronic health records provide an easily accessible approach to investigate TRD clinical and genetic characteristics. MDD defined from primary care records in UK Biobank (UKB) and EXCEED studies was compared with other measures of depression and tested for association with MDD polygenic risk score (PRS). Using prescribing records, TRD was defined from at least two switches between antidepressant drugs, each prescribed for at least 6 weeks. Clinical-demographic characteristics, SNP-based heritability (h2SNP) and genetic overlap with psychiatric and non-psychiatric traits were compared in TRD and non-TRD MDD cases. In 230,096 and 8926 UKB and EXCEED participants with primary care data, respectively, the prevalence of MDD was 8.7% and 14.2%, of which 13.2% and 13.5% was TRD, respectively. In both cohorts, MDD defined from primary care records was strongly associated with MDD PRS, and in UKB it showed overlap of 71–88% with other MDD definitions. In UKB, TRD vs healthy controls and non-TRD vs healthy controls h2SNP was comparable (0.25 [SE = 0.04] and 0.19 [SE = 0.02], respectively). TRD vs non-TRD was positively associated with the PRS of attention deficit hyperactivity disorder, with lower socio-economic status, obesity, higher neuroticism and other unfavourable clinical characteristics. This study demonstrated that MDD and TRD can be reliably defined using primary care records and provides the first large scale population assessment of the genetic, clinical and demographic characteristics of TRD.
Pediatric subspecialty telemedicine use from the patient and provider perspective
Authors: Pooni Rajdeep , Pageler Natalie M. , Sandborg Christy , Lee Tzielan
Published: March 2021

Background

To characterize telemedicine use among pediatric subspecialties with respect to clinical uses of telemedicine, provider experience, and patient perceptions during the COVID-19 pandemic.

Methods

We performed a mixed-methods study of telemedicine visits across pediatric endocrinology, nephrology, orthopedic surgery, and rheumatology at a large children’s hospital. We used deductive analysis to review observational data from 40 video visits. Providers and patients/caregivers were surveyed around areas of satisfaction and communication.

Results

We found adaptations of telemedicine including shared-screen use and provider-guided parent procedures among others. All providers felt that it was safest for their patients to conduct visits by video, and 72.7% reported completing some component of a clinical exam. Patients rated the areas of being respected by the clinical staff/provider and showing care and concern highly, and the mean overall satisfaction was 86.7 ± 19.3%.

Conclusions

Telemedicine has been used to deliver care to pediatric patients during the pandemic, and we found that patients were satisfied with the telemedicine visits during this stressful time and that providers were able to innovate during visits. Telemedicine is a tool that can be successfully adapted to patient and provider needs, but further studies are needed to fully explore its integration in pediatric subspecialty care.

Impact

This study describes telemedicine use at the height of the COVID-19 pandemic from both a provider and patient perspective, in four different pediatric subspecialties.

Prior to COVID-19, pediatric telehealth landscape analysis suggested that many pediatric specialty practices had pilot telehealth programs, but there are few published studies evaluating telemedicine performance through the simultaneous patient and provider experience as part of standard care.

We describe novel uses and adaptations of telemedicine during a time of rapid deployment in pediatric specialty care.
EVI1 dysregulation: impact on biology and therapy of myeloid malignancies
Authors: Birdwell Christine , Fiskus Warren , Kadia Tapan M. , DiNardo Courtney D. , Mill Christopher P. , Bhalla Kapil N.
Published: March 2021

