bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and Verbal Fluency in Alzheimer’s Disease and Frontotemporal Dementia: Clinical and Metabolic Correlates
Authors: Delgado-Álvarez Alfonso , Cabrera-Martín María Nieves , Pytel Vanesa , Delgado-Alonso Cristina , Matías-Guiu Jorge , Matias-Guiu Jordi A. 
Published: September 2021

AbstractObjective:Cognitive processes underlying verbal and design fluency, and their neural correlates in patients with Alzheimer’s disease (AD) and behavioural variant Frontotemporal Dementia (bvFTD) remain unclear. We hypothesised that verbal and design fluency may be associated with distinct neuropsychological processes in AD and FTD, showing different patterns of impairment and neural basis.Methods:We enrolled 142 participants including patients with AD (n = 80, mean age = 74.71), bvFTD (n = 34, mean age = 68.18), and healthy controls (HCs) (n = 28, mean age = 71.14), that underwent cognitive assessment and 18F-fluorodeoxyglucose positron emission tomography imaging.Results:Semantic and phonemic fluency showed the largest effect sizes between groups, showing lower scores in bvFTD than AD and HCs, and lower scores in AD than HC. Both AD and bvFTD showed a lower number of unique designs in design fluency in comparison to HC. Semantic fluency was correlated with left frontotemporal lobe in AD, and with left frontal, caudate, and thalamus in bvFTD. Percentage of unique designs in design fluency was associated with the metabolism of the bilateral fronto-temporo-parietal cortex in AD, and the bilateral frontal cortex with right predominance in bvFTD. Repetitions in AD were correlated with bilateral frontal, temporal, and parietal lobes, and with left prefrontal cortex in bvFTD.Conclusions:Our findings demonstrate differential underlying cognitive processes in verbal and design fluency in AD and bvFTD. While memory and executive functioning associated with fronto-temporo-parietal regions were key in AD, attention and executive functions correlated with the frontal cortex and played a more significant role in bvFTD during fluency tasks.
Is Alteration of Magnetite During Rock Weathering Climate‐Dependent?
Authors: Zhang Qi , Appel Erwin , Basavaiah Nathani , Hu Shouyun , Zhu Xiuhua , Neumann Udo 
Published: September 2021

AbstractMagnetic records in sedimentary sequences are often used as paleoclimate proxies. Climate‐specific alteration of magnetite during rock weathering in the catchment might contribute to proxy variations in sediment sinks. In an actualistic study, we investigated the effects of magnetite alteration using weathered pebble material on basaltic parent rock. We collected samples from the Deccan basalts (India) across a large difference of mean annual precipitation (MAP; ∼800–3,200 mm), and also from the Emeishan basalts (SW‐China) to compare alteration effects at similar MAP (∼1,100 mm) but ∼12°C–15°C lower mean annual temperature (MAT). We used rocks with lamellar magnetite‐ilmenite texture to ensure the best possible uniform parent rock magnetic mineralogy. We separated the weathered material into five groups by grain size, assuming that alteration increases in finer pebbles. Only magnetic susceptibility (χ) shows a systematic change, with an increase that is weakly stronger for higher MAP. Consistent with a simplified model, the χ‐increase may represent progressive maghemitization. For the Emeishan basalts, we found a significantly stronger degree of alteration, including loss of magnetite. We explain this effect, which is surprising regarding the clearly lower MAT, by frost‐induced micro‐cracks due to physical weathering that opens pathways for oxygen and humidity into particle interiors. Based on these findings, we conclude that climate‐related alteration effects of magnetite during rock weathering are in most cases outweighed by parent rock heterogeneity, and magnetic proxy records in derived sediment archives are unlikely to record climate‐related magnetite alteration acquired during rock weathering, at least for catchment with basalts.
Surface Current Variations and Oceanic Fronts in the Southern East China Sea: Drifter Experiments, Coastal Radar Applications, and Satellite Observations
Authors: Hsu Po‐Chun , Centurioni Luca , Shao Huan‐Jie , Zheng Quanan , Lu Ching‐Yuan , Hsu Tai‐Wen , Tseng Ruo‐Shan 
Published: September 2021

