bluuebunny/crossref_metadata_2025 huggingface dataset:
Ratgeber Akzeptanz- und Commitment-Therapie (ACT)
Authors: Klein Jan Philipp , Burian Ronald
Published: April 2024

ACT ist das englische Wort für „Handeln“ und ACT ist die Abkürzung für eine bestimmte Form der Psychotherapie, nämlich der Akzeptanz- und Commitment-Therapie, an der sich dieser Ratgeber orientiert. ACT wird heutzutage nicht nur in der Behandlung von psychischen Problemen wie Ängsten oder Depressionen eingesetzt, sondern auch dann, wenn Menschen durch körperliche Beschwerden stark belastet sind. ACT kann auch Menschen helfen, die den Eindruck haben, dass ihr Leben scheinbar die Richtung und den Sinn verloren hat. Und sie kann Menschen unterstützen, die merken, dass ihre Sehnsüchte auf eine schmerzhafte Art und Weise unerfüllt sind und ihr Leben sich aus diesem Grund nicht mehr lebendig anfühlt, sondern wie festgefahren.
Nach einer Einführung in die Akzeptanz- und Commitment-Therapie hilft Ihnen der Ratgeber mithilfe zahlreicher Übungen herauszufinden, was für Sie ein sinnerfülltes Leben in Ihrer aktuellen Situation bedeutet. Zudem zeigt der Ratgeber Ihnen, wie Sie angesichts Ihrer Probleme und Belastungen handlungsfähig bleiben können, indem Sie anfangen, wieder Dinge zu tun, die Ihnen am Herzen liegen. Auf diese Weise wird oftmals ein sinnerfülltes und lebendiges Leben wieder möglich. Die Anwendung von ACT verbessert nicht nur die Lebenszufriedenheit, sondern fördert auch die Fähigkeit, bei auftretenden Belastungen weiterhin diejenigen Dinge zu verfolgen, die einem im Leben wirklich wichtig sind.
Ein Teil der Übungen liegt zusätzlich als Audioaufnahme vor. Diese Übungen können Sie nach erfolgter Registrierung von der Hogrefe Website herunterladen und anhören. Außerdem enthält der Ratgeber zahlreiche Illustrationen, die der Veranschaulichung der Inhalte dienen. Sie können den Ratgeber als Ergänzung zu einer Psychotherapie nutzen, um besser zu verstehen, was in der ACT passiert, Sie können den Ratgeber aber auch alleine für sich durcharbeiten.
Exposure to Smoke From Wildfire, Prescribed, and Agricultural Burns Among At‐Risk Populations Across Washington, Oregon, and California
Authors: Schollaert C. L. , Marlier M. E. , Marshall J. D. , Spector J. T. , Busch Isaksen T.
Published: April 2024

Wildfires, prescribed burns, and agricultural burns all impact ambient air quality across the Western U.S.; however, little is known about how communities across the region are differentially exposed to smoke from each of these fire types. To address this gap, we quantify smoke exposure stemming from wildfire, prescribed, and agricultural burns across Washington, Oregon, and California from 2014 to 2020 using a fire type‐specific biomass burning emissions inventory and the GEOS‐Chem chemical transport model. We examine fire type‐specific PM2.5 concentration by race/ethnicity, socioeconomic status, and in relation to the Center for Disease Control's Social Vulnerability Index. Overall, population‐weighted PM2.5 concentrations are greater from wildfires than from prescribed and from agricultural burns. While we found limited evidence of exposure disparities among sub‐groups across the full study area, we did observe disproportionately higher exposures to wildfire‐specific PM2.5 exposures among Native communities in all three states and, in California, higher agricultural burn‐specific PM2.5 exposures among lower socioeconomic groups. We also identified, for all three states, areas of significant spatial clustering of smoke exposures from all fire types and increased social vulnerability. These results provide a first look at the differential contributions of smoke from wildfires, prescribed burns, and agricultural burns to PM2.5 exposures among demographic subgroups, which can be used to inform more tailored exposure reduction strategies across sources.
Statistical Distribution of Whistler Mode Waves in the Martian Induced Magnetosphere Based on MAVEN Observations
Authors: Du Hengle , Cao Xing , Ni Binbin , Fu Song , Jin Taifeng , Yun Xiaotong , Long Minyi , Pang Shuyue
Published: April 2024

Whistler mode waves are a common type of electromagnetic waves in the Martian induced magnetosphere. Using high‐resolution magnetic field data from the Magnetometer (MAG) instrument onboard Mars Atmosphere and Volatile Evolution (MAVEN) from October 2014 to November 2022, we perform a detailed analysis of the statistical distribution of the occurrence rate, averaged amplitude, peak frequency, wave normal angle and ellipticity of left‐hand and right‐hand polarized whistler mode waves in the Martian induced magnetosphere. Our results show that whistler mode waves are mainly observed in the subsolar and magnetic pileup region, with the occurrence rate of right‐hand mode waves higher than that of left‐hand mode waves. The averaged wave amplitude ranges from 0.02 to 0.13 nT and peak wave frequency ranges from 2 to 9 Hz. We also find that the wave normal angles for both left‐hand and right‐hand polarized whistler waves are relatively larger in the subsolar region and magnetic pileup region where the corresponding wave ellipticity is closer to the linear polarization. Our results are valuable to in‐depth understanding of the generation mechanism of whistler mode waves as well as their contributions to the electron dynamics in the Martian induced magnetosphere.
Integrating Tide‐Driven Wetland Soil Redox and Biogeochemical Interactions Into a Land Surface Model
Authors: Sulman Benjamin N. , Wang Jiaze , LaFond‐Hudson Sophie , O’Meara Theresa A. , Yuan Fengming , Molins Sergi , Hammond Glenn , Forbrich Inke , Cardon Zoe G. , Giblin Anne
Published: April 2024