Ecotropic viral integration site 1 (Evi1) was discovered in 1988 as a common site of ecotropic viral integration resulting in myeloid malignancies in mice. EVI1 is an oncogenic zinc-finger transcription factor whose overexpression contributes to disease progression and an aggressive phenotype, correlating with poor clinical outcome in myeloid malignancies. Despite progress in understanding the biology of EVI1 dysregulation, significant improvements in therapeutic outcome remain elusive. Here, we highlight advances in understanding EVI1 biology and discuss how this new knowledge informs development of novel therapeutic interventions. EVI1 is overexpression is correlated with poor outcome in some epithelial cancers. However, the focus of this review is the genetic lesions, biology, and current therapeutics of myeloid malignancies overexpressing EVI1.
Skeleton-vasculature chain reaction: a novel insight into the mystery of homeostasis
Authors: Chen Ming , Li Yi , Huang Xiang , Gu Ya , Li Shang , Yin Pengbin , Zhang Licheng , Tang Peifu
Published: March 2021

Angiogenesis and osteogenesis are coupled. However, the cellular and molecular regulation of these processes remains to be further investigated. Both tissues have recently been recognized as endocrine organs, which has stimulated research interest in the screening and functional identification of novel paracrine factors from both tissues. This review aims to elaborate on the novelty and significance of endocrine regulatory loops between bone and the vasculature. In addition, research progress related to the bone vasculature, vessel-related skeletal diseases, pathological conditions, and angiogenesis-targeted therapeutic strategies are also summarized. With respect to future perspectives, new techniques such as single-cell sequencing, which can be used to show the cellular diversity and plasticity of both tissues, are facilitating progress in this field. Moreover, extracellular vesicle-mediated nuclear acid communication deserves further investigation. In conclusion, a deeper understanding of the cellular and molecular regulation of angiogenesis and osteogenesis coupling may offer an opportunity to identify new therapeutic targets.
Engineered cells as glioblastoma therapeutics
Authors: Ramanathan Aparna , Lorimer Ian A. J.
Published: March 2021

In spite of significant recent advances in our understanding of the genetics and cell biology of glioblastoma, to date, this has not led to improved treatments for this cancer. In addition to small molecule, antibody, and engineered virus approaches, engineered cells are also being explored as glioblastoma therapeutics. This includes CAR-T cells, CAR-NK cells, as well as engineered neural stem cells and mesenchymal stem cells. Here we review the state of this field, starting with clinical trial studies. These have established the feasibility and safety of engineered cell therapies for glioblastoma and show some evidence for activity. Next, we review the preclinical literature and compare the strengths and weaknesses of various starting cell types for engineered cell therapies. Finally, we discuss future directions for this nascent but promising modality for glioblastoma therapy.
PARsylated transcription factor EB (TFEB) regulates the expression of a subset of Wnt target genes by forming a complex with β-catenin-TCF/LEF1
Authors: Kim Soyoung , Song Gahyeon , Lee Taebok , Kim Minseong , Kim Jeongrae , Kwon Hyeryun , Kim Jiyoung , Jeong Wonyoung , Lee Ukjin , Na Chaebin , Kang Sangwon , Kim Wantae , Seong Je Kyung , Jho Eek-hoon
Published: March 2021

Wnt signaling is mainly transduced by β-catenin via regulation of the β-catenin destruction complex containing Axin, APC, and GSK3β. Transcription factor EB (TFEB) is a well-known master regulator of autophagy and lysosomal biogenesis processes. TFEB’s nuclear localization and transcriptional activity are also regulated by various upstream signals. In this study, we found that Wnt signaling induces the nuclear localization of TFEB and the expression of Wnt target genes is regulated by TFEB-β-catenin-TCF/LEF1 as well as β-catenin-TCF/LEF1 complexes. Our biochemical data revealed that TFEB is a part of the β-catenin destruction complex, and destabilization of the destruction complex by knockdown of either Axin or APC causes nuclear localization of TFEB. Interestingly, RNA-sequencing analysis revealed that about 27% of Wnt3a-induced genes were TFEB dependent. However, these “TFEB mediated Wnt target genes” were different from TFEB target genes involved in autophagy and lysosomal biogenesis processes. Mechanistically, we found that Tankyrase (TNKS) PARsylates TFEB with Wnt ON signaling, and the nuclear localized PARsylated TFEB forms a complex with β-catenin-TCF/LEF1 to induce the “TFEB mediated Wnt target genes”. Finally, we found that in various types of cancer, the levels of TFEB mediated Wnt target genes exhibit strong correlations with the level of Axin2, which represents the activity of Wnt signaling. Overall, our data suggest that Wnt signaling induces the expression of a subset of genes that are distinct from previously known genes regulated by the β-catenin-TCF/LEF1 complex or TFEB, by forming a transcription factor complex consisting of PARsylated TFEB and β-catenin-TCF/LEF1.
FGF21 facilitates autophagy in prostate cancer cells by inhibiting the PI3K–Akt–mTOR signaling pathway
Authors: Dai Han , Hu Wenjing , Zhang Lianying , Jiang Feiyu , Mao Xiongmin , Yang Gangyi , Li Ling
Published: March 2021

