bluuebunny/crossref_metadata_2025 huggingface dataset:
Thalamic dysconnectivity in the psychosis risk syndrome and early illness schizophrenia
Authors: Fryer Susanna L. , Ferri Jamie M. , Roach Brian J. , Loewy Rachel L. , Stuart Barbara K. , Anticevic Alan , Ford Judith M. , Mathalon Daniel H.
Published: March 2021

Background

Schizophrenia (SZ) is associated with thalamic dysconnectivity. Compared to healthy controls (HCs), individuals with SZ have hyperconnectivity with sensory regions, and hypoconnectivity with cerebellar, thalamic, and prefrontal regions. Despite replication of this pattern in chronically ill individuals, less is known about when these abnormalities emerge in the illness course and if they are present prior to illness onset.

Methods

Resting-state functional magnetic resonance imaging data were collected from psychosis risk syndrome (PRS) youth (n = 45), early illness SZ (ESZ) (n = 74) patients, and HCs (n = 85). Age-adjusted functional connectivity, seeded from the thalamus, was compared among the groups.

Results

Significant effects of group were observed in left and right middle temporal regions, left and right superior temporal regions, left cerebellum, and bilateral thalamus. Compared to HCs, ESZ demonstrated hyperconnectivity to all temporal lobe regions and reduced connectivity with cerebellar, anterior cingulate, and thalamic regions. Compared to HCs, PRS demonstrated hyperconnectivity with the left and right middle temporal regions, and hypoconnectivity with the cerebellar and other thalamic regions. Compared to PRS participants, ESZ participants were hyperconnected to temporal regions, but did not differ from PRS in hypoconnectivity with cerebellar and thalamic regions. Thalamic dysconnectivity was unrelated to positive symptom severity in ESZ or PRS groups.

Conclusions

PRS individuals demonstrated an intermediate level of thalamic dysconnectivity, whereas ESZ showed a pattern consistent with prior observations in chronic samples. These cross-sectional findings suggest that thalamic dysconnectivity may occur prior to illness onset and become more pronounced in early illness stages.
Mobilization Campaigns and Rural Development
Authors: Looney Kristen E.
Published: March 2021

Most accounts of East Asian economic growth have focused on the role of developmental states in successful industrialization. This article expands and challenges that framework by showing that rural policy was different from industrial policy. A key finding is that for more than a century, East Asian states have relied on mass mobilization campaigns rather than on technocratic planning and market-conforming institutions to achieve rural development. Based on case studies of Japan, South Korea, Taiwan, and China, the author argues that three main factors explain the rise of campaign states: revolutionary traditions, rural populism, and policy learning. A brief assessment of outcomes illustrates the payoffs and costs of campaigns and the practical considerations that drive them. The author’s analysis offers a new perspective on the East Asian model and disputes the widely held view that campaigns are tragic exercises in social control, demonstrating instead that they were central to the region’s rural transformation.
Historicizing the comparative survey of freedom: tracing the social trajectory of an influential indicator
Authors: Zerndt Emily
Published: March 2021

Argument

The Comparative Survey of Freedom, first published by Freedom House in 1973, is now the most widely used indicator of democracy by both academics and the U.S. government alike. However, literature examining the Survey’s origins is virtually nonexistent. In this article, I use archival records to challenge Freedom House’s retrospective account of the indicator’s creation. Rather than the outcome of a scientific methodology by multiple social scientists, the Survey was produced by a single political scientist, Raymond Gastil, according to his own hunches and impressions. How, then, did this indicator rise to such prominence? I argue that the Survey’s notoriety can be attributed to its early promotion in both political science and American foreign policy decision-making, as well as the fact that it fit the dominant scientific and political paradigms of the time.
A Monte Carlo evaluation of growth mixture modeling
Authors: Shader Tiffany M. , Beauchaine Theodore P.
Published: March 2021

Growth mixture modeling (GMM) and its variants, which group individuals based on similar longitudinal growth trajectories, are quite popular in developmental and clinical science. However, research addressing the validity of GMM-identified latent subgroupings is limited. This Monte Carlo simulation tests the efficiency of GMM in identifying known subgroups (k = 1–4) across various combinations of distributional characteristics, including skew, kurtosis, sample size, intercept effect size, patterns of growth (none, linear, quadratic, exponential), and proportions of observations within each group. In total, 1,955 combinations of distributional parameters were examined, each with 1,000 replications (1,955,000 simulations). Using standard fit indices, GMM often identified the wrong number of groups. When one group was simulated with varying skew and kurtosis, GMM often identified multiple groups. When two groups were simulated, GMM performed well only when one group had steep growth (whether linear, quadratic, or exponential). When three to four groups were simulated, GMM was effective primarily when intercept effect sizes and sample sizes were large, an uncommon state of affairs in real-world applications. When conditions were less ideal, GMM often underestimated the correct number of groups when the true number was between two and four. Results suggest caution in interpreting GMM results, which sometimes get reified in the literature.
Liver fibrosis in patients with tetralogy of Fallot, an unrecognised complication?
Authors: Ravndal Maren E. H. , Borgwardt Lise , Juul Klaus , Nielsen Jon , Borgwardt Lotte , Henriksen Birthe M. , Willemoe Gro L. , Jensen Annette S. , Christensen Vibeke B. , Kjær Mette S.
Published: March 2021

Objectives:

Improved survival has led to a growing population of adults with congenital heart disease (CHD), followed by numerous reports of late complications. Liver disease is a known complication in some patients, with most studies focusing on Fontan associated liver disease. Whether liver disease also exists in other patients with CHD is not fully investigated. Elevated central venous pressure is considered pivotal in the development of liver disease in Fontan associated liver disease, and other patients with alterations in central venous pressure may also be at risk for developing liver fibrosis. We wanted to see if liver fibrosis is present in patients with tetralogy of Fallot. Many patients with tetralogy of Fallot have severe pulmonary regurgitation, which can lead to elevated central venous pressure. Patients with tetralogy of Fallot may be at risk of developing liver fibrosis.