Redox processes, aqueous and solid‐phase chemistry, and pH dynamics are key drivers of subsurface biogeochemical cycling and methanogenesis in terrestrial and wetland ecosystems but are typically not included in terrestrial carbon cycle models. These omissions may introduce errors when simulating systems where redox interactions and pH fluctuations are important, such as wetlands where saturation of soils can produce anoxic conditions and coastal systems where sulfate inputs from seawater can influence biogeochemistry. Integrating cycling of redox‐sensitive elements could therefore allow models to better represent key elements of carbon cycling and greenhouse gas production. We describe a model framework that couples the Energy Exascale Earth System Model (E3SM) Land Model (ELM) with PFLOTRAN biogeochemistry, allowing geochemical processes and redox interactions to be integrated with land surface model simulations. We implemented a reaction network including aerobic decomposition, fermentation, sulfate reduction, sulfide oxidation, methanogenesis, and methanotrophy as well as pH dynamics along with iron oxide and iron sulfide mineral precipitation and dissolution. We simulated biogeochemical cycling in tidal wetlands subject to either saltwater or freshwater inputs driven by tidal hydrological dynamics. In simulations with saltwater tidal inputs, sulfate reduction led to accumulation of sulfide, higher dissolved inorganic carbon concentrations, lower dissolved organic carbon concentrations, and lower methane emissions than simulations with freshwater tidal inputs. Model simulations compared well with measured porewater concentrations and surface gas emissions from coastal wetlands in the Northeastern United States. These results demonstrate how simulating geochemical reaction networks can improve land surface model simulations of subsurface biogeochemistry and carbon cycling.
Improved 30‐m Evapotranspiration Estimates Over 145 Eddy Covariance Sites in the Contiguous United States: The Role of ECOSTRESS, Harmonized Landsat Sentinel‐2 Imagery, Climate Reanalysis, and Deep Neural Network Postprocessing
Authors: Rashid Taufiq , Tian Di
Published: April 2024

This study developed and evaluated 30‐m daily evapotranspiration (ET) estimates using the Priestley‐Taylor Jet Propulsion Laboratory (PT‐JPL) model with ECOSTRESS, Moderate MODIS, harmonized Landsat Sentinel‐2 (HLS) imagery, ERA5‐Land reanalysis, and eddy covariance measurements. The new daily 30‐m ET showed significantly improved performance (overall, r = 0.8, RMSE = 1.736, KGE = 0.466) at 145 EC sites over contiguous United States compared to the current 70‐m ECOSTRESS ET (overall, r = 0.485, RMSE = 4.696, KGE = −0.841). A deep neural network postprocessing model trained with ET measurements from EC sites further improved the performance on test sites that were not used for model training (overall, r = 0.842, RMSE = 0.88, KGE = 0.792). The 30‐m ET estimation biases were significantly related to the biases in the upwelling longwave (RUL) and downwelling shortwave radiation (RDS) inputs, with ET estimates driven by MODIS radiation showing higher biases compared to those driven by ERA5‐Land radiation. The error diagnosis using random forest indicates that ET biases tend to be larger under higher ET estimates, and RUL and RDS were the primary contributors to the high bias at the higher ET ranges, with partial dependence plots revealing that the estimation biases tend to be higher under more humid environment, denser vegetation covers, and high net radiation conditions. In conclusion, higher spatial resolution satellite imagery of vegetation characteristics and higher temporal resolution radiation data, combined with continent‐wide EC measurements and deep learning, provided substantial added value for improving ET estimations at the field scale (30‐m).
Effects of Selenium and Cadmium on Human Liver and Kidney Functions in Exposed Black Shale Areas
Authors: Li Minglong , Qiu Liang , Ai Xunru , Xu Keyuan , Peng Min , Sun Guogen , Zhang Kai , Huang Chuying
Published: April 2024

Animal experiments suggest that selenium (Se) may alleviate cadmium (Cd) toxicity in animal liver and kidneys, but its effect on human liver and kidneys remains uncertain. In China, areas with black shale have shown elevated levels of Se and Cd. According to the USEPA (U.S. Environmental Protection Agency) evaluation method, the soil and rice in these areas pose significant risks. In black shale regions such as Enshi and Zhuxi County, residents who long‐term consume local rice may surpass safe Se and Cd intake levels. Significantly high median blood Se (B‐Se) and urine selenium (U‐Se) levels were detected in these areas, measuring 416.977 μg/L and 352.690 μg/L and 104.527 μg/L and 51.820 μg/L, respectively. Additionally, the median blood Cd (B‐Cd) and urine Cd (U‐Cd) levels were markedly elevated at 4.821 μg/L and 3.848 μg/L and at 7.750 μg/L and 7.050 μg/L, respectively, indicating substantial Cd exposure. Nevertheless, sensitive liver and kidney biomarkers in these groups fall within healthy reference ranges, suggesting a potential antagonistic effect of Se on Cd in the human body. Therefore, the USEPA method may not accurately assess Cd risk in exposed black shale areas. However, within the healthy ranges, residents in the Enshi study area had significantly greater median levels of serum creatinine and cystatin C, measuring 67.3 μmol/L and 0.92 mg/L, respectively, than those in Zhuxi did (53.6 μmol/L and 0.86 mg/L). In cases of excessive Se and Cd exposure, high Se and Cd levels impact the filtration function of the human kidney to some extent.
Strain Localization in Sandstone‐Derived Fault Gouges Under Conditions Relevant to Earthquake Nucleation
Authors: Hung Chien‐Cheng , Niemeijer André R. , Vasconcelos Ivan
Published: April 2024

