bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common genetic variants contribute to heritability of age at onset of schizophrenia
Authors: Sada-Fuente Ester , Aranda Selena , Papiol Sergi , Heilbronner Urs , Moltó María Dolores , Aguilar Eduardo J. , González-Peñas Javier , Andreu-Bernabeu Álvaro , Arango Celso , Crespo-Facorro Benedicto , González-Pinto Ana , Fañanás Lourdes , Arias Barbara , Bobes Julio , Costas Javier , Martorell Lourdes , Schulze Thomas G. , Kalman Janos L. , Vilella Elisabet , Muntané Gerard 
Published: June 2023

AbstractSchizophrenia (SCZ) is a complex disorder that typically arises in late adolescence or early adulthood. Age at onset (AAO) of SCZ is associated with long-term outcomes of the disease. We explored the genetic architecture of AAO with a genome-wide association study (GWAS), heritability, polygenic risk score (PRS), and copy number variant (CNV) analyses in 4 740 subjects of European ancestry. Although no genome-wide significant locus was identified, SNP-based heritability of AAO was estimated to be between 17 and 21%, indicating a moderate contribution of common variants. We also performed cross-trait PRS analyses with a set of mental disorders and identified a negative association between AAO and common variants for SCZ, childhood maltreatment and attention-deficit/hyperactivity disorder. We also investigated the role of copy number variants (CNVs) in AAO and found an association with the length and number of deletions (P-value = 0.03), whereas the presence of CNVs previously reported in SCZ was not associated with earlier onset. To our knowledge, this is the largest GWAS of AAO of SCZ to date in individuals from European ancestry, and the first study to determine the involvement of common variants in the heritability of AAO. Finally, we evidenced the role played by higher SCZ load in determining AAO but discarded the role of pathogenic CNVs. Altogether, these results shed light on the genetic architecture of AAO, which needs to be confirmed with larger studies.
Downregulation of N6-methyladenosine-modified LINC00641 promotes EMT, but provides a ferroptotic vulnerability in lung cancer
Authors: Xi Shu , Ming Dao-Jing , Zhang Jin-Hui , Guo Meng-Meng , Wang Shuang-Ying , Cai Yi , Liu Meng-Yang , Wang Dan-Qi , Zhang Yi-Jie , Li Yafei , Yuan Shuai 
Published: June 2023

AbstractThe prognosis of lung cancer is poor with few effective therapies. Targeting ferroptosis is a new promising strategy for cancer therapy. LINC00641 has been involved in several cancers, however, its specific roles in lung cancer treatment remain largely unknown. Here, we reported that LINC00641 was down-regulated in tumor tissues and its downregulation was associated with poor outcomes in lung adenocarcinoma. LINC00641 was localized primarily in the nucleus and was modified by m6A. The nuclear m6A reader YTHDC1 regulated LINC00641 expression by affecting its stability. We demonstrated that LINC00641 suppressed lung cancer by inhibiting migration and invasion in vitro and metastasis in vivo. Knockdown of LINC00641 upregulated HuR protein level (especially in the cytoplasm), which subsequently increased N-cadherin levels by stabilizing its mRNA, then ultimately promoted EMT. Interestingly, LINC00641 knockdown in lung cancer cells increased the arachidonic acid metabolism and promoted ferroptosis sensitivity. Our findings identified LINC00641 as a tumor suppressor through inhibiting EMT. In another aspect, low expression of LINC00641 caused a ferroptotic vulnerability in lung cancer cells, which may serve as a potential ferroptosis-related therapeutic target for lung cancer.
Early presence of Homo sapiens in Southeast Asia by 86–68 kyr at Tam Pà Ling, Northern Laos
Authors: Freidline Sarah E. , Westaway Kira E. , Joannes-Boyau Renaud , Duringer Philippe , Ponche Jean-Luc , Morley Mike W. , Hernandez Vito C. , McAllister-Hayward Meghan S. , McColl Hugh , Zanolli Clément , Gunz Philipp , Bergmann Inga , Sichanthongtip Phonephanh , Sihanam Daovee , Boualaphane Souliphane , Luangkhoth Thonglith , Souksavatdy Viengkeo , Dosseto Anthony , Boesch Quentin , Patole-Edoumba Elise , Aubaile Françoise , Crozier Françoise , Suzzoni Eric , Frangeul Sébastien , Bourgon Nicolas , Zachwieja Alexandra , Dunn Tyler E. , Bacon Anne-Marie , Hublin Jean-Jacques , Shackelford Laura , Demeter Fabrice 
Published: June 2023