Materials and methods:

Ten patients (24–56 years) with tetralogy of Fallot and pulmonary regurgitation were investigated for liver fibrosis. All patients were examined with magnetic resonance elastography of liver, hepatobiliary iminodiacetic acid scan, indocyanine green elimination by pulse spectrophotometry, elastography via FibroScan, abdominal ultrasound including liver elastography, and blood samples including liver markers.

Results:

Three out of ten patients had findings indicating possible liver fibrosis. Two of these had a liver biopsy performed, which revealed fibrosis stage 1 and 2, respectively. The same three patients had an estimated elevated central venous pressure in previous echocardiograms.

Conclusions:

Mild liver fibrosis was present in selected patients with tetralogy of Fallot and may be related to elevated central venous pressure.
Magnesium intake, insulin resistance and markers of endothelial function among women
Authors: Bavani Narges Ghorbani , Saneei Parvane , Hassanzadeh Keshteli Ammar , Yazdannik Ahmadreza , Falahi Ebrahim , Sadeghi Omid , Esmaillzadeh Ahmad
Published: March 2021

Objective:

We investigated the association of dietary Mg intake with insulin resistance and markers of endothelial function among Iranian women.

Design:

A cross-sectional study.

Setting:

Usual dietary intakes were assessed using a validated FFQ. Dietary Mg intake was calculated by summing up the amount of Mg in all foods. A fasting blood sample was taken to measure serum concentrations of glycemic indices (fasting plasma glucose and insulin) and endothelial function markers (E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1). Insulin resistance and sensitivity were estimated using the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), Homeostasis Model Assessment β-cell function (HOMA-β) and quantitative insulin sensitivity check index (QUICKI).

Participants:

Iranian female nurses (n 345) selected by a multistage cluster random sampling method.

Results:

The Mg intake across energy-adjusted quartiles was 205 (se 7), 221·4 (se 8), 254·3 (se 7) and 355·2 (se 9) mg/d, respectively. After adjustments for potential confounders, QUICKI level was significantly different across quartiles of Mg intake (Q1: 0·34 (se 0·02), Q2: 0·36 (se 0·01), Q3: 0·40 (se 0·01), and Q4: 0·39 (se 0·02), P = 0·02); however, this association disappeared after considering markers of endothelial function, indicating that this relation might be mediated through endothelial dysfunction. After controlling for all potential confounders, Mg intake was inversely, but not significantly, associated with serum concentrations of sICAM (Q1: 239 (se 17), Q2: 214 (se 12), Q3: 196 (se 12), and Q4: 195 (se 17), P = 0·29). There was no other significant association between dietary Mg intake and other indicators of glucose homoeostasis or endothelial markers.

Conclusions:

Higher dietary Mg intake was associated with better insulin sensitivity in Iranian females. This linkage was mediated through reduced endothelial dysfunction.
Happiness at the end of life: A qualitative study
Authors: Beng Tan Seng , Ghee Wong Ka , Hui Ng Yun , Yin Ooi Chieh , Kelvin Khoo Wei Shen , Yiling See Toh , Huey Tan Ai , Capelle David Paul , Zainuddin Sheriza Izwa , Chin Loh Ee , Loong Lam Chee
Published: March 2021

Objective

Dying is mostly seen as a dreadful event, never a happy experience. Yet, as palliative care physicians, we have seen so many patients who remained happy despite facing death. Hence, we conducted this qualitative study to explore happiness in palliative care patients at the University of Malaya Medical Centre.

Method

Twenty terminally ill patients were interviewed with semi-structured questions. The results were thematically analyzed.

Results

Eight themes were generated: the meaning of happiness, connections, mindset, pleasure, health, faith, wealth, and work. Our results showed that happiness is possible at the end of life. Happiness can coexist with pain and suffering. Social connections were the most important element of happiness at the end of life. Wealth and work were given the least emphasis. From the descriptions of our patients, we recognized a tendency for the degree of importance to shift from the hedonic happiness to eudaimonic happiness as patients experienced a terminal illness.