Constraining strain localization and the growth of shear fabrics within brittle fault zones at sub‐seismic slip rates is important for understanding fault strength and frictional stability. We conducted direct shear experiments on simulated sandstone‐derived fault gouges at an effective normal stress of 40 MPa, a pore pressure of 15 MPa, and a temperature of 100°C. Using a passive strain marker and X‐ray Computed Tomography, we analyzed the spatial distribution of deformation in gouges deformed in the strain‐hardening, subsequent strain‐softening, and then steady‐state regimes at displacement rates of 1, 30, and 1,000 µm/s. We developed a machine‐learning‐based automatic boundary detection method to recognize the shear fabrics and quantify displacement partitioning between each fabric element. Our results show fabrics oriented along R1 and Y (including boundary) shears are the two major fabric elements. At rates of 1 and 30 µm/s, the relative amount of displacement on R1 shears is displacement dependent, increasing to ∼20% of the total displacement up to the strain‐softening stage, then decreasing to ∼10%–18% at the steady state. This trend is absent at the high rate where ∼18% of the displacement occurs on R1 shears throughout all investigated stages. At all rates, the relative amount of displacement on Y shears increases linearly with displacement to a total of larger than 50% at the steady state. Our study provides constraints on the development of the active slip zone, which is an important factor controlling heating and weakening associated with small‐magnitude earthquakes with limited displacement (mm‐dm), such as induced seismicity.
Through-polymer, via technology-enabled, flexible, lightweight, and integrated devices for implantable neural probes
Authors: Zhou Cunkai , Tian Ye , Li Gen , Ye Yifei , Gao Lusha , Li Jiazhi , Liu Ziwei , Su Haoyang , Lu Yunxiao , Li Meng , Zhou Zhitao , Wei Xiaoling , Qin Lunming , Tao Tiger H. , Sun Liuyang
Published: April 2024

In implantable electrophysiological recording systems, the headstage typically comprises neural probes that interface with brain tissue and integrated circuit chips for signal processing. While advancements in MEMS and CMOS technology have significantly improved these components, their interconnection still relies on conventional printed circuit boards and sophisticated adapters. This conventional approach adds considerable weight and volume to the package, especially for high channel count systems. To address this issue, we developed a through-polymer via (TPV) method inspired by the through-silicon via (TSV) technique in advanced three-dimensional packaging. This innovation enables the vertical integration of flexible probes, amplifier chips, and PCBs, realizing a flexible, lightweight, and integrated device (FLID). The total weight of the FLIDis only 25% that of its conventional counterparts relying on adapters, which significantly increased the activity levels of animals wearing the FLIDs to nearly match the levels of control animals without implants. Furthermore, by incorporating a platinum-iridium alloy as the top layer material for electrical contact, the FLID realizes exceptional electrical performance, enabling in vivo measurements of both local field potentials and individual neuron action potentials. These findings showcase the potential of FLIDs in scaling up implantable neural recording systems and mark a significant advancement in the field of neurotechnology.
Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency
Authors: Delling Jan Philipp , Bauer Helen Friedericke , Gerlach-Arbeiter Susanne , Schön Michael , Jacob Christian , Wagner Jan , Pedro Maria Teresa , Knöll Bernd , Boeckers Tobias M.
Published: April 2024

Synaptic dysfunction is a key feature of SHANK-associated disorders such as autism spectrum disorder, schizophrenia, and Phelan-McDermid syndrome. Since detailed knowledge of their effect on synaptic nanostructure remains limited, we aimed to investigate such alterations in ex11|SH3 SHANK3-KO mice combining expansion and STED microscopy. This enabled high-resolution imaging of mosaic-like arrangements formed by synaptic proteins in both human and murine brain tissue. We found distinct shape-profiles as fingerprints of the murine postsynaptic scaffold across brain regions and genotypes, as well as alterations in the spatial and molecular organization of subsynaptic domains under SHANK3-deficient conditions. These results provide insights into synaptic nanostructure in situ and advance our understanding of molecular mechanisms underlying synaptic dysfunction in neuropsychiatric disorders.
Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk
Authors: Callander Natalie S. , Silbermann Rebecca , Kaufman Jonathan L. , Godby Kelly N. , Laubach Jacob , Schmidt Timothy M. , Sborov Douglas W. , Medvedova Eva , Reeves Brandi , Dhakal Binod , Rodriguez Cesar , Chhabra Saurabh , Chari Ajai , Bal Susan , Anderson Larry D. , Dholaria Bhagirathbhai R. , Nathwani Nitya , Hari Parameswaran , Shah Nina , Bumma Naresh , Holstein Sarah A. , Costello Caitlin , Jakubowiak Andrzej , Wildes Tanya M. , Orlowski Robert Z. , Shain Kenneth H. , Cowan Andrew J. , Pei Huiling , Cortoos Annelore , Patel Sharmila , Lin Thomas S. , Giri Smith , Costa Luciano J. , Usmani Saad Z. , Richardson Paul G. , Voorhees Peter M.
Published: April 2024