AbstractThe timing of the first arrival ofHomo sapiensin East Asia from Africa and the degree to which they interbred with or replaced local archaic populations is controversial. Previous discoveries from Tam Pà Ling cave (Laos) identifiedH. sapiensin Southeast Asia by at least 46 kyr. We report on a recently discovered frontal bone (TPL 6) and tibial fragment (TPL 7) found in the deepest layers of TPL. Bayesian modeling of luminescence dating of sediments and U-series and combined U-series-ESR dating of mammalian teeth reveals a depositional sequence spanning ~86 kyr. TPL 6 confirms the presence ofH. sapiensby 70 ± 3 kyr, and TPL 7 extends this range to 77 ± 9 kyr, supporting an early dispersal ofH. sapiensinto Southeast Asia. Geometric morphometric analyses of TPL 6 suggest descent from a gracile immigrant population rather than evolution from or admixture with local archaic populations.
Cell type-specific mapping of ion distribution in Arabidopsis thaliana roots
Authors: Giehl Ricardo F. H. , Flis Paulina , Fuchs Jörg , Gao Yiqun , Salt David E. , von Wirén Nicolaus 
Published: June 2023

AbstractCell type-specific mapping of element distribution is critical to fully understand how roots partition nutrients and toxic elements with aboveground parts. In this study, we developed a method that combines fluorescence-activated cell sorting (FACS) with inductively coupled plasma mass spectrometry (ICP-MS) to assess the ionome of different cell populations within Arabidopsis thaliana roots. The method reveals that most elements exhibit a radial concentration gradient increasing from the rhizodermis to inner cell layers, and detected previously unknown ionomic changes resulting from perturbed xylem loading processes. With this approach, we also identify a strong accumulation of manganese in trichoblasts of iron-deficient roots. We demonstrate that confining manganese sequestration in trichoblasts but not in endodermal cells efficiently retains manganese in roots, therefore preventing toxicity in shoots. These results indicate the existence of cell type-specific constraints for efficient metal sequestration in roots. Thus, our approach opens an avenue to investigate element compartmentation and transport pathways in plants.
Holocentromeres can consist of merely a few megabase-sized satellite arrays
Authors: Kuo Yi-Tzu , Câmara Amanda Souza , Schubert Veit , Neumann Pavel , Macas Jiří , Melzer Michael , Chen Jianyong , Fuchs Jörg , Abel Simone , Klocke Evelyn , Huettel Bruno , Himmelbach Axel , Demidov Dmitri , Dunemann Frank , Mascher Martin , Ishii Takayoshi , Marques André , Houben Andreas 
Published: June 2023

AbstractThe centromere is the chromosome region where microtubules attach during cell division. In contrast to monocentric chromosomes with one centromere, holocentric species usually distribute hundreds of centromere units along the entire chromatid. We assembled the chromosome-scale reference genome and analyzed the holocentromere and (epi)genome organization of the lilioid Chionographis japonica. Remarkably, each of its holocentric chromatids consists of only 7 to 11 evenly spaced megabase-sized centromere-specific histone H3-positive units. These units contain satellite arrays of 23 and 28 bp-long monomers capable of forming palindromic structures. Like monocentric species, C. japonica forms clustered centromeres in chromocenters at interphase. In addition, the large-scale eu- and heterochromatin arrangement differs between C. japonica and other known holocentric species. Finally, using polymer simulations, we model the formation of prometaphase line-like holocentromeres from interphase centromere clusters. Our findings broaden the knowledge about centromere diversity, showing that holocentricity is not restricted to species with numerous and small centromere units.
Low-spin state of Fe in Fe-doped NiOOH electrocatalysts
Authors: He Zheng-Da , Tesch Rebekka , Eslamibidgoli Mohammad J. , Eikerling Michael H. , Kowalski Piotr M. 
Published: June 2023

AbstractDoping with Fe boosts the electrocatalytic performance of NiOOH for the oxygen evolution reaction (OER). To understand this effect, we have employed state-of-the-art electronic structure calculations and thermodynamic modeling. Our study reveals that at low concentrations Fe exists in a low-spin state. Only this spin state explains the large solubility limit of Fe and similarity of Fe-O and Ni-O bond lengths measured in the Fe-doped NiOOH phase. The low-spin state renders the surface Fe sites highly active for the OER. The low-to-high spin transition at the Fe concentration of ~ 25% is consistent with the experimentally determined solubility limit of Fe in NiOOH. The thermodynamic overpotentials computed for doped and pure materials, η = 0.42 V and 0.77 V, agree well with the measured values. Our results indicate a key role of the low-spin state of Fe for the OER activity of Fe-doped NiOOH electrocatalysts.
Quantitative evaluation of large corporate climate action initiatives shows mixed progress in their first half-decade
Authors: Ruiz Manuel Ivan , Blok Kornelis 
Published: June 2023

