bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the severity of depression: do nondepressive symptoms influence global ratings of depression severity?
Authors: Zimmerman Mark , Balling Caroline , Chelminski Iwona , Dalrymple Kristy 
Published: November 2019

AbstractObjective.Almost all depression measures have been developed without discussing how to best conceptualize and assess the severity of depression. It is therefore not surprising that measures differ in both how items are rated and item content. The question that we address in the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project is whether a measure of depression severity should include symptoms that are frequent in depressed patients but are defining features of other disorders (eg, anxiety, irritability)Methods.Patients were evaluated with a semi-structured interview and severity ratings were made of each symptom of major depressive disorder (MDD) as well as anxiety, irritability, and somatization. Patients were also rated on the Clinical Global Index of severity (CGI).Results.Three of the 5 nondepressive symptoms (psychic anxiety, somatic anxiety, and subjective anger) were significantly correlated with the CGI. The correlation between the sum of all 5 nondepressive symptoms and the CGI was significantly lower than the correlation between the sum of the depressive symptom severity ratings (0.12 vs 0.52, z = 11.0, p < .001). The partial correlation between the CGI and the nondepressive symptom severity ratings (after controlling for the total depressive symptom ratings) was nonsignificant.Discussion.After accounting for the severity of depressive symptoms, the severity of the nondepressive symptoms was not associated with global ratings of depressive severity. These findings raise questions regarding the appropriateness of including ratings of anxiety, irritability, and somatization on a measure that purportedly assesses the severity of depression.
Ingestion of magnesium was not associated with coronary calcium score	in a cross-sectional study
Authors: Levy Jéssica , Miranda Andreia Alexandra Machado , De Carli Eduardo , Bittencourt Marcio Sommer , Benseñor Isabela Judith , Lotufo Paulo Andrade , Marchioni Dirce Maria 
Published: November 2019

Abstract. Background and aims: Magnesium plays a key role in glucose metabolism, vascular tone, and inflammation. Therefore, it might be a dietary risk factor for cardiovascular diseases. In vitro and animal studies have suggested a decrease in vascular calcification with an increase in the magnesium intake. The objective of the present study was to investigate the association between magnesium intake and coronary artery calcium (CAC) score among participants of the ELSA-Brasil. Methods: This is an observational, cross-sectional study undertaken with a sub-sample from the ELSA-Brasil baseline data. In this sub-sample, only participants with CAC examination data were included (n = 4,306). Dietary intake was assessed by a validated food frequency questionnaire. The association between magnesium intake and presence of CAC (0 versus > 0) was investigated using multiple logistic regression models. Results: The participants were predominantly female (54.4 %), with self-reported white skin color (59.1 %), no smoking habit (53.7 %) and undergraduate or postgraduate education (44.4 %). The range of magnesium consumption was 37.24 – 1266.31 mg/day. CAC prevalence was 28.4 %. No significant association was found between magnesium intake and CAC after adjustments for diet, lifestyle, and clinical characteristics. In a first univariate model, the fifth quintile of magnesium intake, in comparison to the first quintile (lowest intake), resulted in an OR = 1.25, 95 % CI: 1.01 – 1.54 ( P-linear trend = 0.005). However, in the last fully adjusted model, the fifth quintile of magnesium intake resulted in OR = 0.86, 95 % CI: 0.64 – 1.17 ( P-linear trend = 0.239). Conclusions: In ELSA-Brasil, the intake of magnesium was not associated with the presence of coronary artery calcification.
Delayed Weakening and Reactivation of Rate‐and‐State Faults Driven by Pressure Changes Due to Fluid Injection
Authors: Andrés Sandro , Santillán David , Mosquera Juan Carlos , Cueto‐Felgueroso Luis 
Published: November 2019

