bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kutane Sarkoidose – eine granulomatöse Modellerkrankung
Authors: Redl A. , Stary G. 
Published: April 2022

ZusammenfassungSarkoidose ist eine entzündliche Erkrankung unklarer Genese, welche zur Gruppe der granulomatösen Erkrankungen gehört. Sie ist durch die Bildung von typischen nichtverkäsenden Granulomen in betroffenen Organen charakterisiert, die als persistierende Entzündungsreaktion schlussendlich zu organschädigender Fibrose führen können. Die Lunge stellt das am häufigsten betroffene Organ dar, gefolgt von Lymphknoten und Haut. Die kutane Sarkoidose kann sich in vielen Formen und Krankheitsverläufen präsentieren. Sie kann den Beginn der Erkrankung ankündigen oder später im Verlauf zusätzlich zu einer bestehenden Organmanifestation auftreten. Die Therapie der kutanen Sarkoidose kann den behandelnden Arzt vor eine Herausforderung stellen. Neueste Ergebnisse aus der Forschung im Bereich der Sarkoidose eröffnen neue Therapiemöglichkeiten zur Behandlung der kutanen Sarkoidose. Dabei gilt zu beachten, dass es keine universelle Therapie gibt, sondern das Ansprechen in Abhängigkeit des Patienten und der Morphologie der Erkrankung stark schwanken kann.
Pietra Alberese: from Traditional Building Material of the Tuscan Countryside to the Present Use (Tuscany, Italy)
Authors: Fratini Fabio , Rescic Silvia , Arrighetti Andrea , Cantisani Emma , Pecchioni Elena 
Published: April 2022

AbstractIn Tuscany, the vernacular architecture of the countryside between Siena and Florence (Chianti territory), and the monumental architecture of towns such as Prato and Pistoia together with the surrounding villages, extensively used a local limestone, the Pietra Alberese. It is a grey marly limestone, very resistant to decay, which takes on a whitish colour upon exposure to atmospheric agents. In addition, the Pietra Alberese was used to produce lime, being the only limestone cropping out in this territory. In this work, the Pietra Alberese is characterized, from a geological, mineralogical and petrographic point of view, highlighting its problems of conservation. Furthermore, the use in the historical architecture (both vernacular and monumental) and in the twentieth century architecture is illustrated.
Fine-scale habitat selection of a small mammalian urban adapter: the West European hedgehog (Erinaceus europaeus)
Authors: Gazzard Abigail , Yarnell Richard W. , Baker Philip J. 
Published: April 2022

AbstractUnderstanding patterns of habitat selection and factors affecting space use is fundamental in animal conservation. In urban landscapes, such knowledge can be used to advise householders on how best to manage their gardens for wildlife. In this study, we tracked 28 West European hedgehogs (Erinaceus europaeus), a species of conservation concern in the UK, in an area of high-density housing using radio and GPS tags to quantify patterns of habitat use and identify factors associated with the proportion of time spent in individual gardens. Both males and females exhibited a preference for residential gardens, but there were subtle differences between the sexes in relation to house type and front versus back gardens. Hedgehogs spent significantly more time in gardens where artificial food was provided, where a compost heap was present, if foxes (Vulpes vulpes) were infrequent visitors, if it rained overnight and as daylength increased (i.e., shorter nights); garden use was not significantly associated with variables potentially likely to reflect invertebrate prey abundance. These data suggest that the primary positive action that householders can undertake for urban hedgehogs is providing supplementary food. However, householders often feed hedgehogs after they know they are already visiting their garden. Consequently, the presence of artificial food may make it difficult to identify other important influences affecting garden use. Finally, we report that a GPS fix acquisition rate < 60% likely had no major effect on the results of our analyses, but should be a consideration in future studies using this technique on this species and in this habitat.
A 20‐Year Study of Melt Processes Over Larsen C Ice Shelf Using a High‐Resolution Regional Atmospheric Model: 2. Drivers of Surface Melting
Authors: Gilbert E. , Orr A. , Renfrew I. A. , King J. C. , Lachlan‐Cope T. 
Published: April 2022