In the MASTER study (NCT03224507), daratumumab+carfilzomib/lenalidomide/dexamethasone (D-KRd) demonstrated promising efficacy in transplant-eligible newly diagnosed multiple myeloma (NDMM). In GRIFFIN (NCT02874742), daratumumab+lenalidomide/bortezomib/dexamethasone (D-RVd) improved outcomes for transplant-eligible NDMM. Here, we present a post hoc analysis of patients with high-risk cytogenetic abnormalities (HRCAs; del[17p], t[4;14], t[14;16], t[14;20], or gain/amp[1q21]). Among 123 D-KRd patients, 43.1%, 37.4%, and 19.5% had 0, 1, or ≥2 HRCAs. Among 120 D-RVd patients, 55.8%, 28.3%, and 10.8% had 0, 1, or ≥2 HRCAs. Rates of complete response or better (best on study) for 0, 1, or ≥2 HRCAs were 90.6%, 89.1%, and 70.8% for D-KRd, and 90.9%, 78.8%, and 61.5% for D-RVd. At median follow-up (MASTER, 31.1 months; GRIFFIN, 49.6 months for randomized patients/59.5 months for safety run-in patients), MRD-negativity rates as assessed by next-generation sequencing (10–5) were 80.0%, 86.4%, and 83.3% for 0, 1, or ≥2 HRCAs for D-KRd, and 76.1%, 55.9%, and 61.5% for D-RVd. PFS was similar between studies and superior for 0 or 1 versus ≥2 HRCAs: 36-month PFS rates for D-KRd were 89.9%, 86.2%, and 52.4%, and 96.7%, 90.5%, and 53.5% for D-RVd. These data support the use of daratumumab-containing regimens for transplant-eligible NDMM with HCRAs; however, additional strategies are needed for ultra-high–risk disease (≥2 HRCAs).
CK2α-mediated phosphorylation of GRP94 facilitates the metastatic cascade in triple-negative breast cancer
Authors: Kim Hye-Youn , Kim Young-Mi , Hong Suntaek
Published: April 2024

Distant metastasis is a significant hallmark affecting to the high death rate of patients with triple-negative breast cancer (TNBC). Thus, it is crucial to identify and develop new therapeutic strategies to hinder cancer metastasis. While emerging studies have hinted a pivotal role of glucose-regulated protein 94 (GRP94) in tumorigenesis, the exact biological functions and molecular mechanisms of GRP94 in modulating cancer metastasis remain to be elucidated. Our study demonstrated an increased expression of GRP94 in TNBC correlated with metastatic progression and unfavorable prognosis in patients. Functionally, we identified that GRP94 depletion significantly diminished TNBC tumorigenesis and subsequent lung metastasis. In contrast, GRP94 overexpression exacerbated the invasiveness, migration, and lung metastasis of non-TNBC cells. Mechanistically, we found that casein kinase 2 alpha (CK2α) active in advanced breast cancer phosphorylated GRP94 at a conserved serine 306 (S306) residue. This phosphorylation increased the stability of GRP94 and enhanced its interaction with LRP6, leading to activation of canonical Wnt signaling. From a therapeutic standpoint, we found that benzamidine, a novel CK2α inhibitor, effectively suppressed GRP94 phosphorylation, LRP6 stabilization, and metastasis of TNBC. Our results point to the critical role of CK2α-mediated GRP94 phosphorylation in TNBC metastasis through activation of Wnt signaling, highlighting GRP94 as a therapeutic target to impede TNBC metastasis.
Stable skyrmion bundles at room temperature and zero magnetic field in a chiral magnet
Authors: Zhang Yongsen , Tang Jin , Wu Yaodong , Shi Meng , Xu Xitong , Wang Shouguo , Tian Mingliang , Du Haifeng
Published: April 2024

Topological spin textures are characterized by magnetic topological charges, Q, which govern their electromagnetic properties. Recent studies have achieved skyrmion bundles with arbitrary integer values of Q, opening possibilities for exploring topological spintronics based on Q. However, the realization of stable skyrmion bundles in chiral magnets at room temperature and zero magnetic field — the prerequisite for realistic device applications — has remained elusive. Here, through the combination of pulsed currents and reversed magnetic fields, we experimentally achieve skyrmion bundles with different integer Q values — reaching a maximum of 24 at above room temperature and zero magnetic field — in the chiral magnet Co8Zn10Mn2. We demonstrate the field-driven annihilation of high-Q bundles and present a phase diagram as a function of temperature and field. Our experimental findings are consistently corroborated by micromagnetic simulations, which reveal the nature of the skyrmion bundle as that of skyrmion tubes encircled by a fractional Hopfion.
Fabrication-induced even-odd discrepancy of magnetotransport in few-layer MnBi2Te4
Authors: Li Yaoxin , Wang Yongchao , Lian Zichen , Li Hao , Gao Zhiting , Xu Liangcai , Wang Huan , Lu Rui’e , Li Longfei , Feng Yang , Zhu Jinjiang , Liu Liangyang , Wang Yongqian , Fu Bohan , Yang Shuai , Yang Luyi , Wang Yihua , Xia Tianlong , Liu Chang , Jia Shuang , Wu Yang , Zhang Jinsong , Wang Yayu , Liu Chang
Published: April 2024

