bluuebunny/crossref_metadata_2025_split huggingface dataset:
Planet Size Controls Fe Isotope Fractionation Between Mantle and Core
Authors: Ni Peng , Shahar Anat , Badro James , Yang Jing , Bi Wenli , Zhao Jiyong , Hu Michael Y. , Alp Esen E. 
Published: October 2022

AbstractAs an element ubiquitous in the Solar system, the isotopic composition of iron exhibits rich variations in different planetary reservoirs. Such variations reflect the diverse range of differentiation and evolution processes experienced by their parent bodies. A key in deciphering iron isotope variations among planetary samples is to understand how iron isotopes fractionate during core formation. Here we report new Nuclear Resonant Inelastic X‐ray Scattering experiments on silicate glasses of bulk silicate Earth compositions to measure their force constants at high pressures of up to 30 GPa. The force constant results are subsequently used to constrain iron isotope fractionation during core formation on terrestrial planets. Using a model that integrates temperature, pressure, core composition, and redox state of the silicate mantle, we show that core formation might lead to an isotopically light mantle for small planetary bodies but a heavy one for Earth‐sized terrestrial planets.
Analysis of Turbulence Reports and ERA5 Turbulence Diagnostics in a Tropopause‐Based Vertical Framework
Authors: Kaluza T. , Kunkel D. , Hoor P. 
Published: October 2022

AbstractIn the tropopause region turbulence exhibits a common feature with posing a threat for aviation as well as presenting a pathway for cross tropopause exchange. However, current numerical weather prediction and in particular climate models still struggle to resolve a large part of the dynamics responsible for turbulence generation. This renders high resolution observations of turbulence to be very valuable to identify the spatio‐temporal distribution of turbulence. In this study we use aircraft observations along with reanalysis data over the North Atlantic during winter season to analyze turbulence occurrence. Using a tropopause‐based coordinate system, we found that turbulence occurs within a sharp unimodal distribution which maximizes just below the tropopause. Turbulence also significantly affects the first 2 km above the tropopause which highlights its potential impact on the formation of the so called extratropical mixing layer around the tropopause.
Seasonal‐Interannual Predictions of Summer Precipitation Over the Tibetan Plateau in North American Multimodel Ensemble
Authors: Wang Lin , Ren Hong‐Li , Xu Xiangde , Huang Bohua , Wu Jie , Liu Jingpeng 
Published: October 2022

AbstractVariations of precipitation over the Tibetan Plateau (TP) have great hydrometeorological impacts on local and surrounding areas. Focusing on the TP precipitation in the boreal summer, this study investigates the seasonal‐interannual predictions of eight dynamical models from the North‐American Multi‐Model Ensemble (NMME) using different observational data sets for verification. Results show dynamical prediction skill of the TP precipitation is regionally dependent with significantly high skills in the southwestern TP up to about three‐season ahead. Prediction skill of precipitation anomalies over the southwestern TP is significantly reliant on the models' ability in reproducing the observed relationship between the anomalous southwest‐TP precipitation and Pacific Sea surface temperature (SST). Using the different gridded observational data sets as verifications can lead to variations in prediction skills, and the multi‐observation mean tends to obtain the highest skills over the southwestern TP. These results provide a deeper understanding of dynamical seasonal‐interannual predictability of summer precipitation in TP.
Geomagnetic Disturbances That Cause GICs: Investigating Their Interhemispheric Conjugacy and Control by IMF Orientation
Authors: Engebretson Mark J. , Simms Laura E. , Pilipenko Viacheslav A. , Bouayed Lilia , Moldwin Mark B. , Weygand James M. , Hartinger Michael D. , Xu Zhonghua , Clauer C. Robert , Coyle Shane , Willer Anna N. , Freeman Mervyn P. , Gerrard Andy J. 
Published: October 2022