AbstractOcean currents in the southern East China Sea (ECS) are complex and have long lacked systematic observational data. Observations from coastal radars in northern Taiwan, along with several drifters and satellite data, reveal a detailed ECS surface flow structure and thermal front. Drifter trajectories followed the seasonal flow field and were oscillatory and trapped due to strong tidal currents. Three drifters crossed the oceanic front off the northern coast of Taiwan following the tidal motion with a rapid change in the sea surface temperature by 2.5°C, which was recorded within a small distance of 500 m. A significant seasonal water mass exchange cycle occurred in the southern ECS. Starting in October, the Kuroshio Current intrudes onto the ECS shelf, causing the formation of a southwestward Northern Taiwan Coastal Current that mixes with the China Coastal Current to form a southward flow in the northern Taiwan Strait. Beginning in March, the ocean current off northwestern Taiwan shifts northward and then gradually flows eastward into the Kuroshio region. With satellite‐derived and model‐simulated surface currents contradicting each other over long periods of time, hourly coastal radar data have not only successfully explained the spatiotemporal variations in the sea surface temperature, salinity, and chlorophyll concentration observed by satellites but have also resolved the long‐standing disputes over the surface currents in the southern ECS.
Multi‐Source Data Based Investigation of Aerosol‐Cloud Interaction Over the North China Plain and North of the Yangtze Plain
Authors: Yang Yikun , Zhao Chuanfeng , Wang Yang , Zhao Xin , Sun Wenxiao , Yang Jie , Ma Zhanshan , Fan Hao 
Published: September 2021

AbstractAlthough great progress has been made in the study of aerosol‐cloud interactions (ACIs), representation of ACI is still the largest uncertainty in current weather and climate models. In this study, the ACI over the North China Plain and north of the Yangtze Plain is investigated using multi‐source data including satellite, ground‐based, reanalysis, and fusion data. The effects of aerosol characteristics (PM2.5, PM10, and PM2.5/PM10 ratio), atmospheric conditions including liquid water path (LWP) and lower tropospheric stability (LTS), and drizzle on ACI are analyzed. Results suggest that both aerosol characteristics and atmospheric conditions can affect cloud effective radius (), but drizzle in clouds plays a decisive role on ACI. In the case of fixed LTS and LWP, the average cloud droplet increases first and then fluctuates for all clouds examined with the increase of PM2.5 concentration. The PM2.5 concentration corresponding to the turning point of increases with the increasing LWP due to the increased chance of collision and coalescence. In contrast, the average cloud droplet and PM2.5 concentration show a negative correlation for clouds without drizzle, which is mainly caused by competition of water vapor. The quantitative ACI results show that the values of the aerosol first indirect effect are negative for most cases when considering all clouds examined, but positive when only considering clouds without drizzle.
TCF4 enhances hepatic metastasis of colorectal cancer by regulating tumor-associated macrophage via CCL2/CCR2 signaling
Authors: Tu Wei , Gong Jin , Zhou Zhenzhen , Tian Dean , Wang Zhijun 
Published: September 2021

AbstractColorectal cancer (CRC) liver metastasis is a significant clinical problem for which better therapies are urgently needed. Tumor-associated macrophage, a major cell population in the tumor microenvironment, is a known contributor to primary cancer progression and cancer metastasis. Here, we found TAM recruitment and M2 polarization were increased in the hepatic metastatic lesion compared with the primary site of human CRC tissues. Moreover, Pearson correlation analysis showed that TAM recruitment and polarization were closely correlated with the elevated TCF4 expression in the metastatic site. To investigate the role of TCF4 in CRC liver metastasis, we generated a syngeneic mouse model using MC38 cells splenic injection. Results from in vivo experiments and mouse models revealed that TCF4 deficiency in MC38 cells does not affect their proliferation and invasion; however, it reduces TAM infiltration and M2 polarization in the metastasis site. Further studies indicated that these effects are mediated by the TCF4 regulated CCL2 and CCR2 expression. TCF4 or CCL2 silencing in the tumor cells prevent CRC liver metastasis in the mouse model. Altogether, these findings suggest that the TCF4-CCL2-CCR2 axis plays an essential role in CRC liver metastasis by enhancing TAMs recruitment and M2 polarization.
USP7 facilitates SMAD3 autoregulation to repress cancer progression in p53-deficient lung cancer
Authors: Huang Yu-Ting , Cheng An-Chieh , Tang Hui-Chi , Huang Guo-Cheng , Cai Ling , Lin Ta-Hsien , Wu Kou-Juey , Tseng Ping-Hui , Wang Greg G. , Chen Wei-Yi 
Published: September 2021