The van der Waals antiferromagnetic topological insulator MnBi2Te4 represents a promising platform for exploring the layer-dependent magnetism and topological states of matter. Recently observed discrepancies between magnetic and transport properties have aroused controversies concerning the topological nature of MnBi2Te4 in the ground state. In this article, we demonstrate that fabrication can induce mismatched even-odd layer dependent magnetotransport in few-layer MnBi2Te4. We perform a comprehensive study of the magnetotransport properties in 6- and 7-septuple-layer MnBi2Te4, and reveal that both even- and odd-number-layer device can show zero Hall plateau phenomena in zero magnetic field. Importantly, a statistical survey of the optical contrast in more than 200 MnBi2Te4 flakes reveals that the zero Hall plateau in odd-number-layer devices arises from the reduction of the effective thickness during the fabrication, a factor that was rarely noticed in previous studies of 2D materials. Our finding not only provides an explanation to the controversies regarding the discrepancy of the even-odd layer dependent magnetotransport in MnBi2Te4, but also highlights the critical issues concerning the fabrication and characterization of 2D material devices.
A global meta-analysis on the effects of organic and inorganic fertilization on grasslands and croplands
Authors: Shi Ting-Shuai , Collins Scott L. , Yu Kailiang , Peñuelas Josep , Sardans Jordi , Li Hailing , Ye Jian-Sheng
Published: April 2024

A central role for nature-based solution is to identify optimal management practices to address environmental challenges, including carbon sequestration and biodiversity conservation. Inorganic fertilization increases plant aboveground biomass but often causes a tradeoff with plant diversity loss. It remains unclear, however, whether organic fertilization, as a potential nature-based solution, could alter this tradeoff by increasing aboveground biomass without plant diversity loss. Here we compile data from 537 experiments on organic and inorganic fertilization across grasslands and croplands worldwide to evaluate the responses of aboveground biomass, plant diversity, and soil organic carbon (SOC). Both organic and inorganic fertilization increase aboveground biomass by 56% and 42% relative to ambient, respectively. However, only inorganic fertilization decreases plant diversity, while organic fertilization increases plant diversity in grasslands with greater soil water content. Moreover, organic fertilization increases SOC in grasslands by 19% and 15% relative to ambient and inorganic fertilization, respectively. The positive effect of organic fertilization on SOC increases with increasing mean annual temperature in grasslands, a pattern not observed in croplands. Collectively, our findings highlight organic fertilization as a potential nature-based solution that can increase two ecosystem services of grasslands, forage production, and soil carbon storage, without a tradeoff in plant diversity loss.
Towards atom-level understanding of metal oxide catalysts for the oxygen evolution reaction with machine learning
Authors: Lunger Jaclyn R. , Karaguesian Jessica , Chun Hoje , Peng Jiayu , Tseo Yitong , Shan Chung Hsuan , Han Byungchan , Shao-Horn Yang , Gómez-Bombarelli Rafael
Published: April 2024

Green hydrogen production is crucial for a sustainable future, but current catalysts for the oxygen evolution reaction (OER) suffer from slow kinetics, despite many efforts to produce optimal designs, particularly through the calculation of descriptors for activity. In this study, we develop a dataset of density functional theory calculations of bulk and surface perovskite oxides, and adsorption energies of OER intermediates, which includes compositions up to quaternary and facets up to (555). We demonstrate that per-site properties of perovskite oxides such as Bader charge or band center can be tuned through element substitution and faceting, and develop a machine learning model that accurately predicts these properties directly from the local chemical environment. We leverage these per-site properties to identify promising perovskites with high theoretical OER activity. The identified design principles and promising materials provide a roadmap for closing the gap between current artificial catalysts and biological enzymes such as photosystem II.
Longitudinal cognitive decline characterizes the profile of non-PD-manifest GBA1 mutation carriers
Authors: Roeben Benjamin , Liepelt-Scarfone Inga , Lerche Stefanie , Zimmermann Milan , Wurster Isabel , Sünkel Ulrike , Schulte Claudia , Deuschle Christian , Eschweiler Gerhard W. , Maetzler Walter , Gasser Thomas , Berg Daniela , Brockmann Kathrin
Published: April 2024

With disease-modifying treatment for Parkinson’s disease (PD) associated with variants in the glucocerebrosidase gene (GBA1) under way, the challenge to design clinical trials with non-PD-manifest GBA mutation carriers (GBA1NMC) comes within close reach. To delineate trajectories of motor and non-motor markers as well as serum neurofilament light (sNfL) levels and to evaluate clinical endpoints as outcomes for clinical trials in GBA1NMC, longitudinal data of 56 GBA1NMC carriers and 112 age- and sex-matched GBA1 wildtype participants (GBA1wildtype) with up to 9 years of follow-up was analyzed using linear mixed-effects models (LMEM) and Kaplan–Meier survival analysis of clinical endpoints for motor and cognitive function. GBA1NMC showed worse performance in Pegboard, 20 m fast walking, global cognition as well as in executive and memory function at baseline. Longitudinally, LMEM revealed a higher annual increase of the MDS-UPDRS III bradykinesia subscore in GBA1NMC compared to GBA1wildtype, but comparable trajectories of all other motor and non-motor markers as well as sNfL. Kaplan–Meier survival analysis showed a significantly earlier progression to clinical endpoints of cognitive decline in GBA1NMC. Incidence of PD was significantly higher in GBA1NMC. In conclusion, our study extends data on GBA1NMC indicating early cognitive decline as a potentially characteristic feature. Comprehensive longitudinal assessments of cognitive function are crucial to delineate the evolution of early changes in GBA1NMC enabling a more accurate stratification and allow for a more precise definition of trial design and sample size.
Interferon-induced transmembrane protein-1 competitively blocks Ephrin receptor A2-mediated Epstein–Barr virus entry into epithelial cells
Authors: Yang Yinggui , Ding Tengteng , Cong Ying , Luo Xiaomin , Liu Changlin , Gong Ting , Zhao Min , Zheng Xichun , Li Chenglin , Zhang Yuanbin , Zhou Jiayi , Ni Chuping , Zhang Xueyu , Ji Ziliang , Wu Tao , Yang Shaodong , Zhou Qingchun , Wu Dinglan , Gong Xinqi , Zheng Qingyou , Li Xin
Published: April 2024

