bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gestational diabetes: changed health beliefs in migrant women from five Asian countries living in Sweden: a prospective qualitative study
Authors: Hjelm Katarina , Bard Karin , Apelqvist Jan 
Published: January 2022

AbstractAim:The aim of this study was to explore the temporal development of beliefs about health, illness and health care in migrant women with gestational diabetes (GD) born in Asia residing in Sweden, and the influence on health-related behaviour in terms of self-care and seeking care.Background:Migrant Asian women are a high-risk group for developing GD. Adapting to the culture in the new society and the healthcare system, being diagnosed with GD and becoming a mother is demanding. The question is whether Asian migrants’ patterns of beliefs and behaviour change over time, as no previous study has been revealed on this topic.Method:Qualitative prospective exploratory study. Semi-structured interviews were held on three occasions: during pregnancy and three and fourteen months after delivery, with women born in Asia, diagnosed with GD. Data were analysed with qualitative content analysis.Findings:There was a temporal change of beliefs influencing health-related behaviour, showing a rising curve in risk awareness. An increasing number of persons described developing a healthy diet/lifestyle based on initial advice and shifted focus from the child to worries about the woman’s health and risk of developing type 2 diabetes and being unable to care for the child/family. Also, the number of women perceiving GD as a transient condition decreased and more believed it would last forever. Beliefs about health care were unchanged, the healthcare model was perceived working well but information about GD and follow-ups was requested even after delivery, and competent staff was expected. Health professionals’ beliefs about the seriousness of GD influence patients’ beliefs and need to be considered. Migrant women need support with adequate information, based on their individual beliefs, to continue develop a sustainable healthy lifestyle even after giving birth, to promote health and prevent type 2 diabetes.
North Atlantic Cooling is Slowing Down Mass Loss of Icelandic Glaciers
Authors: Noël Brice , Aðalgeirsdóttir Guðfinna , Pálsson Finnur , Wouters Bert , Lhermitte Stef , Haacker Jan M. , van den Broeke Michiel R. 
Published: January 2022

AbstractIcelandic glaciers have been losing mass since the Little Ice Age in the mid‐to‐late 1800s, with higher mass loss rates in the early 21st century, followed by a slowdown since 2011. As of yet, it remains unclear whether this mass loss slowdown will persist in the future. By reconstructing the contemporary (1958–2019) surface mass balance of Icelandic glaciers, we show that the post‐2011 mass loss slowdown coincides with the development of the Blue Blob, an area of regional cooling in the North Atlantic Ocean to the south of Greenland. This regional cooling signal mitigates atmospheric warming in Iceland since 2011, in turn decreasing glacier mass loss through reduced meltwater runoff. In a future high‐end warming scenario, North Atlantic cooling is projected to mitigate mass loss of Icelandic glaciers until the mid‐2050s. High mass loss rates resume thereafter as the regional cooling signal weakens.
Orbital Forcing Strongly Influences the Poleward Shift of the Spring Himalayan Jet During the Past Millennium
Authors: Thapa U. K. , Stevenson S. , Midhun M. 
Published: January 2022

AbstractThe latitudinal position of the subtropical jet over the Himalayas (Himalayan jet latitude or HJL) controls the region's climate during winter and spring by guiding moisture‐delivering storms. Here we use the Community Earth System Model‐Last Millennium Ensemble to diagnose forced trends in HJL during the past millennium. During 850–1849, there is a weak equatorward trend in winter HJL. In contrast, the spring HJL has a relatively larger poleward trend, and increases in both variance and frequency of poleward/equatorward excursions. We demonstrate changes in orbital precession reduced the thermal gradient between tropical and subtropical Asia, shifting the spring HJL poleward. During 1850–2005, the spring HJL exhibits no trend due to compensating influences from orbital and anthropogenic greenhouse gas forcings. These findings suggest it is essential climate models properly simulate the effects of and potential interactions between orbital forcing and anthropogenic factors to accurately project Himalayan jet variability and associated storm tracks.
Dynamics of ENSO Phase–Locking and Its Biases in Climate Models
Authors: Chen Han‐Ching , Jin Fei‐Fei 
Published: January 2022

