bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healthcare utilization, psychiatric disorders, and physical illnesses shortly before suicide mortality in adolescents in Taiwan
Authors: Lee Wan-Chen , Lai Jou-Yin , Pan Chun-Hung , Su Sheng-Siang , Yang Tien-Wei , Tsai Shang-Ying , Chen Chiao-Chicy , Kuo Chian-Jue 
Published: December 2021

AbstractBackgroundThis study examined the pattern of medical utilization and the distribution of comorbidities shortly before death among adolescents who died from suicide and compared these data with those of living controls.MethodsFrom Taiwan's National Health Insurance Research Database, this study identified adolescents aged 10–19 years who died from suicide (n = 935) between 1 January 2000, and 31 December 2016, by linking each patient with the national mortality database. The researchers conducted a nested case–control study through risk set sampling, and for each case, 20 age- and sex-matched controls (n = 18 700) were selected from the general population. The researchers applied conditional logistic regression to investigate differences in medical utilization and physical and psychiatric comorbidities between cases and controls.ResultsCases had a higher proportion of contact with the psychiatric department but a similar proportion of contact with any non-psychiatric medical department within 1 year before suicide compared with controls. There were 18.6% of adolescent suicide victims who only had contacted with a psychiatric department 3 months before suicide. Moreover, cases had a higher proportion of contact with non-psychiatric services within 3 months before suicide, particularly with emergency, surgery, and internal medicine departments. Cases had higher risks of several psychiatric disorders and physical illnesses, including heart diseases, pneumonia, and ulcer disease, than did controls.ConclusionsThe findings of increased medical utilization and higher risks of physical and psychiatric comorbidities in adolescent suicide victims are crucial for developing specific interventions to prevent suicide in this population.
A Dusty Atmospheric River Brings Floods to the Middle East
Authors: Dezfuli Amin , Bosilovich Michael G. , Barahona Donifan 
Published: December 2021

AbstractTorrential rainfall and rapid snowmelt in April 2017 caused deadly floods in northwestern Iran. An atmospheric river (AR), propagating across the Middle East and North Africa, was found responsible for this extreme event. The snowmelt was triggered by precipitation and warm advection associated with the AR. Total satellite‐based rainfall for April 2017 was moderately below normal, suggesting that a heavy flood can happen during dry years. The AR was fed by moisture from the Mediterranean and Red Seas. Despite its adverse societal consequences, this event was beneficial to the recovery of the desiccating Lake Urmia. The impacts of this AR were not limited to flooding; it also facilitated dust transport to the region. This distinct characteristic of the ARs in the Middle East is attributed to major mineral dust sources located along their pathways. This event was reasonably predicted at 7‐day lead time, crucially important for successful early warning systems.
Multiple Strokes Along the Same Channel to Ground in Positive Lightning Produced by a Supercell
Authors: Zhu Yanan , Bitzer Phillip , Rakov Vladimir , Stock Michael , Lapierre Jeff , DiGangi Elizabeth , Ding Ziqin , Medina Bruno , Carey Lawrence , Lang Timothy 
Published: December 2021

AbstractPrevious studies have shown that subsequent leaders in positive cloud‐to‐ground lightning (+CG) flashes rarely traverse pre‐existing channels to ground. In this paper, we present evidence that this actually can be common, at least for some thunderstorms. Observations of +CG flashes in a supercell storm in Argentina by Córdoba Argentina Marx Meter Array (CAMMA) are presented, in which 54 (64%) of 84 multiple‐stroke +CG flashes had subsequent leaders following a pre‐existing channel to ground. These subsequent positive leaders are found to behave similarly to their negative counterparts, including propagation speeds along pre‐existing channels with a median of 8 × 106 m/s, which is comparable to that of negative dart leaders. Two representative multiple‐stroke +CG flashes are presented and discussed in detail. The observations reported herein call for an update to the traditional explanation of the disparity between positive and negative lightning.
In Situ Measurements of Thermal Ion Temperature in the Martian Ionosphere
Authors: Hanley K. G. , McFadden J. P. , Mitchell D. L. , Fowler C. M. , Stone S. W. , Yelle R. V. , Mayyasi M. , Ergun R. E. , Andersson L. , Benna M. , Elrod M. K. , Jakosky B. M. 
Published: December 2021