AbstractFault reactivation induced by pore pressure changes involves complex frictional phenomena because effective normal stresses vary in space and time due to fluid flow and rock deformation. The impact of time‐varying normal stresses on fault friction has been characterized in stress‐step laboratory experiments and modeled through extended rate‐and‐state laws that incorporate a stressing‐rate dependence of the state variable. Building on these rate‐and‐state models, we use 2‐D poroelastic simulations to understand how the evolution of pore pressures due to fluid injection affects fault strength and reactivation. A sharp increase in pore pressure, associated with fluid injection, leads to an increase in friction coefficient and to a delayed weakening of the fault. Conversely, a sharp pressure decrease during extraction leads to a delayed strengthening. Stressing‐rate effects emerge as a purely frictional mechanism that delays or accelerates the onset of fault slip, suggesting that reactivation under fluid injection may occur long after flow rates have decreased and pore pressures have stabilized at the fault. Hence, earthquakes induced by injection may ensue as a deferred process triggered several days later than predicted by simple estimates based on constant friction. The duration of the delay depends on the type of rate‐and‐state law used in calculations and on a characteristic relaxation time: The memory time over which the state variable evolves under stationary contact. Our results help understand the connection between injection protocols and frictional weakening mechanisms, suggesting that injection processes can be engineered to minimize the risk of induced seismicity for a given injected volume.
Earthquake Initiation From Laboratory Observations and Implications for Foreshocks
Authors: McLaskey Gregory C. 
Published: November 2019

AbstractThis paper reviews laboratory observations of earthquake initiation and describes new experiments on a 3‐m rock sample where the nucleation process is imaged in detail. Many of the laboratory observations are consistent with previous work that showed a slow and smoothly accelerating earthquake nucleation process that expands to a critical nucleation length scale Lc, before it rapidly accelerates to dynamic fault rupture. The experiments also highlight complexities not currently considered by most theoretical and numerical models. This includes a loading rate dependency where a “kick” above steady state produces smaller and more abrupt initiation. Heterogeneity of fault strength also causes abrupt initiation when creep fronts coalesce on a stuck patch that is somewhat stronger than the surrounding fault. Taken together, these two mechanisms suggest a rate‐dependent “cascade up” model for earthquake initiation. This model simultaneously accounts for foreshocks that are a by‐product of a larger nucleation process and similarities between initial P wave signatures of small and large earthquakes. A diversity of nucleation conditions are expected in the Earth's crust, ranging from slip limited environments with Lc < 1 m, to ignition‐limited environments with Lc > 10 km. In the latter case, Lc fails to fully characterize the initiation process since earthquakes nucleate not because a slipping patch reaches a critical length but because fault slip rate exceeds a critical power density needed to ignite dynamic rupture.
Seismic Tomography Using Variational Inference Methods
Authors: Zhang Xin , Curtis Andrew 
Published: November 2019

AbstractSeismic tomography is a methodology to image the interior of solid or fluid media and is often used to map properties in the subsurface of the Earth. In order to better interpret the resulting images, it is important to assess imaging uncertainties. Since tomography is significantly nonlinear, Monte Carlo sampling methods are often used for this purpose, but they are generally computationally intractable for large data sets and high‐dimensional parameter spaces. To extend uncertainty analysis to larger systems, we use variational inference methods to conduct seismic tomography. In contrast to Monte Carlo sampling, variational methods solve the Bayesian inference problem as an optimization problem yet still provide fully nonlinear, probabilistic results. In this study, we applied two variational methods, automatic differential variational inference and Stein variational gradient descent, to 2‐D seismic tomography problems using both synthetic and real data, and we compare the results to those from two different Monte Carlo sampling methods. The results show that automatic differential variational inference provides a biased approximation because of its implicit transformed‐Gaussian approximation, and it cannot be used to find generally multimodal posteriors; Stein variational gradient descent produces more accurate approximations to the results of Monte Carlo sampling methods. Both methods estimate the posterior distribution at significantly lower computational cost, provided that gradients of parameters with respect to data can be calculated efficiently. We expect that the methods can be applied fruitfully to many other types of geophysical inverse problems.
Electron Temperature Response to Solar Forcing in the Low‐Latitude Martian Ionosphere
Authors: Pilinski M. , Andersson L. , Fowler C. , Peterson W. K. , Thiemann E. , Elrod M. K. 
Published: November 2019