AbstractThe contributions of different oceanic feedbacks to the El Niño–Southern Oscillation (ENSO) phase‐locking are examined by deriving ENSO dynamics based on the recharge‐discharge framework. In observations, the significant winter preference of the ENSO peak is determined by a strong seasonal modulation of SST growth rate, which is controlled by the zonal advective and thermodynamic feedbacks. However, the majority of climate models fail to simulate ENSO phase‐locking because the contribution of zonal advective feedback to the seasonal modulation of the SST growth rate is much smaller compared to observations. The weak annual cycle of the SST‐current coupling coefficient and small annual mean of the negative climatological zonal SST gradient are two factors contributing to the weak‐biased seasonality of zonal advective feedback. Further analysis shows that the Niño3.4 SSTA has better phase‐locking performance than Niño3 SSTA in the climate models due to the better simulation of zonal advection feedback in the Niño3.4 region.
Analysis of E × B Drifts in Earth's Magnetosphere During Geomagnetic Reversals: Potential Consequences for Plasmasphere Behavior and Stability
Authors: Caggiano J. A. , Paty C. S. 
Published: January 2022

AbstractGeomagnetic pole reversals occur frequently throughout geologic history, although one has not yet occurred in recorded time. Magnetohydrodynamic models of Earth's core have revealed that during a reversal, the magnetic dipole moment disappears, leaving higher‐order moments. Previous research examined quadrupole magnetic field topologies and quantitatively specified the magnetic equators of those topologies but did not fully examine charged particle drift motion and stability in the inner magnetosphere. Earth's closed magnetosphere is primarily dominated by two electric fields, the corotational and convection generated electric fields. drifts from these fields ultimately drives the behavior of the cold plasma of the plasmasphere. In a quadrupole‐dominated magnetic field, the plasma motion generated by the drifts would be dramatically different from the classical dipole field plasma convection. Three quadrupole topologies were evaluated, and the drift was analyzed along the magnetic equators of these topologies to characterize and quantify the resultant plasma motion and evaluate the behavior, structure and stability of the plasmasphere. We also tested for plasmaspause and magnetopause boundary sensitivity to magnetic field strength. The direction of the convection flow is hemispherically dependent for the η = 0 and 0.5 quadrupole topologies, that is, the plasma in the Northern Hemisphere convects tailward, and the Southern Hemisphere convects sunward. The η = 1 topology demonstrates evidence of strong plasmasphere erosion due to the intersection of the magnetic equators, and the magnetopause and plasmapause of the η = 1 topology are particularly sensitive to reductions in magnetic field strength.
Understanding the Paths of Surface Ozone Abatement in the Los Angeles Basin
Authors: Kim Si‐Wan , McDonald Brian C. , Seo Seunghwan , Kim Kyoung‐Min , Trainer Michael 
Published: January 2022

AbstractOzone in the urban atmosphere can accumulate from photochemistry involving nitrogen oxides, carbon monoxide, and volatile organic compounds mainly emitted from fossil fuel combustions and volatile chemical products. Concentrated ozone near the earth's surface has a detrimental impact on the ecosystem and our health. The Los Angeles Basin is a classic example of an urban region with long‐standing ozone pollution, frequently in violation of its standard, designated by the US Environmental Protection Agency (EPA). Studies have reported substantial declines of ozone and their precursor concentrations over the past half century in this area due to extensive pollution controls. Since 2000, however, the ozone design value has remained the same and has not been able to fully reach the air quality standard set by the EPA despite decreases in its precursor concentrations. To understand this phenomenon, we utilize a chemical transport modeling approach to reproduce historical ozone trends and to conduct sensitivity runs relative to a 2010 baseline. Based on our analysis of the model simulations comparing the weekends and weekdays, rather than focusing only on the weekly averages, we diagnose that the Los Angeles Basin is actually going under a significant transition in photochemistry toward a lower ozone concentration. This reveals how air quality management strategies are slowly moving towards a pathway of reducing ozone concentrations in the future. Our study, however, suggests that further reductions of NOx emissions can lead to continued improvement of ozone pollution in this area.
Studies on the Competition Between Homogeneous and Heterogeneous Ice Nucleation in Cirrus Formation
Authors: Kärcher B. , DeMott P. J. , Jensen E. J. , Harrington J. Y. 
Published: January 2022