Significance of results

To increase the happiness of palliative care patients, it is crucial to assess the meaning of happiness for each patient and the degree of importance for each happiness domain to allow targeted interventions.
Morphological characterization and genotypic identity of African yam bean (Sphenostylis stenocarpaHochst ex. A. Rich. Harms) germplasm from diverse ecological zones
Authors: Shitta Ndenum Suzzy , Abtew Wosene Gebresalassie , Ndlovu Noel , Oselebe Happiness O. , Edemodu Alex Chukwudi , Abebe Abush Tesfaye
Published: March 2021

African yam bean (AYB) is an affordable protein source capable of diversifying the food base in sub-Saharan Africa. However, research efforts made towards the crop's improvement and in expanding production are limited. This study characterized 169 AYB accessions at Jimma, Ethiopia, using 31 phenotypic characters. The analysis of variance revealed highly significant (P< 0.01) differences for days to 50% flowering, days to first flowering, leaf area, number of seeds per pod, pod length, seed thickness, total seed weight, petiole length and significant (P< 0.05) difference for terminal leaf length. Accession TSs62B produced the highest number of seeds per pod (17.65) and recorded the highest 100 seed weight (25.30 g), while 3A was the earliest to flower at an average of 84.50 d. Principal component analysis (PCA) of qualitative traits attributed 77.6% of observed variations to the first five principal components, of which the first two PC axes accounted for 53.6% of total variations. Cluster analysis and PCA biplot distinctly grouped the accessions into two major groups, cluster I had the highest number of accessions (108). The analytical approaches used confirmed considerable diversity across the germplasm with a distance matrix ranging from 0.37 to 0.85. The extent of diversity reflected in the current study provides breeders the baseline information to design breeding strategies, which might help identify materials for release as variety or parental lines for hybridization programmes.
Ethics, Epistemology, and Openness in Research with Human Participants
Authors: Kapiszewski Diana , Wood Elisabeth Jean
Published: March 2021

The political science discipline has recently engaged in contentious debate about the value of “research transparency,” particularly for research with human participants. The discipline is also holding vital conversations about research ethics and is rekindling dialogue about different ways of knowing. We offer an integrated account of how the actions that scholars who conduct human participant research take to respect ethical principles (which vary by research substance and settings), and their epistemological commitments (which vary across researchers), influence openness, a broader concept than “transparency.” These principles and commitments shape scholars’ openness practices simultaneously—both independently and in concert—serving as a prism through which multiple features of a research project are refracted, and resulting in a scholar’s inclination and ability to pursue openness in different ways and to different degrees with the audiences of her work. We also show how ethical principles and epistemological commitments can not only constrain and prevent openness, but also animate and require it. We suggest that scholars pursuing openness ethically, and in ways that honor their epistemological commitments, represents good social science, and we offer strategies for doing so. To develop our argument, we focus primarily on two research methods, ethnography and interviews, and on openness toward two audiences, human participants and research communities. Our account illuminates how the heterogeneity of human participant research makes it inappropriate, indeed impossible, to develop blanket rules for pursuing openness. Throughout, we highlight the importance of reflexivity for the ethical conduct of, and for being ethically open about, political science research.
Miniaturized four-port UWB MIMO antennas with triple-band rejection using single EBG structures
Authors: Thakur Ekta , Jaglan Naveen , Dev Gupta Samir
Published: March 2021

This research paper introduces a ultra-wideband (UWB) multiple input multiple output (MIMO)/diversity antenna with three rejected bands using one compact electromagnetic band gap (EBG) structure. The suggested EBG structure rejects three bands at WiMAX, WLAN, and the X-band within the passband of the UWB antenna. To achieve compactness in the conventional EBG structure, two via and square slots are introduced. This structure contributes to better impedance matching by using tapered feedline and slots in the radiating patch. To improve the isolation among all four compact UWB monopoles, decoupling strips are extended from the ground plane. Furthermore, the |S21| is below 17 dB in between the antenna elements and the envelope correlation coefficient is below 0.5, which are tolerable values within the UWB range. Furthermore, different MIMO/diversity characteristics are also discussed. An FR-4 substrate with dimensions of 38 × 45 × 1.6 mm3 is used for the fabrication of the suggested structure.
Thermo‐Mechanical Numerical Modeling of the South American Subduction Zone: A Multi‐Parametric Investigation
Authors: Strak V. , Schellart W. P.
Published: March 2021

The South American subduction zone is enigmatic due to its fast subducting plate consumption, strong oscillation in subducting plate velocity, and deep mantle subduction. A key to help understand these subduction zone characteristics is through studying its dynamics with buoyancy‐driven numerical modeling that uses independent variables to best approximate the dynamics of the real subduction system. We conduct a parametric investigation on the effect of upper mantle rheology, subduction interface yield stress and slab thermal weakening. To constrain those model variables, we attempt to find best‐fits by comparing our model outcomes with the present‐day slab geometry and estimates of Cenozoic velocities in the center of the South American subduction zone. Key ingredients that need to be reproduced are low slab dip angles close to the surface, steeper lower mantle dip angles, strong oscillation of the fast Farallon‐Nazca subducting plate velocity and a progressive decrease in trench retreat rate during long‐term subduction. We include these ingredients to define a model fitting score using 10 criteria. Our best fitting models involve a weak subduction zone interface (yield stress of ∼20 MPa) and significant slab thermal weakening to attain the fast Farallon‐Nazca subducting plate velocity and to better reproduce the subduction partitioning since 48 Ma due to reduced shear stresses resisting downdip slab sinking and reduced slab bending resistance. Furthermore, a non‐Newtonian upper mantle promotes slab folding and realistic oscillation of the subducting plate velocity. Whether and how this slab folding process induces temporal variations in Andean deformation remains an open question.
Rates and Mechanisms of Turbulent Mixing in a Coastal Embayment of the West Antarctic Peninsula
Authors: Scott Ryan M. , Brearley J. Alexander , Naveira Garabato Alberto C. , Venables Hugh J. , Meredith Michael P.
Published: March 2021