AbstractCorporate climate initiatives such as the Science-Based Targets initiative and RE100 have gained significant prominence in recent years, with considerable increases in membership and several ex-ante studies stating how they could bring substantive emissions reductions beyond national goals. However, studies evaluating their progress are scarce, raising questions on how members achieve targets and whether their contributions are genuinely additional. Here we assess these initiatives by disaggregating membership by sector and geographic region and then thoroughly evaluating their progress between 2015–2019 using public environmental data disclosed by 102 of their largest members by revenue. Our results show that the collective Scope 1 and 2 emissions of these companies have fallen by 35.6%, with companies generally on track or exceeding scenarios keeping global warming below 2 °C. However, most of these reductions are concentrated in a small number of intensive companies. Most members show little evidence of emission reductions within their operations, only achieving progress via renewable electricity purchases. We highlight how intermediate steps regarding data robustness and implementation of sustainability measures are lacking: 75% of public company data is independently verified at low levels of assurance, and 71% of renewable electricity is obtained through low-impact or undisclosed sourcing models.
Directed differentiation of mouse pluripotent stem cells into functional lung-specific mesenchyme
Authors: Alber Andrea B. , Marquez Hector A. , Ma Liang , Kwong George , Thapa Bibek R. , Villacorta-Martin Carlos , Lindstrom-Vautrin Jonathan , Bawa Pushpinder , Wang Feiya , Luo Yongfeng , Ikonomou Laertis , Shi Wei , Kotton Darrell N. 
Published: June 2023

AbstractWhile the generation of many lineages from pluripotent stem cells has resulted in basic discoveries and clinical trials, the derivation of tissue-specific mesenchyme via directed differentiation has markedly lagged. The derivation of lung-specific mesenchyme is particularly important since this tissue plays crucial roles in lung development and disease. Here we generate a mouse induced pluripotent stem cell (iPSC) line carrying a lung-specific mesenchymal reporter/lineage tracer. We identify the pathways (RA and Shh) necessary to specify lung mesenchyme and find that mouse iPSC-derived lung mesenchyme (iLM) expresses key molecular and functional features of primary developing lung mesenchyme. iLM recombined with engineered lung epithelial progenitors self-organizes into 3D organoids with juxtaposed layers of epithelium and mesenchyme. Co-culture increases yield of lung epithelial progenitors and impacts epithelial and mesenchymal differentiation programs, suggesting functional crosstalk. Our iPSC-derived population thus provides an inexhaustible source of cells for studying lung development, modeling diseases, and developing therapeutics.
Excessive copper impairs intrahepatocyte trafficking and secretion of selenoprotein P
Authors: Schwarz Maria , Meyer Caroline E. , Löser Alina , Lossow Kristina , Hackler Julian , Ott Christiane , Jäger Susanne , Mohr Isabelle , Eklund Ella A. , Patel Angana A. H. , Gul Nadia , Alvarez Samantha , Altinonder Ilayda , Wiel Clotilde , Maares Maria , Haase Hajo , Härtlova Anetta , Grune Tilman , Schulze Matthias B. , Schwerdtle Tanja , Merle Uta , Zischka Hans , Sayin Volkan I. , Schomburg Lutz , Kipp Anna P. 
Published: June 2023

AbstractSelenium homeostasis depends on hepatic biosynthesis of selenoprotein P (SELENOP) and SELENOP-mediated transport from the liver to e.g. the brain. In addition, the liver maintains copper homeostasis. Selenium and copper metabolism are inversely regulated, as increasing copper and decreasing selenium levels are observed in blood during aging and inflammation. Here we show that copper treatment increased intracellular selenium and SELENOP in hepatocytes and decreased extracellular SELENOP levels. Hepatic accumulation of copper is a characteristic of Wilson’s disease. Accordingly, SELENOP levels were low in serum of Wilson’s disease patients and Wilson’s rats. Mechanistically, drugs targeting protein transport in the Golgi complex mimicked some of the effects observed, indicating a disrupting effect of excessive copper on intracellular SELENOP transport resulting in its accumulation in the late Golgi. Our data suggest that hepatic copper levels determine SELENOP release from the liver and may affect selenium transport to peripheral organs such as the brain.
hapln1a+ cells guide coronary growth during heart morphogenesis and regeneration
Authors: Sun Jisheng , Peterson Elizabeth A. , Chen Xin , Wang Jinhu 
Published: June 2023