AbstractIn situ measurements of ionospheric and thermospheric temperatures are experimentally challenging because orbiting spacecraft typically travel supersonically with respect to the cold gas and plasma. We present temperatures in Mars' ionosphere derived from data measured by the SupraThermal And Thermal Ion Composition instrument onboard the Mars Atmosphere and Volatile EvolutioN spacecraft. We focus on data obtained during nine special orbit maneuvers known as Deep Dips, during which MAVEN lowered its periapsis altitude from the nominal 150 to 120 km for 1 week in order to sample the ionospheric main peak and approach the homopause. We use two independent techniques to calculate ion temperatures from the measured energy and angular widths of the supersonic ram ion beam. After correcting for background and instrument response, we are able to measure ion temperatures as low as 100 K with associated uncertainties as low as 10%. It is theoretically expected that ion temperatures will converge to the neutral temperature at altitudes below the exobase region (∼180–200 km) due to strong collisional coupling; however, no evidence of the expected thermalization is observed. We have eliminated several possible explanations for the observed temperature difference between ions and neutrals, including Coulomb collisions with electrons, Joule heating, and heating caused by interactions with the spacecraft. The source of the energy maintaining the high ion temperatures remains unclear, suggesting that a fundamental piece of physics is missing from existing models of the Martian ionosphere.
Global Evolution and Dynamics of the Geomagnetic Field in the 15–70 kyr Period Based on Selected Paleomagnetic Sediment Records
Authors: Panovska Sanja , Korte Monika , Liu Jiabo , Nowaczyk Norbert 
Published: December 2021

AbstractReconstructions of the geomagnetic field on long time scales are important to understand the geodynamo processes in the Earth's core. The geomagnetic field exhibits a range of variations that vary from normal, dipole‐dominated secular variation to geomagnetic excursions and reversals. These transitional events are associated with significant directional deviations and very low intensities. Here we present a new, global geomagnetic field model spanning the period 70–15 ka (GGFSS70) that includes three excursions: Norwegian‐Greenland Sea, Laschamps, and Mono Lake/Auckland. The model is built from nine globally distributed, high‐resolution, well‐dated, sedimentary paleomagnetic records. The GGFSS70 indicates that the axial‐dipole component changed sign for about 300 years in the middle of the Laschamps excursion (41.25–40.93 ka). The energy comparison at the Earth's surface reveals that the axial‐dipole energy is always higher than the non‐axial‐dipole except over the Laschamps. In the other two excursions, the axial‐dipole is reduced by about one order of magnitude for the Norwegian‐Greenland Sea excursion and less for the Mono Lake/Auckland. At the core‐mantle boundary, the large‐scale non‐axial‐dipole power is comparable to the axial‐dipole power, except over the excursions when the axial‐dipole decreases, though less clearly for the Mono Lake/Auckland excursion. The axial dipole moment over the 15–70 ka varies from 0 to 8 × 1022 Am2, with an average and standard deviation of 5.1 ± 1.5 × 1022Am2. The Laschamps excursion is associated with growth and poleward movement of reversed flux patches and reversed field in the tangent cylinder at the excursion midpoint, which is not the case for the other two excursions.
Two‐Dimensional Idealized Hadley Circulation Simulation for Global High Resolution Model Development
Authors: Yoshida Ryuji , Yamaguchi Takanobu , Feingold Graham 
Published: December 2021

AbstractA new framework for the development of global high resolution models using a vertical‐meridional, two‐dimensional pole‐to‐pole domain is proposed. Compared with the three‐dimensional global model, the two‐dimensional framework can simulate cloud‐scale convection at significantly reduced computational cost, data volume, and turn‐around time, and accelerate the development phase. Although idealized, it allows for simulation of various clouds and scale interactions under a wide range of environmental conditions, even though zonal waves such as mid latitude storms cannot be simulated. Physics schemes can be tested and assessed over a full array of simultaneously occurring cloud regimes. The framework can serve as an intermediate step between a one‐dimensional simulation and a full three‐dimensional global model. Using this framework, we analyze the resolution dependencies of simulated clouds and the Hadley circulation in a range of global high resolution models by performing multiple 1000‐day simulations; for some resolutions tested, for example, 2 km horizontal resolution, three‐dimensional simulation is not feasible at the present time. Analysis shows that both horizontal and vertical resolution determine the properties of the Hadley circulation and clouds, and that the differences among the simulated Hadley circulations are understood as differences in scale interactions influenced by resolution.
ALKBH5-mediated m6A demethylation of KCNK15-AS1 inhibits pancreatic cancer progression via regulating KCNK15 and PTEN/AKT signaling
Authors: He Yuan , Yue HongQin , Cheng Ying , Ding Zhilong , Xu Zhen , Lv Chunyang , Wang Zheng , Wang Jing , Yin Chenglong , Hao Huihui , Chen Chuang 
Published: December 2021