AbstractNearly all studies of impulsive geomagnetic disturbances (GMDs, also known as magnetic perturbation events MPEs) that can produce dangerous geomagnetically induced currents (GICs) have used data from the northern hemisphere. In this study, we investigated GMD occurrences during the first 6 months of 2016 at four magnetically conjugate high latitude station pairs using data from the Greenland West Coast magnetometer chain and from Antarctic stations in the conjugate AAL‐PIP magnetometer chain. Events for statistical analysis and four case studies were selected from Greenland/AAL‐PIP data by detecting the presence of >6 nT/s derivatives of any component of the magnetic field at any of the station pairs. For case studies, these chains were supplemented by data from the BAS‐LPM chain in Antarctica as well as Pangnirtung and South Pole in order to extend longitudinal coverage to the west. Amplitude comparisons between hemispheres showed (a) a seasonal dependence (larger in the winter hemisphere), and (b) a dependence on the sign of the By component of the interplanetary magnetic field (IMF): GMDs were larger in the north (south) when IMF By was >0 (<0). A majority of events occurred nearly simultaneously (to within ±3 min) independent of the sign of By as long as |By| ≤ 2 |Bz|. As has been found in earlier studies, IMF Bz was <0 prior to most events. When IMF data from Geotail, Themis B, and/or Themis C in the near‐Earth solar wind were used to supplement the time‐shifted OMNI IMF data, the consistency of these IMF orientations was improved.
Middle Miocene Climate and Stable Oxygen Isotopes in Europe Based on Numerical Modeling
Authors: Botsyun Svetlana , Ehlers Todd A. , Koptev Alexander , Böhme Madelaine , Methner Katharina , Risi Camille , Stepanek Christian , Mutz Sebastian G. , Werner Martin , Boateng Daniel , Mulch Andreas 
Published: October 2022

AbstractThe Middle Miocene (15.99–11.65 Ma) of Europe witnessed major climatic, environmental, and vegetational change, yet we are lacking detailed reconstructions of Middle Miocene temperature and precipitation patterns over Europe. Here, we use a high‐resolution (∼0.75°) isotope‐enabled general circulation model (ECHAM5‐wiso) with time‐specific boundary conditions to investigate changes in temperature, precipitation, and δ18O in precipitation (δ18Op). Experiments were designed with variable elevation configurations of the European Alps and different atmospheric CO2 levels to examine the influence of Alpine elevation and global climate forcing on regional climate and δ18Op patterns. Modeling results are in agreement with available paleobotanical temperature data and with low‐resolution Middle Miocene experiments of the Miocene Model Intercomparison Project (MioMIP1). However, simulated precipitation rates are 300–500 mm/yr lower in the Middle Miocene than for pre‐industrial times for central Europe. This result is consistent with precipitation estimates from herpetological fossil assemblages, but contradicts precipitation estimates from paleobotanical data. We attribute the Middle Miocene precipitation change in Europe to shifts in large‐scale pressure patterns in the North Atlantic and over Europe and associated changes in wind direction and humidity. We suggest that global climate forcing contributed to a maximum δ18Op change of ∼2‰ over high elevation (Alps) and ∼1‰ over low elevation regions. In contrast, we observe a maximum modeled δ18Op decrease of 8‰ across the Alpine orogen due to Alpine topography. However, the elevation‐δ18Op lapse rate shallows in the Middle Miocene, leading to a possible underestimation of paleotopography when using present‐day δ18Op—elevation relationships data for stable isotope paleoaltimetry studies.
Impact of the COVID-19 pandemic on non-COVID-19 hospital mortality in patients with schizophrenia: a nationwide population-based cohort study
Authors: Boyer Laurent , Fond Guillaume , Pauly Vanessa , Orléans Veronica , Auquier Pascal , Solmi Marco , Correll Christoph U. , Yon Dong Keon , Llorca Pierre-Michel , Baumstarck-Barrau Karine , Duclos Antoine 
Published: October 2022