Quantifying and understanding the processes driving turbulent mixing around Antarctica are key to closing the Southern Ocean's heat budget, an essential component of the global climate system. In 2016, a glider deployed in Ryder Bay, West Antarctic Peninsula, collected hydrographic and microstructure data, obtaining some of the first direct measurements of turbulent kinetic energy dissipation off West Antarctica. Elevated dissipation O(10−8) W kg−1 is found above a topographic ridge separating the 520‐m‐deep bay, where values are O(10−10) W kg−1, from a deep fjord of the continental shelf, suggesting the ridge is important in driving upward mixing of warm Circumpolar Deep Water. The 12 glider transects reveal significant temporal variability in hydrographic and dissipation conditions. Mooring‐based current and nearby meteorological data are used to attribute thermocline shoaling (deepening) to Ekman upwelling (downwelling) at Ryder Bay's southern boundary, driven by ∼3‐day‐long south‐westward (north‐westward) wind events. Anticyclonic winds generated near‐inertial shear in the bay's upper layers, causing elevated bay‐wide shear and dissipation ∼1.7 days later. High dissipation over the ridge appears to be controlled hydraulically, being co‐located (and moving) with steeply sloping isopycnals. These are observed in ∼60% of the transects, with a corresponding mean upward heat flux of ∼2.4 W m−2. The ridge, therefore, provides sustained heat to the base of the thermocline, which can be released into overlying waters during the bay‐wide, thermocline‐focused dissipation events (mean heat flux of ∼1.3 W m−2). This highlights the role of ridges, which are widespread across the West Antarctic Peninsula, in the regional heat budget.
Indispensable Role of the Madden‐Julian Oscillation in the 2019 Extreme Autumn Drought Over Eastern China
Authors: Qi Li , Ji Yue , Zhang Wenjun
Published: March 2021

Eastern China suffered an extensive drought during autumn (September–October 2019) with precipitation deficits reaching as high as 70% of the climatology, the worst on record since the 1980s. Concurrent with this extreme drought, the tropical Indo–Pacific oceans experienced a central–Pacific (CP) El Niño event with the westernmost location, and the third–ranking positive Indian Ocean Dipole (IOD) event. However, the CP El Niño associated convection anomalies are unexpectedly absent over the western equatorial Pacific, leading to the decoupling of traditional atmospheric–oceanic connections between the tropical Pacific and Indian Oceans. A strong Madden–Julian oscillation (MJO) event stayed in the western Indian Ocean for 32 days during September–October 2019, nearly triple the frequency of climatology. This extraordinary long–lasting MJO activity suppressed the western Pacific convection associated with the CP El Niño and simultaneously enhanced the local IOD–related sea surface temperature anomalies via the atmospheric forcing. The MJO associated convection over the Indian Ocean can excite an anomalous cyclone in the western North Pacific, producing persistently extensive precipitation deficiencies over eastern China. It highlights that the abnormal MJO activity plays a crucial role on the Indo–Pacific atmospheric–oceanic features and the extreme precipitation deficits over eastern China.
Modeling Northern Hemispheric Ice Sheet Dynamics, Sea Level Change, and Solid Earth Deformation Through the Last Glacial Cycle
Authors: Han Holly Kyeore , Gomez Natalya , Pollard David , DeConto Robert
Published: March 2021

Retreat or advance of an ice sheet perturbs the Earth's solid surface, rotational vector, and the gravitational field, which in turn feeds back onto the evolution of the ice sheet over a range of timescales. Throughout the last glacial cycle, ice sheets over the Northern Hemisphere have gone through multiple growth and retreat phases, but the dynamics during these phases are not well understood. In this study, we apply a coupled ice sheet‐glacial isostatic adjustment model to simulate the Northern Hemisphere Ice Sheets over the last glacial cycle. We focus on understanding the influence of solid Earth deformation and gravitational field perturbations associated with surface (ice and water) loading changes on the dynamics of terrestrial and marine‐based ice sheets during different phases of the glacial cycle. Our results show that solid Earth deformation enhances glaciation during growth phases and melting during retreat phases in terrestrial regions through ice‐elevation feedback, and gravitational field perturbations have a stabilizing influence on marine‐based ice sheets in regions such as Hudson Bay in North America and Barents and Kara Seas in Eurasia during retreat phases through sea‐level feedback. Our results also indicate that solid Earth deformation influences the relative sensitivity of the North American and Eurasian ice sheets to climate and thus the timing and magnitude of their fluctuations throughout the last glacial cycle.
Recreating the Horizontal Magnetic Field at Colaba During the Carrington Event With Geospace Simulations
Authors: Blake Seán P. , Pulkkinen Antti , Schuck Peter W. , Glocer Alex , Oliveira Denny M. , Welling Daniel T. , Weigel Robert S. , Quaresima Gary
Published: March 2021