AbstractLong noncoding RNAs (lncRNAs) are regarded as crucial regulators in tumor progression. Potassium two pore domain channel subfamily K member 15 and WISP2 antisense RNA 1 (KCNK15-AS1) has been confirmed to inhibit the migration and invasion of pancreatic cancer (PC) cells. However, its downstream mechanism and effect on other cellular functions in PC remain unknown. This study probed the function and potential mechanism of KCNK15-AS1 in PC cell growth. RT-qPCR and western blot were employed to measure gene expression in PC cells. ISH was applied to analyze KCNK15-AS1 expression in PC tissues. Functional assays were utilized to evaluate PC cell proliferation, apoptosis, migration and EMT. Mechanical experiments were adopted to detect gene interaction in PC cells. The obtained data indicated that KCNK15-AS1 was down-regulated in PC cells and tissues. Overexpressing KCNK15-AS1 hindered cell proliferation, migration and EMT while facilitated cell apoptosis in PC. Mechanically, alkylation repair homolog protein 5 (ALKBH5) was verified to induce m6A demethylation of KCNK15-AS1 to mediate KCNK15-AS1 up-regulation. KCNK15-AS1 combined with KCNK15 5’UTR to inhibit KCNK15 translation. Moreover, KCNK15-AS1 recruited MDM2 proto-oncogene (MDM2) to promote RE1 silencing transcription factor (REST) ubiquitination, thus transcriptionally upregulating phosphatase and tensin homolog (PTEN) to inactivate AKT pathway. In conclusion, our study first confirmed that KCNK15-AS1 hinders PC cell growth by regulating KCNK15 and PTEN, suggesting KCNK15-AS1 as a potential biomarker of PC.
Targeting SYK of monocyte-derived macrophages regulates liver fibrosis via crosstalking with Erk/Hif1α and remodeling liver inflammatory environment
Authors: Chen Xuejiao , Wang Ziyi , Han Sheng , Wang Zeng , Zhang Yu , Li Xiangdong , Xia Nan , Yu Wenjie , Jia Chenyang , Ni Yong , Pu Liyong 
Published: December 2021

AbstractLiver fibrosis is a danger signal indicating a huge risk of liver cancer occurrence, but there is still no effective clinical means to regulate the progress of liver fibrosis. Although a variety of drugs targeting SYK have been developed for tumors and autoimmune diseases, the mechanism and specific efficacy of SYK’s role in liver fibrosis are not yet clear. Our studies based on chronic CCL4, bile duct ligation, and subacute TAA mouse models show that SYK in monocyte-derived macrophages (MoMFs) is fully dependent on phosphorylation of Erk to up-regulate the expression of Hif1α, thereby forming the crosstalk with SYK to drive liver fibrosis progress. We have evaluated the ability of the small molecule SYK inhibitor GS9973 in a variety of models. Contrary to previous impressions, high-frequency administration of GS9973 will aggravate CCL4-induced liver fibrosis, which is especially unsuitable for patients with cholestasis whose clinical features are bile duct obstruction. In addition, we found that inhibition of MoMFs SYK impairs the expression of CXCL1, on one hand, it reduces the recruitment of CD11bhiLy6Chi inflammatory cells, and on the other hand, it promotes the phenotype cross-dress process of pro-resolution MoMFs, thereby remodeling the chronic inflammatory environment of the fibrotic liver. Our further findings indicate that on the basis of the administration of CCR2/CCR5 dual inhibitor Cenicriviroc, further inhibiting MoMFs SYK may give patients with fibrosis additional benefits.
Phase shift in skyrmion crystals
Authors: Hayami Satoru , Okubo Tsuyoshi , Motome Yukitoshi 
Published: December 2021