AbstractIt remains unknown to what degree resource prioritization toward SARS-CoV-2 (2019-nCoV) coronavirus (COVID-19) cases had disrupted usual acute care for non-COVID-19 patients, especially in the most vulnerable populations such as patients with schizophrenia. The objective was to establish whether the impact of the COVID-19 pandemic on non-COVID-19 hospital mortality and access to hospital care differed between patients with schizophrenia versus without severe mental disorder. We conducted a nationwide population-based cohort study of all non-COVID-19 acute hospitalizations in the pre-COVID-19 (March 1, 2019 through December 31, 2019) and COVID-19 (March 1, 2020 through December 31, 2020) periods in France. We divided the population into patients with schizophrenia and age/sex-matched patients without severe mental disorder (1:10). Using a difference-in-differences approach, we performed multivariate patient-level logistic regression models (adjusted odds ratio, aOR) with adjustment for complementary health insurance, smoking, alcohol and substance addiction, Charlson comorbidity score, origin of the patient, category of care, intensive care unit (ICU) care, major diagnosis groups and hospital characteristics. A total of 198,186 patients with schizophrenia were matched with 1,981,860 controls. The 90-day hospital mortality in patients with schizophrenia increased significantly more versus controls (aOR = 1.18; p < 0.001). This increased mortality was found for poisoning and injury (aOR = 1.26; p = 0.033), respiratory diseases (aOR = 1.19; p = 0.008) and for both surgery (aOR = 1.26; p = 0.008) and medical care settings (aOR = 1.16; p = 0.001). Significant changes in the case mix were noted with reduced admission in the ICU and for several somatic diseases including cancer, circulatory and digestive diseases and stroke for patients with schizophrenia compared to controls. These results suggest a greater deterioration in access to, effectiveness and safety of non-COVID-19 acute care in patients with schizophrenia compared to patients without severe mental disorders. These findings question hospitals’ resilience pertaining to patient safety and underline the importance of developing specific strategies for vulnerable patients in anticipation of future public health emergencies.
Deciphering transcriptome alterations in bone marrow hematopoiesis at single-cell resolution in immune thrombocytopenia
Authors: Liu Yan , Zuo Xinyi , Chen Peng , Hu Xiang , Sheng Zi , Liu Anli , Liu Qiang , Leng Shaoqiu , Zhang Xiaoyu , Li Xin , Wang Limei , Feng Qi , Li Chaoyang , Hou Ming , Chu Chong , Ma Shihui , Wang Shuwen , Peng Jun 
Published: October 2022

AbstractImmune thrombocytopenia (ITP) is an autoimmune disorder, in which megakaryocyte dysfunction caused by an autoimmune reaction can lead to thrombocytopenia, although the underlying mechanisms remain unclear. Here, we performed single-cell transcriptome profiling of bone marrow CD34+ hematopoietic stem and progenitor cells (HSPCs) to determine defects in megakaryopoiesis in ITP. Gene expression, cell-cell interactions, and transcriptional regulatory networks varied in HSPCs of ITP, particularly in immune cell progenitors. Differentially expressed gene (DEG) analysis indicated that there was an impaired megakaryopoiesis of ITP. Flow cytometry confirmed that the number of CD9+ and HES1+ cells from Lin−CD34+CD45RA− HSPCs decreased in ITP. Liquid culture assays demonstrated that CD9+Lin−CD34+CD45RA− HSPCs tended to differentiate into megakaryocytes; however, this tendency was not observed in ITP patients and more erythrocytes were produced. The percentage of megakaryocytes differentiated from CD9+Lin−CD34+CD45RA− HSPCs was 3-fold higher than that of the CD9− counterparts from healthy controls (HCs), whereas, in ITP patients, the percentage decreased to only 1/4th of that in the HCs and was comparable to that from the CD9− HSPCs. Additionally, when co-cultured with pre-B cells from ITP patients, the differentiation of CD9+Lin−CD34+CD45RA− HSPCs toward the megakaryopoietic lineage was impaired. Further analysis revealed that megakaryocytic progenitors (MkP) can be divided into seven subclusters with different gene expression patterns and functions. The ITP-associated DEGs were MkP subtype-specific, with most DEGs concentrated in the subcluster possessing dual functions of immunomodulation and platelet generation. This study comprehensively dissects defective hematopoiesis and provides novel insights regarding the pathogenesis of ITP.
Cryptic and ubiquitous aplastidic cryptophytes are key freshwater flagellated bacterivores
Authors: Šimek Karel , Mukherjee Indranil , Szöke-Nagy Tiberiu , Haber Markus , Salcher Michaela M , Ghai Rohit 
Published: October 2022