An intriguing aspect of the famous September 2, 1859 geomagnetic disturbance (or “Carrington” event) is the horizontal magnetic (BH) data set measured in Colaba, India (magnetic latitude approximately 20°N). The field exhibits a sharp decrease of over 1,600 nT and a quick recovery of about 1,300 nT, all within a few hours during the daytime. The mechanism behind this has previously been attributed to magnetospheric processes, ionospheric processes or a combination of both. In this study, we outline our efforts to replicate this low‐latitude magnetic field using the Space Weather Modeling Framework. By simulating an extremely high pressure solar wind scenario, we can emulate the low‐latitude surface magnetic signal at Colaba. In our simulation, magnetospheric currents adjacent to the near‐Earth magnetopause and strong Region 1 field‐aligned currents are the main contributors to the large Colaba BH. The rapid recovery of BH in our simulated scenario is due to the retreat of these magnetospheric currents as the magnetosphere expands, as opposed to ring current dynamics. In addition, we find that the scenario that best emulated the surface magnetic field observations during the Carrington event had a minimum calculated Dst value between −431 and −1,191 nT, indicating that Dst may not be a suitable estimate of storm intensity for this kind of event.
Fault Throw and Regional Uplift Histories From Drainage Analysis: Evolution of Southern Italy
Authors: Quye‐Sawyer Jennifer , Whittaker Alexander C. , Roberts Gareth G. , Rood Dylan H.
Published: March 2021

Landscapes can record elevation changes caused by multiple tectonic processes. Here, we show how coeval histories of spatially coincident normal faulting and regional uplift can be deconvolved from river networks. We focus on Calabria, a tectonically active region incised by rivers containing knickpoints and knickzones. Marine fauna indicate that Calabria has been uplifted by >1 km since ∼0.8–1.2 Ma, which we used to calibrate parameters in a stream power erosional model. To deconvolve the local and regional uplift contributions to topography, we performed a spatiotemporal inversion of 994 fluvial longitudinal profiles. Uplift rates from fluvial inversion replicate the spatial trend of rates derived from dated Mid‐Late Pleistocene marine terraces, and the magnitude of predicted uplift rates matches the majority of marine terrace uplift rates. We used the predicted uplift history to analyze long‐term fault throw, and combined throw estimates with ratios of footwall uplift to hanging wall subsidence to isolate the nonfault related contribution to uplift. Increases in fault throw rate—which may suggest fault linkage and growth—have been identified on two major faults from fluvial inverse modeling, and total fault throw is consistent with independent estimates. The temporal evolution of nonfault related regional uplift is similar at three locations. Our results may be consistent with toroidal mantle flow generating uplift, perhaps if faulting reduces the strength of the overriding plate. In conclusion, fluvial inverse modeling can be an effective technique to quantify fault array evolution and can deconvolve different sources of uplift that are superimposed in space and time.
Random‐Walk Modeling of Reactive Transport in Porous Media With a Reduced‐Order Chemical Basis of Conservative Components
Authors: Sole‐Mari Guillem , Schmidt Michael J. , Bolster Diogo , Fernàndez‐Garcia Daniel
Published: March 2021

In this work we employ a reduced‐order basis of conservative chemical components to model reactive transport using a Lagrangian (particle tracking) method. While this practice is well‐understood in the Eulerian (grid‐based) context, its adaptation to a Lagrangian context requires a novel reformulation of particle transport properties. Because the number of conservative‐species particles need not change during simulation, spatial resolution stays constant in time, and there is no increase in computational expense due to increasing numbers of product particles. Additionally, this treatment simplifies the interaction between equilibrium and kinetic reactions and allows the use of species‐dependent transport operators at the same time. We apply this method to model a suite of simple test problems that include equilibrium and kinetic reactions, and results exhibit excellent match with base‐case Eulerian results. Finally, we apply the new method to model a 2D problem concerning the mobilization of cadmium by a CO2 leak, showing the potential applicability of the proposed methodology.
Melting Dynamics of Late Cretaceous Lamprophyres in Central Asia Suggest a Mechanism to Explain Many Continental Intraplate Basaltic Suite Magmatic Provinces
Authors: Dai Hong‐Kun , Oliveira Beñat , Zheng Jian‐Ping , Griffin William L. , Afonso Juan Carlos , Xiong Qing , O'Reilly Suzanne Y.
Published: March 2021

Intraplate small‐volume mafic magmatism is spatially and temporally widespread in central and eastern Asia, but the relevant melting dynamics have remained enigmatic. Here, we report Ar‐Ar ages, mineral and whole‐rock compositions on newly found ∼81 Ma lamprophyre dykes from central Asia, aiming to constrain the source characteristics and the melting dynamics in this intraplate setting. Mineral chemistry of the lamprophyres shows that pre‐emplacement magmas equilibrated at 970–1060°C (probably at the base of the crust) and contained 1.4–2.1 wt% water. The source region of the lamprophyres is shown to have H contents equivalent to H2O = ∼150 ppm, and to be lithologically heterogeneous with silica‐deficient pyroxenite embedded in peridotite. Because of the thermodynamic complexities involved in calculating melting scenarios with major elements for such mantle domains, we have conducted a grid search with a forward‐modeling methodology that can simulate the adiabatic decompression melting of a lithologically heterogeneous mantle using incompatible trace elements. The modeling results indicate that original melting occurred at a potential temperature of ∼1400°C under a thinned lithosphere (∼70 km, corresponding to a final melting pressure of 2.3 GPa). Combining these conditions with constraints from regional geology and the tectonic history, the lamprophyres are inferred to have formed by decompression melting induced by small‐scale asthenospheric upwellings due to the edge effects under a corrugated lithospheric lower boundary. We suggest that this scenario has global relevance and represents a likely mechanism for the initiation of relatively small‐scale intraplate magmatism within continents.
Thank You to Our 2020 Reviewers
Authors: Brewer Peter , Chambers Don , Friedrichs Marjorie A. M. , Hetland Robert D. , Karnauskas Kristopher B. , Moran S. Bradley , Oey Lie‐Yauw , Padman Laurie , Pinardi Nadia , Zhou Lei , Mulligan Ryan
Published: March 2021