AbstractThe magnetic skyrmion crystal is a periodic array of a swirling topological spin texture. Since it is regarded as an interference pattern by multiple helical spin density waves, the texture changes with the relative phase shifts among the constituent waves. Although such a phase degree of freedom is relevant to not only magnetism but also transport properties, its effect has not been elucidated thus far. We here theoretically show that a phase shift in the skyrmion crystals leads to a tetra-axial vortex crystal and a meron-antimeron crystal, both of which show a staggered pattern of the scalar spin chirality and give rise to nonreciprocal transport phenomena without the spin-orbit coupling. We demonstrate that such a phase shift can be driven by exchange interactions between the localized spins, thermal fluctuations, and long-range chirality interactions in spin-charge coupled systems. Our results provide a further diversity of topological spin textures and open a new field of emergent electromagnetism by the phase shift engineering.
Counteraction between Astrin-PP1 and Cyclin-B-CDK1 pathways protects chromosome-microtubule attachments independent of biorientation
Authors: Song Xinhong , Conti Duccio , Shrestha Roshan L. , Braun Dominique , Draviam Viji M. 
Published: December 2021

AbstractDefects in chromosome-microtubule attachment can cause chromosomal instability (CIN), frequently associated with infertility and aggressive cancers. Chromosome-microtubule attachment is mediated by a large macromolecular structure, the kinetochore. Sister kinetochores of each chromosome are pulled by microtubules from opposing spindle-poles, a state called biorientation which prevents chromosome missegregation. Kinetochore-microtubule attachments that lack the opposing-pull are detached by Aurora-B/Ipl1. It is unclear how mono-oriented attachments that precede biorientation are spared despite the lack of opposing-pull. Using an RNAi-screen, we uncover a unique role for the Astrin-SKAP complex in protecting mono-oriented attachments. We provide evidence of domains in the microtubule-end associated protein that sense changes specific to end-on kinetochore-microtubule attachments and assemble an outer-kinetochore crescent to stabilise attachments. We find that Astrin-PP1 and Cyclin-B-CDK1 pathways counteract each other to preserve mono-oriented attachments. Thus, CIN prevention pathways are not only surveying attachment defects but also actively recognising and stabilising mature attachments independent of biorientation.
The biogenesis and function of nucleosome arrays
Authors: Singh Ashish Kumar , Schauer Tamás , Pfaller Lena , Straub Tobias , Mueller-Planitz Felix 
Published: December 2021

AbstractNumerous chromatin remodeling enzymes position nucleosomes in eukaryotic cells. Aside from these factors, transcription, DNA sequence, and statistical positioning of nucleosomes also shape the nucleosome landscape. The precise contributions of these processes remain unclear due to their functional redundancy in vivo. By incisive genome engineering, we radically decreased their redundancy in Saccharomyces cerevisiae. The transcriptional machinery strongly disrupts evenly spaced nucleosomes. Proper nucleosome density and DNA sequence are critical for their biogenesis. The INO80 remodeling complex helps space nucleosomes in vivo and positions the first nucleosome over genes in an H2A.Z-independent fashion. INO80 requires its Arp8 subunit but unexpectedly not the Nhp10 module for spacing. Cells with irregularly spaced nucleosomes suffer from genotoxic stress including DNA damage, recombination and transpositions. We derive a model of the biogenesis of the nucleosome landscape and suggest that it evolved not only to regulate but also to protect the genome.
Siderophore-mediated zinc acquisition enhances enterobacterial colonization of the inflamed gut
Authors: Behnsen Judith , Zhi Hui , Aron Allegra T. , Subramanian Vivekanandan , Santus William , Lee Michael H. , Gerner Romana R. , Petras Daniel , Liu Janet Z. , Green Keith D. , Price Sarah L. , Camacho Jose , Hillman Hannah , Tjokrosurjo Joshua , Montaldo Nicola P. , Hoover Evelyn M. , Treacy-Abarca Sean , Gilston Benjamin A. , Skaar Eric P. , Chazin Walter J. , Garneau-Tsodikova Sylvie , Lawrenz Matthew B. , Perry Robert D. , Nuccio Sean-Paul , Dorrestein Pieter C. , Raffatellu Manuela 
Published: December 2021

AbstractZinc is an essential cofactor for bacterial metabolism, and many Enterobacteriaceae express the zinc transporters ZnuABC and ZupT to acquire this metal in the host. However, the probiotic bacterium Escherichia coli Nissle 1917 (or “Nissle”) exhibits appreciable growth in zinc-limited media even when these transporters are deleted. Here, we show that Nissle utilizes the siderophore yersiniabactin as a zincophore, enabling Nissle to grow in zinc-limited media, to tolerate calprotectin-mediated zinc sequestration, and to thrive in the inflamed gut. We also show that yersiniabactin’s affinity for iron or zinc changes in a pH-dependent manner, with increased relative zinc binding as the pH increases. Thus, our results indicate that siderophore metal affinity can be influenced by the local environment and reveal a mechanism of zinc acquisition available to commensal and pathogenic Enterobacteriaceae.
Structural basis for the E3 ligase activity enhancement of yeast Nse2 by SUMO-interacting motifs
Authors: Varejão Nathalia , Lascorz Jara , Codina-Fabra Joan , Bellí Gemma , Borràs-Gas Helena , Torres-Rosell Jordi , Reverter David 
Published: December 2021