AbstractElectron temperatures are a key parameter for understanding the ionosphere‐thermosphere system. This study uses in situ data from the MAVEN mission to investigate the level of coupling between the Martian ionospheric electrons and the neutral thermosphere below the altitude of 190 km. Such coupling is responsible for significant diurnal variations and dawn/dusk asymmetries in both the neutral and plasma portions of the ionosphere‐thermosphere system. Earlier theoretical studies suggested that neutral species controlled the electron temperature by collisional cooling thus implying a diurnal trend in electron temperatures due to the diurnal variability of the neutrals. This hypothesis is evaluated across the dayside ionosphere in the present work. Observations of neutral densities confirm that neutral‐electron collisions are the primary process controlling the cooling of electrons in the Martian ionosphere below ~190 km. The consequence of this is that electron temperatures can be anticorrelated with the extreme ultraviolet (EUV) irradiance due to enhanced electron cooling brought about by an expansion of neutral densities. The results also indicate that in the afternoon sector, neutral densities are less responsive to changes in EUV. This might be associated with enhanced winds leading to dynamic cooling that mitigates the thermal expansion of the thermosphere in the afternoon region. Subsequently, the electron temperature as a function of EUV is relatively uncorrelated in the afternoon sector.
Representing Intrahillslope Lateral Subsurface Flow in the Community Land Model
Authors: Swenson Sean C. , Clark Martyn , Fan Ying , Lawrence David M. , Perket Justin 
Published: November 2019

AbstractThe concept of using representative hillslopes to simulate hydrologically similar areas of a catchment has been incorporated in many hydrologic models but few Earth system models. Here we describe a configuration of the Community Land Model version 5 in which each grid cell is decomposed into one or more multicolumn hillslopes. Within each hillslope, the intercolumn connectivity is specified, and the lateral saturated subsurface flow from each column is passed to its downslope neighbor. We first apply the model to simulate a headwater catchment and assess the results against runoff and evapotranspiration flux measurements. By redistributing soil water within the catchment, the model is able to reproduce the observed difference between evapotranspiration in the upland and lowland portions of the catchment. Next, global simulations based on hypothetical hillslope geomorphic parameters are used to show the model's sensitivity to differences in hillslope shape and discretization. Differences in evapotranspiration between upland and lowland hillslope columns are found to be largest in arid and semiarid regions, while humid tropical and high‐latitude regions show limited evapotranspiration increases in lowlands relative to uplands.
Efficient treatment of murine acute GvHD by in vitro expanded donor regulatory T cells
Authors: Riegel Christin , Boeld Tina J. , Doser Kristina , Huber Elisabeth , Hoffmann Petra , Edinger Matthias 
Published: November 2019

Abstract
Acute graft-versus-host disease (aGvHD) is a frequent complication after allogeneic bone marrow/stem cell transplantation (BMT/SCT) induced by co-transplanted alloreactive conventional donor T cells. We previously demonstrated that the adoptive transfer of donor CD4+CD25+Foxp3+ regulatory T cells (Treg) at the time of BMT prevents aGvHD in murine models. Yet, the therapeutic potential of donor Treg for the treatment of established aGvHD has not yet been studied in detail. We now used in vitro expanded phenotypically and functionally stable murine Treg to explore their therapeutic efficacy in haploidentical aGvHD models. Upon transfer donor Treg ameliorate clinical and histologic signs of aGvHD and significantly improve survival. They migrate to lymphoid as well as aGvHD target organs, predominantly the gastrointestinal tract, where they inhibit the proliferation of conventional T cells, reduce the influx of myeloid cells, and the accumulation of inflammatory cytokines. Successfully treated animals restore aGvHD-induced tissue damage in target organs and lymphoid tissues, thereby supporting lymphocyte reconstitution. The therapeutically applied Treg population survives long term without conversion into pathogenic effector T cells. These results demonstrate that donor Treg not only prevent aGvHD, but are also efficacious for the treatment of this life-threatening BMT complication.
Inhibiting lysine 353 oxidation of GRP78 by a hypochlorous probe targeting endoplasmic reticulum promotes autophagy in cancer cells
Authors: Ning Junya , Lin Zhaomin , Zhao Xuan , Zhao Baoxiang , Miao Junying 
Published: November 2019