AbstractAlthough several tissues and chemokines orchestrate coronary formation, the guidance cues for coronary growth remain unclear. Here, we profile the juvenile zebrafish epicardium during coronary vascularization and identifyhapln1a+cells enriched with vascular-regulating genes.hapln1a+cells not only envelop vessels but also form linear structures ahead of coronary sprouts. Live-imaging demonstrates that coronary growth occurs along these pre-formed structures, with depletion ofhapln1a+cells blocking this growth.hapln1a+cells also pre-lead coronary sprouts during regeneration andhapln1a+cell loss inhibits revascularization. Further, we identifyserpine1expression inhapln1a+cells adjacent to coronary sprouts, andserpine1inhibition blocks vascularization and revascularization. Moreover, we observe thehapln1asubstrate, hyaluronan, forming linear structures along and preceding coronary vessels. Depletion ofhapln1a+cells orserpine1activity inhibition disrupts hyaluronan structure. Our studies reveal thathapln1a+cells andserpine1are required for coronary production by establishing a microenvironment to facilitate guided coronary growth.
Optimizing intra-arterial hypothermia scheme for acute ischemic stroke in an MCAO/R rat model
Authors: Zeng Yuqi , Hao Lei , Chen Yue , Liu Shuyi , Fan Yong , Zhao Zhenhua , Wang Yinzhou , Chen Qi , Li Yongkun 
Published: June 2023

AbstractHypothermia is a promising neuroprotective treatment. This study aims to explore and optimize the intervention scheme of intra-arterial hypothermia (IAH) in a middle cerebral artery occlusion and reperfusion (MCAO/R) rat model. The MCAO/R model was established with a thread that could be retracted 2 h after occlusion. Cold normal saline was injected into the internal carotid artery (ICA) through a microcatheter in different infusion conditions. Grouping followed an orthogonal design (L9[34]) based on three critical factors closely associated with IAH: perfusate temperature (4, 10, 15 °C), infusion flow rate (1/3, 1/2, 2/3 blood flow rate of ICA), and duration (10, 20, 30 min), resulting in 9 subgroups (H1, H2 to H9). A myriad of indexes were monitored, such as vital signs, blood parameters, changes in local ischemic brain tissue temperature (Tb), ipsilateral jugular venous bulb temperature (Tjvb), and the core temperature of the anus (Tcore). After 24 h and 72 h of cerebral ischemia, cerebral infarction volume, cerebral water content, and neurological function were assessed to explore the optimal IAH conditions. The results revealed that the three critical factors were independent predictors for cerebral infarction volume, cerebral water content, and neurological function. The optimal perfusion conditions were 4 °C, 2/3 RICA (0.50 ml/min) for 20 min, and there was a significant correlation between Tb and Tjvb (R = 0.994, P < 0.001). The vital signs, blood routine tests and biochemical indexes showed no significant abnormal changes. These findings revealed that IAH was safe and feasible with the optimized scheme in an MCAO/R rat model.
Pleobot: a modular robotic solution for metachronal swimming
Authors: Oliveira Santos Sara , Tack Nils , Su Yunxing , Cuenca-Jiménez Francisco , Morales-Lopez Oscar , Gomez-Valdez P. Antonio , Wilhelmus Monica M. 
Published: June 2023

AbstractMetachronal propulsion is widespread in aquatic swarming organisms to achieve performance and maneuverability at intermediate Reynolds numbers. Studying only live organisms limits our understanding of the mechanisms driving these abilities. Thus, we present the design, manufacture, and validation of the Pleobot—a unique krill-inspired robotic swimming appendage constituting the first platform to study metachronal propulsion comprehensively. We combine a multi-link 3D printed mechanism with active and passive actuation of the joints to generate natural kinematics. Using force and fluid flow measurements in parallel with biological data, we show the link between the flow around the appendage and thrust. Further, we provide the first account of a leading-edge suction effect contributing to lift during the power stroke. The repeatability and modularity of the Pleobot enable the independent manipulation of particular motions and traits to test hypotheses central to understanding the relationship between form and function. Lastly, we outline future directions for the Pleobot, including adapting morphological features. We foresee a broad appeal to a wide array of scientific disciplines, from fundamental studies in ecology, biology, and engineering, to developing new bio-inspired platforms for studying oceans across the solar system.
Current treatments for endometriosis in South Korea: an analysis of nationwide data from 2010 to 2019
Authors: Kim Han Kyul , Kim Eun-San , Park Kyoung Sun , Lee Yoon Jae , Ha In-Hyuk 
Published: June 2023