AbstractUSP7, one of the most abundant ubiquitin-specific proteases (USP), plays multifaceted roles in many cellular events, including oncogenic pathways. Accumulated studies have suggested that USP7, through modulating the MDM2/MDMX-p53 pathway, is a promising target for cancer treatment; however, little is known about the function of USP7 in p53-deficient tumors. Here we report that USP7 regulates the autoregulation of SMAD3, a key regulator of transforming growth factor β (TGFβ) signaling, that represses the cell progression of p53-deficient lung cancer. CRISPR/Cas9-mediated inactivation of USP7 in p53-deficient lung cancer H1299 line resulted in advanced cell proliferation in vitro and in xenograft tumor in vivo. Genome-wide analyses (ChIP-seq and RNA-seq) of USP7 KO H1299 cells reveal a dramatic reduction of SMAD3 autoregulation, including decreased gene expression and blunted function of associated super-enhancer (SE). Furthermore, biochemical assays show that SMAD3 is conjugated by mono-ubiquitin, which negatively regulates the DNA-binding function of SMAD3, in USP7 KO cells. In addition, cell-free and cell-based analyses further demonstrate that the deubiquitinase activity of USP7 mediates the removal of mono-ubiquitin from SMAD3 and facilitates the DNA-binding of SMAD3-SMAD4 dimer at SMAD3 locus, and thus enhance the autoregulation of SMAD3. Collectively, our study identified a novel mechanism by which USP7, through catalyzing the SMAD3 de-monoubiquitination, facilitates the positive autoregulation of SMAD3, and represses the cancer progression of p53-deficient lung cancer.
Water modulates the lamellar structure and interlayer correlation of poly(perfluorooctyl acrylate) films: a specular and off-specular neutron scattering study
Authors: Yamamoto Akihisa , Higaki Yuji , Thoma Judith , Kimmle Esther , Ishige Ryohei , Demé Bruno , Takahara Atsushi , Tanaka Motomu 
Published: September 2021

AbstractComb-like polymers with pendant-like perfluorocarbon side chains self-assemble into smectic lamellae and have been extensively used as water-repellent, hydrophobic coating materials characterized by large water contact angles (θ > 120°). As poly(perfluorooctyl acrylate) films are “apparently hydrophobic” (θ > 120°), the interaction of such materials and water molecules has been largely overlooked. To unravel the molecular-level interactions between water and apparently hydrophobic polymers, specular and off-specular neutron scattering experiments were conducted at defined osmotic pressure ΠH2O. The poly{2-[(perfluorooctylethyl)carbamate]ethyl} acrylate (PFAUr-C8), which had a carbamate linker, transitioned to another lamellar phase at 89 °C. At T = 25 °C; the lamellar periodicity of PFAUr-C8 slightly increased with decreasing osmotic pressure, while the vertical correlation length increased. However, the poly[(perfluorooctyl)ethyl] acrylate (PFA-C8) that did not contain a carbamate linker directly transitioned to a disordered phase at 84 °C. The lamellar periodicity of PFA-C8 was largely independent of the osmotic pressure, suggesting that PFA-C8 was poorly hydrated. Remarkably, the vertical correlation length decreased with decreasing osmotic pressure. Because hydration facilitated by the linker modulated the smectic lamellae of the poly(perfluoroalkyl acrylate), water molecules could be used to optimize the self-assembly of apparently hydrophobic liquid crystalline polymers.
Virus detection via programmable Type III-A CRISPR-Cas systems
Authors: Sridhara Sagar , Goswami Hemant N. , Whyms Charlisa , Dennis Jonathan H. , Li Hong 
Published: September 2021

AbstractAmong the currently available virus detection assays, those based on the programmable CRISPR-Cas enzymes have the advantage of rapid reporting and high sensitivity without the requirement of thermocyclers. Type III-A CRISPR-Cas system is a multi-component and multipronged immune effector, activated by viral RNA that previously has not been repurposed for disease detection owing in part to the complex enzyme reconstitution process and functionality. Here, we describe the construction and application of a virus detection method, based on an in vivo-reconstituted Type III-A CRISPR-Cas system. This system harnesses both RNA- and transcription-activated dual nucleic acid cleavage activities as well as internal signal amplification that allow virus detection with high sensitivity and at multiple settings. We demonstrate the use of the Type III-A system-based method in detection of SARS-CoV-2 that reached 2000 copies/μl sensitivity in amplification-free and 60 copies/μl sensitivity via isothermal amplification within 30 min and diagnosed SARS-CoV-2-infected patients in both settings. The high sensitivity, flexible reaction conditions, and the small molecular-driven amplification make the Type III-A system a potentially unique nucleic acid detection method with broad applications.
Comprehensive deletion landscape of CRISPR-Cas9 identifies minimal RNA-guided DNA-binding modules
Authors: Shams Arik , Higgins Sean A. , Fellmann Christof , Laughlin Thomas G. , Oakes Benjamin L. , Lew Rachel , Kim Shin , Lukarska Maria , Arnold Madeline , Staahl Brett T. , Doudna Jennifer A. , Savage David F. 
Published: September 2021