AbstractCirrus ice crystals are produced heterogeneously on ice‐nucleating particles (INPs) and homogeneously in supercooled liquid solution droplets. They grow by uptake of water molecules from the ice‐supersaturated vapor. The precursor particles, characterized by disparate ice nucleation abilities and number concentrations, compete for available vapor during ice formation events. We investigate cirrus formation events systematically in different temperature and updraft regimes, and for different INP number concentrations and time‐independent nucleation efficiencies. We consider vertical air motion variability due to mesoscale gravity waves and effects of supersaturation‐dependent deposition coefficients for water molecules on ice surfaces. We analyze ice crystal properties to better understand the dynamics of competing nucleation processes. We study the reduction of ice crystal numbers produced by homogeneous freezing due to INPs in both, individual simulations assuming constant updraft speeds and in ensemble simulations based on a stochastic representation of vertical wind speed fluctuations. We simulate and interpret probability distributions of total nucleated ice crystal number concentrations, showing signatures of homogeneous and heterogeneous nucleation. At typically observed, mean updraft speeds (≈15 cm s−1) competing nucleation should occur frequently, even at rather low INP number concentrations (<10 L−1). INPs increase cirrus occurrence and may alter cirrus microphysical properties without entirely suppressing homogeneous freezing events. We suggest to improve ice growth models, especially for low cirrus temperatures (<220 K) and low ice supersaturation (<0.3).
Estimating Soil Surface Roughness With Models Based on the Information About Tillage Practises and Soil Parameters
Authors: Herodowicz‐Mleczak Karolina , Piekarczyk Jan , Kaźmierowski Cezary , Nowosad Jakub , Mleczak Mateusz 
Published: January 2022

AbstractThe quantitative description of the soil surface roughness is necessary for effective monitoring of wind, water and tillage erosion, hydrological processes or greenhouse gas emissions. The aim of this work was to build soil roughness predictive models based on the type of tillage tool, the roughness indices and soil properties. The roughness formed by five tillage tools was determined. Two surface roughness indices: Height Standard Deviation (HSD) and T3D (Tortuosity index) were calculated from Digital Elevation Model. The both roughness indices demonstrated a significant correlation, however, they provided different information about soil roughness. The HSD describes roughness on the “macro,” while T3D refers to the “micro” scale. Hence, our findings show that a single index is not sufficient to describe the roughness of post‐treatment surface. The linear and random forest models were built to describe the relationships between the roughness indices, type of tillage tool and soil properties. The HSD analysis indicated that the type of tillage tools had the greatest impact on post‐treatment roughness. In contrast, T3D analysis found soil texture to have a significant effect, together with tillage tools. In all modeling scenarios, T3D was more accurately predicted than HSD by both the linear (R2 = 0.62 vs. R2 = 0.60) and random forest models (R2 = 0.58 vs. R2 = 0.55). Predictive soil surface roughness models can be applied effectively for estimating water retention in soil, the intensity and speed of surface water flow, soil erosion, the level of reflected shortwave solar radiation or soil properties by remote sensing techniques.
Rare and localized events stabilize microbial community composition and patterns of spatial self-organization in a fluctuating environment
Authors: Ciccarese Davide , Micali Gabriele , Borer Benedict , Ruan Chujin , Or Dani , Johnson David R 
Published: January 2022