Abstract
Morphology-based microscopic approaches are insufficient for a taxonomic classification of bacterivorous heterotrophic nanoflagellates (HNF) in aquatic environments since their cells do not display reliably distinguishable morphological features. This leads to a considerable lack of ecological insights into this large and taxonomically diverse functional guild. Here, we present a combination of fluorescence in situ hybridization followed by catalyzed reporter deposition (CARD-FISH) and environmental sequence analyses which revealed that morphologically indistinguishable, so far largely cryptic and uncultured aplastidic cryptophytes are ubiquitous and prominent protistan bacterivores in diverse freshwater ecosystems. Using a general probe for Cryptophyceae and its heterotrophic CRY1 lineage, we analyzed different water layers in 24 freshwater lakes spanning a broad range of trophic states, sizes and geographical locations. We show that bacterivorous aplastidic cryptophytes and the CRY1 lineage accounted for ca. 2/3 and ¼ of total HNF, respectively, in both epilimnetic and hypolimnetic samples. These heterotrophic cryptophytes were generally smaller and more abundant than their chloroplast-bearing counterparts. They had high uptake rates of bacteria, hinting at their important roles in channeling carbon flow from prokaryotes to higher trophic levels. The worldwide ubiquity of Cryptophyceae and its CRY1 lineage was supported by 18S rRNA gene sequence analyses across a diverse set of 297 freshwater metagenomes. While cryptophytes have been considered to be mainly plastidic “algae”, we show that it is the aplastidic counterparts that contribute considerably to bacterial mortality rates. Additionally, our results suggest an undiscovered diversity hidden amongst these abundant and morphologically diverse aplastidic cryptophytes.
Genetic and functional analyses implicate microRNA 499A in bipolar disorder development
Authors: Tielke Aileen , Martins Helena , Pelzl Michael A. , Maaser-Hecker Anna , David Friederike S. , Reinbold Céline S. , Streit Fabian , Sirignano Lea , Schwarz Markus , Vedder Helmut , Kammerer-Ciernioch Jutta , Albus Margot , Borrmann-Hassenbach Margitta , Hautzinger Martin , Hünten Karola , Degenhardt Franziska , Fischer Sascha B. , Beins Eva C. , Herms Stefan , Hoffmann Per , Schulze Thomas G. , Witt Stephanie H. , Rietschel Marcella , Cichon Sven , Nöthen Markus M. , Schratt Gerhard , Forstner Andreas J. 
Published: October 2022

AbstractBipolar disorder (BD) is a complex mood disorder with a strong genetic component. Recent studies suggest that microRNAs contribute to psychiatric disorder development. In BD, specific candidate microRNAs have been implicated, in particular miR-137, miR-499a, miR-708, miR-1908 and miR-2113. The aim of the present study was to determine the contribution of these five microRNAs to BD development. For this purpose, we performed: (i) gene-based tests of the five microRNA coding genes, using data from a large genome-wide association study of BD; (ii) gene-set analyses of predicted, brain-expressed target genes of the five microRNAs; (iii) resequencing of the five microRNA coding genes in 960 BD patients and 960 controls and (iv) in silico and functional studies for selected variants. Gene-based tests revealed a significant association with BD for MIR499A, MIR708, MIR1908 and MIR2113. Gene-set analyses revealed a significant enrichment of BD associations in the brain-expressed target genes of miR-137 and miR-499a-5p. Resequencing identified 32 distinct rare variants (minor allele frequency < 1%), all of which showed a non-significant numerical overrepresentation in BD patients compared to controls (p = 0.214). Seven rare variants were identified in the predicted stem-loop sequences of MIR499A and MIR2113. These included rs142927919 in MIR2113 (pnom = 0.331) and rs140486571 in MIR499A (pnom = 0.297). In silico analyses predicted that rs140486571 might alter the miR-499a secondary structure. Functional analyses showed that rs140486571 significantly affects miR-499a processing and expression. Our results suggest that MIR499A dysregulation might contribute to BD development. Further research is warranted to elucidate the contribution of the MIR499A regulated network to BD susceptibility.
Betaine promotes osteogenic differentiation in immortalized human dental pulp-derived cells
Authors: Kornsuthisopon Chatvadee , Nantanapiboon Dusit , Rochanavibhata Sunisa , Nowwarote Nunthawan , Namangkalakul Worachat , Osathanon Thanaphum 
Published: October 2022

Abstract
Objectives
This study aimed to evaluate the effect of betaine (BET) on immortalized human dental pulp stem cell (ihDP) osteogenic differentiation.