AbstractProteins evolve through the modular rearrangement of elements known as domains. Extant, multidomain proteins are hypothesized to be the result of domain accretion, but there has been limited experimental validation of this idea. Here, we introduce a technique for genetic minimization by iterative size-exclusion and recombination (MISER) for comprehensively making all possible deletions of a protein. Using MISER, we generate a deletion landscape for the CRISPR protein Cas9. We find that the catalytically-dead Streptococcus pyogenes Cas9 can tolerate large single deletions in the REC2, REC3, HNH, and RuvC domains, while still functioning in vitro and in vivo, and that these deletions can be stacked together to engineer minimal, DNA-binding effector proteins. In total, our results demonstrate that extant proteins retain significant modularity from the accretion process and, as genetic size is a major limitation for viral delivery systems, establish a general technique to improve genome editing and gene therapy-based therapeutics.
Near-infrared manipulation of multiple neuronal populations via trichromatic upconversion
Authors: Liu Xuan , Chen Heming , Wang Yiting , Si Yueguang , Zhang Hongxin , Li Xiaomin , Zhang Zhengcheng , Yan Biao , Jiang Su , Wang Fei , Weng Shijun , Xu Wendong , Zhao Dongyuan , Zhang Jiayi , Zhang Fan 
Published: September 2021

AbstractUsing multi-color visible lights for independent optogenetic manipulation of multiple neuronal populations offers the ability for sophisticated brain functions and behavior dissection. To mitigate invasive fiber insertion, infrared light excitable upconversion nanoparticles (UCNPs) with deep tissue penetration have been implemented in optogenetics. However, due to the chromatic crosstalk induced by the multiple emission peaks, conventional UCNPs or their mixture cannot independently activate multiple targeted neuronal populations. Here, we report NIR multi-color optogenetics by the well-designed trichromatic UCNPs with excitation-specific luminescence. The blue, green and red color emissions can be separately tuned by switching excitation wavelength to match respective spectral profiles of optogenetic proteins ChR2, C1V1 and ChrimsonR, which enables selective activation of three distinct neuronal populations. Such stimulation with tunable intensity can not only activate distinct neuronal populations selectively, but also achieve transcranial selective modulation of the motion behavior of awake-mice, which opens up a possibility of multi-color upconversion optogenetics.
Plasmodium falciparum is evolving to escape malaria rapid diagnostic tests in Ethiopia
Authors: Feleke Sindew M. , Reichert Emily N. , Mohammed Hussein , Brhane Bokretsion G. , Mekete Kalkidan , Mamo Hassen , Petros Beyene , Solomon Hiwot , Abate Ebba , Hennelly Chris , Denton Madeline , Keeler Corinna , Hathaway Nicholas J. , Juliano Jonathan J. , Bailey Jeffrey A. , Rogier Eric , Cunningham Jane , Aydemir Ozkan , Parr Jonathan B. 
Published: September 2021

AbstractIn Africa, most rapid diagnostic tests (RDTs) for falciparum malaria recognize histidine-rich protein 2 antigen. Plasmodium falciparum parasites lacking histidine-rich protein 2 (pfhrp2) and 3 (pfhrp3) genes escape detection by these RDTs, but it is not known whether these deletions confer sufficient selective advantage to drive rapid population expansion. By studying blood samples from a cohort of 12,572 participants enroled in a prospective, cross-sectional survey along Ethiopia’s borders with Eritrea, Sudan and South Sudan using RDTs, PCR, an ultrasensitive bead-based immunoassay for antigen detection and next-generation sequencing, we estimate that histidine-rich protein 2-based RDTs would miss 9.7% (95% confidence interval 8.5–11.1) of P. falciparum malaria cases owing to pfhrp2 deletion. We applied a molecular inversion probe-targeted deep sequencing approach to identify distinct subtelomeric deletion patterns and well-established pfhrp3 deletions and to uncover recent expansion of a singular pfhrp2 deletion in all regions sampled. We propose a model in which pfhrp3 deletions have arisen independently multiple times, followed by strong positive selection for pfhrp2 deletion owing to RDT-based test-and-treatment. Existing diagnostic strategies need to be urgently reconsidered in Ethiopia, and improved surveillance for pfhrp2 deletion is needed throughout the Horn of Africa.
A best–worst scaling experiment to prioritize concern about ethical issues in citizen science reveals heterogeneity on people-level v. data-level issues
Authors: Guerrini Christi J. , Crossnohere Norah L. , Rasmussen Lisa , Bridges John F. P. 
Published: September 2021