Epstein–Barr virus (EBV) can infect both B cells and epithelial cells (ECs), causing diseases such as mononucleosis and cancer. It enters ECs via Ephrin receptor A2 (EphA2). The function of interferon-induced transmembrane protein-1 (IFITM1) in EBV infection of ECs remains elusive. Here we report that IFITM1 inhibits EphA2-mediated EBV entry into ECs. RNA-sequencing and clinical sample analysis show reduced IFITM1 in EBV-positive ECs and a negative correlation between IFITM1 level and EBV copy number. IFITM1 depletion increases EBV infection and vice versa. Exogenous soluble IFITM1 effectively prevents EBV infection in vitro and in vivo. Furthermore, three-dimensional structure prediction and site-directed mutagenesis demonstrate that IFITM1 interacts with EphA2 via its two specific residues, competitively blocking EphA2 binding to EBV glycoproteins. Finally, YTHDF3, an m6A reader, suppresses IFITM1 via degradation-related DEAD-box protein 5 (DDX5). Thus, this study underscores IFITM1’s crucial role in blocking EphA2-mediated EBV entry into ECs, indicating its potential in preventing EBV infection.
Multimodal cell atlas of the ageing human skeletal muscle
Authors: Lai Yiwei , Ramírez-Pardo Ignacio , Isern Joan , An Juan , Perdiguero Eusebio , Serrano Antonio L. , Li Jinxiu , García-Domínguez Esther , Segalés Jessica , Guo Pengcheng , Lukesova Vera , Andrés Eva , Zuo Jing , Yuan Yue , Liu Chuanyu , Viña José , Doménech-Fernández Julio , Gómez-Cabrera Mari Carmen , Song Yancheng , Liu Longqi , Xu Xun , Muñoz-Cánoves Pura , Esteban Miguel A.
Published: April 2024

Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.
Cortical gene expression architecture links healthy neurodevelopment to the imaging, transcriptomics and genetics of autism and schizophrenia
Authors: Dear Richard , Wagstyl Konrad , Seidlitz Jakob , Markello Ross D. , Arnatkevičiūtė Aurina , Anderson Kevin M. , Bethlehem Richard A. I. ,   Lifespan Brain Chart Consortium, Raznahan Armin , Bullmore Edward T. , Vértes Petra E.
Published: April 2024

Human brain organization involves the coordinated expression of thousands of genes. For example, the first principal component (C1) of cortical transcription identifies a hierarchy from sensorimotor to association regions. In this study, optimized processing of the Allen Human Brain Atlas revealed two new components of cortical gene expression architecture, C2 and C3, which are distinctively enriched for neuronal, metabolic and immune processes, specific cell types and cytoarchitectonics, and genetic variants associated with intelligence. Using additional datasets (PsychENCODE, Allen Cell Atlas and BrainSpan), we found that C1–C3 represent generalizable transcriptional programs that are coordinated within cells and differentially phased during fetal and postnatal development. Autism spectrum disorder and schizophrenia were specifically associated with C1/C2 and C3, respectively, across neuroimaging, differential expression and genome-wide association studies. Evidence converged especially in support of C3 as a normative transcriptional program for adolescent brain development, which can lead to atypical supragranular cortical connectivity in people at high genetic risk for schizophrenia.
Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation
Authors: Liu Julio C. Y. , Ackermann Leena , Hoffmann Saskia , Gál Zita , Hendriks Ivo A. , Jain Charu , Morlot Louise , Tatham Michael H. , McLelland Gian-Luca , Hay Ronald T. , Nielsen Michael Lund , Brummelkamp Thijn , Haahr Peter , Mailand Niels
Published: April 2024

Protein SUMOylation provides a principal driving force for cellular stress responses, including DNA–protein crosslink (DPC) repair and arsenic-induced PML body degradation. In this study, using genome-scale screens, we identified the human E3 ligase TOPORS as a key effector of SUMO-dependent DPC resolution. We demonstrate that TOPORS promotes DPC repair by functioning as a SUMO-targeted ubiquitin ligase (STUbL), combining ubiquitin ligase activity through its RING domain with poly-SUMO binding via SUMO-interacting motifs, analogous to the STUbL RNF4. Mechanistically, TOPORS is a SUMO1-selective STUbL that complements RNF4 in generating complex ubiquitin landscapes on SUMOylated targets, including DPCs and PML, stimulating efficient p97/VCP unfoldase recruitment and proteasomal degradation. Combined loss of TOPORS and RNF4 is synthetic lethal even in unstressed cells, involving defective clearance of SUMOylated proteins from chromatin accompanied by cell cycle arrest and apoptosis. Our findings establish TOPORS as a STUbL whose parallel action with RNF4 defines a general mechanistic principle in crucial cellular processes governed by direct SUMO–ubiquitin crosstalk.
CROPGRIDS: a global geo-referenced dataset of 173 crops
Authors: Tang Fiona H. M. , Nguyen Thu Ha , Conchedda Giulia , Casse Leon , Tubiello Francesco N. , Maggi Federico
Published: April 2024