AbstractThe level of hypochlorous acid (HOCl) in cancer cells is higher than that in non-cancer cells. HOCl is an essential signal for the regulation of cell fate and works mainly through the protein post-translational modifications in cancer cells. However, the mechanism of HOCl regulating autophagy has not been clarified. Here we reported that a HOCl probe named ZBM-H targeted endoplasmic reticulum and induced an intact autophagy flux in lung cancer cells. Furthermore, ZBM-H promoted the binding of GRP78 to AMPK and increased the phosphorylation of AMPK in a dose- and time-dependent manner. GRP78 knockdown inhibited ZBM-H-induced AMPK phosphorylation and ZBM-H-stimulated autophagy. In addition, mass spectrometry combined with point mutation experiments revealed that ZBM-H increased GRP78 activity by inhibiting HOCl-induced lysine 353 oxidation of GRP78. Following ZBM-H treatment in vitro and in vivo, cell growth was significantly inhibited while apoptosis was induced. Nevertheless, exogenous HOCl partially reversed ZBM-H-inhibited cell growth and ZBM-H-induced GRP78 activation. In brief, we found that an endoplasmic reticulum-targeted HOCl probe named ZBM-H, acting through attenuating HOCl-induced GRP78 oxidation, inhibited tumor cell survival by promoting autophagy and apoptosis. Overall, these data demonstrated a novel mechanism of hypochlorous acid regulating autophagy by promoting the oxidation modification of GRP78.
Endogenous alpha-synuclein monomers, oligomers and resulting pathology: let’s talk about the lipids in the room
Authors: Killinger Bryan A. , Melki Ronald , Brundin Patrik , Kordower Jeffrey H. 
Published: November 2019

AbstractAlpha-synuclein is an intrinsically disordered, highly dynamic protein that pathogenically aggregates into inclusion structures called Lewy bodies, in several neurogenerative diseases termed synucleinopathies. Despite its importance for understanding disease, the oligomerization status of alpha-synuclein in healthy cells remains unclear. Alpha-synuclein may exist predominantly as either a monomer or a variety of oligomers of different molecular weights. There is solid evidence to support both theories. Detection of apparent endogenous oligomers are intimately dependent on vesicle and lipid interactions. Here we consider the possibility that apparent endogenous alpha-synuclein oligomers are in fact conformations of membrane-bound alpha-synuclein and not a bona fide stable soluble species. This perspective posits that the formation of any alpha-synuclein oligomers within the cell is likely toxic and interconversion between monomer and oligomer is tightly controlled. This differs from the hypothesis that there is a continuum of endogenous non-toxic oligomers and they convert, through unclear mechanisms, to toxic oligomers. The distinction is important, because it clarifies the biological origin of synucleinopathy. We suggest that a monomer-only, lipid-centric view of endogenous alpha-synuclein aggregation can explain how alpha-synuclein pathology is triggered, and that the interactions between alpha-synuclein and lipids can represent a target for therapeutic intervention. This discussion is well-timed due to recent studies that show lipids are a significant component of Lewy pathology.
Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification
Authors: La Merrill Michele A. , Vandenberg Laura N. , Smith Martyn T. , Goodson William , Browne Patience , Patisaul Heather B. , Guyton Kathryn Z. , Kortenkamp Andreas , Cogliano Vincent J. , Woodruff Tracey J. , Rieswijk Linda , Sone Hideko , Korach Kenneth S. , Gore Andrea C. , Zeise Lauren , Zoeller R. Thomas 
Published: November 2019

Abstract
Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that interfere with hormone action, thereby increasing the risk of adverse health outcomes, including cancer, reproductive impairment, cognitive deficits and obesity. A complex literature of mechanistic studies provides evidence on the hazards of EDC exposure, yet there is no widely accepted systematic method to integrate these data to help identify EDC hazards. Inspired by work to improve hazard identification of carcinogens using key characteristics (KCs), we have developed ten KCs of EDCs based on our knowledge of hormone actions and EDC effects. In this Expert Consensus Statement, we describe the logic by which these KCs are identified and the assays that could be used to assess several of these KCs. We reflect on how these ten KCs can be used to identify, organize and utilize mechanistic data when evaluating chemicals as EDCs, and we use diethylstilbestrol, bisphenol A and perchlorate as examples to illustrate this approach.
Clinical and genetic variability in children with partial albinism
Authors: Campbell Patrick , Ellingford Jamie M. , Parry Neil R. A. , Fletcher Tracy , Ramsden Simon C. , Gale Theodora , Hall Georgina , Smith Katherine , Kasperaviciute Dalia , Thomas Ellen , Lloyd I. Chris , Douzgou Sofia , Clayton-Smith Jill , Biswas Susmito , Ashworth Jane L. , Black Graeme C. M. , Sergouniotis Panagiotis I. 
Published: November 2019