Abstract“Citizen science” refers to the participation of lay individuals in scientific studies and other activities having scientific objectives. Citizen science gives rise to unique ethical issues that stem from the potentially multifaceted contributions of citizen scientists to the research process. We sought to explore the ethical issues that are most concerning to citizen scientist practitioners, participants, and scholars to support ethical practices in citizen science. We developed a best–worst scaling experiment using a balanced incomplete block design and fielded it with respondents recruited through the U.S.-based Citizen Science Association. Respondents were shown repeated subsets of 11 ethical issues and identified the most and least concerning issues in each subset. Latent class analysis revealed two respondent classes. The “Power to the People” class was most concerned about power imbalance between project leaders and participants, exploitation of participants, and lack of diverse participation. The “Show Me the Data” class was most concerned about the quality of data generated by citizen science projects and failure of projects to share data and other research outputs.
Immersive virtual reality interferes with default head–trunk coordination strategies in young children
Authors: Miehlbradt Jenifer , Cuturi Luigi F. , Zanchi Silvia , Gori Monica , Micera Silvestro 
Published: September 2021

AbstractThe acquisition of postural control is an elaborate process, which relies on the balanced integration of multisensory inputs. Current models suggest that young children rely on an ‘en-block’ control of their upper body before sequentially acquiring a segmental control around the age of 7, and that they resort to the former strategy under challenging conditions. While recent works suggest that a virtual sensory environment alters visuomotor integration in healthy adults, little is known about the effects on younger individuals. Here we show that this default coordination pattern is disrupted by an immersive virtual reality framework where a steering role is assigned to the trunk, which causes 6- to 8-year-olds to employ an ill-adapted segmental strategy. These results provide an alternate trajectory of motor development and emphasize the immaturity of postural control at these ages.
Time-efficient three-dimensional transmural scar assessment provides relevant substrate characterization for ventricular tachycardia features and long-term recurrences in ischemic cardiomyopathy
Authors: Merino-Caviedes Susana , Gutierrez Lilian K. , Alfonso-Almazán José Manuel , Sanz-Estébanez Santiago , Cordero-Grande Lucilio , Quintanilla Jorge G. , Sánchez-González Javier , Marina-Breysse Manuel , Galán-Arriola Carlos , Enríquez-Vázquez Daniel , Torres Carlos , Pizarro Gonzalo , Ibáñez Borja , Peinado Rafael , Merino Jose Luis , Pérez-Villacastín Julián , Jalife José , López-Yunta Mariña , Vázquez Mariano , Aguado-Sierra Jazmín , González-Ferrer Juan José , Pérez-Castellano Nicasio , Martín-Fernández Marcos , Alberola-López Carlos , Filgueiras-Rama David 
Published: September 2021

AbstractDelayed gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging requires novel and time-efficient approaches to characterize the myocardial substrate associated with ventricular arrhythmia in patients with ischemic cardiomyopathy. Using a translational approach in pigs and patients with established myocardial infarction, we tested and validated a novel 3D methodology to assess ventricular scar using custom transmural criteria and a semiautomatic approach to obtain transmural scar maps in ventricular models reconstructed from both 3D-acquired and 3D-upsampled-2D-acquired LGE-CMR images. The results showed that 3D-upsampled models from 2D LGE-CMR images provided a time-efficient alternative to 3D-acquired sequences to assess the myocardial substrate associated with ischemic cardiomyopathy. Scar assessment from 2D-LGE-CMR sequences using 3D-upsampled models was superior to conventional 2D assessment to identify scar sizes associated with the cycle length of spontaneous ventricular tachycardia episodes and long-term ventricular tachycardia recurrences after catheter ablation. This novel methodology may represent an efficient approach in clinical practice after manual or automatic segmentation of myocardial borders in a small number of conventional 2D LGE-CMR slices and automatic scar detection.