CROPGRIDS is a comprehensive global geo-referenced dataset providing area information for 173 crops for the year 2020, at a resolution of 0.05° (about 5.6 km at the equator). It represents a major update of the Monfredaet al. (2008) dataset (hereafter MRF), the most widely used geospatial dataset previously available, covering 175 crops with reference year 2000 at 10 km spatial resolution. CROPGRIDS builds on information originally provided in MRF and expands it using 27 selected published gridded datasets, subnational data of 52 countries obtained from National Statistical Offices, and the 2020 national-level statistics from FAOSTAT, providing more recent harvested and crop (physical) areas for 173 crops at regional, national, and global levels. The CROPGRIDS data advance the current state of knowledge on the spatial distribution of crops, providing useful inputs for modelling studies and sustainability analyses relevant to national and international processes.
An annotated street view image dataset for automated road damage detection
Authors: Ren Miao , Zhang Xianfeng , Zhi Xiaobo , Wei Yuanjia , Feng Ziyuan
Published: April 2024

Road damage is a great threat to the service life and safety of roads, and the early detection of pavement damage can facilitate maintenance and repair. Street view images serve as a new solution for the monitoring of pavement damage due to their wide coverage and regular updates. In this study, a road pavement damage dataset, the Street View Image Dataset for Automated Road Damage Detection (SVRDD), was developed using 8000 street view images acquired from Baidu Maps. Based on these images, over 20,000 damage instances were visually recognized and annotated. These instances were distributed in five administrative districts of Beijing City. Ten well-established object detection algorithms were trained and assessed using the SVRDD dataset. The results have demonstrated the performances of these algorithms in the detection of pavement damages. To the best of our knowledge, SVRDD is the first public dataset based on street view images for pavement damages detection. It can provide reliable data support for future development of deep learning algorithms based on street view images.
Investigation of thrombin concentration at the time of clot formation in simultaneous thrombin and fibrin generation assays
Authors: Tarandovskiy Ivan D. , Surov Stepan S. , Parunov Leonid A. , Liang Yideng , Jankowski Wojciech , Sauna Zuben E. , Ovanesov Mikhail V.
Published: April 2024

Thrombin generation (TG) and fibrin clot formation represent the central process of blood coagulation. Up to 95% of thrombin is considered to be generated after the clot is formed. However, this was not investigated in depth. In this study, we conducted a quantitative analysis of the Thrombin at Clot Time (TCT) parameter in 5758 simultaneously recorded TG and clot formation assays using frozen plasma samples from commercial sources under various conditions of activation. These samples were supplemented with clotting factor concentrates, procoagulant lipid vesicles and a fluorogenic substrate and triggered with tissue factor (TF). We found that TCT is often close to a 10% of thrombin peak height (TPH) yet it can be larger or smaller depending on whether the sample has low or high TPH value. In general, the samples with high TPH are associated with elevated TCT. TCT appeared more sensitive to some procoagulant phenotypes than other commonly used parameters such as clotting time, TPH or Thrombin Production Rate (TPR). In a minority of cases, TCT were not predicted from TG parameters. For example, elevated TCT (above 15% of TPH) was associated with either very low or very high TPR values. We conclude that clotting and TG assays may provide complementary information about the plasma sample, and that the TCT parameter may serve as an additional marker for the procoagulant potential in plasma sample.
Predictors of pathological gambling behaviours in parents population in Nigeria
Authors: Ede Moses Onyemaechi , Nwosu Kingsley Chinaza , Okeke Chinedu Ifedi , Oneli Joy Obiageli
Published: April 2024

The increasing incidence of psychological pains, burnout, and anxiety among gamblers in Nigeria is high. This is because pathological gambling (PG) is on the rise and it is linked to many social vices such as stealing, drug abuse, and sexual abuse. It is important to investigate the trajectories of PG in Nigeria. A cross-sectional survey design was employed in our study with 197 participants sampled from 28 gambling venues in Nigeria made up the study’s sample size. Of the 197, 131 (66.5%) were males and 66 (33.5%) were females. 50 (25.4%) were within the age range of 20–30 years, 42 (21.3%) were within 31–40 years, 40 (20.3%) were within 41–50 years, 35 (17.8%) were within 51–60 years, and 30 (15.2%) were within 61 and above. Using the hierarchical regression analysis, our finding revealed a significant association between psychological distress and our respondents’ pathological gambling behaviour whereas none of the sociodemographic variables made a significant contribution to their pathological gambling behaviour. We concluded that gamblers’ psychological well-being is crucial to understanding their problematic gambling behaviours in the context of a developing nation such as Nigeria, and that this could be similar among our respondents. Implications of our findings were highlighted.
The design and evaluation of gamified online role-play as a telehealth training strategy in dental education: an explanatory sequential mixed-methods study
Authors: Teerawongpairoj Chayanid , Tantipoj Chanita , Sipiyaruk Kawin
Published: April 2024