Key Point

The editors thank the 2020 peer reviewers
A novel missense variant of the GNAI3 gene and recognisable morphological characteristics of the mandibula in ARCND1
Authors: Yanagi Kumiko , Morimoto Noriko , Iso Manami , Abe Yukimi , Okamura Kohji , Nakamura Tomoo , Matsubara Yoichi , Kaname Tadashi
Published: March 2021

Auriculocondylar syndrome (ARCND) is an autosomal monogenic disorder characterised by external ear abnormalities and micrognathia due to hypoplasia of the mandibular rami, condyle and coronoid process. Genetically, three subtypes of ARCND (ARCND1, ARCND2 and ARCND3) have been reported. To date, five pathogenic variants of GNAI3 have been reported in ARCND1 patients. Here, we report a novel variant of GNAI3 (NM_006496:c.807C>A:p.(Asn269Lys)) in a Japanese girl with micrognathia using trio-based whole exome sequencing analysis. The GNAI3 gene encodes a heterotrimeric guanine nucleotide-binding protein. The novel variant locates the guanine nucleotide-binding site, and the substitution was predicted to interfere with guanine nucleotide-binding by in silico structural analysis. Three-dimensional computer tomography scan, or cephalogram, displayed severely hypoplastic mandibular rami and fusion to the medial and lateral pterygoid plates, which have been recognised in other ARCND1 patients, but have not been described in ARCND2 and ARCND3, suggesting that these may be distinguishable features in ARCND1.
Ultrahigh numerical aperture meta-fibre for flexible optical trapping
Authors: Plidschun Malte , Ren Haoran , Kim Jisoo , Förster Ronny , Maier Stefan A. , Schmidt Markus A.
Published: March 2021

Strong focusing on diffraction-limited spots is essential for many photonic applications and is particularly relevant for optical trapping; however, all currently used approaches fail to simultaneously provide flexible transportation of light, straightforward implementation, compatibility with waveguide circuitry, and strong focusing. Here, we demonstrate the design and 3D nanoprinting of an ultrahigh numerical aperture meta-fibre for highly flexible optical trapping. Taking into account the peculiarities of the fibre environment, we implemented an ultrathin meta-lens on the facet of a modified single-mode optical fibre via direct laser writing, leading to a diffraction-limited focal spot with a record-high numerical aperture of up to NA ≈ 0.9. The unique capabilities of this flexible, cost-effective, bio- and fibre-circuitry-compatible meta-fibre device were demonstrated by optically trapping microbeads and bacteria for the first time with only one single-mode fibre in combination with diffractive optics. Our study highlights the relevance of the unexplored but exciting field of meta-fibre optics to a multitude of fields, such as bioanalytics, quantum technology and life sciences.
Musashi-2 (MSI2) regulates epidermal growth factor receptor (EGFR) expression and response to EGFR inhibitors in EGFR-mutated non-small cell lung cancer (NSCLC)
Authors: Makhov Petr , Bychkov Igor , Faezov Bulat , Deneka Alexander , Kudinov Alexander , Nicolas Emmanuelle , Brebion Rohan , Avril Eleanor , Cai Kathy Q. , Kharin Leonid V. , Voloshin Mark , Frantsiyants Elena , Karnaukhov Nikolay , Kit Oleg I. , Topchu Iuliia , Fazliyeva Rushaniya , Nikonova Anna S. , Serebriiskii Ilya G. , Borghaei Hossein , Edelman Martin , Dulaimi Essel , Golemis Erica A. , Boumber Yanis
Published: March 2021

Non-small cell lung cancer (NSCLC) has limited treatment options. Expression of the RNA-binding protein (RBP) Musashi-2 (MSI2) is elevated in a subset of non-small cell lung cancer (NSCLC) tumors upon progression, and drives NSCLC metastasis. We evaluated the mechanism of MSI2 action in NSCLC to gain therapeutically useful insights. Reverse phase protein array (RPPA) analysis of MSI2-depleted versus control KrasLA1/+; Trp53R172HΔG/+ NSCLC cell lines identified EGFR as a MSI2-regulated protein. MSI2 control of EGFR expression and activity in an NSCLC cell line panel was studied using RT-PCR, Western blots, and RNA immunoprecipitation. Functional consequences of MSI2 depletion were explored for cell growth and response to EGFR-targeting drugs, in vitro and in vivo. Expression relationships were validated using human tissue microarrays. MSI2 depletion significantly reduced EGFR protein expression, phosphorylation, or both. Comparison of protein and mRNA expression indicated a post-transcriptional activity of MSI2 in control of steady state levels of EGFR. RNA immunoprecipitation analysis demonstrated that MSI2 directly binds to EGFR mRNA, and sequence analysis predicted MSI2 binding sites in the murine and human EGFR mRNAs. MSI2 depletion selectively impaired cell proliferation in NSCLC cell lines with activating mutations of EGFR (EGFRmut). Further, depletion of MSI2 in combination with EGFR inhibitors such as erlotinib, afatinib, and osimertinib selectively reduced the growth of EGFRmut NSCLC cells and xenografts. EGFR and MSI2 were significantly co-expressed in EGFRmut human NSCLCs. These results define MSI2 as a direct regulator of EGFR protein expression, and suggest inhibition of MSI2 could be of clinical value in EGFRmut NSCLC.
Inhibition of mTOR signaling by genetic removal of p70 S6 kinase 1 increases anxiety-like behavior in mice
Authors: Koehl Muriel , Ladevèze Elodie , Catania Caterina , Cota Daniela , Abrous Djoher Nora
Published: March 2021