AbstractPost-translational modification of proteins by ubiquitin and ubiquitin-like modifiers, such as SUMO, are key events in protein homeostasis or DNA damage response. Smc5/6 is a nuclear multi-subunit complex that participates in the recombinational DNA repair processes and is required in the maintenance of chromosome integrity. Nse2 is a subunit of the Smc5/6 complex that possesses SUMO E3 ligase activity by the presence of a SP-RING domain that activates the E2~SUMO thioester for discharge on the substrate. Here we present the crystal structure of the SUMO E3 ligase Nse2 in complex with an E2-SUMO thioester mimetic. In addition to the interface between the SP-RING domain and the E2, the complex reveals how two SIM (SUMO-Interacting Motif) -like motifs in Nse2 are restructured upon binding the donor and E2-backside SUMO during the E3-dependent discharge reaction. Both SIM interfaces are essential in the activity of Nse2 and are required to cope with DNA damage.
Platelet PD-L1 reflects collective intratumoral PD-L1 expression and predicts immunotherapy response in non-small cell lung cancer
Authors: Hinterleitner Clemens , Strähle Jasmin , Malenke Elke , Hinterleitner Martina , Henning Melanie , Seehawer Marco , Bilich Tatjana , Heitmann Jonas , Lutz Martina , Mattern Sven , Scheuermann Sophia , Horger Marius , Maurer Stefanie , Walz Juliane , Fend Falko , Handgretinger Rupert , Seitz Christian , Weigelin Bettina , Singer Stephan , Salih Helmut , Borst Oliver , Kopp Hans-Georg , Zender Lars 
Published: December 2021

AbstractImmune-checkpoint inhibitors (ICI) have transformed oncological therapy. Up to 20% of all non-small cell lung cancers (NSCLCs) show durable responses upon treatment with ICI, however, robust markers to predict therapy response are missing. Here we show that blood platelets interact with lung cancer cells and that PD-L1 protein is transferred from tumor cells to platelets in a fibronectin 1, integrin α5β1 and GPIbα-dependent manner. Platelets from NSCLC patients are found to express PD-L1 and platelet PD-L1 possess the ability to inhibit CD4 and CD8 T-cells. An algorithm is developed to calculate the activation independent adjusted PD-L1 payload of platelets (pPD-L1Adj.), which is found to be superior in predicting the response towards ICI as compared to standard histological PD-L1 quantification on tumor biopsies. Our data suggest that platelet PD-L1 reflects the collective tumor PD-L1 expression, plays important roles in tumor immune evasion and overcomes limitations of histological quantification of often heterogeneous intratumoral PD-L1 expression.
Kinetic and structural mechanism for DNA unwinding by a non-hexameric helicase
Authors: Carney Sean P. , Ma Wen , Whitley Kevin D. , Jia Haifeng , Lohman Timothy M. , Luthey-Schulten Zaida , Chemla Yann R. 
Published: December 2021

AbstractUvrD, a model for non-hexameric Superfamily 1 helicases, utilizes ATP hydrolysis to translocate stepwise along single-stranded DNA and unwind the duplex. Previous estimates of its step size have been indirect, and a consensus on its stepping mechanism is lacking. To dissect the mechanism underlying DNA unwinding, we use optical tweezers to measure directly the stepping behavior of UvrD as it processes a DNA hairpin and show that UvrD exhibits a variable step size averaging ~3 base pairs. Analyzing stepping kinetics across ATP reveals the type and number of catalytic events that occur with different step sizes. These single-molecule data reveal a mechanism in which UvrD moves one base pair at a time but sequesters the nascent single strands, releasing them non-uniformly after a variable number of catalytic cycles. Molecular dynamics simulations point to a structural basis for this behavior, identifying the protein-DNA interactions responsible for strand sequestration. Based on structural and sequence alignment data, we propose that this stepping mechanism may be conserved among other non-hexameric helicases.