AbstractQuantifying the relative importance of the atmospheric drivers of surface melting on the Larsen C ice shelf is critical in the context of recent and future climate change. Here, we present analysis of a new multidecadal, high‐resolution model hindcast using the Met Office Unified Model, described in Part 1 of this study. We evaluate the contribution of various atmospheric conditions in order to identify and rank, for the first time, the most significant causes of melting over the recent past. We find the primary driver of surface melting on Larsen C is solar radiation. Foehn events are the second most important contributor to surface melting, especially in nonsummer seasons when less solar radiation is received at the surface of the ice shelf. Third, cloud influences surface melting via its impact on the surface energy balance (SEB); when the surface temperature is warm enough, cloud can initiate or prolong periods of melting. Lastly, large‐scale circulation patterns such as the Southern Annular Mode (SAM), El Niño Southern Oscillation, and Amundsen Sea Low control surface melting on Larsen C by influencing the local meteorological conditions and SEB. These drivers of melting interact and overlap, e.g., the SAM influences the frequency of foehn, commonly associated with leeside cloud clearances and sunnier conditions. Ultimately, these drivers matter because sustained surface melting on Larsen C could destabilize the ice shelf via hydrofracturing, which would have consequences for the fate of the ice shelf and sea levels worldwide.
Interacting plexcitons for designed ultrafast optical nonlinearity in a monolayer semiconductor
Authors: Tang Yuxiang , Zhang Yanbin , Liu Qirui , Wei Ke , Cheng Xiang’ai , Shi Lei , Jiang Tian 
Published: April 2022

AbstractSearching for ideal materials with strong effective optical nonlinear responses is a long-term task enabling remarkable breakthroughs in contemporary quantum and nonlinear optics. Polaritons, hybridized light-matter quasiparticles, are an appealing candidate to realize such nonlinearities. Here, we explore a class of peculiar polaritons, named plasmon–exciton polaritons (plexcitons), in a hybrid system composed of silver nanodisk arrays and monolayer tungsten-disulfide (WS2), which shows giant room-temperature nonlinearity due to their deep-subwavelength localized nature. Specifically, comprehensive ultrafast pump–probe measurements reveal that plexciton nonlinearity is dominated by the saturation and higher-order excitation-induced dephasing interactions, rather than the well-known exchange interaction in traditional microcavity polaritons. Furthermore, we demonstrate this giant nonlinearity can be exploited to manipulate the ultrafast nonlinear absorption properties of the solid-state system. Our findings suggest that plexcitons are intrinsically strongly interacting, thereby pioneering new horizons for practical implementations such as energy-efficient ultrafast all-optical switching and information processing.
Nanoscale plasma-activated aerosol generation for in situ surface pathogen disinfection
Authors: Chew Nicholas S. L. , Wong Kiing S. , Chang Wei S. , Ooi Chien W. , Yeo Leslie Y. , Tan Ming K. 
Published: April 2022

AbstractPlasma treatment constitutes an efficient method for chemical-free disinfection. A spray-based system for dispensing plasma-activated aerosols onto surfaces would facilitate disinfection of complex and/or hidden surfaces inaccessible to direct line-of-sight (for example, UV) methods. The complexity and size of current plasma generators (for example, plasma jet and cometary plasma systems)—which prohibit portable operation, together with the short plasma lifetimes, necessitate a miniaturized in situ technique in which a source can be simultaneously activated and administered on-demand onto surfaces. Here, we demonstrate this possibility by combining two nanoscale technologies for plasma and aerosol generation into an integrated device that is sufficiently small and lightweight. Plasma is generated on a carpet of zinc oxide nanorods comprising a nanoneedle ensemble, which when raised to a high electric potential, constitutes a massive point charge array with near-singular electric fields to effect atmospheric breakdown. The plasma is then used to activate water transported through an underlying capillary wick, that is subsequently aerosolized under MHz-order surface acoustic waves. We show that the system, besides being amenable to miniaturization and hence integration into a chipscale device, leads to a considerable improvement in plasma-activation over its macroscale cometary discharge predecessor, with up to 20% and 127% higher hydrogen peroxide and nitrite ion concentrations that are respectively generated in the plasma-activated aerosols. This, in turn, leads to a 67% reduction in the disinfection time to achieve 95% bacterial load reduction, therefore demonstrating the potential of the technology as an efficient portable platform for on-demand field-use surface disinfection.
Micromechanical mode-localized electric current sensor
Authors: Li Han , Zhang Zhao , Zu Luhan , Hao Yongcun , Chang Honglong 
Published: April 2022