AbstractIndividuals who have ocular features of albinism and skin pigmentation in keeping with their familial background present a considerable diagnostic challenge. Timely diagnosis through genomic testing can help avert diagnostic odysseys and facilitates accurate genetic counselling and tailored specialist management. Here, we report the clinical and gene panel testing findings in 12 children with presumed ocular albinism. A definitive molecular diagnosis was made in 8/12 probands (67%) and a possible molecular diagnosis was identified in a further 3/12 probands (25%).TYRwas the most commonly mutated gene in this cohort (75% of patients, 9/12). A disease-causingTYRhaplotype comprised of two common, functional polymorphisms,TYRc.[575 C > A;1205 G > A] p.[(Ser192Tyr);(Arg402Gln)], was found to be particularly prevalent. One participant hadGPR143-associated X-linked ocular albinism and another proband had biallelic variants inSLC38A8, a glutamine transporter gene associated with foveal hypoplasia and optic nerve misrouting without pigmentation defects. Intriguingly, 2/12 individuals had a single, rare, likely pathogenic variant in each ofTYRandOCA2– a significant enrichment compared to a control cohort of 4046 individuals from the 100,000 genomes project pilot dataset. Overall, our findings highlight that panel-based genetic testing is a clinically useful test with a high diagnostic yield in children with partial/ocular albinism.
Determinants of Childhood Anemia in India
Authors: Onyeneho Nkechi G. , Ozumba Benjamin C. , Subramanian S. V. 
Published: November 2019

AbstractWe analyzed a sample of 112714 children from the 2015–2016 Indian National Fertility and Health Survey with available data on hemoglobin. Multinomial logistic regression models were used to establish associations between parent anemia, household characteristics and nutritional intake of children. Linear regression analysis was also conducted to see the link between the household characteristic and childhood nutritional intake on one hand and hemoglobin levels on the other hand. A number of socio-demographic factors, namely maternal age, type of residence and maternal education, as well as wealth index, among others correlate with incidence of childhood anemia. For instance, whereas 52.9% of children in the richest households were anemic, 63.2% of children in the poorest household were anemic (p < 0.001). Mean Vitamin A intake in the last six months was 0.63 (0.626–0.634) which was 0.18% of the recommended intake. Mean iron intake, from sources other than breast milk, in the last 24 hours was 0.29 (0.286–0.294) and 2.42% of the recommended daily intake. Fifty-nine percent (58.5%) of the children surveyed were anemic (Hb level: 9.75 g/dL [9.59–9.91]). Children with anemia were more prone to being iron deficient (odds ratio [OR]: 0.981 (0.961–1.001), Vitamin A deficient (OR: 0.813 (0.794–0.833)), and have lower maternal hemoglobin level (OR: 1.992 (1.957–2.027)). Combining nutritional supplementation and food-fortification programmes with reduction in maternal anemia and family poverty may yield optimal improvement of childhood anemia in India.
Anthropogenic aerosol drives uncertainty in future climate mitigation efforts
Authors: Larson E. J. L. , Portmann R. W. 
Published: November 2019

AbstractThe 2016 Paris agreement set a global mean surface temperature (GMST) goal of not more than 2 degrees Celsius above preindustrial. This is an ambitious goal that will require substantial decreases in emission rates of long-lived greenhouse gasses (GHG). This work provides a mathematical framework, based on current state of the art climate models, to calculate the GHG emissions consistent with prescribed GMST pathways that meet the Paris agreement goal. The unique capability of this framework, to start from a GMST timeseries and efficiently calculate the emissions required to meet that temperature pathway, makes it a powerful resource for policymakers. Our results indicate that aerosol emissions play a large role in determining the near-term allowable greenhouse gas emissions that will limit future warming to 2 °C, however in the long term, drastic GHG emissions reductions are required under any reasonable aerosol scenario. With large future aerosol emissions, similar to present day amounts, GHG emissions need to be reduced 8% by 2040 and 74% by 2100 to limit warming to 2 °C. Under a more likely low aerosol scenario, GHG emissions need to be reduced 36% and 80% by 2040 and 2100, respectively. The Paris agreement Intended Nationally Determined Contributions are insufficient to meet this goal.