To evaluate user perceptions and educational impact of gamified online role-play in teledentistry as well as to construct a conceptual framework highlighting how to design this interactive learning strategy, this research employed an explanatory sequential mixed-methods design. Participants were requested to complete self-perceived assessments toward confidence and awareness in teledentistry before and after participating in a gamified online role-play. They were also asked to complete a satisfaction questionnaire and participate in an in-depth interview to investigate their learning experience. The data were analyzed using descriptive statistics, paired sample t-test, one-way analysis of variance, and framework analysis. There were 18 participants who completed self-perceived assessments and satisfaction questionnaire, in which 12 of them participated in a semi-structured interview. There were statistically significant increases in self-perceived confidence and awareness after participating in the gamified online role-play (P < 0.001). In addition, the participants were likely to be satisfied with this learning strategy, where usefulness was perceived as the most positive aspect with a score of 4.44 out of 5, followed by ease of use (4.40) and enjoyment (4.03). The conceptual framework constructed from the qualitative findings has revealed five key elements in designing a gamified online role-play, including learner profile, learning settings, pedagogical components, interactive functions, and educational impact. The gamified online role-play has demonstrated its potential in improving self-perceived confidence and awareness in teledentistry. The conceptual framework developed in this research could be considered to design and implement a gamified online role-play in dental education. This research provides valuable evidence on the educational impact of gamified online role-play in teledentistry and how it could be designed and implemented in dental education. This information would be supportive for dental instructors or educators who are considering to implement teledentistry training in their practice.
Enhanced Stability, Superior Anti-Corrosive, and Tribological Performance of Al2O3 Water-based Nanofluid Lubricants with Tannic Acid and Carboxymethyl Cellulose over SDBS as Surfactant
Authors: Rahmadiawan Dieter , Shi Shih-Chen
Published: April 2024

In this research work, the stability, tribological, and corrosion properties of a water-based Al2O3 nanofluid (0.5 wt%) formulated with tannin acid (TA) and carboxymethyl cellulose (CMC) as dispersants or surfactants were investigated. For comparative purposes, sodium dodecylbenzene sulfonate (SDBS) was also incorporated. The stability of the nanofluid was assessed through zeta potential measurements and photo-capturing, revealing the effectiveness of TA and CMC in preventing nanoparticle agglomeration. Tribological properties were examined using a pin-on-disk apparatus, highlighting the tribofilm of Al2O3 that enhanced lubricating properties of the nanofluid by the SEM, resulting in reduced friction and wear of the contacting surfaces. Sample with the addition of both TA and CMC exhibited the best tribological performance, with a ~ 20% reduction in the friction coefficient and a 59% improvement in wear rate compared to neat nanofluid without TA and CMC. Additionally, the corrosion resistance of the nanofluids were evaluated via weight loss and electrochemical impedance spectroscopy. The nanofluid sample containing both TA and CMC exhibited the lowest corrosion rate, with 97.6% improvement compared to sample without them. This study provides valuable insights into the potential applications of TA and CMC-based Al2O3 nanofluids as effective and environmentally friendly solutions for coolant or lubrication in cutting processes.
Etiologic evaluation and pregnancy outcomes of fetal growth restriction (FGR) associated with structural malformations
Authors: Wu Xiaoqing , He Shuqiong , Shen Qingmei , Xu Shiyi , Guo Danhua , Liang Bin , Wang Xinrui , Cao Hua , Huang Hailong , Xu Liangpu
Published: April 2024

This study aimed to evaluate the etiology and pregnancy outcomes of fetuses underwent invasive prenatal diagnosis for fetal growth restriction (FGR) accompanied by structural malformations. Data from 130 pregnancies referred for prenatal diagnosis for FGR accompanied by structural malformations were obtained between July 2011 and July 2023. Traditional karyotyping was conducted for all the subjects. A total of 37 (28.5%) cases of chromosomal abnormalities were detected by karyotyping, including 30 cases of numerical anomalies and seven cases of unbalanced structural anomalies. Trisomy 18 was the most common abnormalities, accounting for 51.4%, significantly higher than any other chromosomal abnormality. The cohort was predominantly comprised of early-onset FGR (88.5%) compared to late-onset FGR (11.5%). The incidences of chromosomal abnormalities in this two groups were 29.6% (34/115) and 20.0% (3/15), respectively (p > 0.05). The majority (74.6%, 97/130) of the cohort were affected by a single system malformation, with chromosomal abnormalities found in 19.6% (19/97) of cases. In pregnancies of structural malformations involving two and multiple systems, the frequencies were 56.5% (13/23), and 50.0% (5/10), respectively. Single nucleotide polymorphism array (SNP array) was performed in parallel for 65 cases, revealing additional 7.7% cases of copy number variants (CNVs) compared to karyotyping. Polymerase chain reaction (PCR) was used for detection of cytomegalovirus (CMV) DNA in 92 cases. All fetuses with FGR associated with two or more system malformations were either terminated or stillborn, irrespective of chromosomal aberrations. Conversely, 71.8% of pregnancies with a single-system malformation and normal genetic testing results resulted in live births. Furthermore, two (2.2%) cases tested positive for CMV DNA, leading to one termination and one case of serious developmental disorder after birth. Our study suggests that structural malformations associated with FGR are more likely to affect a single organ system. When multiple systems are involved, the incidence of chromosomal abnormalities and termination rates are notably high. We advocate for the use of CMA and CMV DNA examinations in FGR cases undergo invasive prenatal diagnosis, as these tests can provide valuable insights for etiological exploration and pregnancy management guidance.