Materials and methods
hDPs were immortalized using SV40 T-antigen transfection. Characterization, multilineage differentiation, proliferation, cell cycle, colony-forming unit, and cellular senescence were evaluated (n = 4). The effect of BET on ihDP response was assessed (n = 4). Osteogenic differentiation was detected using ALP, ARS staining, and RT-qPCR (n = 4). To investigate the involvement of calcium signaling, the cells were pretreated with either 8-(NN-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) or thapsigargin before BET treatment (n = 6).

Results
ihDPs retained similar phenotypic characteristics presented in hDPs but exhibited an increase in cell proliferation and extended culture to passage 25. An increased proportion of cells in S and G2/M phases without senescence was observed in ihDPs. BET (50 mM) treatment significantly increased mineral deposition at 14 days and upregulated ALP, MSX2, BMP2, and RUNX2 expression. TMB-8 pretreatment reduced the effect of BET-induced ihDP osteogenic differentiation, whereas thapsigargin promoted osteogenic differentiation in ihDPs synergistically with BET.

Conclusion
ihDPs showed superior proliferation ability and a longer life span, which could serve as a promising cell for regenerative dentistry. BET promoted odonto/osteogenic differentiation via intracellular calcium regulation.
Does the pursuit of scientific excellence serve or hamper translational medical research: an historical perspective from hematological malignancies
Authors: Bunce Chris M. , Khanim Farhat L. , Drayson Mark T. 
Published: October 2022

AbstractDespite enormous global investment, translational medical research faces considerable challenges and patients, and their doctors are frequently frustrated by the apparent lack of research activity or progress. Understanding the factors that prevent innovative research discoveries from making it to clinical trials is a multifaceted problem. However, one question that must be addressed is whether the nature of current research activity and the factors that influence the conduct of pre-clinical research, permit, or hamper the timely progression of laboratory-based observations to proof of concept (PoC) clinical trials. Inherent in this question is to what extent a deep mechanistic understanding of a potential new therapy is required before commencing PoC studies, and whether patients are better served when mechanistic and clinical studies progress side by side rather than in a more linear fashion. Here we address these questions by revisiting the historical development of hugely impactful and paradigm-changing innovations in the treatment of hematological cancers. First, we compare the history and route to clinical PoC, of two molecularly-targeted therapies that are BCR:ABL inhibitors in chronic myeloid leukaemia and all-trans retinoic acid (ATRA) in acute promyelocytic leukaemia (APL). We then discuss the history of arsenic trioxide as additional APL therapy, and the repurposing of thalidomide as effective multiple myeloma therapy. These stories have surprising elements of commonality that demand debate about the modern-day hard and soft governance of medical research and whether these processes appropriately align the priorities of advancing scientific knowledge and the need of patients.
Relationship between dietary intake and erythrocyte PUFA in adolescents from a Western Australian cohort
Authors: Wan Fuzhen , Pan Feng , Mori Trevor A. , O’Sullivan Therese A. , Beilin Lawrence J. , Oddy Wendy H. 
Published: October 2022

Abstract
Background
Population-based studies show that the intake of omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFA) are associated with a range of health conditions. Therefore, the reliability of food frequency questionnaires (FFQ) as rapid and easily accessible screening tools for PUFA intake deserve investigation.

Objective
We aimed to assess the relationship between erythrocyte fatty acids and fatty acid intake collected using the Commonwealth Scientific and Industrial Research Organisation (CSIRO) food frequency questionnaire in an adolescent cohort.

Design
A cross-sectional study using data from 1155 young adolescents participating in the 14-year follow-up of the Raine Study. Bland–Altman plots were used to determine the agreement between dietary intake and erythrocyte levels of each fatty acid.

Results
The main dietary source of n-3 long-chain (LC) PUFA was ‘fresh fish’ (53% of total n-3 LC-PUFA). Docosahexaenoic acid (DHA) showed the strongest correlation between erythrocyte and diet assessment (r = 0.274; p < 0.001), whilst linoleic acid (LA) (r = 0.103; p < 0.001) and arachidonic acid (AA) (r = −0.06; p = 0.042) showed weaker correlations, with limits of agreement relatively narrow. Bland–Altman plots showed a dose-dependent bias between the FFQ fatty acid data and corresponding erythrocyte data.

Conclusions
For the major n-3 and n-6 PUFA, dietary intakes derived from the FFQ showed weaker correlations and poorer agreement with erythrocyte levels, and the deviation between the two increased with higher intake levels.