Fibroblast growth factor 21 (FGF21) plays an important role in regulating glucose and lipid metabolism, but its role in cancer is less well-studied. We aimed to investigate the action of FGF21 in the development of prostate cancer (PCa). Herein, we found that FGF21 expression was markedly downregulated in PCa tissues and cell lines. FGF21 inhibited the proliferation and clone formation of LNCaP cells (a PCa cell line) and promoted apoptosis. FGF21 also inhibited PCa cell migration and invasiveness. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that FGF21 was related to autophagy and the phosphatidylinositol 3-kinase–Akt kinase–mammalian target of rapamycin (PI3K–Akt–mTOR) pathway. Mechanistically, FGF21 promoted autophagy in LNCaP cells by inhibiting the PI3K–Akt–mTOR–70S6K pathway. In addition, FGF21 inhibited PCa tumorigenesis in vivo in nude mice. Altogether, our findings show that FGF21 inhibits PCa cell proliferation and promoted apoptosis in PCa cells through facilitated autophagy. Therefore, FGF21 might be a potential novel target in PCa therapy.
Non-canonical role of wild-type SEC23B in the cellular stress response pathway
Authors: Yehia Lamis , Liu Darren , Fu Shuai , Iyer Pranav , Eng Charis
Published: March 2021

While germline recessive loss-of-function mutations in SEC23B in humans cause a rare form of anaemia, heterozygous change-of-function mutations result in increased predisposition to cancer. SEC23B encodes SEC23 homologue B, a component of coat protein complex II (COPII), which canonically transports proteins from the endoplasmic reticulum (ER) to the Golgi. Despite the association of SEC23B with anaemia and cancer, the precise pathophysiology of these phenotypic outcomes remains unknown. Recently, we reported that mutant SEC23B has non-canonical COPII-independent function, particularly within the ER stress and ribosome biogenesis pathways, and that may contribute to the pathobiology of cancer predisposition. In this study, we hypothesized that wild-type SEC23B has a baseline function within such cellular stress response pathways, with the mutant protein reflecting exaggerated effects. Here, we show that the wild-type SEC23B protein localizes to the nucleus in addition to classical distribution at the ER/Golgi interface and identify multiple putative nuclear localization and export signals regulating nuclear–cytoplasmic transport. Unexpectedly, we show that, independently of COPII, wild-type SEC23B can also localize to cell nucleoli under proteasome inhibition conditions, with distinct distribution patterns compared to mutant cells. Unbiased proteomic analyses through mass spectrometry further revealed that wild-type SEC23B interacts with a subset of nuclear proteins, in addition to central proteins in the ER stress, protein ubiquitination, and EIF2 signalling pathways. We validate the genotype-specific differential SEC23B–UBA52 (ribosomal protein RPL40) interaction. Finally, utilizing patient-derived lymphoblastoid cell lines harbouring either wild-type or mutant SEC23B, we show that SEC23B levels increase in response to ER stress, further corroborating its role as a cellular stress response sensor and/or effector. Overall, these observations suggest that SEC23B, irrespective of mutation status, has unexplored roles in the cellular stress response pathway, with implications relevant to cancer and beyond that, CDAII and normal cell biology.