AbstractThis paper outlines the design of a novel mode-localized electric current sensor based on a mechanically sensitive element of weakly coupled resonator systems. With the advantage of a high voltage sensitivity of weakly coupled resonator systems, the current under test is converted to voltage via a silicon shunt resistor, which causes stiffness perturbation to one resonator. The mode-localization phenomenon alters the energy distribution in the weakly coupled resonator system. A theoretical model of current sensing is established, and the performance of the current sensor is determined: the sensitivity of the electric current sensor is 567/A, the noise floor is 69.3 nA/√Hz, the resolution is 183.6 nA, and the bias instability is 81.6 nA. The mode-localized electric current sensor provides a new approach for measuring sub-microampere currents for applications in nuclear physics, including for photocurrent signals and transistor leakage currents. It could also become a key component of a portable mode-localized multimeter when combined with a mode-localized voltmeter. In addition, it has the potential for use in studying sensor arrays to achieve higher resolution.
Validation of ketamine as a pharmacological model of thalamic dysconnectivity across the illness course of schizophrenia
Authors: Abram Samantha V. , Roach Brian J. , Fryer Susanna L. , Calhoun Vince D. , Preda Adrian , van Erp Theo G. M. , Bustillo Juan R. , Lim Kelvin O. , Loewy Rachel L. , Stuart Barbara K. , Krystal John H. , Ford Judith M. , Mathalon Daniel H. 
Published: April 2022

AbstractN-methyl-D-aspartate receptor (NMDAR) hypofunction is a leading pathophysiological model of schizophrenia. Resting-state functional magnetic resonance imaging (rsfMRI) studies demonstrate a thalamic dysconnectivity pattern in schizophrenia involving excessive connectivity with sensory regions and deficient connectivity with frontal, cerebellar, and thalamic regions. The NMDAR antagonist ketamine, when administered at sub-anesthetic doses to healthy volunteers, induces transient schizophrenia-like symptoms and alters rsfMRI thalamic connectivity. However, the extent to which ketamine-induced thalamic dysconnectivity resembles schizophrenia thalamic dysconnectivity has not been directly tested. The current double-blind, placebo-controlled study derived an NMDAR hypofunction model of thalamic dysconnectivity from healthy volunteers undergoing ketamine infusions during rsfMRI. To assess whether ketamine-induced thalamic dysconnectivity was mediated by excess glutamate release, we tested whether pre-treatment with lamotrigine, a glutamate release inhibitor, attenuated ketamine’s effects. Ketamine produced robust thalamo-cortical hyper-connectivity with sensory and motor regions that was not reduced by lamotrigine pre-treatment. To test whether the ketamine thalamic dysconnectivity pattern resembled the schizophrenia pattern, a whole-brain template representing ketamine’s thalamic dysconnectivity effect was correlated with individual participant rsfMRI thalamic dysconnectivity maps, generating “ketamine similarity coefficients” for people with chronic (SZ) and early illness (ESZ) schizophrenia, individuals at clinical high-risk for psychosis (CHR-P), and healthy controls (HC). Similarity coefficients were higher in SZ and ESZ than in HC, with CHR-P showing an intermediate trend. Higher ketamine similarity coefficients correlated with greater hallucination severity in SZ. Thus, NMDAR hypofunction, modeled with ketamine, reproduces the thalamic hyper-connectivity observed in schizophrenia across its illness course, including the CHR-P period preceding psychosis onset, and may contribute to hallucination severity.
Mouse models of immune dysfunction: their neuroanatomical differences reflect their anxiety-behavioural phenotype
Authors: Fernandes Darren J. , Spring Shoshana , Corre Christina , Tu Andrew , Qiu Lily R. , Hammill Christopher , Vousden Dulcie A. , Spencer Noakes T. Leigh , Nieman Brian J. , Bowdish Dawn M. E. , Foster Jane A. , Palmert Mark R. , Lerch Jason P. 
Published: April 2022

AbstractExtensive evidence supports the role of the immune system in modulating brain function and behaviour. However, past studies have revealed striking heterogeneity in behavioural phenotypes produced from immune system dysfunction. Using magnetic resonance imaging, we studied the neuroanatomical differences among 11 distinct genetically modified mouse lines (n = 371), each deficient in a different element of the immune system. We found a significant and heterogeneous effect of immune dysfunction on the brains of both male and female mice. However, by imaging the whole brain and using Bayesian hierarchical modelling, we were able to identify patterns within the heterogeneous phenotype. Certain structures—such as the corpus callosum, midbrain, and thalamus—were more likely to be affected by immune dysfunction. A notable brain–behaviour relationship was identified with neuroanatomy endophenotypes across mouse models clustering according to anxiety-like behaviour phenotypes reported in literature, such as altered volume in brains regions associated with promoting fear response (e.g., the lateral septum and cerebellum). Interestingly, genes with preferential spatial expression in the most commonly affected regions are also associated with multiple sclerosis and other immune-mediated diseases. In total, our data suggest that the immune system modulates anxiety behaviour through well-established brain networks.
The differential diagnostic value of dual-phase 18F-DCFPyL PET/CT in prostate carcinoma
Authors: Tian Aijuan , Lin Runlong , Yu Jing , Zhang Fan , Zheng Qiang , Yuan Xin , Sun Zhanhua , Zhong Zhaoyan 
Published: April 2022