The mechanistic target of rapamycin (mTOR) is a ubiquitously expressed kinase that acts through two complexes, mTORC1 and mTORC2, to regulate protein homeostasis, as well as long lasting forms of synaptic and behavioral plasticity. Alteration of the mTOR pathway is classically involved in neurodegenerative disorders, and it has been linked to dysregulation of cognitive functions and affective states. However, information concerning the specific involvement of the p70 S6 kinase 1 (S6K1), a downstream target of the mTORC1 pathway, in learning and memory processes and in the regulation of affective states remains scant. To fill this gap, we exposed adult male mice lacking S6K1 to a battery of behavioral tests aimed at measuring their learning and memory capabilities by evaluating reference memory and flexibility with the Morris water maze, and associative memory using the contextual fear conditioning task. We also studied their anxiety-like and depression-like behaviors by, respectively, performing elevated plus maze, open field, light-dark emergence tests, and sucrose preference and forced swim tests. We found that deleting S6K1 leads to a robust anxious phenotype concomitant with associative learning deficits; these symptoms are associated with a reduction of adult neurogenesis and neuronal atrophy in the hippocampus. Collectively, these results provide grounds for the understanding of anxiety reports after treatments with mTOR inhibitors and will be critical for developing novel compounds targeting anxiety.
Predicting alcohol use disorder remission: a longitudinal multimodal multi-featured machine learning approach
Authors: Kinreich Sivan , McCutcheon Vivia V. , Aliev Fazil , Meyers Jacquelyn L. , Kamarajan Chella , Pandey Ashwini K. , Chorlian David B. , Zhang Jian , Kuang Weipeng , Pandey Gayathri , Viteri Stacey Subbie-Saenz de. , Francis Meredith W. , Chan Grace , Bourdon Jessica L. , Dick Danielle M. , Anokhin Andrey P. , Bauer Lance , Hesselbrock Victor , Schuckit Marc A. , Nurnberger John I. , Foroud Tatiana M. , Salvatore Jessica E. , Bucholz Kathleen K. , Porjesz Bernice
Published: March 2021

Predictive models for recovering from alcohol use disorder (AUD) and identifying related predisposition biomarkers can have a tremendous impact on addiction treatment outcomes and cost reduction. Our sample (N = 1376) included individuals of European (EA) and African (AA) ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA) who were initially assessed as having AUD (DSM-5) and reassessed years later as either having AUD or in remission. To predict this difference in AUD recovery status, we analyzed the initial data using multimodal, multi-features machine learning applications including EEG source-level functional brain connectivity, Polygenic Risk Scores (PRS), medications, and demographic information. Sex and ancestry age-matched stratified analyses were performed with supervised linear Support Vector Machine application and were calculated twice, once when the ancestry was defined by self-report and once defined by genetic data. Multifeatured prediction models achieved higher accuracy scores than models based on a single domain and higher scores in male models when the ancestry was based on genetic data. The AA male group model with PRS, EEG functional connectivity, marital and employment status features achieved the highest accuracy of 86.04%. Several discriminative features were identified, including collections of PRS related to neuroticism, depression, aggression, years of education, and alcohol consumption phenotypes. Other discriminated features included being married, employed, medication, lower default mode network and fusiform connectivity, and higher insula connectivity. Results highlight the importance of increasing genetic homogeneity of analyzed groups, identifying sex, and ancestry-specific features to increase prediction scores revealing biomarkers related to AUD remission.
The association between family history and genomic burden with schizophrenia mortality: a Swedish population-based register and genetic sample study
Authors: Kowalec Kaarina , Lu Yi , Song Jie , Dalman Christina , Hultman Christina M. , Larsson Henrik , Lichtenstein Paul , Sullivan Patrick F.
Published: March 2021

Individuals with schizophrenia (SCZ) have a 2–3-fold higher risk of mortality than the general population. Heritability of mortality in psychiatric disorders has been proposed; however, few have investigated SCZ family history and genetic variation, with all-cause and specific causes of death. We aimed to identify correlates of SCZ mortality using genetic epidemiological and genetic modelling in two samples: a Swedish national population sample and a genotyped subsample. In the Swedish national population sample followed from the first SCZ treatment contact until emigration, death or end of the follow-up, we investigated a standardised measure of SCZ family history. In a subgroup with comprehensive genetic data, we investigated the impact of common and rare genetic variation. Cox proportional hazards regression was used to estimate the association between various factors and mortality (all and specific causes). A total of 13727 SCZ cases fulfilled criteria for the population-based analyses (1268 deaths, 9.2%). The genomic subset contained 4991 cases (1353 deaths, 27.1%). Somatic mutations associated with clonal hematopoiesis with unknown drivers were associated with all-cause mortality (HR 1.77, 95% CI: 1.26–2.49). No other heritable measures were associated with all-cause mortality nor with any specific causes of death. Future studies in larger, comparable cohorts are warranted to further understand the association between hereditary measures and mortality in SCZ.
Magnetic resonance imaging for individual prediction of treatment response in major depressive disorder: a systematic review and meta-analysis
Authors: Cohen Sem E. , Zantvoord Jasper B. , Wezenberg Babet N. , Bockting Claudi L. H. , van Wingen Guido A.
Published: March 2021