Abstract
Spatial self-organization is a hallmark of surface-associated microbial communities that is governed by local environmental conditions and further modified by interspecific interactions. Here, we hypothesize that spatial patterns of microbial cell-types can stabilize the composition of cross-feeding microbial communities under fluctuating environmental conditions. We tested this hypothesis by studying the growth and spatial self-organization of microbial co-cultures consisting of two metabolically interacting strains of the bacterium Pseudomonas stutzeri. We inoculated the co-cultures onto agar surfaces and allowed them to expand (i.e. range expansion) while fluctuating environmental conditions that alter the dependency between the two strains. We alternated between anoxic conditions that induce a mutualistic interaction and oxic conditions that induce a competitive interaction. We observed co-occurrence of both strains in rare and highly localized clusters (referred to as “spatial jackpot events”) that persist during environmental fluctuations. To resolve the underlying mechanisms for the emergence of spatial jackpot events, we used a mechanistic agent-based mathematical model that resolves growth and dispersal at the scale relevant to individual cells. While co-culture composition varied with the strength of the mutualistic interaction and across environmental fluctuations, the model provides insights into the formation of spatially resolved substrate landscapes with localized niches that support the co-occurrence of the two strains and secure co-culture function. This study highlights that in addition to spatial patterns that emerge in response to environmental fluctuations, localized spatial jackpot events ensure persistence of strains across dynamic conditions.
Efficacy and safety of enasidenib and azacitidine combination in patients with IDH2 mutated acute myeloid leukemia and not eligible for intensive chemotherapy
Authors: Venugopal Sangeetha , Takahashi Koichi , Daver Naval , Maiti Abhishek , Borthakur Gautam , Loghavi Sanam , Short Nicholas. J. , Ohanian Maro , Masarova Lucia , Issa Ghayas , Wang Xuemei , Carlos Bueso-Ramos , Yilmaz Musa , Kadia Tapan , Andreeff Michael , Ravandi Farhad , Konopleva Marina , Kantarjian Hagop M. , DiNardo Courtney D. 
Published: January 2022

AbstractPreclinically, enasidenib and azacitidine (ENA + AZA) synergistically enhance cell differentiation, and venetoclax (VEN), a small molecule Bcl2 inhibitor (i) is particularly effective in IDH2 mutated acute myeloid leukemia (IDH2mutAML). This open label phase II trial enrolled patients (pts) with documented IDH2mutAML. All patients received AZA 75 mg/m2/d x 7 d/cycle and ENA 100 mg QD continuously. Concomitant Bcl2i and FLT3i were allowed (NCT03683433).Twenty-six pts received ENA + AZA (median 68 years, range, 24–88); 7 newly diagnosed (ND) and 19 relapsed/refractory (R/R). In R/R AML patients, three had received prior ENA and none had received prior VEN. The composite complete remission rate (CRc) [complete remission (CR) or complete remission with incomplete hematologic recovery (CRi)] was 100% in ND AML, and 58% in R/R AML. Median OS was not reached in ND AML with median follow-up of 13.1 months (mo); Pts treated in first relapse had improved OS than those with ≥2 relapse (median OS not reached vs 5.2 mo; HR 0.24, 95% CI 0.07–0.79, p = 0.04). Two patients received ENA + AZA with a concomitant FLT3i, one responding ND AML patient and one nonresponding R/R AML patient. Seven R/R AML pts received ENA + AZA + VEN triplet, and with median follow up of 11.2 mo, median OS was not reached and 6-mo OS was 70%. The most frequent treatment-emergent adverse events include febrile neutropenia (23%). Adverse events of special interest included all-grade IDH differentiation syndrome (8%) and indirect hyperbilirubinemia (35%). ENA + AZA was a well-tolerated, and effective therapy for elderly pts with IDH2mut ND AML as well as pts with R/R AML. The addition of VEN to ENA + AZA appears to improve outcomes in R/R IDH2mutAML.Clinical trial registration information: https://clinicaltrials.gov/.NCT03683433
Theobroma cacao improves bone growth by modulating defective ciliogenesis in a mouse model of achondroplasia
Authors: Martin Ludovic , Kaci Nabil , Benoist-Lasselin Catherine , Mondoloni Marine , Decaudaveine Suzanne , Estibals Valentin , Cornille Maxence , Loisay Léa , Flipo Justine , Demuynck Benoît , de la Luz Cádiz-Gurrea Maria , Barbault Florent , Fernández-Arroyo Salvador , Schibler Laurent , Segura-Carretero Antonio , Dambroise Emilie , Legeai-Mallet Laurence 
Published: January 2022