Abstract
Objective
Binding of 18F-DCFPyL at prostate cancer (PC) cells increases over time. The dual-phase protocol may be helpful in separating benign lesions from malignant ones associated with prostate cancer. The purpose of this study was to retrospectively analyze the incremental diagnostic value of 18F-DCFPyL dual-time imaging in patients with prostate cancer.

Method
114 prostate-related malignant lesions and 43 benign lesions in 38 patients with prostate cancer were retrospectively analyzed. Maximum standardized uptake value (SUVmax) for benign and prostate-related malignant lesions were calculated at min 60 and min 120 of PET/CT imaging. In order to calculate SUV ratio, the SUVmax of left gluteus maximus was measured at the same time. The difference of SUVmax metrics and SUV ratio between malignant and benign lesions was statistically analyzed, the cut-off value of ROC curve was calculated, and the diagnostic efficacy of SUVmax index and SUV ratio at two time points was compared.

Results
SUVmax metrics and SUV ratio of early and delayed imaging of PC-related malignant lesions were significantly higher than those of benign lesions (p < 0.05). In terms of individual indicators, the highest accuracy and sensitivity was in the delayed SUV ratio (89.2% and 94.7%), the best specificity was in the early SUVmax (93.0%). When the individual and combined indicators were compared together, the SUV ratio in the delay period still showed the best diagnostic sensitivity and accuracy, and the best specificity were SUVmax early and ▵SUVmax, SUVmax early and RI.

Conclusions
Uptake of 18F-DCFPyL increased over time in prostate-associated malignant lesions compared with benign tissue. For single-phase imaging, 2-hour (delayed) imaging has better diagnostic performance. However, the dual-phase imaging (1 and 2 h) are helpful in the differential diagnosis of prostate-associated malignant lesions and benign lesions.
Microvascular stabilization via blood-brain barrier regulation prevents seizure activity
Authors: Greene Chris , Hanley Nicole , Reschke Cristina R. , Reddy Avril , Mäe Maarja A. , Connolly Ruairi , Behan Claire , O’Keeffe Eoin , Bolger Isobel , Hudson Natalie , Delaney Conor , Farrell Michael A. , O’Brien Donncha F. , Cryan Jane , Brett Francesca M. , Beausang Alan , Betsholtz Christer , Henshall David C. , Doherty Colin P. , Campbell Matthew 
Published: April 2022

AbstractBlood-brain barrier (BBB) dysfunction is associated with worse epilepsy outcomes however the underlying molecular mechanisms of BBB dysfunction remain to be elucidated. Tight junction proteins are important regulators of BBB integrity and in particular, the tight junction protein claudin-5 is the most enriched in brain endothelial cells and regulates size-selectivity at the BBB. Additionally, disruption of claudin-5 expression has been implicated in numerous disorders including schizophrenia, depression and traumatic brain injury, yet its role in epilepsy has not been fully deciphered. Here we report that claudin-5 protein levels are significantly diminished in surgically resected brain tissue from patients with treatment-resistant epilepsy. Concomitantly, dynamic contrast-enhanced MRI in these patients showed widespread BBB disruption. We show that targeted disruption of claudin-5 in the hippocampus or genetic heterozygosity of claudin-5 in mice exacerbates kainic acid-induced seizures and BBB disruption. Additionally, inducible knockdown of claudin-5 in mice leads to spontaneous recurrent seizures, severe neuroinflammation, and mortality. Finally, we identify that RepSox, a regulator of claudin-5 expression, can prevent seizure activity in experimental epilepsy. Altogether, we propose that BBB stabilizing drugs could represent a new generation of agents to prevent seizure activity in epilepsy patients.
Dissecting extracellular and intracellular distribution of nanoparticles and their contribution to therapeutic response by monochromatic ratiometric imaging
Authors: Yan Yue , Chen Binlong , Yin Qingqing , Wang Zenghui , Yang Ye , Wan Fangjie , Wang Yaoqi , Tang Mingmei , Xia Heming , Chen Meifang , Liu Jianxiong , Wang Siling , Zhang Qiang , Wang Yiguang 
Published: April 2022