No tools are currently available to predict whether a patient suffering from major depressive disorder (MDD) will respond to a certain treatment. Machine learning analysis of magnetic resonance imaging (MRI) data has shown potential in predicting response for individual patients, which may enable personalized treatment decisions and increase treatment efficacy. Here, we evaluated the accuracy of MRI-guided response prediction in MDD. We conducted a systematic review and meta-analysis of all studies using MRI to predict single-subject response to antidepressant treatment in patients with MDD. Classification performance was calculated using a bivariate model and expressed as area under the curve, sensitivity, and specificity. In addition, we analyzed differences in classification performance between different interventions and MRI modalities. Meta-analysis of 22 samples including 957 patients showed an overall area under the bivariate summary receiver operating curve of 0.84 (95% CI 0.81–0.87), sensitivity of 77% (95% CI 71–82), and specificity of 79% (95% CI 73–84). Although classification performance was higher for electroconvulsive therapy outcome prediction (n = 285, 80% sensitivity, 83% specificity) than medication outcome prediction (n = 283, 75% sensitivity, 72% specificity), there was no significant difference in classification performance between treatments or MRI modalities. Prediction of treatment response using machine learning analysis of MRI data is promising but should not yet be implemented into clinical practice. Future studies with more generalizable samples and external validation are needed to establish the potential of MRI to realize individualized patient care in MDD.
Transcriptome alterations are enriched for synapse-associated genes in the striatum of subjects with obsessive-compulsive disorder
Authors: Piantadosi Sean C. , McClain Lora L. , Klei Lambertus , Wang Jiebiao , Chamberlain Brittany L. , Springer Sara A. , Lewis David A. , Devlin Bernie , Ahmari Susanne E.
Published: March 2021

Obsessive-compulsive disorder (OCD) is a chronic and severe psychiatric disorder for which effective treatment options are limited. Structural and functional neuroimaging studies have consistently implicated the orbitofrontal cortex (OFC) and striatum in the pathophysiology of the disorder. Recent genetic evidence points to involvement of components of the excitatory synapse in the etiology of OCD. However, the transcriptional alterations that could link genetic risk to known structural and functional abnormalities remain mostly unknown. To assess potential transcriptional changes in the OFC and two striatal regions (caudate nucleus and nucleus accumbens) of OCD subjects relative to unaffected comparison subjects, we sequenced messenger RNA transcripts from these brain regions. In a joint analysis of all three regions, 904 transcripts were differentially expressed between 7 OCD versus 8 unaffected comparison subjects. Region-specific analyses highlighted a smaller number of differences, which concentrated in caudate and nucleus accumbens. Pathway analyses of the 904 differentially expressed transcripts showed enrichment for genes involved in synaptic signaling, with these synapse-associated genes displaying lower expression in OCD subjects relative to unaffected comparison subjects. Finally, we estimated that cell type fractions of medium spiny neurons were lower whereas vascular cells and astrocyte fractions were higher in tissue of OCD subjects. Together, these data provide the first unbiased examination of differentially expressed transcripts in both OFC and striatum of OCD subjects. These transcripts encoded synaptic proteins more often than expected by chance, and thus implicate the synapse as a vulnerable molecular compartment for OCD.
Canonical TGF-β signaling regulates the relationship between prenatal maternal depression and amygdala development in early life
Authors: Qiu Anqi , Zhang Han , Wang Changqing , Chong Yap-Seng , Shek Lynette P. , Gluckman Peter D. , Meaney Michael J. , Fortier Marielle V. , Wu Yonghui
Published: March 2021

Canonical transforming growth factor-beta (TGF-β) signaling exerts neuroprotection and influences memory formation and synaptic plasticity. It has been considered as a new target for the prevention and treatment of depression. This study aimed to examine its modulatory role in linking prenatal maternal depressive symptoms and the amygdala volumes from birth to 6 years of age. We included mother–child dyads (birth: n = 161; 4.5 years: n = 131; 6 years: n = 162) and acquired structural brain images of children at these three time points. Perinatal maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) questionnaire to mothers at 26 weeks of pregnancy and 3 months postpartum. Our findings showed that the genetic variants of TGF-β type I transmembrane receptor (TGF-βRI) modulated the association between prenatal maternal depressive symptoms and the amygdala volume consistently from birth to 6 years of age despite a trend of significance at 4.5 years of age. Children with a lower gene expression score (GES) of TGF-βRI exhibited larger amygdala volumes in relation to greater prenatal maternal depressive symptoms. Moreover, children with a lower GES of the TGF-β type II transmembrane receptor (TGF-βRII), Smad4, and Smad7 showed larger amygdala volumes at 6 years of age in relation to greater prenatal maternal depressive symptoms. These findings support the involvement of the canonical TGF-β signaling pathway in the brain development of children in the context of in utero maternal environment. Such involvement is age-dependent.