AbstractA gain-of-function mutation in the fibroblast growth factor receptor 3 gene (FGFR3) results in achondroplasia (ACH), the most frequent form of dwarfism. Constitutive activation of FGFR3 impairs bone formation and elongation and many signal transduction pathways. Identification of new and relevant compounds targeting the FGFR3 signaling pathway is of broad importance for the treatment of ACH, and natural plant compounds are prime drug candidate sources. Here, we found that the phenolic compound (-)-epicatechin, isolated from Theobroma cacao, effectively inhibited FGFR3’s downstream signaling pathways. Transcriptomic analysis in an Fgfr3 mouse model showed that ciliary mRNA expression was modified and influenced significantly by the Indian hedgehog and PKA pathways. (-)-Epicatechin is able to rescue mRNA expression impairments that control both the structural organization of the primary cilium and ciliogenesis-related genes. In femurs isolated from a mouse model (Fgfr3Y367C/+) of ACH, we showed that (-)-epicatechin eliminated bone growth impairment during 6 days of ex vivo culture. In vivo, we confirmed that daily subcutaneous injections of (-)-epicatechin to Fgfr3Y367C/+ mice increased bone elongation and rescued the primary cilium defects observed in chondrocytes. This modification to the primary cilia promoted the typical columnar arrangement of flat proliferative chondrocytes and thus enhanced bone elongation. The results of the present proof-of-principle study support (-)-epicatechin as a potential drug for the treatment of ACH.
KRAS(G12D) can be targeted by potent inhibitors via formation of salt bridge
Authors: Mao Zhongwei , Xiao Hongying , Shen Panpan , Yang Yu , Xue Jing , Yang Yunyun , Shang Yanguo , Zhang Lilan , Li Xin , Zhang Yuying , Du Yanan , Chen Chun-Chi , Guo Rey-Ting , Zhang Yonghui 
Published: January 2022

AbstractKRAS mutation occurs in nearly 30% of human cancers, yet the most prevalent and oncogenic KRAS(G12D) variant still lacks inhibitors. Herein, we designed a series of potent inhibitors that can form a salt bridge with KRAS’s Asp12 residue. Our ITC results show that these inhibitors have similar binding affinity with both GDP-bound and GTP-bound KRAS(G12D), and our crystallographic studies reveal the structural basis of inhibitor binding-induced switch-II pocket in KRAS(G12D), experimentally confirming the formation of a salt bridge between the piperazine moiety of the inhibitors and the Asp12 residue of the mutant protein. Among KRAS family proteins and mutants, both ITC and enzymatic assays demonstrate the selectivity of the inhibitors for KRAS(G12D); and the inhibitors disrupt the KRAS–CRAF interaction. We also observed the inhibition of cancer cell proliferation as well as MAPK signaling by a representative inhibitor (TH-Z835). However, since the inhibition was not fully dependent on KRAS mutation status, it is possible that our inhibitors may have off-target effects via targeting non-KRAS small GTPases. Experiments with mouse xenograft models of pancreatic cancer showed that TH-Z835 significantly reduced tumor volume and synergized with an anti-PD-1 antibody. Collectively, our study demonstrates proof-of-concept for a strategy based on salt-bridge and induced-fit pocket formation for KRAS(G12D) targeting, which warrants future medicinal chemistry efforts for optimal efficacy and minimized off-target effects.
Systematic decomposition of sequence determinants governing CRISPR/Cas9 specificity
Authors: Fu Rongjie , He Wei , Dou Jinzhuang , Villarreal Oscar D. , Bedford Ella , Wang Helen , Hou Connie , Zhang Liang , Wang Yalong , Ma Dacheng , Chen Yiwen , Gao Xue , Depken Martin , Xu Han 
Published: January 2022

AbstractThe specificity of CRISPR/Cas9 genome editing is largely determined by the sequences of guide RNA (gRNA) and the targeted DNA, yet the sequence-dependent rules underlying off-target effects are not fully understood. To systematically explore the sequence determinants governing CRISPR/Cas9 specificity, here we describe a dual-target system to measure the relative cleavage rate between off- and on-target sequences (off-on ratios) of 1902 gRNAs on 13,314 synthetic target sequences, and reveal a set of sequence rules involving 2 factors in off-targeting: 1) a guide-intrinsic mismatch tolerance (GMT) independent of the mismatch context; 2) an “epistasis-like” combinatorial effect of multiple mismatches, which are associated with the free-energy landscape in R-loop formation and are explainable by a multi-state kinetic model. These sequence rules lead to the development of MOFF, a model-based predictor of Cas9-mediated off-target effects. Moreover, the “epistasis-like” combinatorial effect suggests a strategy of allele-specific genome editing using mismatched guides. With the aid of MOFF prediction, this strategy significantly improves the selectivity and expands the application domain of Cas9-based allele-specific editing, as tested in a high-throughput allele-editing screen on 18 cancer hotspot mutations.