AbstractWhile a wide range of treatments, including medical therapies and surgery, are used to manage endometriosis, the characteristics and treatment status of patients who received these treatments have not been investigated in Korea. This study analyzed the Korean Health Insurance Review & Assessment Service—National Patient Sample (HIRA-NPS) data from 2010 to 2019 with 7530 patients diagnosed with endometriosis. Annual trends in the types of visit and surgery, medication prescriptions and associated costs were investigated. The analysis showed that surgery slightly decreased among the types of utilized healthcare services (2010: 16.3, 2019: 12.7), dienogest prescription rapidly increased due to national health insurance coverage from 2013 (2013: 12.1, 2019: 36.0), and the use of gonadotrophin-releasing hormone analogues decreased (2010: 33.6, 2019: 16.4). There was no significant change in total and outpatient costs per person over time. Regarding endometriosis treatment, conservative treatment mainly based on prescribed medications has been gradually replacing surgery. Particularly, the listing of dienogest for national health insurance coverage might have affected the trend. However, there were no significant changes in terms of total and medication costs per person.
Associations of air pollutant concentrations with longitudinal kidney function changes in patients with chronic kidney disease
Authors: Chung Cheng-Yin , Wu Shang-Yu , Chiu Huei-Hsuan , Wu Tzu-Ning , Wang Your-Tong , Lin Ming-Yen ,   on behalf of the iH3 Research Group
Published: June 2023

AbstractThis longitudinal cohort study investigated the associations of air pollutant exposures, including CO, NO, NO2, NOx, O3, PM10, PM2.5, and SO2, with long-term kidney function changes in patients with chronic kidney disease (CKD). We enrolled 447 CKD patients who took part in a universal hospital pre-ESRD care program during 2011–2015. The daily average air pollutant exposures and temperature were estimated for each patient, with different levels of air pollutant concentrations defined by 5-knot and restricted cubic spline function. Predicted annual estimated glomerular filtration (eGFR) slope values by one mixed model were considered as the study outcome. The average age of the study population was 77.1 ± 12.6 years, and the median annual eGFR decreased by 2.1 ml/min/1.73 m2 per year from 30 ml/min/1.73 m2 at baseline during a mean follow-up time of 3.4 years. The univariable and multivariable analyses revealed no significant linear and non-linear associations between 5-knot air pollutant concentrations and annual eGFR slope. In addition, the visualized spline effect plots show insignificant variation patterns in annual eGFR slope values with increased air pollutant concentrations. These results encourage more extensive studies to clarify the causal relationships and mechanisms of long-term specific air pollutant exposures and longitudinal kidney function change, especially in CKD populations.
Linear and symmetric synaptic weight update characteristics by controlling filament geometry in oxide/suboxide HfOx bilayer memristive device for neuromorphic computing
Authors: Sahu Dwipak Prasad , Park Kitae , Chung Peter Hayoung , Han Jimin , Yoon Tae-Sik 
Published: June 2023

AbstractMemristive devices have been explored as electronic synaptic devices to mimic biological synapses for developing hardware-based neuromorphic computing systems. However, typical oxide memristive devices suffered from abrupt switching between high and low resistance states, which limits access to achieve various conductance states for analog synaptic devices. Here, we proposed an oxide/suboxide hafnium oxide bilayer memristive device by altering oxygen stoichiometry to demonstrate analog filamentary switching behavior. The bilayer device with Ti/HfO2/HfO2−x(oxygen-deficient)/Pt structure exhibited analog conductance states under a low voltage operation through controlling filament geometry as well as superior retention and endurance characteristics thanks to the robust nature of filament. A narrow cycle-to-cycle and device-to-device distribution were also demonstrated by the filament confinement in a limited region. The different concentrations of oxygen vacancies at each layer played a significant role in switching phenomena, as confirmed through X-ray photoelectron spectroscopy analysis. The analog weight update characteristics were found to strongly depend on the various conditions of voltage pulse parameters including its amplitude, width, and interval time. In particular, linear and symmetric weight updates for accurate learning and pattern recognition could be achieved by adopting incremental step pulse programming (ISPP) operation scheme which rendered a high-resolution dynamic range with linear and symmetry weight updates as a consequence of precisely controlled filament geometry. A two-layer perceptron neural network simulation with HfO2/HfO2−x synapses provided an 80% recognition accuracy for handwritten digits. The development of oxide/suboxide hafnium oxide memristive devices has the capacity to drive forward the development of efficient neuromorphic computing systems.