AbstractEfficient delivery of payload to intracellular targets has been identified as the central principle for nanomedicine development, while the extracellular targets are equally important for cancer treatment. Notably, the contribution of extracellularly distributed nanoparticles to therapeutic outcome is far from being understood. Herein, we develop a pH/light dual-responsive monochromatic ratiometric imaging nanoparticle (MRIN), which functions through sequentially lighting up the intracellular and extracellular fluorescence signals by acidic endocytic pH and near-infrared light. Enabled by MRIN nanotechnology, we accurately quantify the extracellular and intracellular distribution of nanoparticles in several tumor models, which account for 65–80% and 20–35% of total tumor exposure, respectively. Given that the majority of nanoparticles are trapped in extracellular regions, we successfully dissect the contribution of extracellularly distributed nanophotosensitizer to therapeutic efficacy, thereby maximize the treatment outcome. Our study provides key strategies to precisely quantify nanocarrier microdistribtion and engineer multifunctional nanomedicines for efficient theranostics.
A pair of non-Mendelian genes at the Ga2 locus confer unilateral cross-incompatibility in maize
Authors: Chen Zhibin , Zhang Zhaogui , Zhang Huairen , Li Kai , Cai Darun , Zhao Li , Liu Juan , Chen Huabang 
Published: April 2022

AbstractMaize unilateral cross-incompatibility (UCI) that causes non-Mendelian segregation ratios has been documented for more than a century.Ga1,Ga2, andTcb1are three major UCI systems, described but not fully understood. Here, we report comprehensive genetic studies on theGa2locus and map-based cloning of the tightly linked male determinantZmGa2Pand female determinantZmGa2Fthat govern pollen-silk compatibility among different maize genotypes. Both determinants encode putative pectin methylesterases (PME). A significantly higher degree of methyl esterification is detected in the apical region of pollen tubes growing in incompatible silks. No direct interaction between ZmGa2P and ZmGa2F is detected in the yeast two-hybrid system implying a distinct mechanism from that of self-incompatibility (SI). We also demonstrate the feasibility ofGa2as a reproductive barrier in commercial breeding programs and stackingGa2withGa1could strengthen the UCI market potentials.
Blood-based tumor mutational burden as a biomarker for atezolizumab in non-small cell lung cancer: the phase 2 B-F1RST trial
Authors: Kim Edward S. , Velcheti Vamsidhar , Mekhail Tarek , Yun Cindy , Shagan Sarah M. , Hu Sylvia , Chae Young Kwang , Leal Ticiana A. , Dowell Jonathan E. , Tsai Michaela L. , Dakhil Christopher S. R. , Stella Philip , Jin Yanling , Shames David S. , Schleifman Erica , Fabrizio David A. , Phan See , Socinski Mark A. 
Published: April 2022

AbstractTumor mutational burden (TMB) in circulating tumor DNA (ctDNA) has shown promise in predicting benefit from PD-L1/PD-1 inhibitors in retrospective studies. Aiming to assess blood TMB (bTMB) prospectively, we conducted B-F1RST (NCT02848651), an open-label, phase 2 trial that evaluated bTMB as a predictive biomarker for first-line atezolizumab monotherapy in locally advanced or metastatic stage IIIB–IVB non-small cell lung cancer (n = 152). The co-primary endpoints were investigator-assessed objective response rate (ORR) per RECIST version 1.1 and investigator-assessed progression-free survival (PFS) between high and low bTMB subgroups at the pre-defined bTMB ≥ 16 (14.5 mutations per megabase) cutoff. Secondary endpoints included investigator-assessed PFS, overall survival (OS) and duration of response at various bTMB cutoffs, as well as safety. Investigator-assessed PFS in the bTMB ≥ 16 versus bTMB < 16 groups was not statistically significant. However, bTMB ≥ 16 was associated with higher ORR, and ORR improved as bTMB cutoffs increased. No new safety signals were seen. In exploratory analyses, patients with maximum somatic allele frequency (MSAF) < 1% had higher ORR than patients with MSAF ≥ 1%. However, further analysis showed that this effect was driven by better baseline prognostics rather than by MSAF itself. At 36.5-month follow-up, an exploratory analysis of OS found that bTMB ≥ 16 was associated with longer OS than bTMB < 16. Further study and assay optimization will be required to develop bTMB as a predictive, standalone biomarker of immunotherapy or for use in conjunction with other biomarkers.